Steven Mocking¹, Priya Garg², Aurauma Chutinet³, William A. Copen⁴, A. Gregory Sorensen⁵, and Ona Wu^6
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, ³Department of Neurology, Massachusetts General Hospital, United States, ⁴Department of Radiology, Massachusetts General Hospital, ⁵Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital, ⁶Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital

Four voxel-based classifiers (ADC-thresholding, k-nearest neighbor, k-means and ISODATA) are evaluated for accuracy and execution speed in automatically outlining stroke lesions. Clinically acquired diffusion imaging (DWI, ADC and T2WI) of 159 cases imaged <12h after stroke onset was obtained. The classifiers are found insufficient by themselves, but could be useful as part of semi-automatic approaches. Three of them have runtimes <10 seconds. Future work could be done with classifiers that maximize spatial coherence.

Efrat Kliper^1,2, Einor Ben Assayag³, Shani Shenhar-Tsarfaty^2,3, Lodmila Shopin³, Hen Hallevi³, Eitan Uriel³, Amos Korczyn A³, Natan Meir Bornstein³, Talma Hendler¹, Orna Aizenstein⁴, and Dafna Ben Bashat D^5
1The Wohl institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, ²Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, ³Departments of Neurology, Tel Aviv Sourasky Medical Center, Israel, Israel, ⁴Departments of Radiology, Tel Aviv Sourasky Medical Center, Israel, Israel, ⁵The Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Israel, Israel

Patients with ischemic stroke are at risk for developing cognitive impairment. Hippocampal size was calculated from 102 first-ever stroke patients using FreeSurfer. At baseline, patients with smaller hippocampi (below median) did not differ in their parameters (cognitive scores, NIHSS and years of education) from those with larger hippocampi. Six months after the event, improvements were observed in cognitive scores for both groups. However, 12 months post-stroke, patients with larger hippocampi presented better cognitive function compared to the other group. These preliminary results may suggest that stroke patients presenting with smaller hippocampi are prone to develop cognitive decline 12 months later.

Dandan Zheng¹, Zhenghua Liu², Xiaoying Wang^1,2, Jue Zhang^1,3, and Jing Fang^1,3
1Academy for Advanced Interdisciplinary Studies, Peking University, BEIJING, BEIJING, China, People's Republic of, ²Dept. of Radiology, Peking University First Hospital, BEIJING, BEIJING, China, People's Republic of, ³College of Engineering, Peking University, BEIJING, China, People's Republic of

Cerebral ischemia is a principal cause of death and severe disability globally. Previous studies showed that DW-MRS offers excellent tools to specifically measure the intracellular response to cerebral injury. The purpose of this study is using DW-MRS to investigate the pathological related changes in apparent diffusion coefficient (ADC) values of metabolites in cerebral ischemia in vivo. The results demonstrate that the ADC values of the cerebral metabolites significantly decrease and increase in the acute and subacute stages of ischemia respectively, compared to the age matched healthy controls.

Alan J Huang^1,2, Li An³, Jun Hua¹, Manus Donahue⁴, Steven Warach³, and Peter van Zijl^1
1FM Kirby Research Center, Johns Hopkins University, BALTIMORE, MD, United States, ²Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ³National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, ⁴Department of Radiology, Vanderbilt University, Nashville, TN, United States

Acute stroke patients require a rapid and individualized diagnosis to evaluate whether thrombolysis treatment is necessary. Vascular Space Occupancy (VASO) MRI is a non-invasive technique that allows for imaging of increased microvascular blood volume, a marker for tissue at risk of infarction. An initial evaluation of five patients imaged within 7 hrs post-ischemic onset shows that VASO can be used to assess CBV increases in white matter. Our results show that VASO can potentially spatially localize the ischemic penumbra better than current perfusion weighted imaging.

