Stroke & Neurovascular: Animal Studies

Wednesday 3 June 2015

Do-Wan Lee^1,2, Dong-Cheol Woo², Minyoung Lee^2,3, Chul-Woong Woo², Sang-Tae Kim², Choong Gon Choi⁴, Bo-Young Choe¹, and Byong Sop Lee^3
1Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul, Seoul, Korea, ²Asan Institute for Life Sciences, Asan Medical Center, Seoul, Seoul, Korea, ³Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea,⁴Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

The purpose of this study was to quantitatively determine the influence of the time-dependent effects of hypoxic-ischemic-encephalopathy (HIE) on cerebral metabolite changes in a neonatal rat model of severe HIE. Our results exhibited that a total of 16 metabolite signals in HIE rats were significantly altered with increased periods of development (at PD7, PD14, and PD28), compared to the CNTL. The present study is unique in that we discovered not only the usefulness of traditional markers (NAA, Cr, and choline-containing-compounds) but also several new results (Ala, Asp, Glu, Gln, and GSH, etc.) from a neonatal rat model of severe HIE.

Yuhao Sun^1,2, Qiang Shen¹, Shiliang Huang¹, and Timothy Q. Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States, ²Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Subarachnoid hemorrhage (SAH) is a medical emergency. Vasospasm is widely reported. However, its effects on cerebral blood flow (CBF) and cerebrovascular reactivity are seldom studied. We found SAH induced marked perturbations of basal CBF and cerebrovascular reactivity in an established animal of SAH from day 0 to 7. CBF and cerebrovascular reactivity recovered gradually by day 7. This study investigated the effects of SAH on CBF and CO2 reactivity in an established rat model. We concluded that hemodynamic disturbance in the brain after subarachnoid hemorrhage could contribute to progressive neurological deficits.

Shi Chang-Zheng¹, Jing Zhen¹, Ruan Yiwen¹, and Huang Li¡¯an^1
1Jinan University, Guangzhou, Guangdong, China

Most pathological changes were elicited when BCCAO was induced simultaneously at both the left and right CCAs. Another model was later introduced where BCCAO was induced with one week interval between the first and second CCA occlusions . The latter allows gradual development of CCH within the brain. Although the pathological mechanisms of these models have been widely studied, dynamic changes in CBF and angiogenesis are not completely understood.

Qiang Shen¹, Shiliang Huang¹, and Timothy Q Duong^1
1Research Imaging Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Percent change of T2*-weighted signal following oxygen challenge (OC) has been used as a biomarker of penumbra. However, T2*-weighted MRI of OC challenge in delineating tissue at risk has low contrast-to-noise sensitivity and there are significant false positive and negative pixels, particular from pixels that contain large vessels. In order for this biomarker to be practical, it is necessary to improve its specificity and sensitivity. The goal of this study was to explore the use of the time-to-peak of OC response to further improve the identification of at-risk tissue in ischemic stroke.

Jens T Rosenberg^1,2, Avigdor Leftin³, Eddy Soloman³, Lucio Frydman^1,3, and Samuel C Grant^1,2
1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, ²Chemical & Biomedical Engineering, Florida State University, Tallahassee, FL, United States, ³Chemical Physics, Weizmann Institute of Science, Rehovot, Israel

Diffusion-weighted spatiotemporal encoding (DW-SPEN) was used to evaluate a pre-clinical in vivo model of ischemic stroke under treatment with super-paramagnetic iron-oxide labeled human mesenchymal stem cells at 21.1 T. In the presence of the induced background susceptibility gradient, this work demonstrates more robust quantification of in vivo diffusion parameters in DW-SPEN to DW-EPI and DW spin-echo acquisition methods.

Dan Wu¹, Frances J Northington², Lee J Martin³, and Jiangyang Zhang^4
1Biomedical Engineering, Johns Hopkins University School of Medicine, BALTIMORE, Maryland, United States, ²Pediatrics, Johns Hopkins University School of Medicine, Maryland, United States, ³Neuroscience, Johns Hopkins University School of Medicine, Maryland, United States, ⁴Radiology, Johns Hopkins University School of Medicine, Maryland, United States

The oscillating gradient diffusion MRI (OGSE) is useful in probing restricted diffusion in short-diffusion time, and thus is sensitive to microstructural changes in small scales. We used OGSE (50-200Hz) to examine hypoxic-ischemic (HI) injury in neonatal mouse brains at 3hrs and 24hrs after injury. Compared to PGSE, OGSE results revealed elevated ADC in external capsule in mild injury mice at 3hrs post-HI, and expanded lesion areas around the external capsule at 24hrs post-HI. The enhanced edema contrast in OGSE-ADC maps may correlate with microstructural pathology in astrocytes as shown in histology.

Ramesh Paudyal¹, Silun Wang¹, Yonggang Li², Byron D Ford², and Xiaodong Zhang^1
1Yerkes Imaging Center, Yerkes Regional Primate Research Center, Emory University, Atlanta, GA, United States, ²Neurobiology, Neurosciences Institute, Morehouse School of Medicine, Atlanta, GA, United States

The aim of this study was to assess the blood brain barrier permeability in a rat stroke model induced by a permanent middle cerebral artery occlusion (i.e., pMCAo) using dynamic susceptibility contrast-MRI at 48 hr. Our findings demonstrated that a leakage corrected blood volume indicated the disruption of BBB in ischemic injury at 48 hr.

Yong Zhang¹, Jiangliang Cheng¹, Yanan Lin¹, Lu Yang¹, Shanshan Zhao¹, and Dandan Zheng^2
1Dept. of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China, ²GE Healthcare, China, Beijing, China

The mechanism of cerebral infarction might be related to the theory of crossed cerebral-cerebellar diaschisis which pointed out that supratentorial focal brain damage could cause short functional changes in its fiber linked distant areas. In this study, we detected FA and the RGMa protein expression in remote regions of the infarct core in rats after MCAO at a continuous time point. The two values were analyzed to reveal the diffusion condition and pathological changes of the bilateral cerebellar hemispheres and hope to give more evidences about the relevant mechanism of crossed cerebellar diaschisis.

Yu-Chieh Jill Kao^1,2, Esteban A Oyarzabal¹, Hua Zhang³, James E Faber³, and Yen-Yu Ian Shih^1
1Neurology and BRIC, University of North Carolina, Chapel Hill, NC, United States, ²Imaging Research Center, Taipei Medical University, Taipei, Taipei, Taiwan, ³Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC, United States

By using two genetically engineered mouse strains that differ in collateral extent, the present study demonstrated that collateral circulation significantly suppresses the expansion of ischemic core, restores area with cerebral blood flow deficit and reduces final infarct size.

Ramesh Paudyal¹, Yonggang Li², Silun Wang¹, Byron D. Ford², and Xiaodong Zhang^1
1Yerkes Imaging Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA, United States, ²Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, United States

Neuregulin-1 (NRG-1) has shown the neuroprotective effects in ischemic brain injury by reducing infarct volume and protecting neurons from ischemic damage. This study evaluates the neuroprotective effect of NRG-1 in a rat stroke model induced by permanent middle cerebral artery occlusion (pMCAo) using perfusion-and diffusion weighted magnetic resonance imaging (MRI) at 3hr and 48 hr and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and cresyl violet staining (CV) at 48 hr. Results showed that the vehicle treated group has a significantly greater ischemic lesion volume and mismatch region at 3hr than NRG-1 treated group. Our finding showed that NRG-1 served as a potent neuroprotectants in ischemic injury.

Harriet J Rogers¹, Bryony L McGarry¹, Kimmo T Jokivarsi², Michael J Knight¹, Alejandra Sierra Lopez², Olli HJ Gröhn², and Risto A Kauppinen^1
1School of Experimental Psychology and CRIC, University of Bristol, Bristol, United Kingdom, ²Department of Neurobiology, University of Eastern Finland, Kuopio, Finland

Thrombolytic therapy for acute ischaemic stroke requires known symptom onset time, however for many patients this is unknown. We determined time-dependent changes of T₁and T₂ in ischaemic rat brain. Both T₁ and T₂ relaxation times increased linearly in the ischaemic lesion for the observation time of 5 hours. T₁and T₂ prolongation occurred in different regions in early moments and overlapped at later time-points. Volume of overlap increased linearly with time, thus combining these parameters provides a further proxy for stroke onset time and assessment of tissue status. Quantitative relaxometry bears potentials for acute stroke patient stratification.

Bang-Bon Koo¹, Mary Orczykowski^1,2, Kevin Arndt¹, Yansong Zhao³, Tara Moore¹, and Ron J. Killiany^1
1Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, United States, ²Boston University School of Medicine, MA, United States, ³Philips Healthcare, Cleveland, OH, United States

In this work, we investigated causal relationships on the lesions on both cognitive and brain structural and resting-functional network changes in rhesus monkeys.

Pavel Rodriguez¹, Jiang (John) Zhao^1,2, and Timothy Q. Duong^1
1Research Imaging Institute, The University of Texas Health Science Center, San Antonio, Texas, United States, ²Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, United States

We previously reported that a single-dose methylene blue (MB), an energy-enhancing drug, given hyperacutely reduced infarct volume in permanent and transient MCAO in rats using MRI up to 2 days. This study investigated the effect of chronic MB therapy on ischemic stroke volume along with behavioral score correlations 28 days after stroke. We administered MB at day 0, 2, 7, 14 and obtained stroke volume and functional behavioral measurements out to 28 days. We also used a new more aggressive treatment paradigm that involves doubling MB dose over permanent ischemia and after reperfusion. We hypothesized that this new MB treatment paradigm is safe, decreases final stroke volumes and functional sensorimotor deficit.

Yash Vardhan Tiwari^1,2 and Timothy Duong^1
1Research Imaging Institute, UT Health Science Center, San Antonio, Texas, United States, ²Biomedical Engineering, UT, San Antonio, Texas, United States

Apparent diffusion coefficient is a highly sensitive marker for ischemic insult, but lacks desired specificity in distinguishing salvageable versus non-salvageable tissue. There is an ever urgent need to define ADC threshold correlates of cerebral blood flow (CBF) and tissue deoxygenation in ischemia. This study incorporated simultaneous tPO2 measurement with interleaved perfusion and diffusion MRI at high temporal resolution to measure patterns of ADC changes in correlation to CBF and tPO2 response immediately following global cerebral ischemia.

Jed Wingrove*¹, Daniel Stcukey*¹, Valerie Taylor¹, Thomas Roberts¹, Rajiv Ramasawmy¹, Bernard Siow+¹, and Mark Lythgoe+^1
1Centre for Advanced Biomedical Imaging, Department of Medicine, University College London, London, United Kingdom

Small animal stroke research commonly uses histological analysis for the evaluation of pathological severity, however, histology precludes longitudinal studies of stroke evolution. Non-invasive, in vivo MRI has become increasingly prominent in pre-clinical settings, hugely benefiting the prediction of long-term pharmacological outcomes. However, most pre-clinical MRI systems operate at high field (≥ 4.7T), requiring cryogen cooling and are expensive to purchase and maintain. Recently, low-field (1T) “benchtop” MRI scanners have emerged which may be a cost-effective alternative. In this study, we demonstrate that a 1T benchtop MRI scanner is well suited to assessing stroke lesions in a rodent model of stroke.

Ursula Tuor¹, Min Qiao², Manasi Sule², Qinbo Deng², Melissa Morgunov², David Rushforth², and Tadeusz Foniok^2
1Physiology and Pharmacology, Cl Neurosciences and Radiology, University of Calgary, Calgary, AB, Canada, ²University of Calgary, Calgary, AB, Canada

We investigated whether differing severities of photothrombotic insults could be produced in immature brain as observed in adult rats previously. Mild lesions in neonatal cortex consisted of small hyperintense DW regions corresponding to marked increases in T2. In contrast, adults had hyperintense DW regions corresponding to marked T2 increases but also modest T2 increases beyond the DW lesion border. In contrast to neonatal brain, T2 is more sensitive for detecting ischemic injury than DW in adult brain. The results indicate a promising approach to study thrombotic occlusion and reperfusion injury and its MR diagnosis using quantitative T2, DW and ADC.

Guangliang Ding¹, Tao Yan¹, Jieli Chen¹, Michael Chopp^1,2, Lian Li¹, Qingjiang Li¹, Chengcheng Cui¹, Ruizhuo Ning¹, and Quan Jiang^1
1Neurology, Henry Ford Hospital, Detroit, Michigan, United States, ²Physics, Oakland University, Rochester, Michigan, United States

Using a suture 2h occlusion and reperfusion stroke model and a low dose Streptozotocin injection combined with a high fat food diet diabetic model of young adult Wistar rats, Gd-DTPA leakage measured by CE-T1WI indicates that T2DM rats suffered more severe BBB disruption from 1 to 5 weeks after stroke (p<0.005), and SWI identified significant larger hemorrhagic volumes in T2DM rats throughout 5w after stroke (p<0.05), compared with WT rats. FA values of ischemic boundary in the striatum were consistently lower in the T2DM rats than in the WT controls, which suggest that T2DM hampers axonal density increase.

Shannon P. Holmes¹, Simon R. Platt², Liya Wang³, Vivian Lau², Grace Harrison², Hui Mao³, and Franklin West^2
1Veterinary Biosciences & Diagnostic Imaging, University of Georgia, Athens, GA, United States, ²University of Georgia, GA, United States, ³Emory University, GA, United States

Large animal models of stroke are needed for improved translation of novel therapeutics. The pig has been proposed as ideal, because of similar gyrification, gray-white matter composition and size to the human brain. This study developed a Landrace pig middle cerebral artery occlusion (MCAO) model. Anatomic and quantitative MRI techniques were used to evaluate the stroke, including DWI, spectroscopy, DTI and PWI. Anatomic studies, with DWI/ADC, measured the penumbra and ischemic zone. Significant differences were detected in neural metabolites and fractional anistrophy of white matter. Therefore, the Landrace pig MCAO model is feasible and produces in vivo quantifiable changes.

Silun Wang¹, Yonggang Li², Ramesh Paudyal¹, Byron D. Ford², and Xiaodong Zhang^1,3
1YERKES IMAGING CENTER, Emory University, Atlanta, GA, United States, ²Department of Neurobiology, Morehouse School of Medicine, GA, United States, ³Division of Neuropharmacology and Neurologic Diseases, Emory University, GA, United States

We evaluated the NRG-1 treatment response in a rat model of ischemic stroke using DTI. Results indicated that significantly lower infraction volume in the treatment group than in control group. Especially, it is shown the neuroprotective efficacy of NRG-1 is more evident in stroke rats with mild CBF reduction (<70% reduction). Significantly lower FA values were found in the vehicle group compared to NRG-1 treatment group, indicating less ischemic injury after NRG-1 administration. Our results support the use of DTI as a biomarker to non-invasively monitor the NRG-1 treatment response in ischemia induced brain injury.

Silun Wang¹, Xiaohuan Gu², Ramesh Paudyal¹, Shan Ping Yu², and Xiaodong Zhang^1,3
1YERKES IMAGING CENTER, Emory University, Atlanta, GA, United States, ²Department of Anesthesiology and Department of Neurology, Emory University School of Medicine, GA, United States, ³Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research Center, GA, United States

We evaluated the pharmacologically induced hypothermia treatment response in focal cerebral ischemia induced brain injury in a mice model using DTI. Results indicated that significantly lower infraction volume in the treatment group than control group. Less reduction of ADC values were found in the hypothermia treatment group. Our results support the use of DTI as a biomarker to non-invasively monitor the hypothermia treatment response in ischemia induced brain injury.

Mario G Lepore¹, Corina Berset¹, Rolf Gruetter^2,3, and Hongxia Lei^1,4
1AIT, Center for Biomedical Imaging (CIBM), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, ²Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Vaud, Switzerland, ³University of Lausanne, Lausanne, Vaud, Switzerland, ⁴University of Geneva, Geneva, Geneva, Switzerland

We illustrated that MR angiography and 1H MRS can be applied to identity 4-vessel-occlusion in rat.

Ji-Yeon Suh¹, Hoesu Jung², Hyung Joon Cho², Young Ro Kim³, Jeong Kon Kim⁴, and Gyunggoo Cho^1
1Magnetic Resonance Research, Korea Basic Science Institute, Cheongju, Chungbuk, Korea, ²Nano-Bioscience and Chemical Engineering, Ulsan National Institute of Science & Technology (UNIST), Ulsan, Korea, ³Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Massachusetts, United States, ⁴Asan Medical Center University of Ulsan college of Medicine, Seoul, Korea

To study the altered cerebrovascular tones following focal or global cerebral ischemia, infrequently measuring changes in T2(*)-driven relative blood volumes have been performed. In the current study, using the concurrent T1-T2 effects of the exogenous contrast agent, dual contrasts acquisitions were established in the acute phase of rat ischemia model. Co-acquisitions of positive (T1) and negative (T2(*)) contrasts provide complementary information on neurovascular traits such as absolute and relative cerebral blood volume and microvascular volume. This work may supply an important basis for understanding the impaired cerebrovascular changes involved with ischemic damage.

Tom Dresselaers¹, Annelies Quaegebeur^2,3, Kristof Govaerts¹, Inmaculada Segura^2,3, Robin Lemmens⁴, Peter Carmeliet^2,3, and Uwe Himmelreich^1
1Dept. of Imaging and Pathology, KU Leuven, Leuven, Belgium, ²Vesalius Research Center, VIB, Belgium, ³KU Leuven, Leuven, Belgium, ⁴VIB, Belgium

In this study we characterized the stroke lesion in mice resulting from a permanent distal MCAO. At 2, 24h and 1 week post occlusion quantitative perfusion data based on pulsed ASL and ADC, T1 and T2 maps were recorded. Images were analyzed using either manual delineation or a threshold based approach with the contra-lateral cortex as a reference region. We demonstrate that lesion characterization via MRI in this distal MCAO mouse stroke model is feasible thereby opening up the possibility to non-invasively monitor stroke development in different transgenic animal models related to for example oxygen sensors or hypoxia.

Silun Wang¹, Yonggang Li², Ramesh Paudyal¹, Byron D. Ford², and Xiaodong Zhang^1
1YERKES IMAGING CENTER, Emory University, Atlanta, GA, United States, ²Department of Neurobiology, Morehouse School of Medicine, GA, United States

We have demonstrated that DTI indices could provide promise diagnostic information to evaluate white matter and grey matter injury in an rat model of ischemic stroke treated by Neuregulin 1 as well as to characterize the penumbra evolution after stroke onset. The severity of white matter and cortex injury are highly associated with the location of infarct and vascular territory. In addition, the neuroprotective effects could be in vivo monitored using DTI . NRG-1 seems to have significant neuroprotective effects to white matter and cortex especially in acute stroke.

Stroke & Neurovascular: Human Studies

Wednesday 3 June 2015

Huan He¹, Tianyi Qian², Ni Liu¹, Xingli Liu¹, Zhongyan Wang¹, Lu Su¹, and Peiyi Gao^1
1Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing, China, ²MR Collaborations NE Asia, Siemens Healthcare, Beijing, China

The key to thrombolytic therapy in acute ischemic stroke is identifying the areas of infarct lesion in acute stage. By using a prototype simultaneous multi-slice accelerated (SMS) EPI sequence for DKI data recording, the total acquisition time could be cut down to 1/2~1/3 of standard EPI-based DKI without losing SNR. In the identification of the final infarct size in acute ischemic stroke, the volume measurements by SMS DKI in the acute-phase is more reliable than that of ADC, and the DKI data could be acquired in a reasonable time with the SMS EPI sequence.

Michael John Knight¹, Bryony McGarry¹, Harriet Rogers¹, Joanne Robson², Rose Bosnell³, Philip Clatworthy¹, and Risto Kauppinen^1
1School of experimental psychology, University of Bristol, Bristol, avon, United Kingdom, ²Southmead Hospital, Bristol, avon, United Kingdom, ³School of clinical sciences, University of bristol, Bristol, avon, United Kingdom

This work presents a simple, yet robust means for identifying regions of acutely ischaemic tissue, with minimal human intervention, from ADC mapping, and for the assessment of that tissue based on quantitative T2 mapping in ischaemic stroke patients. Having identified ADC lesions(s), we show using T2 mapping that within ischaemia distinct tissue signatures with different relaxation charateristics are separated. In particular, whereas ADC and T2 are positively correlated in healthy tissue, this is not the case in in the ischaemia, which can act as a further restraint for distinguishing between different tissue states and lesion types.