Phillip Zhe SUN¹, Jerry S Cheung¹, Enfeng Wang¹, and Eng H Lo^2
1Radiology, Athinoula. A. Martinos Center for Biomedical Imaging, MGH and Harvard Medical School, Charlestown, MA, United States, ²Radiology and Neurology, Neuroprotection Research Laboratory, MGH and Harvard Medical School, Charlestown, MA, United States

Amide proton transfer (APT), a variation of chemical exchange saturation transfer (CEST) MRI, is sensitive to pH, and has been increasingly used to image stroke. Here, we characterized acute ischemic stroke with localized proton MRS and multi-parametric imaging of pH-weighted APT, perfusion, diffusion and relaxation MRI. We showed that both diffusion and pH-weighted APT MRI strongly correlate with tissue lactate content, while no significant relationship was found for perfusion, T1 and T2 MRI. In summary, our study demonstrated that pH-weighted endogenous APT/CEST MRI, by sensitizing to tissue acidosis, serves as a surrogate metabolic imaging marker for characterizing ischemic tissue damage.

Qiang Shen^1,2, Shiliang Huang¹, Fang Du¹, and Timothy Q Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Oxygen challenge (OC) has been used to test vascular function in disease conditions and to estimate ischemic penumbra with T2*-weighted MRI. However, such T2*-weighted signal sources of OC associated with cerebral ischemia remain not well understood. OC is known to cause T1 changes which affect ASL CBF and BOLD signals if TR is insufficiently long. Ischemia also could change T1, CBF, as well the response to OC. The goal of this study was to investigate the T2*-weighted signal sources during OC by measuring T1, T2 and CBF during air and oxygen inhalation associated with ischemic brain injury.

Yen-Yu Ian Shih¹, Hsiao-Ying Wey¹, Fang Du¹, Shiliang Huang¹, Qiang Shen¹, Kameel M Karkar¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

This study applied rsfMRI to probe acute focal ischemia in rat. During 15 mins acquisition, there were typically a few (3) epochs of spontaneous BOLD waves. Each wave showed 12% BOLD increases (at 7 T) and the duration was on the order of 2-3 mins. The BOLD wave started in the cortex, spread downward, grew in size, and ended in the striatum. These characteristic waves are likely associated with peri-infarct spreading depolarization. This method provides unique and clinically relevant information to probe tissue at risk, which may have long-term clinical applications.

Willem M Otte^1,2, Kajo van der Marel², Maurits P.A. van Meer², Kees P.J. Braun¹, and Rick M Dijkhuizen^2
1Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands, ²Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands

The spatiotemporal dynamics of white matter changes in stroke recovery are poorly characterized. We assessed the contralesional white matter volume serially in a unilateral stroke model in rats using multimodal MRI and supervised segmentation. We found substantial changes in contralesional white matter volume development after stroke. These results indicate the potential role of contralateral white matter structure in stroke recovery and the feasibility of supervised segmentation algorithms in characterizing these volumetric white matter changes.

Anaïck MOISAN^1,2, Pierre BOUZAT^1,3, Olivier DETANTE^1,4, Chantal REMY¹, and Emmanuel Luc BARBIER^1
1Team 5 - INSERM U836 / Joseph Fourier University, Grenoble Institute of Neurosciences (GIN), Grenoble, France, ²Cell and Tissue Therapy Unit, Grenoble University Hospital, Grenoble, France,³Intensive care unit, Grenoble University Hospital, Grenoble, France, ⁴Stroke Unit, Department of Neurology, Grenoble University Hospital, Grenoble, France

In a rat model of stroke, hemodynamic and oxygenation changes during acute cerebral ischemia were studied using a multimodal quantitative BOLD approach (Apparent Diffusion Coefficient (ADC), Blood Volume fraction (BVf) and local Oxygen Saturation (lSO2). We identified the potential ischemic core as the region with low ADC and BVf values and a severe hypoxia (lSO2< 35%) discrepant with tissue survival. The hypoxia ROI was smaller than the decreased ADC one. ADC and BVf values were similar both into the decreased ADC ROI and into the hypoxia ROI. Our method could become a way to investigate patients eligible for thrombolysis.