Dandan Zheng¹, Bing Wu¹, Jiangxi Xiao², Zhenghua Liu², and Zhenyu Zhou^1
1GE Healthcare China, Beijing, Beijing, China, ²Radiology Department, Peking University First Hospital, Beijing, China

The underlying mechanism of neurological symptoms in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is still controversial. Signal abnormalities in conventional MR contrast are indistinguishable from those observed in stroke, especially in the acute stage. In this study, diffusion weighted MR spectroscopy was used to differentiate acute MELAS from acute stroke and also to probe the mechanisms underlying the pathogenesis of MELAS.

Yuiko Sato¹, Kuniaki Ogasawara¹, Shinsuke Narumi², Makoto Sasaki³, Ayumi Saito², Takamasa Namba¹, Masakazu Kobayasi¹, Kenji Yoshida¹, Yasuo Terayama², and Akira Ogawa^1
1Department of Neurosurgery, Iwate Medical Univercity, Morioka, Iwate, Japan, ²Department of Neurology and Gerontology, Iwate Medical Univercity, Morioka, Iwate, Japan,³Division of Ultra-High Field MRI and Department of Radiology, Iwate Medical Univercity, Mrioka, Iwate, Japan

The purpose of the present study was to determine which plaque imaging technique predicts more accurately development of microembolic signals (MES) during carotid dissection in carotid endarterectomy (CEA). Our results demonstrated that non cardiac-gated spin echo (SE) T1-weighted plaque imaging, which discriminated the intraplaque characteristics with the contrast ratio of the plaque signal to the sternomastoid muscle signal and with the three component color-coded map, could predict more accurately development of MES during carotid dissection in CEA than other MR plaque imaging techniques (black-blood fast SE, MPRAGE, the source image of 3D-TOF MRA).

Ting Wang¹, Yanhua Li², Xinhong Guo², Diandian Huang¹, Lin Ma¹, and Xin Lou^1
1Department of Radiology, Chinese PLA General Hospital, Beijing, Beijing, China, ²Department of Cardiology, Chinese PLA General Hospital, Beijing, Beijing, China

White matter (WM) is the predilection area of lacunar infarction in hypertensive patients. It was hypothesized that abnormal CBF in WM appeared at early stage of hypertension, hence, we recruited thirty hypertensive patients and thirty healthy controls of an appropriate age to detect their CBF modifications of normal-appearing WM using 3D pcASL technique. As expected, compare to healthy volunteers, CBF values in various WM regions were observed to be lower in hypertensive patients. This proves that 3D pCASL has ability to detect the subtle hemodynamic abnormalities even at the early stage of hypertension.

Wu Wenbo¹, Yin Zhenyu¹, Zhang Xin², Zhou Fei², Liu Renyuan¹, Wang Huiting², Zhu Bin², Zhang Bing², and Xu Yun^1
1Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China, ²Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu, China

In this abstract, we compared the small-world properties among the MCI patients with or without lacunar infraction and normal aging elderly by applying graph-theoretical analyses.

Jinhao Lyu¹, Ning Ma², Zhongrong Miao², Lin Ma¹, and Xin Lou^1
1Department of Radiology, Chinese PLA General Hospital, Beijing, Beijing, China, ²Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing, China

Three dimensional pseudo-continuous arterial spin labeling(3D pCASL) is able to differentiate delay arrived blood flow form leptomeaningeal collaterals in patients with middle cerebral artery stenosis by applying multiple post labeling delay(PLD). We compared multi-PLD 3D pCASL with conventional angiography capillary index score(CIS) system in leptomeaningeal collaterals assessment.

Luguang Chen¹, Xia Tian¹, Qi Liu¹, Chao Ma¹, Qian Zhan¹, Xuefeng Zhang¹, Yuanliang Jiang¹, and Jianping Lu^1
1Department of Radiology,Changhai Hospital of Shanghai, The Second Military Medical University, Shanghai, Shanghai, China

Intracranial artery atherosclerosis is increasingly being recognized as a major cause of stroke worldwide, and patients with intracranial steno-occlusive disease have an augmented risk of vascular events. Several imaging modalities, including digital subtraction angiography, computed tomography angiography, and magnetic resonance imaging (MRI), are used to assess intracranial atherosclerosis. However, dark blood high-resolution MRI (HRMRI) superiors to other techniques in delineating the wall of the basilar artery (BA) because it is noninvasive and radiation-free.To our knowledge, the scan and rescan reproducibility of quantification of BA plaque has not reported. Therefore, the purpose of the present study is to evaluate of the interscan and intraobserver reproducibility of BA plaque employing dark blood HRMRI at 3Tesla.

Nikki Dieleman¹, Wenjie Yang², Jill Abrigo³, Ka Lok Lee³, Chiu Wing Chu³, Anja G. van der Kolk¹, Jeroen C.W. Siero¹, Ka Sing Wong², Jeroen Hendrikse¹, and Xiang Yan Chen^2
1Department of Radiology, University Medical Center Utrecht, Utrecht, Utrecht, Netherlands, ²Department of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong, China, ³Department of Imaging and Interventional Radiology, Chinese University of Hong Kong, Shatin, Hong Kong, China

In this study we qualitatively evaluated intracranial plaque characteristics (contrast enhancement, thickening and configuration), total plaque burden and distribution in patients with an MCA stenosis using a 3D T1-weighted volumetric isotropic turbo spin-echo acquisition (VISTA) vessel wall sequence at 3 tesla. The sequence was able to identify basic intracranial plaque characteristics and assess total plaque burden and distribution. We demonstrate that intracranial atherosclerotic plaques are mainly associated with an eccentric configuration and a focal thickening pattern. Most of the lesions were found in the anterior circulation, corresponding to similar distributions found for ischemic strokes.

Alexandre Krainik¹, Olivier Heck², Arnaud Attyé², Naila Boudiaf³, Florence Tahon², Kamel Boubagra², Johan Pietras², and Olivier Detante^2
1Neuroradiology and MRI, University hospital of Grenoble, Grenoble, France, ²University hospital of Grenoble, France, ³LPNC, France

Management of patients with Severe Intracranial Arterial Stenosis (SIAS) at risk of stroke events recurrence remains controversial. A better characterization of these patients might be helpful to define therapeutic strategy. BOLD fMRI to hypercapnic challenge has been proposed to identify impaired cerebrovascular reserve (CVR BOLD fMRI). We conducted a prospective study in 35 patients referred for a SIAS to estimate CVR BOLD fMRI, and compared their data a 100 volunteers’ dataset. Eighteen patients out of 35 had significantly impaired CVR. Thus, CVR BOLD fMRI could be helpful to better select patients with SIAS for more invasive treatment.

Diandian Huang¹, Xin Lou¹, Lin Ma¹, and Zhengyu Zhou^2
1radiology, Chinese PLA General Hospital, Beijing, Beijing, China, ²MR Research Center, GE Health care, Beijing, China

Hypertensive group without retinopathy and control group were recruited from the primary care and had a MR scan with the three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) and routine sequences. Compared to the control group, hypertensive patients implied the reduced CBF values on visual cortex without the statistical volume loss which may implicated there is a variety of the hemodynamics prior to the change of the morphology in the visual cortex in hypertension. Future studies in larger cohorts and longitudinal follow-up are needed to investigate the functional and prognostic significance of the early visual cortex perfusion deficits observed.

Xin Lou¹, Ning Ma², Yanhua Li³, Diandian Huang¹, Ting Wang¹, Zhenyu Zhou⁴, Bing Wu⁴, and Lin Ma^1
1Department of Radiology, Chinese PLA General Hospital, Beijing, China, ²Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Beijing, China, ³Department of Cardiology, Chinese PLA General Hospital, Beijing, China, ⁴MR Research Center, GE Healthcare, Beijing, China

The treatment of hypertension with acute ischemic stroke is controversial due to decrease mean arterial pressure may reduce cerebral blood flow to already ischemic regions and result in further ischemic injury after intake of antihypertensive drugs. Our findings suggested that there is a rapid adaptation of the cerebral hemisphere and brain stem to antihypertensive therapy in order to protect those areas of the brain from hypoperfusion; however, an acute reduction in BP may compromise cerebellar perfusion at the initial stage of antihypertensive therapy in patients with hypertension. 3D pCASL can be used for monitoring cerebral blood flow during antihypertensive therapy.

Christopher J. Steele¹, Leonie Lampe¹, Alexander Schaefer^1,2, Alfred Anwander¹, Bernhard Sehm¹, and Arno Villringer^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Sachsen, Germany, ²Department of Electrical and Computer Engineering, Clinical Imaging Research Centre & Singapore Insitu, Singapore, Singapore, Singapore

Current MRI techniques for assessing the impact of brain lesions consider only lesion location, type, and extent, while ignoring how the lesioned region was previously connected to the rest of the brain. To address this, we created a tractography-based network model describing normal white-matter connectivity in the human brain: the TractLAS. Individual patient lesions can be introduced into the model to quantify the effects of disconnection on the network, and relate them to behaviour and functional outcomes. This model helps to advance a network-based understanding of the functional effects of focal brain lesions.

Rebecca J Williams^1,2, Bradley Goodyear^1,2, Stefano Peca³, Cheryl R McCreary^1,2, Richard Frayne^1,2, Eric E Smith^1,2, and G Bruce Pike^1,2
1Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, ²Seaman Family MR Research Centre, Alberta Health Services, Calgary, Alberta, Canada, ³Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada

Cerebral amyloid angiopathy (CAA) is an age-related disease affecting the small blood vessels. Vascular changes resulting from CAA have been detected using fMRI, however modelling the hemodynamic response function (HRF) may provide further information than BOLD signal amplitude alone. Here we characterized the HRF in CAA patients and healthy controls. Subject-specific HRFs were estimated using the sum of two gamma functions model. The time-to-peak (TTP) and full-width at half-maximum (FWHM) of the positive response were calculated from each subject's HRF and quantitatively compared between groups. We found that the FWHM may be a sensitive marker of CAA-related neurovascular changes.

Tianyi Qian¹, Zhigang Qi², Mo Zhang², Kun Zhou³, and Kuncheng Li^2
1MR Collaborations NE Asia, Siemens Healthcare, Beijing, Beijing, China, ²Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China, ³Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, China

Simultaneous Multi slice acceleration (SMS) EPI technique provides a new tool for measuring the DSC-MR and BOLD signal with higher spatial and/or temporal resolution. In this study, we applied an iterative algorithm to extract the global pattern by averaging the time series of each voxel after re-alignment based on its time-shift. In addition, by using SMS EPI sequence for rs-fMRI data acquisition, higher temporal resolution (TR = 1000 ms) and higher spatial resolution can be achieved to provide more accurate results.

Xin Lou¹, Ning Ma², Jinghao Lyv¹, Yang Xu¹, Zhenyu Zhou³, Bing Wu³, and Lin Ma^1
1Department of Radiology, Chinese PLA General Hospital, Beijing, China, ²Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Beijing, China, ³MR Research Center, GE Healthcare, Beijing, China

DSA remains the method that can best evaluate collateral extents, but it is relatively time-consuming, invasive, costly, and cannot provide quantitative measurement. Determining the presence and adequacy of collateral blood flow is important in patients with severe intracranial stenosis or occlusion due to collateral flow can maintain cerebral circulation and may be another potential therapeutic target in acute ischemic stroke. Our study suggests that multi-post labeling delay time 3D pCASL technique may be a useful tool to quantitative the collateral perfusion in patients with intracranial arterial stenosis.

Ulrich Pilatus¹, Johann-Philipp Zöllner², Elke Hattingen¹, and Oliver Singer^2
1Neuroradiology, Goethe-University Frankfurt, Frankfurt, Germany, ²Neurology, Goethe-University Frankfurt, Germany

31P and 1H Magnetic resonance spectroscopic imaging (MRSI) was used to measure pH and energy metabolism in subacute stroke (mean of 6 days after stroke). We found two inorganic phosphate signals in stroke tissue, which indicates a fraction at alcalotic pH (7.38) and one at regular pH (7.03). High energy metabolites were decreased but not totally depleted.

Peng Wu¹, Feiyan Chang², Sheng Xie², and Hua Guo^1
1Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, ²Department of Radiology, China–Japan Friendship Hospital, Beijing, China

Measurements of oxygen extraction fraction are of great importance in the study of brain metabolism. There are several MRI-based methods, this study shows the feasibility of the model proposed by Haccke and Yablonskiy. Six canines with internal carotid arteries ligated on both sides were studied. The data were acquired with ASE-EPI sequence and used to estimate OEF by fitting to the model proposed by Haccke and Yablonskiy. The results showed that the OEF values of these canines increased significantly (p=0.004) after the ligation. DWI images and triphenyl tetrazolium chloride stained sections were consistent with the estimated OEF maps.

Shiteng Suo¹, Zengai Chen¹, and Jianrong Xu^1
1Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, China

The current study demonstrated the utility of bi- and stretched-exponential diffusion models in characterize the non-Gaussian diffusion behavior in acute/subacute stroke. The preliminary results suggest that the bi- and stretched -exponential model can help better describe the complex behavior of water diffusion in acute/subacute stroke, and may provide more detailed and useful metrics for lesion assessment and prognosis.

Takashi Inoue¹, Miki Fujimura², Kuniyasu Niizuma², and Teiji Tominaga^2
1Neurosurgery, Sendai Medical Center, Sendai, Miyagi, Japan, ²Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Timing of the onset of subarachnoid hemorrhage (SAH) is important for treatment decision making, especially as some patients visit hospital several weeks after the onset of SAH. T2*-weighted (T2*W) magnetic resonance (MR) imaging is regarded as a sensitive method for the detection of deoxyhemoglobin or hemosiderin deposits. The abnormal low intensity on T2*W imaging gradually decreased until 90 days from the onset of SAH, but persisted 16 years after the onset. We could predict the day of onset with pure error �}10 days in patients with SAH within 90 days of onset, using our grading system for T2*W images.

Gang Guo¹ and Liuhong Zhu^1
1Radiology, Xiamen Second Hospital, Xiamen, Fujian, China

The performance of diffusion kurtosis imaging (DKI) in the analysis of micro-structural changes of brain tissue affected by acute ischemic stroke was explored. Seventy-two lesions in common affected locations were outlined in fifty-nine patients. Four types of DKI manifestation in acute ischemic stroke lesions were classified according to the changes of DKI signal intensity. Multiple comparisons among types indicated that DKI could stratify heterogeneous and microstructure changes within acute stroke DWI lesions.

Vince I Madai¹, Carla N Wood¹, Ivana Galinovic¹, Ulrike Grittner¹, Gajanan S Revankar¹, Steve Z Martin¹, Olivier Zaro Weber², Walter Möller-Hartmann³, Federico C von Samson-Himmelstjerna^1,4, Wolf-Dieter Heiss², Martin Ebinger⁵, Jochen B Fiebach¹, and Jan Sobesky^1
1Center for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Berlin, Berlin, Germany, ²Max Planck Institute for Metabolism Research, Cologne, Germany,³Department of Radiology, Ludmillenstift Meppen, Meppen, Germany, ⁴Fraunhofer MEVIS, Bremen, Germany, ⁵Centre for Stroke Research Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany

In acute stroke of unknown onset, the DWI-FLAIR mismatch allows for the identification of patients presenting within the thrombolysis time window (<4.5h). FLAIR lesions, however, are difficult to analyze visually. Relative-signal-intensity (rSI) biomarkers derived from MRI sequences, namely DWI or FLAIR, constitute an increasingly investigated observer-independent alternative. In the present work we demonstrate that clinical confounders (e.g. age, NIHSS) significantly influence performance of FLAIR imaging biomarkers in contrast to DWI biomarkers, which are independent of this influence and offer high performance. These results might partly explain heteregenous results for FLAIR biomarkers in the past and support the use of DWI biomarkers.

Marco Piccirelli¹, Bas van Niftrik², Oliver Bozinov², Athina Pangalu¹, Antonios Valavanis¹, Luca Regli², and Jorn Fierstra^2
1Neuroradiology University Hospital, Zurich, ZH, Switzerland, ²Neurosurgery University Hospital, Zurich, ZH, Switzerland

To quantify the local cerebrovascular autoregulation in function of the partial pressure of CO2 (PaCO2), we combined quantitative cerebral flow measurements obtained with ASL and cerebrovascular reactivity (CVR) with BOLD fMRI. To control for PaCO2, a prospective end tidal gas blender was used. This unique combination during a capnic challenge in healthy subjects and steno occlusive patients allows for the assessment of a quantitative CVR curve and deliver a multi-parametric map including cerebrovascular reactivity, reserve capacity and mean cerebral blood flow measurements during known hypocapnic and hypercapnic states.

Neil Chatterjee¹, Shyam Prabhakaran², Sameer Ansari¹, and Timiothy Carroll^1
1Radiology, Northwestern University, Chicago, IL, United States, ²Neurology, Northwestern University, Chicago, IL, United States

Fully automated methods were used to analyze perfusion weighted (PWI) and diffusion weighted (DWI) MR images in a cohort of 109 patients suspected of having a stroke or transient ischemic attack and compared to modified Rankin Scale (mRS) collected after 3 months. Compared to a referece group with an mRS of 0, we found that DWI measurements were only significantly different in patients with an mRS of 4, but PWI measurements were different across a greater range of mRS scores. This may indicate that PWI may be a better predictor for intermediate outcomes.

Hung-Wen Kao^1,2, Yu-Chuan Chang³, Ching-Po Lin^2,4, and Chien-Yuan Eddy Lin^5,6
1Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ²Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan, ³Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan, ⁴Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan, ⁵GE Healthcare, Taipei, Taiwan, ⁶GE Healthcare China, Beijing, China

Susceptibility-weighted imaging (SWI) is very sensitive in detecting blood products and showing blood-oxygen-level dependent (BOLD) signal changes presumably from different concentrations of deoxygenated blood. Therefore, we hypothesize that SWI could provide oxygen metabolic information in relation to perfusion in patients with acute ischemic stroke. In our study, we compared area percentages of increased BOLD signal (IBS) in ROIs of restricted diffusion and perfusion defect. The results suggested a positive correlation between perfusion and IBS, a finding contradicting the implication of IBS as miserable perfusion and indicating a mismatch between perfusion and oxygen metabolism.

Muhammad E Haque¹, Khader M Hasan², Benjamin A Schatz³, Sarah M Lund³, Farhaan S Vahidy⁴, and Sean I Savitz^4
1Neurology, Unversity of Texas Health Science Center at Houston, Houston, TX, United States, ²Diagnostic and Interventional Imaging, Unversity of Texas Health Science Center at Houston, Houston, TX, United States, ³Unversity of Texas Health Science Center at Houston, TX, United States, ⁴Neurology, Unversity of Texas Health Science Center at Houston, TX, United States

Post stroke cell therapy may offer a promising regenerative therapy. There is a need to establish reliable neuroimaging markers to assure safety and help advance neubiological models. In this study we sought to present some quality assurance measures by testing the integrity of white matter fibers in the anterior and posterior corpus callosum regions post MCA stroke.

Xiaoyue Ma¹, Panli Zuo², Benjamin Schmitt³, Dapeng Shi⁴, Jinyuan Zhou⁵, and Meiyun Wang^4
1Radiology, Zhengzhou University People¡¯s Hospital & Henan Provincial People¡¯s Hospital, Zhengzhou, Henan, China, ²Siemens Healthcare, MR Collaboration NE Asia, Beijing, China, ³Siemens Ltd Australia, Healthcare Sector, Macquarie Park, Australia, ⁴Radiology, Henan Provincial People¡¯s Hospital, Zhengzhou, Henan, China, ⁵Radiology, John Hopkins University, Baltimore, United States

Amide Proton Transfer (APT) is a kind of chemical exchange-dependent saturation transfer (CEST) imaging which can detect peptides and endogenous mobile proteins. We aimed to explore the value of non-invasive APT in early detecting intracerebral hemorrhage (ICH) at different stages by comparing it to susceptibility weighted imaging (SWI), the most sensitive tool for detecting ICH. Routine MRI, SWI and APT imaging were performed in 39 patients with ICH at different stages on a 3.0 T. The MRI findings were evaluated, the signal values of SWI and APT in the hemorrhage lesions were measured and compared with the contralateral normal brain tissue. Paired-sample t-test was used for statistical evaluation. SWI showed hypointense signal in 15 cases and heterogeneous signal intensity in the other 14 cases. However, all the ICH lesions were hyperintense on the APT-weighted images. Both the mean values of APT and SWI were higher in the hemorrhagic lesions than in the contralateral normal brain tissue (P<0.01). Routine MR imaging has limitation in detecting ICH because of the various signal intensities at the different stages. SWI is more sensitive than conventional MRIs in detecting ICH. But SWI shows heterogeneous signal intensity in half of the cases with ICH because of the T2 and T1 properties in SWI. As APT can detect endogenous mobile proteins and peptides, the ICH which contains many hemoglobins always shows hyperintensity on APT. In this way, APT imaging is sensitive to detect ICH and may provide a new MRI tool as a routine imaging technique for early detecting ICH. In this way, APT imaging is sensitive to detect ICH and may provide a new MRI tool as a routine imaging technique for early detecting ICH.

Xiao Gao¹, Shengzhang Ji¹, Jinyu Song¹, Xihai Zhao², Haiman Bian¹, Yu Zhang³, Yingyin Feng¹, and Shengli Chen^1
1The 4th center hospital of TianJin, TianJin, TianJin, China, ²Tsinghua University School of Medicine, Beijing, China, ³Philips Healthcare, Beijing, China

Investigate the relativity between vulnerable components and cerebral function by analyzing the plaque characteristics according to NIHSS score.

Zihao Zhang^1,2, Dehe Weng³, Jing An³, Zhentao Zuo¹, Bo Wang¹, Qingle Kong¹, Ning Wei^1,2, Yan Zhuo¹, Xiaohong Joe Zhou⁴, and Rong Xue^1
1State Key Lab of Brain and Cognitive Science, Beijing MR Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, Beijing, China, ²Graduate School, University of Chinese Academy of Sciences, Beijing, Beijing, China, ³Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, Guangdong, China, ⁴Dept. of Radiology, Center for MR Research, University of Illinois, Chicago, Illinois, United States

An automated post-processing pipeline of TOF-MRA is proposed to separate intracranial and extracranial vessels, without the aid of T1w structural images. The post-processing uses nonlinear registration to produce ROIs in individual space. The pipeline was verified to provide clear MIP images of intracranial and extracranial vessels, respectively, which is useful in extra-intracranial bypass surgery.

Suheyla Cetin¹, Berkin Bilgic², Audrey Peiwen Fan³, Kawin Setsompop², and Gozde Unal^1
1Faculty of Natural Sciences and Engineering, Sabanci University, Istanbul, Istanbul, Turkey, ²Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Department of Radiology, Stanford University, CA, United States

Susceptibility MRI provides contrast of the brain’s venous vasculature due to the presence of paramagnetic deoxyhemoglobin molecules in cerebral veins. Although susceptibility-weighted imaging has gained popularity to image veins in clinical applications such as stroke and traumatic brain injury, this method suffers from non-local and orientation-dependent effects that may prevent accurate identification of brain vessels. The purpose of our study is to demonstrate visualization and segmentation of cerebral veins from quantitative susceptibility maps (QSMs), a new MRI contrast reconstructed from phase images.

Monika Huhndorf¹, Christian Stehning², Axel Rohr¹, Michael Helle², Thomas Stehle², Ulrich Katscher², and Olav Jansen^1
1Clinic for Radiology and Neuroradiology, Kiel, Germany, ²Philips Research Europe, Hamburg, Germany

Imaging electric conductivity of tissue with Electric Properties Tomography (EPT) has been introduced first in 2009. Since then it has been used in several studies characterising brain tumors, especially gliomas, showing that EPT is able to distinguish between WHO grade IV gliomas and grade I-III. In this study we tested EPT on different neuroradiologic diagnoses to get an idea which other central nervous system diseases might benefit using conductivity as additional diagnostic parameter. It turned out that EPT has also potential to detect changes in brain tissue due to, e.g., microangiopathy, stroke, and multiple sclerosis.

Tianyi Qian¹, Zhongyan Wang², and Peiyi Gao^2
1MR Collaborations NE Asia, Siemens Healthcare, Beijing, Beijing, China, ²Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, Beijing, China

Low-frequencie fluctuation in the range of 0.01¨C0.1 Hz is commonly observed in BOLD signal and has been widely used for analyzing brain functional activation patterns. In this study, an iterative algorithm was used to extract the time-shift-corrected time series pattern of whole-brain BOLD signal. The iterative algorithm for computing the global template of the time series pattern is able to increase the estimation performance significantly while reducing the amount of required rs-fMRI data; shortening the examination time, which is of great importance for potential future clinical applications.

Mechanisms of Neural Degeneration & Damage

Wednesday 3 June 2015

Koji Kamagata¹, Masaaki Hori¹, Akira Nishikori², Kohei Tsuruta², Ayami Okuzumi³, Taku Hatano³, Kouhei Kamiya⁴, Nobutaka Hattori³, and Shigeki Aoki^1
1Department of Radiology, Juntendo University, Tokyo, Bunkyo-ku, Japan, ²Department of Radiological Sciences, Tokyo Metropolitan University, Tokyo, Hachioji-shi, Japan,³Department of Neurology, Juntendo University, Tokyo, Bunkyo-ku, Japan, ⁴Department of Radiology, the University of Tokyo, Tokyo, Bunkyo-ku, Japan

High-resolution NODDI analysis provides a result that likely reflects a decrease of dendritic length and loss of dendritic spines in the SNpc, consistent with prior pathological research. Because Vic and OD were significantly correlated with disease duration and UPDRS-3, NODDI could become a useful tool for assessing disease progression of PD.

Petr Dusek^1,2, Erik Bahn³, Tomasz Litwin⁴, Christiane Wegner³, Vince Istvan Madai⁵, Matthias Dieringer^6,7, Till Huelnhagen⁶, Michael Knauth¹, Thoralf Niendorf^6,7, Jan Sobesky^5,7, Anna Czlonkowska^4,8, Wolfgang Brueck³, Friedemann Paul⁹, Susanne A Schneider¹⁰, and Jens Wuerfel^1,9
1Institute of Neuroradiology, University Medicine Goettingen, Goettingen, Germany, ²Department of Neurology and Center of Clinical Neuroscience, 1st Faculty of Medicine and General University Hospital in Prague, Prague, Czech Republic, ³Institute of Neuropathology, University Medicine Goettingen, Goettingen, Germany, ⁴2nd Department of Neurology, Institute Psychiatry and Neurology, Warsaw, Poland, ⁵Department of Neurology and Center for Stroke Research Berlin (CSB), Charité-Universitaetsmedizin, Berlin, Germany, ⁶Berlin Ultrahigh Field Facility (B.U.F.F.), Max-Delbrueck Center for Molecular Medicine, Berlin, Germany, ⁷Experimental and Clinical Research Center (ECRC), Charité-Universitaetsmedizin and Max Delbrueck Center for Molecular Medicine (MDC), Berlin, Germany, ⁸Department of Experimental and Clinical Pharmacology, Medical University, Warsaw, Poland, ⁹NeuroCure Clinical Research Center, Charité-Universitaetsmedizin, Berlin, Germany, ¹⁰Neurology Department, University of Kiel, Kiel, Germany

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Peter Latta¹, Amit Khairnar¹, Eva Drazanova², Jana Kucerova¹, Anas Arab¹, Birgit Hutter-Paier³, Daniel Havas³, Manfred Windisch⁴, Zenon Starcuk Jr.², Boguslaw Tomanek^1,5, and Irena Rektorova^1
1Central European Institute of Technology, Masaryk University, Brno, Czech Republic, ²Institute of Scientific Instruments, Academy of Sciences of the Czech Republic, Brno, Czech Republic, ³QPS Austria GmbH, Graz, Austria, ⁴NeuroScios GmbH, Graz, Austria, ⁵University of Alberta, Edmonton, Alberta, Canada

Background: Accumulation and aggregation of α-synuclein contribute to the pathogenesis of Parkinson’s disease (PD). Our aim was to evaluate whether diffusion kurtosis imaging (DKI) will help to differentiate between α-synuclein overexpressing transgenic mouse model of PD (TNWT-61) and wild-type (WT) littermates. Methods: TNWT-61 mice and WT littermates (9 month) underwent behavioral tests and MRI scanning using 9.4 Tesla system in vivo. Results: TNWT-61 mice showed significant motor impairment. Mean and radial diffusion kurtosis were significantly elevated in the TNWT-61 compared to WT Conclusions: The current study provides evidence that DKI might become a candidate diagnostic biomarker with translational potential.

Ravi Prakash Reddy Nanga¹, Kathryn A. Davis², Sandhitsu Das³, Stephanie H. Chen², Peter Hadar², Timothy H. Lucas⁴, Brian Litt², John A. Detre², Hari Hariharan¹, Mark A. Elliott¹, and Ravinder Reddy^1
1Radiology, University of Pennsylvania Health Systems, Philadelphia, Pennsylvania, United States, ²Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ³Penn Image Computing & Science Lab, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ⁴Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Glutamate is widely thought to be central to epileptogenesis. Here we apply a novel noninvasive glutamate imaging technique, GluCEST (Glutamate Chemical Exchange Saturation Transfer) MRI at 7T with an aim to identify seizure foci with finer precision and higher sensitivity than currently used imaging modalities in subjects with Temporal Lobe Epilepsy (TLE).

Jiaying Zhang¹, Rachael I Scahill², Alexandra Durr³, Blair Leavitt⁴, Raymund Roos⁵, Sarah J Tabrizi², and Hui Zhang^1
1Department of Computer Science and Centre for Medical Image Computing, UCL, London, United Kingdom, ²Institute of Neurology, UCL, London, United Kingdom, ³Department of Genetics and Cytogenetics, INSERM UMR S679, APHP Hôpital de la Salpêtrière, Paris, France, ⁴Department of Medical Genetics, University of British Columbia, British Columbia, Canada, ⁵Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands

The early detection of microstructural abnormalities in pre-manifest Huntington’s disease (pre-HD) population is important for the development of suitable biomarkers for clinical trials as well as inform future therapeutic strategy. Although tissue microstructure has traditionally been quantified with DTI, more advanced techniques such as NODDI are now available which may provide more specific measures. This study tests this hypothesis in pre-HD. We find that, compared to DTI, NODDI findings are not only more specific, revealing widespread reductions in neurite density, but also more sensitive, detecting more extensive and more statistically significant differences.

Yue Xing¹, Stefan Schwarz¹, Nin Bajaj², Penny Gowland³, and Dorothee Auer^1
1Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom, ²Division of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, Nottinghamshire, United Kingdom, ³Sir Peter Mansfield Imaging Centre, School of Physics and Astronomy, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Differential functional connectivity patterns of anterior substantial nigra and posterior substantial nigra in Parkinson’s were identified by comparing with age- and sex-matched healthy volunteers with seed-based analysis on cross-scanner resting state fMRI data. This abnormal functional connectivity reduction of the anterior and posterior substantial nigra in Parkinson’s may suggest a link between posterior default-mode network impairment and dopaminergic deficit.

Nadya Pyatigorskaya^1,2, Romain Valabregue^1,3, Cyril Poupon⁴, Marie Vidailhet^3,5, and Stephane Lehericy^1,2
1Centre de NeuroImagerie de Recherche – CENIR, Institut du Cerveau et de la Moelle épinière – ICM, Paris, France, ²Department of Neuroradiology, Hôpital Pitie-Salpetriere, Paris, France, ³Université Pierre et Marie Curie and Inserm UMR-S1127; CNRS, UMR 7225, Institut du Cerveau et de la Moelle épinière – ICM, Paris, France, ⁴NeuroSpin, CEA, Saclay, France, ⁵Federation de Neurologie, Hôpital Pitie-Salpetriere, Paris, France

According to Braak's model, the medulla oblongata and posterior pontine region may be affected early in the course of Parkinson Disease. Therefore, the aim of the present study was to characterize medulla oblongata damage using diffusion tensor imaging (DTI) in PD patients as compared with healthy volunteers. Increased diffusivity was observed in both medulla oblongata and pontine tegmentum. Longitudinal progression of diffusion changes in the medulla oblongata of PD patients and correlations with measures of autonomic dysfunction are currently being investigated

Jianli Wang¹, Thyagarajan Subramanian^2,3, Zachary Mosher¹, Jeffrey Vesek¹, and Qing X Yang^1,4
1Radiology, Penn State College of Medicine, Hershey, Pennsylvania, United States, ²Neurology, Penn State College of Medicine, Hershey, Pennsylvania, United States, ³Neural & Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania, United States, ⁴Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, United States

The central olfactory system is highly affected by PD pathology and olfactory dysfunction is prevalent in Parkinson's disease (PD). With a sniffing-odor stimulation fMRI paradigm, we demonstrated significant reduced odor-induced activation in the primary and secondary olfactory cortex of early-stage PD patients compared to the healthy controls. The observed POC dysfunction was consistent with the impairment of smell identification function detected by the psychophysical test. Conversely, the sniffing function in the POC was less affected at the early stage of disease. In conclusion, olfactory deficits in the early-stage PD are dominantly odor-related.

Lifeng Gao¹, Mingming Huang², Fuchun Lin¹, and Hao Lei^1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China, ²Department of Radiology Affiliated Hospital of Guiyang Medical University, Guiyang, Guizhou, China

Type 1 diabetes was induced in rats by a single injection of streptozotocin (STZ). Diffusion tensor imaging on the visual system were performed at 12 weeks on a 7 T scanner to monitor the microstructure abnormalities induced by diabetes. Fractional anisotropy (FA), axial diffusivity (ADC_||) and radial diffusivity (ADC_¡Í) in the optic tracts and visual cortex were measured. Compared to the control animals, the STZ-treated rats showed significantly reduced FA in both the optic tracts and visual cortex at 12 weeks after diabetes induction. Correspondingly, significantly decreased ADC_|| and significantly increased ADC_¡Í were associated with hyperglycemia. The VC in the diabetic rats had a slight decline in ADC_||, and a slight increase in ADC_¡Í relative to those in controls.

Ileana Zucca¹, Matteo Figini¹, Alessandro Scotti¹, Stefania Marcuzzo², Silvia Bonanno², Victoria Moreno Manzano³, José Manuel Garcia Verdugo⁴, Pia Bernasconi², Renato Mantegazza², and Maria Grazia Bruzzone^5
1Scientific Direction, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Milan, Italy, ²Neurology IV - Neuromuscular Diseases and Neuroimmunology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy, ³Neuronal and Tissue Regeneration laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain, ⁴Unidad de Neurobiología comparada, Universidad de Valencia, Valencia, Spain, ⁵Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy

The aim of this work was to investigate the potential of in vivo DTI parameters to detect WM and GM degeneration in the G93A-SOD1 mouse model of Amyotrophic lateral sclerosis (ALS). 7 G93A-SOD1 mice and 7 WT-SOD1 mice were followed at multiple time points (9, 10, 12, 15 and 17 weeks of age) with a DTI protocol on a 7T MRI scanner. DTI parameters, in particular AD in WM and MD in GM, highlighted very early alterations especially in ventral regions, confirmed by histology and electron microscopy. DTI parameters may therefore be early in vivo biomarkers of neurodegeneration in ALS.

Chiao-Chi V Chen¹, Yi-Hua Hsu¹, Chien-Yuan E Lin^2,3, and Chen Chang^1
1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ²GE Healthcare, Taipei, Taiwan, ³MR Advanced Application and Research Center, GE Healthcare, China

Imaging of dopamine autoreceptor activity is a brand new concept. We took advantage of our recently established noxiousness-evoked functional magnetic resonance imaging (fMRI) paradigm for developing such technique. This enables us to gain understanding about how D2 autoreceptor is affected in PD.

Jan Sedlacik¹, Jan-Rüdiger Schüre^1,2, Kai Boelmans³, and Jens Fiehler^1
1University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany, ²Technical University of Ilmenau, Thüringen, Germany, ³University Hospital of Würzburg, Bayern, Germany

Frontal and central short association fibers (U-fibers) were investigated by Diffusion Tensor Imaging (DTI) in Parkinson's disease (PD) and healthy subjects. Healthy age-related DTI changes were found in control subjects. In detail, axial (AD), radial (RD) and mean diffusivity (MD) increased in frontal and central fibers and fractional anisotropy (FA) decreased in frontal but increased in central fibers. Age matched healthy controls showed slightly lower AD/RD/MD and higher FA as compared to PD patients, which may suggest only a marginal microstructural degeneration of U-fibers in PD patients.

Shannon Kolind¹, Praveena Manogaran¹, Irene Vavasour², Bretta Russell-Schulz², Katrina McMullen¹, Jing Zhang², Cornelia Laule^2,3, Alexander MacKay^2,4, Alexander Rauscher², David Li², and Anthony Traboulsee^1
1Medicine, University of British Columbia, Vancouver, BC, Canada, ²Radiology, University of British Columbia, Vancouver, BC, Canada, ³Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada, ⁴Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada

Neuromyelitis optica (NMO), while similar to multiple sclerosis (MS), has a different mechanism for demyelination and primarily affects the optic nerve and spinal cord. We measured myelin water fraction using a multi-echo GRASE approach (MWF) as well as mcDESPOT (fM) in the optic radiations and corticospinal tract (hypothesized to be demyelinated due to NMO’s primary optic nerve and spinal cord involvement), and the corpus callosum (hypothesized to be unaffected). MWF was reduced in NMO optic radiations and corticospinal tract but not corpus callosum. Contrary to MS findings, fM was not reduced in any region. This finding highlights how differences in pathology are reflected by each approach.

Shalmali Dharmadhikari^1,2, Ruoyun Ma^1,2, Chien- Lin Yeh^1,2, Sandy Snyder¹, S E Zauber³, and Ulrike Dydak^1,2
1School of Health Sciences, Purdue University, W Lafayette, IN, United States, ²Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, United States, ³Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, United States

Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter of the basal ganglia, which is hypothesized to be altered in Parkinson’s disease (PD). Our aim was to evaluate the use of GABA MRS for understanding these alterations and their relation to disease severity, while reducing influence of PD medicines. GABA MRS in PD patients, who were temporarily withheld medication, revealed elevated GABA levels in the thalamus, which were also associated with disease severity as measured clinically by motor scores. Thus GABA MRS confirms the role of GABA in PD and has a potential to be used a non-invasive biomarker of PD.

Maria Guadalupe García-Gomar¹, Francisco Velasco², and Luis Concha^1
1Universidad Nacional Autonoma de Mexico, Santiago de Queretaro, Queretaro, Mexico, ²Hospital General de Mexico, Distrito Federal, Mexico

Synopsis: Prelemniscal radiations (Raprl) are an exquisite neurosurgical target for treatment of tremor and rigidity. Despite its clinical relevance nowadays it remains unknown the anatomical connectivity of this area. Using diffusion MRI and probabilistic tractography we reconstructed different pathways passing trough the Raprl in healthy subjects and Parkinson´s disease patients. We compared the number of streamlines of both groups. Raprl tractography showed connections with motor and premotor cortex, globus pallidus (GP), thalamus, cerebellum and brainstem, having statistical differences between groups in tracts associated to GP and thalamus. Our findings provide new insights into subthalamic anatomic connectivity useful for neurosurgical procedures.

Kaspar-Josche Streitberger^1,2, Andreas Fehlner¹, Friedemann Paul^3,4, Jens Würfel^3,5, Jing Guo¹, Jürgen Braun⁶, and Ingolf Sack^1
1Department of Radiology, Charité - Universitätsmedizin Berlin, Berlin, Germany, ²Department of Neurology with experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany, ³NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany, ⁴Clinical and Experimental Multiple Sclerosis Research Center, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany, ⁵Institute of Neuroradiology, Universitätsmedizin Göttingen, Göttingen, Germany, ⁶Institute of Medical Informatics, Charité - Universitätsmedizin Berlin, Berlin, Germany

High resolution multifrequency MR elastography was applied to patients with Neuromyelitis optica (NMO) – a disease which is characterized by recurrent inflammation and demyelination of the spinal cord and the optical nerves. Our hypothesis was based on reports on the sensitivity of viscoelastic parameters to neuroinflammation and neurodegradation. Consistently, high-resolution maps of the magnitude of the complex shear modulus revealed disseminated softening of cerebral tissue with marked effects on thalamus and white matter. The present study supports the hypothesis of a widespread cerebral neurodegeneraration in NMO and provides further details about regional effects of the disease.