Kevin S Tang¹, Dorit Granot², Shauna L Quinn², and Erik M Shapiro^1,2
1Department of Biomedical Engineering, Yale University, New Haven, CT, United States, ²Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, United States

In stroke, significant brain damage is caused by immune cell infiltration. MRI-based cell tracking using iron oxide particles has been shown to be a promising imaging modality for visualizing this phenomenon. The purpose of this study was to investigate the feasibility of using MPIOs to monitor immune cell infiltration into ET-1 induced, focal cortical stroke in rats. MPIO induced signal voids were present four days following stroke. This coincides with the known monocyte infiltration kinetics into stroke lesions. IHC confirmed that MPIOs were endocytosed within brain resident immune cells.

Mark J.R.J. Bouts¹, Ivo A.C.W. Tiebosch¹, Rene Zwartbol¹, Emily Hoogveld¹, Ona Wu^1,2, and Rick M. Dijkhuizen^1
1Image Sciences Institute, University Medical Center Utrecht, Utrecht, Netherlands, ²Athinoula A. Martinos center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States

MRI-based predictive algorithms may perform favorably in identifying areas at risk of infarction following acute ischemic stroke, compared to the perfusion-diffusion mismatch. However, few studies have considered the ability of these methods to directly identify salvageable tissue. We evaluated four prediction methods in their potential to characterize salvageable tissue in a rat stroke model. A generalized linear model (glm) was tested against a support vector machine and two ensemble methods (adaboost, random forest). Our study shows that, under equal predictive performance of all methods, glm provides the greatest risk map contrast, enabling improved differentiation between irreversibly injured and potentially salvageable tissue after acute ischemic stroke.

Yen-Yu Ian Shih¹, Shiliang Huang¹, Fang Du¹, and Timothy Q Duong^1
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Recent reports showed forepaw electrical stimulation in rats evoked an unexpected sustained decrease in CBV in the striatum. This study applies this novel fMRI procedure to longitudinally investigate the striatal functional integrity after transient focal ischemia (MCAO model). Striatal dysfunction was observed in the acute phase, but partially recovered on Day 7. Our findings complement the existing reports in the sensory cortex. This technique has potential to longitudinally investigate the functional reorganization and treatment efficacy in the striatum of the same rat after stroke.

Patrick Michael Heiler¹, Friederike L Vollmar², Friedrich Wetterling¹, Saema Ansar², Simon Konstandin¹, Marc Fatar², and Lothar Rudi Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²Department of Neurology, Heidelberg University, Mannheim, Germany

This work describes the application of the chemical shift imaging sequence to sodium imaging and shows the applicability to acquire ²³Na images and locally resolved T2* respectively sodium density maps, received by an exponential fit estimation of the time series of each phase encoding. The capability of this technique is in measurements of mice with permanent middle cerebral artery occlusion. Three dimensional ²³Na images with a resolution of 0.6x0.6x1.2 mm³ show hyperintense sodium signal in the infarcted area and an increase in sodium density of more than 200% meanwhile the T2* relaxation rate increases by 10-30% compared to unaffected brain tissue.

Robert A Knight^1,2, Kishor Karki¹, Vijaya Nagesh¹, James R Ewing^1,2, Joseph D Fenstermacher³, and Tavarekere N Nagaraja^3
1Neurology - NMR Research, Henry Ford Hospital, Detroit, MI, United States, ²Physics, Oakland University, Rochester, MI, United States, ³Anesthesiology, Henry Ford Hospital, Detroit, MI, United States

This report tests the hypothesis that the degree of the initial drop in CBF in stroke and the extent of later reperfusion determine the ensuing damage to the BBB. The data obtained suggest that the severity of the acute BBB lesion in reversible cerebral ischemia is determined mainly by the drop in CBF during the first several hours of occlusion and partly support the hypothesis. However, reperfusion after 3 h of occlusion did little to alleviate the damage.

Qiang Shen^1,2, Shiliang Huang¹, Fang Du¹, and Timothy Q Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

The identification of ischemic penumbra and the distinction of this potentially reversible condition from irreversibly damaged tissue is of utmost importance for the initiation of treatment strategies. Although diffusion/perfusion MRI mismatch has been used to be an estimation of penumbra, it has been demonstrated overestimate penumbra. In this study, T2* weighted fMRI responses of stroke rats to oxygen challenge (OC) were investigated. DWI/PWI mismatch region showed significant higher than normal T2* weight signal increase. Tissues with higher than normal T2* weighted signal increase during OC and spatially around the ischemic core could be a better estimation of penumbra.

Shiliang Huang¹, Qiang Shen^1,2, and Timothy Q Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Predicting tissue outcome remains a challenge for stroke magnetic resonance imaging (MRI). In this study, a flexible support vector machine (SVM) algorithm was developed and applied to predict ischemic tissue fate on three stroke groups: 30-min, 60-min and permanent MCAO in rats. CBF, ADC and T2 were acquired during the acute phase up to 3hrs and again at 24hrs followed by histology. Infarct was predicted pixel-by-pixel using only acute (30-min) stroke data. Receiver-operating-characteristic analysis was used to quantify prediction accuracy. It was concluded that the SVM predictive model has the potential to serve as promising metrics for diagnosis, prognosis and therapeutic evaluation of acute stroke.

Xuxia Wang¹, Fuchun Lin¹, and Hao Lei^1
1State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics & Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China, People's Republic of

The white matter (WM) lesions evolution of rat brain induced by bilateral common carotic arteries occlusion (BCCAO) were well studied previously by different ex vivo experiments, yet not well studied in vivo by an noninvasive detection methods. And diffusion tensor imaging (DTI) was used increasing to noninvasively evaluate the WM damage and more sensitivity than conventional T₁and T₂ weighted images. In this study, the optic tract (OT) of BCCAO rat brain damage evolution was investigated. The results showed that in OT reduced the fractional anisotropy (FA) and axial diffusivity (ADC_¡Î), increased radial diffusivity (ADC_¡Í) were occured during the detecting period compared to control.

Hongxia Lei^1,2, Carole Berthet³, Lorenz Hirt³, and Rolf Gruetter^1,4
1Laboratory of Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Radiology, Univeristy of Lausanne, Switzerland, ³Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, Switzerland, ⁴Radiology, University of Geneva, Geneva, Switzerland

1H MRS of animal stroke models sustained biomarkers for identifying cerebral ischemia.

Mélanie Craveiro¹, Laure Quignodon², Carole Berthet³, Matthew Hall², Cristina Cudalbu¹, Lorenz Hirt³, Béatrice Desvergne², and Rolf Gruetter^1,4
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland, ³Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, ⁴Departments of Radiology, Universities of Lausanne and Geneva, Switzerland

Recent studies have shown the neuroprotective role of PPAR (peroxisome proliferator-activated receptor ) in several brain diseases and an increased sensitivity of PPAR-knockout mice to ischemia. The aim of this study was to detect the metabolites involved in the neuroprotection through an early neurochemical comparison between PPAR-knockout and wild-type mice after brain ischemia using MR spectroscopic imaging (SI). The use of SI on an ultra-high field 14.1 T provided a sensitive means to map the in vivo metabolite concentrations and allowed a sensitive localization of the lesion site. Finally, this study provided an optimal evaluation of metabolite concentration alterations inside the lesion caused by the neuroprotective deficit of PPAR-knockout mice.