Silvia Mangia¹, Philip Burton¹, Igor Nestrail¹, Mikko Nissi^1,2, Alejandra Sierra³, Karin Shmueli⁴, Michael Howell⁵, Paul Tuite⁵, and Shalom Michaeli^1
1CMRR, University of Minnesota, Minneapolis, Minnesota, United States, ²University of Oulu, Oulu, Finland, ³A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, ⁴University College London, London, United Kingdom, ⁵Department of Neurology, University of Minnesota, Minneapolis, Minnesota, United States

The findings of this preliminary study support the use of advanced MRI methods based on adiabatic T1ρ, T2ρ RAFF4, QSM, DTI and rsfMRI to characterize the microstructural integrity and functional connectivity of Parkinson’s disease (PD) subjects compared to healthy controls. Ultimately these methods may prove useful as a means to track the course of PD and potentially monitor the response to therapies.

David Raffelt¹, Farnoosh Sadeghian¹, Heather Connor², and Alan Connelly^1,3
1Florey Institute of Neuroscience and Mental Health, Melbourne, VIC, Australia, ²Department of Optometry, Deakin University, Melbourne, VIC, Australia, ³The Florey Department of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC, Australia

Glaucoma is the second leading cause of blindness worldwide with 8.4 million bilaterally blind people. White matter abnormalities have been reported previously in Glaucoma using the diffusion tensor, however these results are difficult to interpret in regions with crossing fibres. In this study we investigate Glaucoma disease using Apparent Fibre Density (AFD), a quantitative measure that is tract specific, even in voxels with multiple fibres. When compared to healthy controls, we observed a decrease in AFD in the optic tract and radiation. Within these tracts we also observed significant AFD correlations with clinical measures of disease severity.

Mohammad Sabati, PhD¹ and Sasha Raju, MBBS^2
1Radiology, University of Miami, Miami, Florida, United States, ²Public Health Program, University of Miami, Miami, Florida, United States

Metabolite concentrations in 47 atlas-defined brain structures of 12 PD patients and 24 age- and gender-matched normal subjects were measured by using a sub-milliliter high-resolution whole-brain MR spectroscopic imaging (MRSI). The distributions as well as the statistically significant alterations of the measured metabolites NAA, Cho, and Cre were regional dependent. The results also indicate that the severity of PD, as measured by motor score, is correlated with the NAA and Cho/NAA in a number of the atlas-defined regions.

Alzheimer's Disease

Wednesday 3 June 2015

James O'Callaghan¹, Holly Holmes¹, Nicholas Powell¹, Ozama Ismail¹, Niall Colgan¹, Jack Wells¹, Bernard Siow¹, Michael O'Neill², Emily Collins³, Karin Shmueli⁴, and Mark Lythgoe^1
1Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom, ²Eli Lilly & Co. Ltd, Windlesham, Surrey, United Kingdom, ³Eli Lilly and Company, Indianapolis, United States, ⁴Department of Medical Physics and Biomedical Engineering, University College London, London, United Kingdom

Alterations to white matter have been implicated in a number of neurodegenerative diseases. In this work we investigate the sensitivity of MRI magnetic susceptibility mapping to these changes using a mouse model of Tauopathy. A non-rigid registration of contrast enhanced, high resolution ex vivo mouse brain images is used to transform susceptibility maps into a common space and a voxel-wise group comparison is performed. Significant differences were observed that may indicate disruption to the tissue of the corpus callosum.

Nick M Powell^1,2, Da Ma^1,2, Ferran Prados¹, Marc Modat¹, Jorge Cardoso¹, Holly E Holmes², Ozama Ismail², Niall Colgan², Michael O'Neill³, Emily Collins⁴, Mark F Lythgoe², and Sebastien Ourselin^1
1Centre for Medical Image Computing, University College London, London, England, United Kingdom, ²Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, ³Eli Lilly & Co. Ltd, Windlesham, Surrey, United Kingdom, ⁴Eli Lilly and Company, Indianapolis, IN, United States

We have for the first time applied the Boundary Shift Integral (BSI), a sensitive measure of atrophy, to structural MR images of a non-human animal: the rTG4510 mouse model of tauopathy. We measured rates of longitudinal atrophy equivalent to over 1% brain volume loss in just 30 days, and compared this to rates of brain volume change in wild-type littermate controls. The measure will be applied to a large cohort of over 200 scans, and shows promise as an early outcome measure for preclinical drug trials.

Elena Makovac¹, Barbara Spano'¹, Giovanni Giulietti¹, Laura Serra¹, Carlo Caltagirone^2,3, Marco Bozzali¹, and Mara Cercignani^1,4
1Neuroimaging laboratory, IRCCS Santa Lucia Foundation, Roma, Italy, Italy, ²Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Roma, Italy, Italy, ³Department of Neuroscience, University of Rome ‘Tor Vergata’, Roma, Italy, Italy, ⁴Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, Sussex, United Kingdom

Patients with amnestic mild cognitive impairment (aMCI) have a higher risk of conversion to AD than healthy elderly subjects. We used probabilistic tractography to perform a multiparametric comparison of diffusion tensor imaging (DTI) and quantitative magnetization transfer (qMT) indices of the principal WM tracts involved by AD pathology between aMCI converting to AD and those who did not. Subtle changes in brain structure associated were more evident in aMCI converters than MCI non converters. RMB0 values correlated with of RDif of in almost all tracts suggesting that the two parameters might reflect similar properties of WM.

Hao Shu^1,2, Yongmei Shi¹, Gang Chen², Zan Wang¹, Duan Liu¹, Chunxian Yue¹, B.Douglas Ward², Wenjun Li², Zhan Xu², Guangyu Chen², Qihao Guo³, Jun Xu⁴, Shi-Jiang Li², and Zhijun Zhang^1
1Department of Neurology, Affiliated ZhongDa Hospital, Neuropsychiatric Institute and Medical School of Southeast University, Nanjing, Jiangsu, China, ²Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ³Department of Neurology, Huashan Hospital, Fudan University, Shanghai, China, ⁴Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, China

The apoliprotein E (APOE) ε4 allele is a risk factor and the ε2 allele is a protective factor for elderly episodic memory (EM) deterioration. However, neural bases linking APOE alleles and EM function remain unclear. This study voxelwisely correlated the hippocampal functional connectivity strength and EM score. It demonstrated the divergence of hippocampal-related network among the three APOE alleles in the cognitively normal elderly subjects, which may contribute to the APOE polymorphism effects on brain activation and associated with their different AD risks.

Cheryl R McCreary^1,2, M Louis Lauzon^1,2, Saima Batool^1,2, Eric E Smith^1,2, and Richard Frayne^1,2
1Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, ²Seaman Family MR Centre, Foothills Medical Centre, Calgary, Alberta, Canada

Quantitative susceptibility mapping (QSM) is a method that can be used to identify iron accumulation in the brain, which is a potential marker of neurodegeneration in aging. In an ongoing longitudinal study, susceptibility weighted imaging (SWI) is used for the identification of cerebral microbleeds (CMBs). In this study, we evaluate cerebral microbleed (CMB) detection on susceptibility-weighted images and images from single-echo data (SWI6e) collected from a multi-echo spoiled gradient echo sequence that can be used for quantitative susceptibility mapping. The CMB contrast was lower and the number of CMBs detected was underestimated in SWI6e images compared to SWI.

Francesco Barban¹, Laura Serra², Roberta Perri³, Roberta Annicchiarico³, Giovanni Augusto Carlesimo^3,4, Matteo Mancini⁵, Fulvia Adriano³, Claudia Ricci³, Maria Giovanna Lombardi³, Mara Cercignani⁶, Lucia Fadda^3,4, Carlo Caltagirone^3,4, and Marco Bozzali^2
1Clinical and Behavioral Neurology Laboratory; Neuroimaging Laboratory, IRCCS S Lucia Foundation, Rome, Rome, Italy, ²Neuroimaging Laboratory, IRCCS S Lucia Foundation, Rome, Rome, Italy, ³Clinical and Behavioral Neurology Laboratory, IRCCS S Lucia Foundation, Rome, Rome, Italy, ⁴Department of Neuroscience, University of Rome "Tor Vergata", Rome, Rome, Italy, ⁵Department of Engineering, University of Rome “Roma Tre”, Rome, Rome, Italy, ⁶Brighton & Sussex Medical School, Clinical Imaging Sciences Centre, University of Sussex, Brighton, Sussex, United Kingdom

The aim of this study was to investigate, with resting state-fMRI, the effects of a computerized cognitive training vs. an active placebo condition on brain networks of 19 mild Alzheimer’s Disease (mAD) patients with a cross-over design. Comparing pre-post training and placebo connectivity matrices, based on the Automated Anatomical Labelling atlas, with Network-Based Statistics, we found no placebo-related changes, whereas during training emerged a significant increased connectivity in brain regions crucial for memory and decreased connectivity in regions probably mediating compensational processes. We show for the first time a of functional connectivity reorganization in mAD after cognitive training.

Holly Elizabeth Holmes¹, Niall Colgan¹, Ozama Ismail¹, Da Ma^2,3, Jack Wells¹, Nicholas Powell^1,3, James O'Callaghan¹, Ian Harrison¹, Manuel Jorge Cardoso³, Marc Modat², Elizabeth MC Fisher⁴, Sebastian Ourselin³, Michael O'Neill⁵, Emily Catherine Collins⁶, and Mark F Lythgoe^2
1Centre for Advanced Biomedical Imaging, University College London, London, Greater London, United Kingdom, ²University College London, London, Greater London, United Kingdom, ³Centre for Medical Image Computing, University College London, London, Greater London, United Kingdom, ⁴Department of Neurodegenerative Diseases, University College London, London, Greater London, United Kingdom, ⁵Eli Lilly & Co. Ltd, Windlesham, Surrey, United Kingdom, ⁶Eli Lilly & Company, Indianapolis, United States

A multi-scale MRI approach has been employed to characterise the rTg4510 mouse model of Alzheimer's disease, following early- and late-stage therapeutic intervention

Keith S Cover¹, Ronald A van Schijndel¹, Adriaan Versteeg¹, Kelvin K Leung², Emma R Mulder¹, Remko A de Jong¹, Peter J Visser¹, Alberto Redolfi³, Jerome Revillard⁴, Baptiste Grenier⁴, David Manset⁴, Soheil Damangir⁵, Hugo Vrenken¹, Bob W van Dijk¹, Nick C Fox², Giovanni Frisoni³, and Frederik Barkhof^1
1VU University Medical Center, Amsterdam, North Holland, Netherlands, ²University College London, London, United Kingdom, ³IRCCS San Giovanni di Dio Fatebenefratelli, Italy, ⁴MAAT, Archamps, France, ⁵Karolinska Institutet, Sweden

To double check a recent reproducibility study that showed the boundary shift algorithm (BSI) is at least 70% more reproducible than the FreeSurfer/ReconAll, manual, AdaBoost and FSL/FIRST methods for measuring hippocampal atrophy rates. A novel statistical test of accuracy was employed based on the accepted hypothesis that, in older subjects, the hippocampus shrinks over time. The 4 other algorithms were found to require sample sizes at least 50% larger than BSI to reject the null hypothesis. The novel statistical test employed provides double check of superior reproducibility of BSI.

Tetsuya Yoneda¹, Koji Hashimoto¹, Akihiko Kuniyasu², Toshinori Hirai¹, Mika Kitajima¹, Mamoru Hashimoto¹, Nan Kurehana¹, Michiya Iwata¹, Motohira Mio³, Sosuke Yoshinaga¹, Hiroaki Terasawa¹, Manabu Ikeda¹, and Yasuyuki Yamashita^1
1Kumamoto University, Kumamoto, Kumamoto, Japan, ²Sojo University, Kumamoto, Japan, ³Fukuoka University Chikushi Hospital, Fukuoka, Japan

In this study, we suggested statistical method to effectively distinguish the signal of AP from phase noise on MR-phase image resulting in reducing scan duration for clinical application of diagnosis of AD. Phase Difference Enhanced Imaging-image of human brain showed dark rim sign expected as AP deposition but did not show background phase noise containing iron deposition due to aging by statistical noise elimination. Our method may be applicable for clinical image diagnosis for AD with reasonable scan duration less than 4 min.

Junxiao Yu¹, Aikaterini Kotrotsou¹, Arnold M. Evia¹, Julie A. Schneider², Sue E. Leurgans², David A. Bennett², and Konstantinos Arfanakis^1
1Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Alzheimer's disease (AD) pathology commonly coexists with other age-related neuropathologies in the brain of older persons. Although brain atrophy is considered a biomarker of AD pathology, other neuropathologies may also lead to brain atrophy, and only a handful of studies with a number of limitations have combined brain MR volumetry/morphometry with measures of neuropathology obtained after death. Thus, the relation between brain atrophy and age-related neuropathology is not well-established. The purpose of this investigation was to assess the neuropathologic correlates of brain macrostructure by combining ex-vivo MRI RAVENS maps and pathology information on a large community cohort of older persons.

Owen R. Phillips^1,2, Shantanu H. Joshi³, Fabrizio Piras⁴, Maria D. Orfei⁴, Mariangela Iorio⁴, Katherine L. Narr³, David W. Shattuck³, Carlo Caltagirone^1,2, Gianfranco Spalletta⁴, and Margherita Di Paola^1,5
1Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, roma, Lazio, Italy, ²Neuroscience, University of Rome “Tor Vergata”, Rome, Roma, Italy, ³Neurology, Ahmanson Lovelace Brain Mapping Center, Los Angeles, CA, United States, ⁴Neuropsychiatry Laboratory, Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Roma, Italy, ⁵Human Studies, LUMSA University, Rome, Italy

The late myelinating superficial white matter (SWM) comprised of intracortical myelin and short-range association fibers has not received much attention in Alzheimer’s disease (AD) research. As the SWM is vulnerable to the normal effects of age, we hypothesized that it would be impaired in AD. We used a combined cortical pattern matching and DTI approach to measure mean diffusivity. We found significant increases in mean diffusivity across most of the brain in AD patients, which suggest the tissue is impaired. Given the unique cellular makeup and its importance in neuronal synchrony, the SWM may play an important role in AD.

Kelly Ann Moore¹, Errol Loïc Samuel², James Tour², and Robia G Pautler^1
1Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, Texas, United States, ²Department of Chemistry, Rice University, Houston, Texas, United States

Studies have shown in multiple models of Alzheimer’s disease that deficits in fast axonal transport develop before amyloid-beta plaque and tau deposition, with oxidative stress being implicated in the process. Using an APP/PSEN1 model of Alzheimer’s disease we demonstrate via manganese enhanced MRI a deficit in the axonal transport of this model. Additionally we show that these deficits can be reversed with the administration of nano-antioxidant PEG-ylated-hydrophilic carbon clusters.

Sheryl L Herrera¹, Heather Whittaker², Shenghua Zhu³, Vanessa L Palmer⁴, Richard Buist⁵, Xin-Min Li⁶, Jonathan D Thiessen^7,8, and Melanie Martin^9,10
1Physics & Astronomy, University of Mantioba, Winnipeg, Manitoba, Canada, ²Biopsychology program, University of Winnipeg, Winnipeg, Manitoba, Canada, ³Pharmacology & Therapeutics, University of Mantioba, Winnipeg, Manitoba, Canada, ⁴Biomedical Engineering, University of Mantioba, Winnipeg, Manitoba, Canada, ⁵Radiology, University of Mantioba, Winnipeg, Manitoba, Canada, ⁶Psychiatry, University of Alberta, Edmonton, Alberta, Canada, ⁷Imaging Program, Lawson Health Research Institute, London, Ontario, Canada, ⁸Medical Biophysics, Western University, London, Ontario, Canada, ⁹Physics, University of Winnipeg, Winnipeg, Manitoba, Canada, ¹⁰Biomedical Engineering, Physics &Astronomy, Pharmacology &Therapeutics, Radiology, University of Mantioba, Winnipeg, Manitoba, Canada

Quantifying structural changes in the hippocampal formation (HF) and surrounding white matter with MRI can improve both the diagnosis and understanding of AD. In this study, anatomical details visible only in DEC maps allowed ROIs to be defined and applied to all quantitative MRI maps. Many significant differences were found in MRI metrics between the transgenic mice when compared with controls and in some cases between transgenic strains themselves. Quantitative MRI methods are useful for determining changes in tissue structure and content within the HF and surrounding WM tracts mouse models of AD. This is the first step toward longitudinal in vivo studies correlated with histopathology.

Christos Michaelides¹, David J Lythgoe¹, Harold G Parkes², Claire Troakes³, Istvan Bodi⁴, Tina Geraki⁵, Amy H Herlihy⁶, and Po-Wah So^1
1IOPPN, King's College London, London, United Kingdom, ²CR-UK Clinical MR Research Group, Institute of Cancer Research, Sutton, London, United Kingdom, ³MRC London Neurodegenerative Diseases Brain Bank, Department of Clinical Neuroscience, IOPPN, King's College London, London, United Kingdom, ⁴Clinical Neuropathology & London Neurodegenerative Diseases Brain Bank, King's College London, London, United Kingdom, ⁵Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, United Kingdom, ⁶Agilent Technologies, Yarnton, Oxfordshire, United Kingdom

Iron dysregulation may be a contributing factor to neuronal cell death in Alzheimer’s disease. MR relaxometry and MT measurements, in fixed post-mortem human AD and control samples, were correlated with direct iron assessment, using synchrotron radiation X-ray fluorescence mapping. The correlation of iron against MT or luxol fast blue staining were significantly different between control and AD samples, indicating a change in the relationship of iron and myelin in AD. R2 and R2* values demonstrated greater correlation to iron in AD-affected white matter than control, potentially impacting the clinical relevance for R2 and R2* relaxometry to assess iron in vivo.

Elena Makovac¹, Laura Serra¹, Chiara Mastropasqua¹, Mario Torso¹, Barbara Spano'¹, Giovanni Giulietti¹, Carlo Caltagirone^2,3, Mara Cercignani^1,4, and Marco Bozzali^1
1Neuroimaging laboratory, IRCCS Santa Lucia Foundation, Rome, Italy, Italy, ²Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Roma, Italy, Italy, ³Department of Neuroscience, University of Rome ‘Tor Vergata’, Rome, Italy, Italy, ⁴Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton, Sussex, United Kingdom

Altered functional characteristics have been reported in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Patients with amnestic mild cognitive impairment (aMCI) have higher probability to convert to AD than elderly controls. Different RS-fMRI networks (i.e., the inter-network connectivity) interact with each other in determining higher level functions and dysfunctions. Here, we report that both intra- and inter-network connectivity can predict in MCI patients the conversion to AD at follow-up. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations and this alteration can be observed already in preclinical stage of the disease.

Wutao Lou¹, Lin Shi², Defeng Wang¹, Winnie CW Chu¹, Vincent CT Mok², Sheung-Tak Cheng^3,4, and Linda CW Lam^5
1Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, ²Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, ³Department of Psychological Studies, Hong Kong Institute of Education, Shatin, Hong Kong, ⁴Center for Psychosocial Health and Aging, Hong Kong Institute of Education, Shatin, Hong Kong, ⁵Department of Psychiatry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong

The background brain activity was considered to reflect the cognitive state of participants maintained the task. In this study, the background network efficiency of the working memory network of 17 aMCI patients and 19 controls were analyzed by using fMRI during a visuospatial working memory task. The aMCI patients showed increased local efficiency compared to normal controls and suggested aMCI patients have to pay more effort to complete the task due to memory impairment and suggest the compensatory property of the background network.

Jing Zhang^1,2, Elizabeth Finger^1,2, Udunna Anazodo^2,3, Julia MacKinley², John Butler², Frank Prato^2,3, and Keith St Lawrence^2,3
1Department of Clinical Neurological Sciences, University of Western Ontario, London, Ontario, Canada, ²Lawson Health Research Institute, London, Ontario, Canada,³Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada

This study compared the ability of ASL and FDG-PET to distinguish FTD patients from controls. ASL and FDG-PET images of 11 FTD patients and 10 age- and gender-matched controls were acquired simultaneously. Cerebral blood flow (CBF) and FDG-PET were positively correlated on the normalized mean values across the gray matter (GM), white matter, frontal and temporal lobes. Significant group differences in both CBF and FDG uptake were found in the GM and the frontal lobe. The results suggest that ASL may be a promising alternative to FDG-PET for detecting regional functional dysfunction associated with FTD.

Hongyan Ni¹, Lixiang Yuan², Yuanyuan Chen³, Man Sun², Jianzhong Yin¹, and Xu Yan^4
1Tianjin First Central Hospital, Tianjin, China, ²First Central Clinical College, Tianjin Medical University, Tianjin, China, ³Tianjin University, Tianjin, China, ⁴MR Collaboration NE Asia, Siemens Healthcare, Shanghai, China

To evaluate the correlation between the whole brain non-Gaussian diffusion changes and cognitive performance in Alzheimer¡¯s disease (AD) patients, voxel-wise multiple regression analyses were performed between the diffusion kurtosis imaging (DKI) indices (MK, FA and MD) and the Mini-Mental Status Examination (MMSE) scores respectively. Results shown that indices of DKI, especially MK detected more regions correlated between the indices and the MMSE scores. Thus DKI may be a more powerful compensatory technique in diagnosing and monitoring the AD progression than conventional diffusion tensor imaging (DTI).

Weiying Dai¹, David C. Alsop¹, and Daniel Z. Press^2
1Radiology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA, United States, ²Neurology, Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA, United States

Increased hippocampal perfusion in early AD has been reported, but the underlying mechanism is still not clear. We hypothesized that epileptiform activity occurs in the hippocampus with AD and causes increased perfusion. Here, we designed a placebo-controlled study using an antiepileptic drug, Levetiracetam to modulate epileptic activity of the hippocampus. Nine subjects with AD were scanned following drug or placebo. We observed increased rather than decreased hippocampal perfusion with Levetiracetam. These findings suggest a more complex behavior of drug and epileptic activity effects in AD.

Nick M Powell^1,2, Holly E Holmes², Da Ma^1,2, Marc Modat¹, Jorge Cardoso¹, Frances K Wiseman³, Victor LJ Tybulewicz⁴, Elizabeth MC Fisher³, Mark F Lythgoe², and Sebastien Ourselin^1
1Centre for Medical Image Computing, University College London, London, England, United Kingdom, ²Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, ³Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, United Kingdom, ⁴MRC National Institute for Medical Research, London, United Kingdom

We applied optimised protocols for high-resolution ex vivo MRI phenotyping of mouse brains, together with a fully automated image processing software pipeline, to perform tensor-based morphometry (TBM) on individual mouse models of Down syndrome and Alzheimer’s disease (the Tc1 and J20 models, respectively), as well as Tc1/J20 double mutants. In a comparison between Tc1/J20 and J20 brains, our analysis revealed significant differences in local morphology (volume) throughout the brain, including within the thalamus, olfactory bulbs and cerebellum. Our analysis highlights potential regions for later histology, and may inform behavioural investigations.

Brain Tumour Spectroscopy

Wednesday 3 June 2015

Katharina Johanna Wenger¹, Oliver Bähr¹, Elke Hattingen², and Ulrich Pilatus^2
1Neurooncology, Goethe-University Frankfurt, Frankfurt, Hessen, Germany, ²Neuroradiology, Goethe-University Frankfurt, Frankfurt, Hessen, Germany

In solid tumors, major changes in the expression and/or activity of plasma membrane ion pumps and transporters facilitate proton efflux and enable tumor cells to maintain a higher intracellular pH (pHi), while the microenvironment (pHe) is commonly more acidic compared to normal differentiated adult cells. An alkaline pHi supports various mechanisms involved in cellular proliferation and limits apoptosis, therefore promoting cell survival. We proposed that these early changes in pH take place before an MR-detectable recurrence occurs. To prove our hypothesis, we employed in-vivo 31P MR spectroscopic imaging (MRSI) in patients with recurrent glioblastoma (rGBM) before and under antiangiogenetic therapy (bevacizumab, BEV) until tumor progression. According to the predefined criteria by Pope et al. for distant or diffuse tumor progression, 14 patients of our institution were selected based on their tumor progression patterns at time of on-study progression (subsequent tumor). An area of interest for voxel selection on baseline MRSI data was defined retrospectively at the site of the subsequent tumor. The area of interest showed no detectable lesions before BEV on standard MRI sequences. The pHi in the area of interest (subsequent tumor) was significantly higher than the pHi of the contralateral normal appearing tissue (control) (p < 0.001) and similar to the pHi of the existing tumor. Elevated pHi in radiographically normal appearing tissue at baseline can predict the site of subsequent progression in patients with recurrent glioblastoma treated with BEV.

Uzay E Emir¹, Sarah Larkin², Nick de Pennington², Natalie Voets¹, Puneet Plaha³, Richard Stacey³, James Mccullagh⁴, Stuart Clare¹, Peter Jezzard¹, Christopher Schofield⁴, Olaf Ansorge², and Tom Cadoux-Hudson^3
1FMRIB Centre, University of Oxford, Oxford, Oxfordshire, United Kingdom, ²Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, Oxfordshire, United Kingdom, ³Department of Neurosurgery, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, Oxfordshire, United Kingdom, ⁴Department of Chemistry, University of Oxford, Oxford, Oxfordshire, United Kingdom

Mutations in IDH1 and IDH2 occur in up to 80% of a variety of glioma sub-types and lead to the production of MR detectable metabolite, 2-hydroxyglutarate (2-HG). In this abstract, we report results from a new acquisition protocol at 7T to detect 2-HG and the rest of the brain chemical profile in mutant IDH1/2 glioma patient with a higher sensitivity than has previously been achieved at clinical field. The new method at 7T is not only expected to increase diagnostic accuracy but also shorten the duration of the scan.

Natalie Rosella Boonzaier^1,2, Timothy J Larkin^2,3, Sarah Leir³, Laila A Mohsen⁴, Adam Young³, Victoria C Lupson², and Stephen J Price^2,3
1Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ²Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, Cambridgeshire, United Kingdom, ³Division of Neurosurgery, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ⁴Department of Radiology, University of Cambridge, Cambridge, United Kingdom

Glioblastomas are the most aggressive of the primary brain tumours in adults. The intratumoral heterogeneity that these lesions demonstrate is most likely the reason behind treatment failure. Characterizing regional heterogeneity, focusing on regions of combined diffusion and perfusion properties with associated metabolically aggressive profiles that go beyond the contrast-enhancing lesion, and into the less-understood non-enhancing component, may aid in understanding treatment failure and inevitable recurrence, a phenomenon that locally begins within the non-enhancing component of the tumor.

Sandeep Ganji¹, Zhongxu An¹, Dianne Mendelsohn¹, Marco Pinho¹, Edward Pan¹, Kevin Choe¹, Elizabeth Maher¹, and Changho Choi^1
1University of Texas Southwestern Medical Center, Dallas, TX, United States

The present work reports first longitudinal MRS imaging of 2-hydroxyglutarate (2HG) measures in brain tumors using optimized PRESS TE = 97 ms at 3T. Metabolites measures were measured in six clinically stable brain tumors, over a period of 8 – 18 months. The coefficient of variance (CoV) of 2HG was 1.1% over six subjects and 22 scans. The CoV of tCho, Glu and Gln were 3.5%, 11.1% and 10.3%, respectively. The mean 2HG levels over the tumor region remained within 0.2 to 0.8 mM across the time points.

Anouk Marsman¹, Sulaiman Sheriff², Doris D. Lin¹, Andrew A. Maudsley², Lawrence Kleinberg³, and Peter B. Barker^1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²Department of Radiology, University of Miami Miller School of Medicine, Miami, Florida, United States, ³Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Volumetric echo-planar spectroscopic imaging (EPSI) is a promising technique for mapping human brain tumors, based on elevated lesion choline (Cho) signals. This abstract reports the results of an interim analysis of an on-going project to determine if post-surgical EPSI has a role in radiotherapy planning in subjects with high-grade glioma, as well as to investigate the effects of treatment on tumor metabolism.

Benita Tamrazi¹, Ashok Panigrahy², and Stefan Bluml^1,3
1Children's Hospital Los Angeles/USC, Los Angeles, CA, United States, ²Children's Hospital of Pittsburgh, Pittsburgh, PA, United States, ³Rudi Schulte Research Institute, Santa Barbara, CA, United States

MRS spectra of pediatric pilocytic astrocytoma generally show low creatine and prominent choline. Perplexingly, most spectra, including those acquired from large lesions with no partial volume of surrounding tissue, also show residual signal that appears to be consistent with N-acetyl-aspartate. In this study we analyze the precise chemical shift of the peak and demonstrate that the signal is indeed not consistent with NAA. We also show that the precise position of this peak improves the separation of regular grade II and grade III astrocytomas from pilocytic astrocytomas.

Stefan Bluml^1,2, Ashley Margol^3,4, Ashok Panigrahy⁵, Richard Sposto^3,6, Rebekah Kennedy³, Marvin D Nelson¹, and Shahab Asgharzadeh^3,4
1Children's Hospital Los Angeles/USC, Los Angeles, CA, United States, ²Rudi Schulte Research Institute, Santa Barbara, CA, United States, ³Children's Hospital Los Angeles and Saban Research Institute, Los Angeles, CA, United States, ⁴Department of Pediatrics, Keck School of Medicine, University of Southern California, CA, United States, ⁵Children's Hospital of Pittsburgh, Pittsburgh, PA, United States, ⁶Department of Preventive Medicine, Keck School of Medicine, University of Southern California, CA, United States

Medulloblastomas are the single most prevalent pediatric brain tumor. Recently, analysis of tumor specimen identified four molecular subtypes, with “sonic hedgehog (SHH)” and “WNT” subtypes carrying significantly lower risk for disease dissemination and poor outcome than “Group 3” or “Group 4”. In this retrospective study we show that in vivo MR spectroscopy (MRS) can be used to predict the molecular subtypes.

Xi Long^1,2, Daniel Ramirez-Gordillo¹, Huijun Liao¹, Ben Rowland¹, Jong-Woo Lee³, Nils Arvold⁴, Patrick Wen⁴, Srinivasan Mukundan¹, Raymond Huang¹, and Alexander P Lin^1
1Center for Clinical Spectroscopy, Brigham and Women’s Hospital, Boston, MA, United States, ²Radiology Department, Union Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, Hubei, China, ³Department of Neurology, Brigham and Women’s Hospital, Boston, MA, United States, ⁴Division of Neuro-Oncology, Brigham and Women’s Hospital, Boston, MA, United States

Non-invasive and quantitative, magnetic resonance spectroscopy is ideally suited for treatment monitoring in brain gliomas. Recent studies have demonstrated the use of two-dimensional correlated spectroscopy (2D-COSY) for the evaluation of multiple metabolites. The goal of this study was to examine the efficacy of 2D-COSY compared to conventional MRS for the evaluation of brain tumors before and after radiochemotherapy. Our results demonstrate that 2D-COSY method provides similar results as 1D-MRS and can potentially provide additional metabolic information that may impact therapy.

Stefan Bluml^1,2 and Ashok Panigrahy^3
1Children's Hospital Los Angeles/USC, Los Angeles, CA, United States, ²Rudi Schulte Research Institute, Santa Barbara, CA, United States, ³Children's Hospital of Pittsburgh/UPMC, Pittsburgh, PA, United States

Diffuse intrinsic pontine glioma (DIPG) carry the worst prognosis in pediatric neurooncology, with the majority of patients dying within six to 18 months after diagnosis. Due to the lack of tissue samples, small patient numbers, and the challenges of clinical research in the pediatric population, there has been no improvement in outcomes for decades. This study demonstrates that serial MRS identifies subgroups of “longer survival” vs. “shorter survival” survival at an early stage of the disease. This finding demonstrates that MRS could be used to adjust therapies in individual patients but also to evaluate the effectiveness of new treatment strategies in a timely fashion.

Changho Choi¹, Sandeep Ganji¹, Zhongxu An¹, Dianne Mendelsohn¹, Marco Pinho¹, Edward Pan¹, Kevin Choe¹, and Elizabeth Maher^1
1University of Texas Southwestern Medical Center, Dallas, Texas, United States

We report Gly elevation in brain tumors. Gly was measured, with PRESS TE=97ms at 3T, in five subjects with gliomas in vivo. In a WHO grade 3 oligodendroglioma patient, the Gly level was substantially higher in the tumor than in the contralateral. In three patients with glioblastomas, Gly was elevated by 10 fold or more. A longitudinal study in an oligoastrocytoma patient indicated that Gly increases with tumor progression. Our data suggest that Gly may be not only a useful biomarker for evaluating the tumor malignancy but also a noninvasive tool for monitoring the malignant transformation.

Yan Li¹, Marisa Lafontaine¹, Susan Chang², and Sarah J Nelson^1,3
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, California, United States, ²Deparmenf of Neurological Surgery, University of California, San Francisco, California, United States, ³Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, California, United States

The purpose of this study was to compare the metabolite profiles that were acquired using conventional long echo time MRSI at 3T with short echo time MRSI at 3T and 7T in patients with glioma. The differences in Cho, Cr and NAA between acquisitions define the critical role of relaxation times in defining the observed signals. With improved quantification and metabolite detection using short echo time MRSI sequence at 7T, it would be possible to examine heterogeneity in T2 but the acquisition is limited in terms of tumor coverage compared to MRSI at 3T.

Shanshan Jiang^1,2, Hao Yu¹, Xianlong Wang¹, Shilong Lu¹, Yi Zhang², Doon-Hoon Lee², Hye-Young Heo², Jinyuan Zhou², and Zhibo Wen^1
1Department of Radiology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China, ²Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States

We explored the imaging features of PCNSL using APT imaging of endogenous mobile proteins and peptides at 3 Tesla. Results showed that the PCNSL tumor core had significantly higher APTW signal intensities, compared to adjacent peritumoral edema and normal-appearing white matter. The PCNSL tumor core had significantly lower APTW signal intensities, intensity distribution, and total CEST signal intensities, as well as significantly higher MTR than the HGG core. APT imaging could provide additional diagnostic information to differentiate PCNSL from HGG non-invasively.

Brain Tumour Multiparametic Assessment

Wednesday 3 June 2015

Maria Liljeroth¹, Kjell Erlandsson², Francesco Fraioli², David Thomas³, Enrico De Vita⁴, Brian Hutton², Anna Barnes⁵, Simon Arridge⁶, Sebastien Ourselin⁷, and David Atkinson^8
1Institute of Nuclear Medicine, Metabolism & Experimental Therapeutics, London, London, United Kingdom, ²Institute of Nuclear Medicine, Metabolism & Experimental Therapeutics, London, United Kingdom, ³Institute of Neurology, Faculty of Brain Sciences, Brain Repair & Rehabilitation, London, United Kingdom, ⁴National Hospital for Neurology and Neurosurgery, Lysholm Department of Neuroradiology, London, United Kingdom, ⁵Institute of Nuclear Medicine, Clinical Physics, London, United Kingdom,⁶Faculty of Engineering Science, Dept of Computer Science, London, United Kingdom, ⁷Dept of Med Phys & Biomedical Eng, London, United Kingdom, ⁸Faculty of Medical Sciences, Div of Medicine, London, United Kingdom

Simultaneous 18FFECho PET and Dynamic Susceptibility Contrast (DSC)/ Dynamic Contrast Enhanced (DCE) MRI has the potential for providing valuable information regarding tumour morphology and aggressiveness, essential for tumour staging. We present data from a conventional EPI perfusion acquisition strategy as well as a dual-echo GRE approach which allows separation of T1 and T2* effects of Gadolinium thus providing inherent rCBV correction and tracer kinetics. Results show elevated rCBV in astrocytoma relative to pineal germinoma. The specificity of 18FFE Cho provides clear outlining of tumourous regions for kinetic evaluation. PET and MRI images are also inherently coregistered using this technique.

Lawrence Kenning¹, Martin Lowry¹, Martin Pickles¹, Chris Rowland-Hill², Shailendra Achawal², Chittoor Rajaraman², and Lindsay Turnbull^1
1Centre for MR Investigations, Hull York Medical School at University of Hull, Hull, United Kingdom, ²Hull and East Yorkshire Hospitals NHS Trust, United Kingdom

We investigated whether MR parameters measured post-surgery prior to chemoradiotherapy could predict progression free survival in high grade gliomas. DTI, DSC and DCE data was acquired from 33 glioma patients prior to chemoradiotherapy. Mean and standard deviations were calculated for each parameter. Kaplan-Meier survival analysis was calculated using dichotomised parameter values. Results suggest that PK parameters derived from DCE-MRI and diffusion tensor metrics prior to adjuvant therapy predict progression-free survival. Elevated values of Ktrans, ve and vb were all significantly associated with a shorter progression-free survival interval. Blood products may prevent DSC from being clinically significant at this scan interval.

Simon Salinas¹, Steve Lau², Kate Drummond³, Christen Barras², Pramit Phal^1,2, Patricia Desmond^1,2, and Bradford Moffat^1
1The University of Melbourne, Melbourne, Victoria, Australia, ²Radiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia, ³Neurosurgery, The University of Melbourne, Melbourne, Victoria, Australia

We evaluated the feasibility of automatic computer assisted RANO classification of glioblastoma response to therapy. We investigated the validity of the RANO criteria in 31 patients undergoing chemo and radiation therapy. It was found that the RANO assessment could be reliably performed in less than 10 minutes per patient, using a dedicated graphical user interface. RANO classification was found to significantly correlate with patient survival with stable disease patients having a significant survival advantage (41 weeks p=0.04) compared to progressive disease patients. This graphical user interface and the validation of the criteria could pave the way for clinical translation.

Kelvin Wong^1,2 and Stephen Wong^1,2
1Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Houston, TX, United States, ²Department of Radiology, Weill Cornell Medical College, New York, NY, United States

Glioblastoma Multiforme (GBM) is the most lethal and common brain cancer in adult. Our goal is to quantitatively extract the infiltrating tumor information from imaging. Infiltrative tumor is with low Gd-enhancement and is difficult to identify. To investigate the prevalence and extent of low Gd-enhancement tumor in GBM, we developed an algorithm to automatically segment the low Gd-enhancement region. The method is applied to the GBM collection in The Cancer Imaging Archive (TCIA). The proposed algorithm can robustly segment different components of the tumor including low Gd-enhancement region.

Sarah A Leir¹, Timothy J Larkin^1,2, Natalie R Boonzaier^2,3, Victoria Lupson², Laila A Mohsen⁴, Adam Young¹, and Stephen J Price^1,3
1Division of Neurosurgery, Addenbrooke's Hospital, Cambridge, Cambridgeshire, United Kingdom, ²Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, Cambridgeshire, United Kingdom, ³Department of Clinical Neurosciences, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ⁴University Department of Radiology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom

Glioblastomas are one of the most lethal cancers to affect humans. The efficacy of surgical resection and radiotherapy, the mainstays of treatment, is limited by our ability to accurately determine tumor margins. Histological evidence suggests that there is a transition zone from tumor to normal brain extending for several centimeters beyond the T1 enhancing lesion. Diffusion-based MR is a promising new imaging technique to study tumor invasion. Using multimodal MR (DTI, perfusion and spectroscopy), we identify, for the first time, that biomarkers of tumor cell presence extend up to 3 centimeters beyond the conventionally determined and subsequently treated tumor margins.

Stephen J. Price^1,2, Adam MH Young¹, William J Scotton¹, Natalie R Boonzaier¹, Victoria C Lupson², Mary A McLean³, and Timothy J Larkin^1,2
1Academic Neurosurgery Division, Dept. Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom, ²Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom, ³Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom

Most patients with glioblastomas will die from disease progressing adjacent to the resected tumor. This invasive margin is a cardinal feature of glioblastomas and cannot be seen on conventional imaging but can be identified with diffusion tensor imaging. By outlining the DTI-defined region of tumour invasion we can use perfusion and MR spectroscopy to explore the microenvironment. This study shows that patients with more metabolically active invasive margins (defined as Cho/NAA > 0.6) have a significantly longer progression free survival. This suggests that cytotoxic therapies have increased efficacy with more proliferative and metabolically active invasive margins.

Adrian Ion-Margineanu^1,2, Sofie Van Cauter³, Diana M Sima^1,2, Frederik Maes^2,4, Stefaan W Van Gool⁵, Stefaan Sunaert³, Uwe Himmelreich⁶, and Sabine Van Huffel^1,2
1STADIUS, KU Leuven - ESAT, Leuven, Belgium, Belgium, ²iMinds Medical IT, Leuven, Belgium, ³Department of Radiology, University Hospitals of Leuven, Leuven, Belgium,⁴PSI, KU Leuven - ESAT, Belgium, ⁵Department of Pedriatic Neuro-oncology, University Hospitals of Leuven, Belgium, ⁶Department of Imaging and Pathology - Biomedical MRI/ MoSAIC, KU Leuven, Belgium

Our study is trying to find a relation between multi-parametric MR data (T1 post contrast - MRI, T2* - MRI, FLAIR, Perfusion MRI, Diffusion MRI, MR Spectroscopy) acquired during the follow-up of 29 glioblastoma multiforme (GBM) patients and the relapse of the brain tumour after surgery, as described by the clinically accepted RANO criteria. We find that ensemble classifiers can accurately predict the outcome of the therapy with approximately one month in advance before doctors. The same results were found also when using just perfusion features.

Chaitra Badve¹, Matthew Rogers², Alice Yu², Dan Ma³, Shivani Pahwa⁴, Andrew Sloan⁵, Jeffrey Sunshine^1,4, Vikas Gulani^1,4, and Mark Griswold^3,4
1Radiology, University Hospitals, Cleveland, Ohio, United States, ²School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States, ³Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, United States, ⁴Radiology, Case Western Reserve University, Cleveland, Ohio, United States, ⁵Neurosurgery, University Hospitals, Cleveland, Ohio, United States

Magnetic resonance fingerprinting was used to develop quantitative relaxometry maps of brain tumors (glioblastoma, metastases, and oligodendrogliomas). The relaxometry values were compared among the different tumors within the solid tumor and peritumoral regions. This study found significant differences in the relaxometry values between each tumor in both regions studied. These findings may aid in future diagnosis and grading of brain tumors, and may serve as quantitative imaging biomarkers by which early treatment can be optimized.

Jörg Mauler¹, Karl-Josef Langen¹, Andrew A. Maudsley², Omid Nikoubashman³, Christian Filss¹, Gabriele Stoffels¹, and N. Jon Shah^1
1Institute of Neuroscience and Medicine, Forschungszentrum Jülich, Jülich, Germany, ²Miller School of Medicine, University of Miami, FL, United States, ³Department of Neuroradiology, RWTH Aachen University, Germany

The association of spatially resolved FET uptake and MRS measures was investigated in high- and low-grade gliomas using a hybrid PET-MR scanner. This is intended to increase the sensitivity of the detection of FET negative low-grade tumours in the future. The MR spectral analysis was carried through with respect to choline, N-acetyl-aspartate, myo-inositol and lactate. 9 low-grade and 9 high-grade gliomas showed no clear association between FET uptake und the pattern of altered metabolite levels. Further investigations on a larger number of subjects are required.

Alexis Arnaud^1,2, Florence Forbes^1,2, Nicolas Coquery^3,4, Emmanuel L Barbier^3,4, and Benjamin Lemasson^3,4
1INRIA, Grenoble, -, France, ²LJK, University Grenoble Alpes, Grenoble, -, France, ³U836, INSERM, Grenoble, -, France, ⁴GIN, University Grenoble Alpes, Grenoble, -, France

Multiparametric MRI combined with multidimensional advanced statistical analysis methods may allow a more efficient brain tumor characterization. We used an Expectation-Maximization algorithm and Bayesian model selection on small animal data collected at 4.7T and using four glioma models (n=37). We first detected and excluded outlier animals (n=1). Then, we built a dictionary of tumor signatures. This dictionary discriminated four tumor models.

Kyung Mi Lee¹, Eui Jong Kim², Ji Hye Jang², and Woo Suk Choi^2
1Kyung Hee University Hospital, Seoul, Seoul, Korea, ²Kyung Hee University Hospital, Seoul, Korea

The DWI, MR spectroscopy, DSC, DCE of brain tumors are now widely used in the diagnosis and post-treatment evaluation of brain tumors. In the clinical setting, functional, quantitative and qualitative approaches with genomic biomarkers (IDH, MGMT, EGFR, PTEN, 1p/19q) are being applied in practice, but there are several pitfalls with all of these approaches. Understanding and applying the different imaging techniques and genomic biomarkers in a multiparametric algorithmic fashion in the clinical and research settings can be shown to increase diagnostic specificity and confidence.

Brain Tumour Diffusion

Wednesday 3 June 2015

Timothy J Larkin¹, Natalie R Boonzaier¹, Laila A Mohsen², and Stephen J Price^1
1Division of Neurosurgery, University of Cambridge, Cambridge, United Kingdom, ²Department of Radiology, University of Cambridge, United Kingdom

Diffusion tensor imaging (DTI) can be used to identify different patterns of tumour invasion in glioblastoma. These patterns of invasion from minimally to locally to diffusely invasive have been shown to correlate with progression free survival in these tumours. We aimed to develop an automated method of classifying patterns of invasion by measuring the distance between the edges of the bulk tumour and the invasive margin defined using DTI. Using our method we are able to distinguish different patterns of invasion.

Sumei Wang¹, Maria Martinez-Lage², Yu Sakai¹, Sanjeev Chawla³, Sungheon G Kim³, Michelle Alonso-Basanta⁴, Robert A Lustig⁴, Steven Brem⁵, Suyash Mohan¹, Ronald L Wolf¹, Arati Desai⁶, and Harish Poptani^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States,³Radiology, New York University School of Medicine, New York, NY, United States, ⁴Radiation Oncology, University of Pennsylvania, Philadelphia, PA, United States, ⁵Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States, ⁶Hematology-Oncology, University of Pennsylvania, Philadelphia, PA, United States

The purpose of this study was to determine whether DTI and DSC MRI can help in differentiating true progression (TP) from pseudo-progression (PsP) and mixed response in glioblastoma patients demonstrating enhancing lesions within six months post chemo-radiation therapy. Nine PsP, 12 mixed response and 21 TP patients underwent DTI and DSC-MRI. Significantly elevated maximum rCBV (rCBVmax), FA, CL, CP and decreased CS were observed in TP compared to PsP. The best logistic regression model to distinguish TP from non-TP (PsP+mixed) consisted of FA, CL and rCBVmax (AUC 0.905). DTI and DSC may be helpful in differentiating PsP from TP.

Jack T Skinner^1,2, Paul L Moots³, Adrienne N Dula^1,2, and C Chad Quarles^1,2
1Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ²Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, United States, ³Neurology, Vanderbilt University Medical Center, Nashville, TN, United States

Intravoxel incoherent motion (IVIM)-MRI has been shown to measure brain tumor perfusion. The effect of longitudinal treatment on IVIM estimates in glioma, however, is unknown. To elucidate these effects, functional IVIM mapping was performed. To implement this technique, IVIM reproducibility was first established in healthy subjects. f and Dwere found to be reproducible (wCV < 10%) while D* was less reproducible (wCV 16%). In patients, functional maps revealed a predominate increase in f with treatment. Though a robust decrease in D was observed, ADC remained relatively unchanged. Functional IVIM mapping may, therefore, help identify local regions of tumor progression or treatment effect.

Yan Tan¹, Hui Zhang², Xiao-chun Wang², Jiang-bo Qin², Xiao-feng Wu², Lei Zhang², and Le Wang^2
1Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan, Shanxi, China, ²Department of Radiology, First Clinical Medical College, Shanxi Medical University, Taiyuan 030001, Shanxi, China

Preoperative differentiation between high-grade astrocytomas (HGA) and solitary brain metastasis (SBM) may contribute to more appropriate treatment plans. Diffusion kurtosis imaging (DKI) is the extension of diffusion tensor imaging (DTI), which is an MRI technique depicting the non-Gaussian water molecule diffusion 1. DKI can be of particular interest for noninvasively differentiating HGA from SBM.

Johannes Slotboom¹, Nuno Pedrosa de Barros¹, Stefan Bauer², Urspeter Knecht¹, Nicole Porz³, Philippe Schucht³, Pica Pica⁴, Andreas Raabe³, Roland Wiest⁵, and Beate Sick^6
1DRNN, Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland, ²Institute of Surgical Technology and Biomechanics, University Bern, Bern, Switzerland, ³DKNS-Neurosurgery, University Hospital Bern, Bern, Switzerland, ⁴DOLS-Radiooncology, University Hospital Bern, Bern, Switzerland, ⁵1DRNN, Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, Bern, Switzerland, ⁶Division of Biostatistics, ISPM, University Zürich, Zürich, Switzerland

Despite the huge amount of information provided by an MR-examination, the initial diagnosis and grading of frequently extremely heterogeneous brain tumors by visual inspection remains a difficult task. A diagnostic text often lists a number of most likely diagnoses, e.g. anaplastic astrocytoma or glioblastoma multiforme. Here we discuss a method for computer aided radiologic diagnostics on how texture parameter analysis in combination with the advanced statistical classification random forest algorithm can be used to solve important differential diagnosis problem for individual diagnostics.

Yuankai Lin¹, Jianrui yuan Li¹, Zhiqiang Zhang¹, Qiang Xu¹, and Zongjun Zhang^1
1Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China

This abstract describes the value of intravoxel incoherent motion (IVIM) diffusion-weighted imaging(DWI) in finding characteristics of glioma and comparison between IVIM and Arterial Spin labeling(ASL) was made. IVIM has capability for detecting differences of diffusion and perfusion properties between low-grade and high-grade gliomas, and has potential as a non-invasive tool for assessment of brain glioma.

Sumei Wang¹, Sungheon G Kim², Maria Martinez-Lage³, Edward B Lee³, Laurie A Loevner¹, Harish Poptani¹, John YK Lee⁴, and Suyash Mohan^1
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Radiology, New York University School of Medicine, New York, NY, United States, ³Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States, ⁴Neurosurgery, University of Pennsylvania, Philadelphia, PA, United States

The purpose of this study was to correlate DTI metrics with the histologic findings including collagen content and Ki-67 labeling index in meningiomas. Forty-five meningiomas underwent DTI studies. High collagen was observed in fibroblastic meningiomas. Atypical meningiomas showed high Ki-67. There was a significant positive correlation between FA and collagen content (r=0.43, p<0.05), and between CP and collagen content (r=0.35, p<0.05). There was a significant negative correlation between MD and Ki67 (r=0.36, p<0.05). DTI can be helpful in predicting tumor consistency and patient outcome.

Ek T Tan¹, Robert J Young², Xiaofeng Liu¹, Marcel Prastawa¹, Kyung K Peck^2,3, Jennifer B Rubel², Jonathan I Sperl⁴, and Luca Marinelli^1
1GE Global Research, Niskayuna, NY, United States, ²Radiology, MSKCC, New York, NY, United States, ³Medical Physics, MSKCC, New York, NY, United States, ⁴GE Global Research, Garching, Munich, Germany

Recent diffusion models such as neurite orientation dispersion and density imaging (NODDI) provide new means to characterize brain tumor tissue, but may require long scan times as multiple b-values and diffusion directionalities are also required. A compressed-sensing (CS)-accelerated diffusion spectrum imaging (DSI) approach was used to provide the data for modeling with NODDI and diffusion kurtosis for whole-brain imaging within 15 minutes. Fifteen subjects with primary brain tumors were imaged with CS-DSI with a conventional 3T scanner and 8-channel brain coil. The results suggest that the NODDI and kurtosis maps may provide improved segmentation and classification of tumor types.

Logan Richard^1,2, Eric Bouffet^1,2, Suzanne Laughlin¹, Normand Laperriere³, Kamila Szulc¹, Douglas Strother⁴, Juliette Hukin⁵, Christopher Fryer⁵, Dina McConnell⁵, Fang Liu¹, Jovanka Skocic¹, Alexandra Mogadam¹, and Donald Mabbott^1,2
1The Hospital for Sick Children, Toronto, Ontario, Canada, ²University of Toronto, Toronto, Ontario, Canada, ³Princess Margaret Hospital, Toronto, Ontario, Canada, ⁴University of Calgary, Calgary, Alberta, Canada, ⁵British Columbia Children's Hospital, Vancouver, British Columbia, Canada

Investigating the longitudinal effects of cancer therapy on childhood brain tumour survivors is important in understanding their quality of life post-treatment. Our study investigates the effects of brain tumour treatment on several white matter (WM) tracts within the brain of childhood cancer survivors. We used diffusion tensor imaging to delineate specific WM tracts in brain tumour patients treated with different therapies and in healthy children. Survivors treated with craniospinal radiation exhibit compromised WM within multiple tracts including the optic radiation and inferior longitudinal fasciculus. This study provides evidence for the long-term effects of craniospinal radiation on the developing brain.

Kesshi Marin Jordan¹, Eduardo Caverzasi^2,3, Valentina Panara^1,4, Bagrat Amirbekian¹, Anisha Keshavan¹, Nico Papinutto^2,5, Mitchel Berger⁶, and Roland Henry^2
1Bioengineering, University of California San Francisco & Berkeley, San Francisco, CA, United States, ²Neurology, University of California San Francisco, San Francisco, CA, United States, ³University of Toronto, Toronto, Canada, ⁴Institute of Advanced Biomedical Technologies, University “G. D'Annunzio", Chieti, Italy, ⁵Bioengineering, University of California San Francisco & Berkeley, CA, United States, ⁶Neurosurgery, University of California San Francisco, San Francisco, United States

Diffusion tractography remains the only method of mapping white matter noninvasively. Fascicle volume definition depends heavily on tractography implementation choices. Safe clinical deployment of these technologies requires methodological variability to be characterized and minimized. This study investigates inter- and intra- operator variability of language fascicle reconstructions in both control subjects and tumor patients, and their dependence on #streamlines/voxel threshold choice. These results indicate that probabilistic tractography methods tend to have an optimal threshold for maximum percent overlap, but reliability varies by fascicle. The analysis of average diffusion metrics show striking average FA changes between commonly used thresholds.

Brain Tumour Perfusion & DCE

Wednesday 3 June 2015

James R. Ewing¹, Stephen L. Brown², Madhava P. Aryal¹, Kelly Ann Keenan³, Rasha M. Elmghirbi⁴, Swayamprav Panda¹, Hassan Bagher-Ebadian¹, and Tavarekere N. Nagaraja^3
1Neurology, Henry Ford Health System, Detroit, MI, United States, ²Radiation Oncology, Henry Ford Health System, Detroit, MI, United States, ³Anesthesiology, Henry Ford Health System, Detroit, MI, United States, ⁴Physics, Oakland University, Rochester, MI, United States

In a U251 rat model of cerebral tumor, extracellular volume was measured in the tumor, and in the normal tissue surround of the tumor via an innovative application of the Logan plot. Similarly, tumor exudate flux through the boundary of the tumor was measure via an application of a Patlak plot. Extracellular volume in the normal rim of the tumor was strongly decreased, implying compression in the tumor periphery. In 18 animals, tumor exudate flux was strongly dependent (R2=0.9) on compression of peritumoral tissue.

Prateek Prasanna¹, Pallavi Tiwari¹, Archana Siddalingappa², Leo Wolansky², Lisa Rogers², Tai-Chung Lam³, Victoria To³, and Anant Madabhushi^1
1Case Western Reserve University, Cleveland, OH, United States, ²University Hospitals, Cleveland, OH, United States, ³Tuen Mun Hospital, Hong Kong, China

In this work, we present the initial results of studying imaging differences of cerebral radiation necrosis on Gadolinium contrast-enhanced (Gd-C) T1-w MRI obtained from a unique cohort of patients treated for (a) nasopharyngeal carcinoma, (b) Glioblastoma Multiforme (GBM), and (c) metastatic brain tumors. Ability to identify changes in imaging characteristics on “pure” Radiation Necrosis (RN) with no cancer presence as observed in nasopharyngeal carcinoma, may allow for improved understanding of the changes in imaging characteristics on “mixed” RN on account of cancer presence in primary and metastatic brain tumors

Tord Hompland¹, Catherine Coolens¹, Brandon Driscoll¹, Warren Foltz¹, Cynthia Menard¹, David A. Jaffray^1,2, and Caroline Chung^1
1Princess Margaret Cancer Centre, Toronto, Ontario, Canada, ²TECHNA Institute/University Health Network, ontario, Canada

Here we communicate a method for measuring interstitial fluid flow in brain metastases, a potential tool to noninvasively measure changes in IFP. With this method we were able to show an increased peritumoral fluid flow 2 days following stereotactic surgery, most likely caused by an increase in tumor vasculature permeability and subsequent increase in IFP. Interstitial fluid flow also correlated with peritumoral edema. Interestingly, we also show that the fluid flow induced contrast agent transport can lead to misinterpretations of tumor volume measured by DCE-MRI depending on the time interval between injection and contrast-enhanced image acquisition.

Mona M Al-Gizawiy¹, Melissa A Prah¹, Wade M Mueller², and Kathleen M Schmainda^1,3
1Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Neurosurgery, Medical College of Wisconsin, Wisconsin, United States, ³Biophysics, Medical College of Wisconsin, Wisconsin, United States

Histopathology remains the gold standard for the diagnosis of brain tumors, even though MR imaging provides invaluable additional information on tumor behavior. Histopathological findings of 157 brain tissue specimens from 34 adult patients were matched to intraoperative surgical navigation snapshots of tissue collection sites. Preoperative leakage-corrected sRCBV differentiated between astrocytoma and oligodendroglioma grades, but this ability to distinguish between the grades was lost when different glioma types were combined for analysis. We present evidence that histologically different gliomas are also biologically distinct, characterized by significant differences in perfusion and diffusion measures, reinforcing the important role of sRCBV in glioma characterization.

Carly Warren¹, Michael Bock¹, Jochen Leupold¹, and Wilfried Reichardt^1,2
1Department of Radiology Medical Physics, Universitiy Medical Center Freiburg, Freiburg, Germany, ²German Cancer Consortium (DKTK), German Cancer Center (DKFZ), Heidelberg, Germany

Glioblastomas are very heterogeneous and diffusely growing brain tumors. They initiate and maintain angiogenesis during their growth. To assess whether a novel therapeutic drug changes the vascular architecture, non-invasive imaging methods to study changes of the neo-angiogenic vasculature are urgently needed. Time-of-Flight (TOF) is an imaging technique used in Magnetic Resonance Angiography (MRA) that is able to depict pathologic vasculature based on the flow of blood. In this study a 3D-phantom is constructed to simulate the vascular tree in a mouse to analyze the effects of TOF-MRA sequence parameters on the signal intensity in the vicinity of a glioblastoma.

Melissa A Prah¹, Steven M Stufflebeam², Eric S Paulson^1,3, Jayashree Kalpathy-Cramer², Elizabeth R Gerstner⁴, Tracy T Batchelor⁴, Daniel P Barboriak⁵, Bruce Rosen², and Kathleen M Schmainda^1,6
1Radiology, Medical College of Wisconsin, Milwaukee, WI, United States, ²Radiology, Massachusetts General Hospital, Charlestown, MA, United States, ³Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States, ⁴Neurology, Massachusetts General Hospital, Boston, MA, United States, ⁵Radiology, Duke University Medical Center, Durham, NC, United States, ⁶Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States

Measures of relative cerebral blood volume (rCBV) have shown to be immensely useful in assessing brain tumor vascularity. This has led to increased interest in the use of rCBV as a biomarker of clinical outcome or in research. This work provides an estimate of the minimum sample-size requirements to power a clinical imaging trial involving glioblastoma patients for six of the most commonly used rCBV estimation methods in order to detect a parameter change of 10% or 20%. Using these results, the efficiency of clinical trials may be improved with methods requiring considerably fewer participants to address a given hypothesis.

Yoon Seong Choi¹, Tyler Hyungtaek Rim², Mina Park¹, Ho-Joon Lee¹, Sung Soo Ahn¹, Jinna Kim¹, and Seung-Koo Lee^1
1department of radiology, Yonsei university college of medicine, Seoul, Seoul, Korea, ²department of ophthalmology, Yonsei university college of medicine, Seoul, Seoul, Korea

We investigated the usefulness of preoperative DCE-MRI in predicting three major genetic profiles of glioblastomas including EGFR, p53 and Ki-67, using histogram analysis. We found that Ktrans values were higher in EGFR positive tumors than EGFR negative tumors, and that Ktrans values were negatively correlated with p53 expression, thus associated with genetic profiles implicating poor prognosis in glioblastomas. We suggest that DCE-MRI might be useful in predicting genetic profiles associated with prognosis, and determining appropriate treatment strategy in patients with glioblastoma.

Mudit Gupta¹, Prativa Sahoo², Ritu Tyagi¹, Rana Patir³, Sandeep Vaishya⁴, Neeraj Prakash⁴, Indrajit Saha², and Rakesh Kumar Gupta^1
1Radiology, Fortis Institute, Gurgaon, Haryana, India, ²Philips Healthcare, Gurgaon, India, ³Neurosurgery, Fortis Institute, Gurgaon, India, ⁴Pathology, Fortis Institute, Gurgaon, India

While conventional post-contrast MRI demonstrates pathologies, perfusion MRI does it better. We evaluated the relative contributions of plasma volume (rPV) and extracellular, extravascular volume (rEV) to the contrast enhancement of intracranial lesions -- gliomas and neurocysticerosis (NCC). Intra-group comparison revealed significantly higher rEV than rPV in NCC and no significant difference in tumors. Inter-group comparison demonstrated significantly higher rPV in gliomas vis-à-vis higher rEV in NCC. We have demonstrated that breakdown of blood-brain barrier is the predominant pathology in enhancing NCC vis-à-vis neoangiogenesis in enhancing gliomas.

Takashi Abe¹, Saho Irahara², Yoichi Otomi², Yuuki Obama², Moriaki Yamanaka², Seiji Iwamoto², Sonoka Hisaoka², Mungunkhuyag Majigsuren², Delgerdalai Khashbat², Mungunbagana Ganbold², and Masafumi Harada^2
1Institute of Health Biosciences The Tokushima University Graduate School, Tokushima, Tokushima, Japan, ²Tokushima University Graduate School, Tokushima, Tokushima, Japan

In the imaging of intra-axial brain tumors, we sometimes found hyper-intensity areas on arterial spin labeling (ASL) outside of the enhanced tumor lesions. This study investigated the clinical significance of this finding in the differential diagnosis. Images from 38 consecutive patients who underwent ASL and CE-MRI with a 3T-MR scanner were examined (21; glioma, 8; metastasis, 9; lymphoma). About one third of cases showed this finding, but any cases with brain metastasis didn’t. This finding indicating the presence of glioma or lymphoma, not brain metastasis, and indicates a new utility for ASL images in the diagnosis of brain tumors.

Houshang Amiri^1,2, Anna C. Navis³, Tom Peeters¹, William P. Leenders³, and Arend Heerschap^1
1Department of Radiology, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands, ²Department of Cognitive Neuroscience, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands, ³Department of Pathology, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands

Arterial spin labeling (ASL) provides valuable information on cerebral blood flow (CBF) by using blood water molecules as an endogenous tracer. We aimed to first evaluate ASL to diagnose diffuse infiltrative glioma in well characterized xenografts mouse models and then to combine it with the commonly used method, i.e. contrast-enhanced (CE) MRI. We showed that ASL has potentials to detect diffuse infiltrative parts of tumors and therefore could be considered as a complementary value to the CE MRI by which compact growing parts of tumors are diagnosed.

Kohsuke Kudo¹, Ikuko Uwano², Toshinori Hirai³, Hideo Nakamura⁴, Noriyuki Fujima¹, Fumio Yamashita², Jonathan Goodwin², Satomi Higuchi², and Makoto Sasaki^2
1Diagnostic and Interventional Radiology, Hokkaido University Hospital, Sapporo, Hokkaido, Japan, ²Ultra-High Field MRI, Iwate Medical University, Morioka, Japan, ³Radiology, Kumamoto University, Kumamoto, Japan, ⁴Neurosurgery, Kumamoto University, Kumamoto, Japan

The purpose of the present study was to compare rCBV value of DSC perfusion and diagnostic performance of rCBV for discriminating low grade and high grade tumor among different software packages in patients with cerebral glioma. CBV maps were generated by 11 different algorithms of four commercially available software and one academic program. Diagnostic performances of rCBV for glioma grading were not statistically significant among post-processing software. However, rCBV values and cut off values for discriminating low grade and high grade gliomas were different among algorithms.

Brain Tumours & fMRI

Wednesday 3 June 2015

Madalina E Tivarus^1,2, Alexander Teghipco², Daniel Cole³, Michael Utz¹, and Ali Hussain^1
1Department of Imaging Sciences, University of Rochester, Rochester, NY, United States, ²Rochester Center for Brain Imaging, University of Rochester, Rochester, NY, United States, ³Department of Psychology, Emory University, GA, United States

Resting state fMRI (rs-fMRI) is emerging as an alternative brain mapping method that is independent of patient’s ability to comply with a task, but it has yet to enter the routine clinical practice due to the complexity of post-processing needed. We proposed an atlas based patient and operator independent seed analysis for processing rs-fMRI that meets the demands of clinical practice while reliably identifying functional networks.

Marc C Mabray¹, Igor J Barani², Suresh E Joel³, Rakesh Mullick³, and Soonmee Cha^1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Radiation Oncology, University of California San Francisco, San Francisco, CA, United States, ³General Electric Global Research, Bangalore, Karnataka, India

We aim to study the effects of radiation therapy on resting state functional connectivity. In this study we evaluated hippocampal functional connectivity in patients with extra-axial tumors receiving focal radiation therapy. We found decreased functional connectivity of the right hippocampus to the right putamen post-radiation therapy as compared to pre-radiation therapy. Further investigation into the effects of radiation dose to the hippocampus on functional connectivity and correlation with neurocognitive function is warranted. This may have implications for radiation therapy planning and provide insight into radiation related neurocognitive dysfunction.

Noora Pauliina Tuovinen¹, Francesco de Pasquale¹, and Umberto Sabatini^1
1Radiology, Santa Lucia Foundation, Rome, Lazio, Italy

For studying the effects of brain tumors on functional connectivity, resting state scans were acquired on 10 post-surgical glioblastoma multiforme patients. We hypothesized that the presence of tumor would affect the overal connectivity in the brain compared to healthy subjects. We ran ICA to recognize resting state networks across patients and defined nodes that were used to run the connectivity analysis. The data was analyzed using tools provided by FSL and Matlab. The results revealed reduced connectivity in the patients.

Chen Niu¹, Pan Lin², Ming Zhang¹, XiaoLong Peng², MaoDe Wang¹, Wei Wang¹, Wenfei Li¹, Xin Liu², and Rana Netra^1
1The First Affiliated Hospital of Medical College, Xi'an Jiaotong university, Xi'an, Shaanxi, China, ²Institute of Biomedical Engineering, Xi'an Jiaotong University, Xi'an, Shaanxi, China

In our study, we tested the hypothesis that the dynamic functional connectivity of the motor network would associate with the underlying motor function abnormality in tumor patients. Here, We used Wavelet transform coherence (WTC) analysis to explore the temporal dynamics of connectivity between key regions of motor networks in patients with different tumor types (Low-grade gliomas, and Meningioma) in order to achieve a better understanding of the relationship underlying brain plasticity mechanisms and dynamic functional connectivity. These results can enhance our understanding of motor network functional reorganization within different tumor type.

Novel Brain & Eye

Wednesday 3 June 2015

Yann Leprince^1,2, Benoît Schmitt¹, Élodie Chaillou³, Christophe Destrieux⁴, Laurent Barantin⁴, Alexandre Vignaud¹, Denis Rivière¹, and Cyril Poupon^1
1NeuroSpin, CEA, Saclay, France, ²Université Paris-Sud, Orsay, France, ³INRA, Tours, France, ⁴Université François-Rabelais, Tours, France

MRI of post-mortem brain specimen is often used because it allows high-resolution imaging thanks to long acquisitions times and the absence of movement. It also allows correlation with histological examination of the tissue. However, fixation with formaldehyde modifies the relaxivity and diffusion properties of tissue. This study investigates the kinetics of these modifications, and their reversibility when free formaldehyde is washed out of the tissue by soaking in saline solution.

Leon C. Ho^1,2, Ian P. Conner^3,4, Xiao-Ling Yang^1,3, Yolandi van der Merwe^1,4, Yu Yu⁵, Christopher K. Leung^6,7, Ian A. Sigal^3,4, Ed X. Wu², Seong-Gi Kim^1,8, Gadi Wollstein³, Joel S. Schuman^3,4, and Kevin C. Chan^1,3
1Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Pokfulam, Hong Kong, China, ³Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁴Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁵Division of Biomedical Engineering, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China, ⁶University Eye Center, Hong Kong Eye Hospital, Hong Kong, China, ⁷Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China, ⁸Center for Neuroscience Imaging Research, Institute for Basic Science, Sungkyunkwan University, Suwon, Korea

Glaucoma is the second leading cause of blindness in the world and is an irreversible neurodegenerative disease of the visual system. To date, limited models have been available to provide sustained intraocular pressure elevation while keeping a clear visual axis for normal visual input to the eye. In this study, we characterized a novel experimental glaucoma model in rats using a crosslinking hydrogel that gives sustained intraocular pressure elevation and a transparent medium after intracameral injection. In vivo anatomical MRI, magic angle-enhanced MRI and diffusion tensor imaging were employed to determine the morphological and microstructural changes in the whole eye and the brain in this model.

Oscar San Emeterio Nateras^1,2, Joseph M Harrison³, Eric R. Muir^2,3, Yi Zhang², Qi Peng^2,4, Steven Chalfin³, Juan E Gutierrez⁵, Daniel A Johnson³, Jeffrey W Kiel³, and Timothy Q Duong^2,3
1Biomedical Engineering, University of Texas at San Antonio, San Antonio, Texas, United States, ²Research Imaging Institute, San Antonio, Texas, United States,³Ophthalmology, University of Health Science Center at San Antonio, Texas, United States, ⁴Radiology, Albert Einstein College of Medicine, and Montefiore Medical Center, Bronx, NY, United States, ⁵Radiology, University of Health Science Center at San Antonio, Texas, United States

The goals of the present study were to assess the visual fixation stability achievable with cued eye blinks for blood-flow MRI and to test the hypothesis that retinal-choroidal blood flow changes with age in humans. Cued visual fixation on a target achieved adequate stability for blood flow MRI measurement. Retinal-choroidal blood flow negatively correlated with age, declining 1.8ml/100ml/min per year. Such decrease in ocular blood flow could impair delivery of oxygen and nutrients, and removal of metabolic waste, making the retina more susceptible to diseases.

Laetitia Maëlle Vionnet¹, Lars Kasper^1,2, Michael Wyss¹, Mike Bruegger^1,3, and Klaas Paul Pruessmann^1
1Institute for Biomedical Engineering, ETH and University Zurich, Zurich, Switzerland, ²Translational Neuromodeling Unit, ETH and University Zurich, Zurich, Switzerland, ³Center of Dental Medicine, University of Zurich, Zurich, Switzerland

Physiological noise in the brainstem is investigated on high-resolution fMRI data. We verify that this source of confound is localized around the brainstem and that a masking procedure enable tSNR enhancement.

Pierre-Louis Bazin¹, Audrey Fan², Gabriela Mianowska³, Agnieska Olbrich³, Andreas Schäfer¹, Arno Villringer¹, and Claudine Gauthier^4
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Stanford University, California, United States, ³AGH University of Science and Technology, Cracow, Poland, ⁴Concordia University, Montréal, Québec, Canada

This work presents a new automated segmentation method to extract detailed brain vasculature from high-resolution quantitative susceptibility maps at high field. Comparison with human raters and susceptibility-weighted contrasts indicate the suitability of the method for measuring local oxygen extraction fraction in small cortical veins.

Yi-Hsin Tsai¹, Hung-Chieh Chen², Hsin Tung³, Da-Chuan Cheng⁴, Clayton Chi-Chang Chen², Jyh-Wen Chai^1,2, Hsiao-Wen Chung⁵, and Wu-Chung Shen^6
1College of Medicine, China Medical University, Taichung, Taichung, Taiwan, ²Department of Radiology, Taichung Veterans General Hospital, Taichung, Taichung, Taiwan,³Neurological Institute, Taichung Veterans General Hospital, Taiwan, Taiwan, ⁴Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taichung, Taiwan, ⁵Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan, ⁶College of Health Care, China Medical University, Taichung, Taichung, Taiwan

Non-invasive MR intracranial pressure measurement (MR-ICP) has limited clinical applicability due to measurement errors, a great portion of which likely comes from internal jugular vein (IJV) pulsations. Experiments on normal volunteers were conducted to evaluate how the IJV flow patterns on various measurement positions affect the peak-to-peak intracranical volume changes (ICVC), which then used to estimate the MR-ICP. Results showed strong correlations between ICVC and IJV pulsatility indexes, both increasing as slices caudally shifted, quite apparently caused by right atrial hemodynamics. With properly positioned IJV measurement, the accuracy and reliability of MR-ICP measurement can be effectively improved.

Head & Neck & Beyond

Wednesday 3 June 2015

Xiaoping Wu¹, Dingxin Wang^1,2, Jinfeng Tian¹, Sebastian Schmitter¹, Vibhas Deshpande³, Tommy Vaughan¹, Kamil Ugurbil¹, and Pierre-Francois Van de Moortele^1
1CMRR, Radiology, University of Minnesota, Minneapolis, MN, United States, ²Siemens Medical Solutions USA, Inc., Minneapolis, MN, United States, ³Siemens Medical Solutions USA, Inc., Austin, TX, United States

Previous studies have demonstrated that the use of dual source parallel RF transmission (pTx) is advantageous over standard single source RF excitation in 3T body imaging. In these studies a single RF shim set was obtained for a multislice sequence to image the entire region of interest and therefore the resulting pulses are of suboptimal performance since the full degrees of freedom (DOF’s) available in the pulse design are not utilized. Recently, a slab-wise pulse design strategy was introduced to make maximum use of the DOF’s in pulse design and was demonstrated capable of providing enhanced RF performance when designing pTx multiband pulses. In this study, we utilize this slab-wise design strategy to evaluate the performance of a 3T birdcage body coil when operated in the dual transmit mode, and compare it to the conventional single transmit circularly polarized mode. RF shimming was conducted with local SAR control based on electromagnetic simulations of the birdcage coil.

Pierre-André Vuissoz^1,2, Freddy Odille^1,2, Yves Laprie^3,4, Emmanuel Vincent^3,5, and Jacques Felblinger^6,7
1Imagerie Adaptative Diagnostique et Interventionnelle, Université de Lorraine, Nancy, France, ²U947, INSERM, Nancy, France, ³LORIA, Université de Lorraine, Nancy, France,⁴LORIA, CNRS, Nancy, France, ⁵LORIA, INRIA, Nancy, France, ⁶University Hospital Nancy, Nancy, France, ⁷CIC-IT 1433, INSERM, Nancy, France

To construct an articulatory model of the vocal tract 10 sentences were pronounced and recorded at 3T using balanced-SSFP multiphase sequences with a resolution of 256x256. An optical microphone was used to record the speech during an 80 second scan. A noise reduction algorithm is applied before aligning each acoustic sentence onto a median template sentence. A cine loop of 128 images for each sentence is reconstructed using a motion compensated sliding window algorithm (80 ms) producing a reconstructed frame rate above 100 Hz. Each cine loop enables the delineation of the vocal tract with sufficient spatial and temporal resolution.

Sjoerd B Vos^1,2, Wieke Haakma^3,4, Huib Versnel¹, Martijn Froeling³, Lucienne Speleman¹, Pieter Dik⁵, Max A Viergever², Alexander Leemans², and Wilko Grolman^1
1Department of Otorhinolaryngology and Head & Neck Surgery, University Medical Center Utrecht, Utrecht, Netherlands, ²Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, ³Department of Radiology, University Medical Center Utrecht, Utrecht, Netherlands, ⁴Department of Forensic Medicine & Comparative Medicine Lab, Aarhus University, Denmark, ⁵Department of Pediatric Urology, University Children's Hospital UMC Utrecht, Utrecht, Netherlands

The viability of the auditory nerve in deaf patients is critical in hearing recovery after cochlear implantation (CI). The nerve degenerates following cochlear hair cell loss and the amount of degeneration varies between ears. DTI may yield a measure of nerve degeneration by allowing noninvasive estimates of the nerve’s microstructure. We show the first use of DTI to image the auditory nerve using a specialized acquisition protocol on a clinical 3T scanner. Our results show a bilateral decrease in FA in unilaterally deaf patients compared to normal-hearing controls. No differences were observed between the deaf and healthy-sided nerves in patients.

Shinji Naganawa¹, Hisashi Kawai¹, Michihiko Sone², and Mitsuru Ikeda^3
1Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan, ²Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan, ³Department of Radiological and Medical Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan

Endolymph size in the vestibule of patients with Isolated vestibular-lateral semicircular canal dysplasia (LSCCD)is larger than those without LSCCD. The current MRI diagnostic cut-off value for significant vestibular endolymphatic hydrops (>50%) might not be appropriate for ears with LSCCD.

John Huston III¹, Arvin Arani¹, Nikoo Fattahi¹, Kevin J Glaser¹, David S Lake¹, Armando Manduca¹, Joshua D Hughes², Jamie J Van Gompel², and Richard L Ehman^1
1Radiology, Mayo Clinic, Rochester, Minnesota, United States, ²Neurosurgery, Mayo Clinic, Rochester, Minnesota, United States

Tumors of the skull base vary in stiffness; however, stiffness cannot reliably be predicted with conventional MRI sequences. Stiff tumors can result in a difficult surgical resection with extended operative time and increased risk to the patient. In addition, with the increasing role of endoscopy, knowing tumor stiffness prior to surgery could be critical to decide between an open or endoscopic approach. The goal of this study was to determine the potential of MR Elastography to preoperatively assess the stiffness of skull base meningiomas, pituitary adenomas, and vestibular schwannomas.

Koji Matsumoto^1,2, Hajime Yokota^3,4, Hiroki Mukai⁴, Ken Motoori⁴, Toshiaki Miyachi², Yoshitada Masuda¹, and Takashi Uno^4
1Department of Radiology, Chiba University Hospital, Chiba, Chiba, Japan, ²Division of Health Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan, ³Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto, Japan, ⁴Diagnostic Radiology and Radiation Oncology, Chiba University, Chiba, Japan

Magnetic resonance (MR) cisternography using three dimensions steady-state free precession (3D-SSFP) is widely used for visualizing the inner ear. However, local magnetic field of the inner ear is easy to be heterogeneous due to surrounding air cells. The heterogeneity causes phase shift in pixels and banding artifact on 3D-SSFP. Although addiction of changing phase cycling is used to reduce banding artifact, it is available only in advanced machines. Varying central frequency can cause phase shift and change locations of banding artifact. The merged images with different central frequencies can reduce banding artifact of 3D-SSFP.

Koji Yamashita¹, Akio Hiwatashi¹, Osamu Togao¹, Kazufumi Kikuchi¹, Tomoyuki Okuaki², Nozomu Matsumoto³, Koji Kobayashi⁴, and Hiroshi Honda^1
1Clinical Radiology, Graduate School of Medical Science, Kyushu University, Fukuoka, Fukuoka, Japan, ²Philips Electronics Japan, Tokyo, Japan, ³Otorhinolaryngology, Kyushu University, Fukuoka, Japan, ⁴Medical Technology, Kyushu University hospital, Fukuoka, Japan

T1ƒÏ weighted imaging is sensitive to slow spin motions in tissue, and may provide information about the macromolecular properties of tissues. Therefore clinical application of the technique is of increasing importance. The aim of our study was to investigate the feasibility of T1ƒÏ imaging in diagnosing cholesteatoma. In this study, we compared the differences of average T1ƒÏ values between cholesteatoma and non-cholesteatoma group. As a result, cholesteatoma can be distinguished from other middle ear diseases. Although the precise mechanism of pathogenesis is not fully elucidate, our results will help us for a better understanding of biological behavior in cholesteatoma.

Arnaud ATTYE^1,2, Alexandre KARKAS³, Irene TROPRES⁴, Laurent LAMALLE⁴, Felix RENARD⁵, Georges BETTEGA⁶, Christian RIGHINI³, and Alexandre KRAINIK^5
1Neuroradiology, Grenoble University Hospital, Grenoble, Rhône Alpes, France, ²UMS IRMaGe, Grenoble, Rhône Alpes, France, ³Otolaryngology, Grenoble University Hospital, Rhône Alpes, France, ⁴UMS IRMaGe, Rhône Alpes, France, ⁵Neuroradiology, Grenoble University Hospital, Rhône Alpes, France, ⁶Maxillofacial Surgery, Grenoble University Hospital, Rhône Alpes, France

Magnetic resonance tractography of the cranial nerves is a promising tool. Yet, in order to validate the quality of quantitative data yielded from this technique, the course of nerve fibres must be confirmed surgically. This prospective study is the first work that assessed the feasibility and reliability of extracranial facial nerve magnetic resonance tractography using in vivo data, based on surgical photos and per-operative nerve stimulation. We successfully identified facial nerve, in relation to the parotid tumors, in all patients and performed quantitative microstructural analysis for 52 facial nerves. The outcome would be to aid future medical studies examining nerve dysfunction.

Heather Ting Ma^1,2, Pengfei Yang¹, Chenfei Ye¹, Jun Wu³, Xuhui Chen³, and Jinbo Ma^1
1Department of Electronic and Information Engineering, Harbin Institute of Technology Shenzhen Graduate School, Shenzhen, Guangdong, China, ²Radiology Department, Johns Hopkins University, Baltimore, MD, United States, ³Department of Neurology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China

This study aimed at exploring lesion detection of multiple sclerosis (MS) which couldn¡¯t be seen on conventional MRI. The whole brain voxel-by-voxel DTI analysis was performed on clinical data with a fusion quantitative analysis model, which was based on TBSS and VBA method with an anisotropic filter. Quantitative comparison result for the fusion model demonstrated statistically significant reduction of FA values in all MS patients compared with controls. The lesions mainly located in corpus callosum, corticospinal tract, occipital lobe, and optic tract. The optic tract lesions may be the direct cause for the typical clinical symptoms of visual dysfunction in MS patients.

Renjie He¹, Yao Ding², Clifton Fuller², Qi Liu¹, and Weiguo Zhang^3
1United Imaging Healthcare America, Houston, Texas, United States, ²MDACC, Texas, United States, ³United Imaging Healthcare, Shanghai, China

Instead of averaging over multiple (repetitive) acquisitions to reduce the parameter map uncertainty caused by noise in the head and neck region, firstly we introduce a non-local means spatial filtering to reduce the noise from a single acquisition. The noise is further suppressed by incorporating model-based filtering originated from the sparse coding theory where a joint-dictionary is applied. The joint-dictionary also provide an approach to extrapolate the flip angles from the collected 6 flip angles data set to the regenerated 28 virtual flip angles. Finally, we construct another model-based full dictionary to retrieve the T1 from the reconstruction of 28 flip angles, and S0 is acquired by least square estimation from the T1 map.

Ning Lang¹, Hon J Yu², Huishu Yuan¹, and Min-Ying Su^2
1Department of Radiology, Peking University Third Hospital, Beijing, China, ²Tu&Yuen Center for Functional Onco-Imaging, University of California, Irvine, CA, United States

DCE-MRI was performed to differentiate 4 spinal lesions (9 myeloma, 85 metastatic cancer, 7 lymphoma, 24 benign tuberculosis). Two-compartmental pharmacokinetic model was used to obtain Ktrans and kep, by using the fast and medium blood curves, with and without considering the vascular term vp. The results showed that despite a rapid wash-in seen in some cases, the obtained vascular component was still low. The kep analyzed by using the medium blood curve was the best parameter to differentiate these 4 lesion groups. When the term vp was considered, it had a diagnostic value, but the kep might become less powerful.

Sanam Assili^1,2, Anahita Fathi Kazerooni^1,3, Mahnaz Nabil^1,4, Leila Agha Ghazvini⁵, Mojtaba Safari¹, and Hamidreza Saligheh Rad^1
1Quantitative MR Imaging and Spectroscopy Group, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran, ²Department of Medical Physics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, ³Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, ⁴Department of Statistics, Tarbiat Modares University, Tehran, Iran, ⁵Department of Radiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Accurate discrimination of benign and malignant parotid tumors in morphological MR images is a challenging issue. On one hand there exist large histological variations throughout the tumor, and on the other hand anatomical MR-derived features have low sensitivity in capturing the physiological non-uniformities of parotid tumors. To overcome this problem, in this work, we have explored and compared several quantitative measures extracted from ADC map to find the best parameters in distinguishing benign and malignant parotid tumors, in an automatic classification scheme.

Gaspar Delso¹, Mohammad Mehdi Khalighi¹, Florian Wiesinger², and Patrick Veit-Haibach^3
1GE Healthcare, Waukesha, WI, United States, ²GE Global Research, Germany, ³University Hospital of Zurich, Switzerland

One of the main challenges of attenuation correction in hybrid PET/MR scanners is the correct identification of bone tissue. A recent development has been the publication of a new bone identification technique, based on 3D radial zero echo time (ZTE) imaging. This sequence provides high-resolution, isotropic images, suitable for bone segmentation, without the need of preparation pulses or multiple echoes, making it a very time-efficient acquisition. The goal of the present study is to compare ZTE bone images of clinical patients with the corresponding CT datasets, obtained using a tri-modality scanner setup.

Marzena Wylezinska¹, Andreia Freitas^1,2, Malcolm Birch¹, and Marc Miquel^1,2
1Clinical Physics, Barts Health NHS Trust, London, United Kingdom, ²William Harvey Research Institute, Queen Mary University of London, London, United Kingdom

The aim of this work was to investigate the performance of k-t BLAST scheme when applied to real-time imaging of speech. We were particularly interested to determine if this method could be used clinically to visualize soft palate motion and velopharyngeal closure during speech. We have also investigated k-t FOCUSS algorithm for reconstruction of dynamic speech data and compared it with commercially available k-t BLAST reconstruction. K-t BLAST scheme is a promising tool to accelerate MRI for speech imaging. K-t FOCUSS reconstruction allowed to improve quality of the images.

Han Lv¹, Zhenchang Wang¹, Zhaohui Liu², Fei Yan², Pengfei Zhao¹, and Ting Li^2
1Beijing Friendship Hospital, Beijing, Beijing, China, ²Beijing Tongren Hospital, Beijing, China

Our results provide insights into the understanding of neural plasticity of PT patients and indicate that a properly chosen frequency band can be more helpful to explore PT-related neural changes.

Tilak Das¹, Andrew J Patterson¹, Paul Meyer², Rachna Murthy², and Martin J Graves^1
1Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, ²Dept of Ophthalmology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

Thyroid eye disease is an autoimmune disorder of orbital tissues that can cause extra-ocular muscle inflammation and enlargement. Fat infiltration of extra-ocular muscles occurs in patients with chronic disease. Quantification of fat in extra-ocular muscles has not been previously described. The purpose of this study was to evaluate the application of fat fraction measurements to extra-ocular muscles in healthy volunteers and patients with thyroid eye disease. Mean fat fraction was significantly greater in thyroid eye disease patients (p=0.021). This study demonstrates the feasibility of measuring fat fraction in extra-ocular muscles as well as detecting differences between groups.

Jr-yuan George Chiou¹, Bruno Madore¹, and Stephan E. Maier^1
1Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States

Quantitative MRI of the human optic nerve in vivo is generally quite challenging because of its small size, its uncontrolled motion, and the presence of local field inhomogeneity. Single-shot echo-planar imaging (EPI) is employed to obtain diffusion-weighted images within hundreds of milliseconds, but images often suffer from significant artifacts. In this study, an accelerated multi-shot diffusion imaging was employed to achieve high resolution, speed and geometric fidelity in optic nerve imaging.

Ming Li^1,2, Paul Gamlin³, Mark S. Bolding^4,5, Ronald J. Beyers¹, Nouha Salibi^1,6, Xiaoxia Zhang^1,2, and Thomas S. Denney Jr.^1,2
1Auburn University MRI Research Center, Auburn University, Auburn, AL, United States, ²Electrical and Computer Engineering, Auburn University, Auburn, AL, United States,³Department of Ophthalmology, University of Alabama at Birmingham, Birmingham, AL, United States, ⁴Departments of Radiology, Vision Sciences, and Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States, ⁵Civitan Functional Neuroimaging Laboratory, University of Alabama at Birmingham, Birmingham, AL, United States,⁶MR R&D, Siemens Healthcare, Malvern, PA, United States

The vitreous humour undergoes mechanical changes that are thought to be related to a range of pathologies including retinal detachment and are reflected on the motion pattern of the vitreous humour during eye movements. We analyzed the in-vivo dynamics of the vitreous humour under smooth pursuit eye movement, using tagged MRI with a standard head coil in a 7 Tesla scanner. We also propose a method for measuring regional shear strain in the vitreous humour, which does not use assumptions on the geometry of the globe or material properties of the vitreous.

Saurav B Chandra¹, Kaiwalya S Deo¹, Eric R Muir¹, Jeffrey W Kiel², and Timothy Q Duong^1
1Research Imaging Institute, UT Health Sc. Center, San Antonio, San Antonio, Texas, United States, ²Ophthalmology, UT Health Sc. Center, San Antonio, San Antonio, Texas, United States

Dorzolamide (DZ) is clinically used to treat glaucoma by reducing intraocular pressure, which could affect blood flow to the eye. The goal of this study was to investigate the effect of topical DZ application on retinal and choroidal blood flow in DBA/2J mice, an established mouse model of glaucoma at different stages of severity. DZ was found to induce measurable and sustained effects in choroidal BF and retinal BF at up to 2 hours post DZ application in late stage glaucoma mice.

Akio Hiwatashi¹, Osamu Togao¹, Koji Yamashita¹, Kazufumi Kikuchi¹, Makoto Obara², and Hiroshi Honda^1
1Radiology, Kyushu University, Fukuoka, Fukuoka, Japan, ²Philips Electronics Japan, Tokyo, Japan

With its insensitivity to field inhomogeneity and high spatial resolution, the 3D DSDE-TFE technique enabled us to discriminate solid tumors from cystic tumors without contrast material.

Suchandrima Banerjee¹, Misung Han², Weitian Chen¹, Christopher P Hess², Roland Krug², Ajit Shankaranarayanan¹, and Yuval Zur^3
1Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States, ²Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ³GE Healthcare, Tirat Carmel, Israel

MRI is moving toward volumetric imaging, because of the flexibility it allows for reformatting a single image volume in any oblique plane and the simplified workflow. Reduced field-of-view (rFOV) capability can enable focused 3D high resolution imaging, even of deep-seated regions, within a short scan time. This work presents an rFOV 3D FSE sequence using outer volume suppression and demonstrates its utility in a challenging application area-MRI of the orbits-in comparison with an existing 2D FSE protocol.

Taihra Zadi¹, Mika Vogel², Magnus Mårtensson³, Piotr A. Wielopolski¹, and Aad van der Lugt^1
1Department of Radiology, Erasmus University Medical Center, Rotterdam, Zuid-Holland, Netherlands, ²Healthcare Systems, General Electric Healthcare, Hoevelaken, Gelderland, Netherlands, ³Applications and Workflow, General Electric Healthcare, Stockholm, Södermanland, Sweden

Previous studies have shown that T1w SE POPELLER is helpful in the reduction of flow artefacts in the brain, especially in the T1w images post-Gd. An additional advantage of SE-PROPELLER sequence is the possibility to reduce bulk motion artefacts. In this study, the effects of the PROPELLER readout are evaluated in the neck region in patients with head and neck tumors, which is usually degraded by motion and flow artefacts. In this work we have shown that with T1w SE-PROPELLER, motion artefacts can be reduced significantly. Flow artefacts in T1w scans are also minimized in the SE PROPELLER.

Jeff A. Kohlmeier¹, Heidi A. Edmonson², Joel P. Felmlee², David W. Stanley³, Fred J. Regennitter¹, and John E. Volz^1
1Department of Orthodontics, Mayo Clinic, Rochester, MN, United States, ²Department of Radiology, Mayo Clinic, Rochester, MN, United States, ³GE Healthcare, Rochester, MN, United States

Orthodontic appliances are well known to produce artifact and geometric distortion in MR imaging of the head and neck. The goal of this study was the quantify the extent of susceptibility artifact induced by common orthodontic appliances and to evaluate the utility of MAVRIC for imaging near the appliances. Various appliances configurations were imaged on an anthropomorphic phantom utilizing T2FSE, T1 Cube, T1 MAVRIC and SL MAVRIC sequences. Our results show a large reduction in signal void when comparing MAVRIC to both T2 FSE and T1 Cube sequences for all appliances (51% and 83% reduction respectively). These results suggest that MAVRIC could decrease the frequency of appliance removal for MR imaging and could be used as a problem solving sequence for tissues near the appliance.

Akinwunmi Oni-Orisan¹, Mayank Kaushal², Wenjun Li¹, B. Doug Ward¹, Aditya Vedantam³, Benjamin Kalinosky², Dana Seslija¹, Matthew Budde¹, Brian Schmit², Shi-Jiang Li¹, Muqeet Vaishnavi¹, and Shekar Kurpad^1
1Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Marquette University, Milwaukee, Wisconsin, United States, ³Baylor College of Medicine, Houston, Texas, United States

We performed a resting-state functional magnetic resonance imaging (rs-fMRI) study to demonstrate alterations in cortical activation maps in patients with spinal cord injury (SCI). After prepreprocessing of functional data using Analysis of Functional NeuroImages (AFNI) software, region of interest (ROI) based analysis was carried out. A general pattern of decreased functional connectivity in sensorimotor cortex and increased connectivity in thalamus was observed in SCI patients compared to controls. Our results provide evidence of abnormal spontaneous brain activations in humans with SCI suggesting a possible SCI-induced reorganization of cerebral cortex on account of ongoing neural plasticity in the central nervous system.

KOUNG MI KANG¹ and Seung Hong Choi^1
1Radiology, Seoul National Univ. Hospital, Seoul, Seoul, Korea

The objective of this study was to prospectively evaluate short-term test-retest reproducibility of IVIM parameters and apparent diffusion coefficient (ADC) of variable tissue in the head and neck using 4b values, 4b values with cardiac gating and 17b values, respectively. As a result, IVIM DWI using 4bvalues with gating was the most reproducible method in the head and neck in comparison with IVIM DWIs using 4b values or 17 values.

Anna Bratasz¹, Esmerina Tili^2,3, Xiaomei Meng², Jean-Jacques Michaille^4,5, Lamia Bouhliqah⁶, Phillip G Popovich⁷, Cynthia Mcallister⁸, D Michele Basso⁹, José J Otero¹⁰, Claudia Kirsch¹¹, Richard Burry⁷, Kimerly A Powell¹, Peter Mohler¹², Carlo M Croce⁴, and Hamdy Awad^2
1Small Animal Imaging Core, The Ohio State University, Columbus, Ohio, United States, ²Department of Anesthesiology, The Ohio State University, Ohio, United States,³Department of Molecular Virology, The Ohio State Univeristy, Ohio, United States, ⁴Department of Molecular Virology, The Ohio State University, Ohio, United States, ⁵Université de Bourgogne, Dijon, France, ⁶Department of ENT, The Ohio State University, Ohio, United States, ⁷Department of Neuroscience, The Ohio State University, Ohio, United States,⁸Nationwide Children Hospital, Ohio, United States, ⁹School of Health and Rehabilitation Sciences, The Ohio State University, Ohio, United States, ¹⁰Department of Pathology, The Ohio State University, Ohio, United States, ¹¹Department of Radiology, The Ohio State University, Ohio, United States, ¹²Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Ohio, United States

MiR-155 ablation was evaluated for its protective effect on ischemic cord injury (SC) in a mouse model of thoraco-abdominal aortic aneurysm (TAAA) repair. MR imaging was used for monitoring the paralysis event in wild type and miR-155 knockout mice. MiR-155-/- mice resulted in reduced number and delayed paralysis events. There was a strong correlation between edema volume and T2 relaxation time values of the SC grey matter in paralyzed versus non-paralyzed mice. Edema was correlated with histological observation of gray matter damage. We believe that reducing miR-155 upregulation after TAAA may be useful for reducing paralysis after surgery.

Chen-Te Wu¹, Cheng-Chih Liao², Chung-Lin Yang², Jiun-Jie Wang³, Ching-Po Lin⁴, and Shih-Tseng Li^2
1Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, ²Departments of Neurosurgery, Chang Gung Memorial Hospital & Chang Gung University, Taiwan, ³Department of Medical Imaging and Radiological Science, Chang Gung University, Taiwan, ⁴Brain Connectivity Lab, Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan

RESOLVE-DTI can help to assess the severity of cervical spinal cord injuries and provide reproducible quantitative measurements with limited distortion in a clinically acceptable scan time. With RESOLVE-DTI, severe and mild grades of cervical spinal cord injuries can be discriminated against the imaging bias of spinal stenosis and spinal cord edema.

Li Min Chen^1,2, Arabinda Mishra^1,2, Feng Wang^1,2, Pai-Feng Yang^1,2, and John C. Gore^1,2
1Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ²Institute of Imaging Science, Vanderbilt University, Nashville, TN, United States

Resting state fMRI has shown that intrinsic functional connectivity networks may be detected in the spinal cord of humans and anesthetized monkeys. The functional relevance of these networks, however, remains to be determined. One way to address this question is to modulate the network and then correlate the changes with behavioral and functional outcomes. In this study we examined the effects of unilateral spinal cord injury on the inter-regional correlation strengths of resting state fMRI signals between spinal horns of gray matter in spinal segments above or below the injury level.

Jos Oudeman¹, Bram F Coolen¹, Camiel Verhamme², Mario Maas¹, Andrew Webb³, Gustav J Strijkers⁴, and Aart J Nederveen^1
1Radiology, Academic Medical Center, Amsterdam, Noord-Holland, Netherlands, ²Neurology, Academic Medical Center, Amsterdam, Noord-Holland, Netherlands, ³Radiology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands, ⁴Biomechanical engineering and physics, Academic Medical Center, Amsterdam, Noord-Holland, Netherlands

New imaging methods of the brachial plexus are believed to assist in diagnosis of immune mediated diseases. In this study, we optimized a 3D diffusion prepared iMSDE sequence to include the full brachial plexus and shoulders. Although giving excellent contrast of the nerves, poor fat-suppression and a poor signal to noise ratio due to B0 inhomogeneities are often a problem. To overcome this problem we tested the use of a neck pillow filled with pineapple juice. Secondly we compared image based shimming to volume shimming. The use of the pillow in combination with IB-shimming showed the best result.

Robert L Barry^1,2, Baxter P Rogers^1,2, Seth A Smith^1,2, and John C Gore^1,2
1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, ²Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States

A recent 7 Tesla study provided evidence for the existence of resting state networks in the human spinal cord by demonstrating inter-subject reproducibility of temporal correlations between ventral (motor) gray matter horns and between dorsal (sensory) gray matter horns in healthy subjects. In this abstract we build upon these findings and present measurements of within-subject reproducibility of within-slice spinal cord functional connectivity between ventral horns and between dorsal horns. This work will be important for future studies that rely upon these measurements to gain insight into how these networks change due to aging, injury, or disease.

Saurav B Chandra¹, Sumathy Mohan², Preethi Janardhanan², Kaiwalya S Deo¹, Eric R Muir¹, and Timothy Q Duong^1
1Research Imaging Institute, UT Health Science Center, San Antonio, TX, United States, ²Pathology, UT Health Sc. Center, San Antonio, TX, United States

Reduced bioavailability of nitric oxide plays a crucial role in endothelial dysfunction in diabetes. The goal of this study was to investigate the effect of eNOS overexpression on cerebral blood flow (CBF) and cerebrovascular reactivity (CR) in diabetic mice, eNOS-overexpressed (TgeNOS) mice, Akita diabetic (Ins2 Akita) mice, and a genetic cross of TgeNOS⨂Ins2 Akita. We hypothesized that eNOS overexpression rescues CBF and CR dysfunction in the diabetic brain.

Evita C. Wiegers¹, Hanne M.M. Rooijackers², Cees J. Tack², Arend Heerschap¹, Bastiaan E. de Galan², and Marinette van der Graaf^1,3
1Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands, ²Internal Medicine, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands, ³Pediatrics, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands

The effect of hypoglycemia on brain lactate content was studied with ¹H-MRS. Difference spectra, acquired with an interleaved J-editing (MEGA) semi-LASER sequence, were used to determine brain lactate levels during stable euglycemic and hypoglycemic conditions. Furthermore, arterial blood samples were taken to determine arterial lactate and glucose levels. The preliminary results, obtained in healthy volunteers, suggest that increased plasma lactate levels during hypoglycemia are not accompanied by an increase in lactate content in the brain.

Fei Gao¹, Guangbin Wang¹, Bin Zhao¹, Wen Ma², Muwei Li³, Fuxin Ren¹, Bo Liu¹, and Weibo Chen^4
1Shandong Medical Imaging Research Institute, Shandong University, Jinan, China, ²The Central Hospital of Jinan City, Shandong University, Jinan, China, ³College of Electronics and Information Engineering, Sichuan University, Chengdu, China, ⁴Philips Healthcare, Shanghai, China

This DTI-based study revealed presbycusis-related integrity change of white matter along auditory pathway as well as several language-related areas. It is believed that our findings could be important for exploring the real imaging evidence of presbycusis and could complement to studies using different imaging modalities or different subject populations.