Fernando Emilio Boada¹, Edwin Nemoto², Yongxian Qian³, Costin Tanase⁴, Charles Jungreis⁵, Jonathan Weimer⁶, and Vincent Lee^6
1Radiology and Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ²Neurosurgery, University of New Mexico, Albuquerque, New Mexico, United States, ³Radiology, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States, ⁵Radiology, Temple University, Philadelphia, Pennsylvania, United States,⁶Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States

In this paper we use a non-human primate model of reversible focal ischemia to present evidence that elevated tissue sodium concentration (>65mM) during focal cerebral ischemia increases the risk of infarction after tissue reperfusion.

Simona Nikolova¹, Zareen Amtul², David Cechetto², Ting-Yim Lee³, Vladimir Hachinski⁴, and Robert Bartha^2,3
1Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada, ²Department of Anatomy, University of Western Ontario, London, ON, Canada, ³Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada, ⁴London Health Sciences Centre, London, ON, Canada

The current work investigates the combined effect of Alzheimer’s and stroke in the rat brain. Four groups of 6 animals participated in the study- a group of animals with a ventricular Aβ injection, a group of animals with a combined stroke and Aβ injection and two groups of control animals (separate control groups for Aβ and stroke were used). The animals underwent CT and MRI examination on day 9, 19 and 29 after surgery. Histology was performed on the brains at the end of the study. Preliminary data suggests that ventricle enlargement and tissue damage were present in the combined Aβ and stroke group. Ventricle enlargement was also present in the Aβ only group, but not in the stroke group only. Alzheimer's disease is characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. Therefore, the observed ventricle enlargement could be a result of atrophy of adjacent brain tissue.

Alexander Drobyshevsky¹, Xinhai Ji¹, Matthew Derrick¹, Lei Yu¹, Ines Batinic-Haberle², and Sidhartha Tan^1
1Pediatrics, Evanston Northshore Healthcare, Evanston, IL, United States, ²Radiation Oncology, Duke University Medical Center, Durham, NC, United States

We have previously shown the ability of diffusion weighted MR-derived index, using the nadir of ADC during hypoxia-ischemia (H-I) to predict postnatal motor deficits in survivors. The contribution of immediate reperfusion injury to motor deficits has not been fully understood. We used a novel lipophilic Mn porphyrin antioxidant in addition to ascorbate + trolox to test our hypothesis. In control saline-administered dams, the incidence of hypertonia in survivors (n=49) was 57% and the odds ratio of hypertonia to occur with a reperfusion drop in ADC was 8.8. Ascorbate + Trolox post-treatment decreased the incidence of hypertonia to 30% (n=30 survivors). MnTnHex-2-PyP post-treatment resulted in 63% hypertonia (n=22 survivors) and more mortality (48% compared to 23% for controls).

Steve J Sawiak¹, Valentina Taviani², Victoria E Young², Joe L Bird³, Hugh K Richards⁴, Andrew J Patterson², Martin J Graves², Adrian T Carpenter¹, and Jonathan H Gillard^2
1Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom, ²Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ³Clinical Pharmacology Unit, University of Cambridge, Cambridge, United Kingdom, ⁴Department of Anesthesia, University of Cambridge, Cambridge, United Kingdom

High-field high-resolution MRI can be used to monitor the onset and progression of disease in a collar-induced rabbit model of atherosclerosis. Two-dimensional fat-suppressed T2- and T1-weighted images with an in-plane resolution of 125μm allowed delineation of the vessel wall three days after surgical implantation of the collar, when intima-media thickening is expected to be minimal. The protocol was complemented by an ECG-gated cine phase contrast pulse sequence which allowed us to acquire spatially- and temporally-resolved flow velocity profiles distal and proximal to the collar.

Fang Du¹, Qiang Shen^1,2, Shiliang Huang¹, and Timothy Q Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Mismatch of diffusion/perfusion by MRI has been used as an estimate of the ischemic penumbra, but there are large parts of the mismatch region appear not to at risk and it was also reported that some of the apparent diffusion coefficient reduction area can be salvaged by early reperfusion. We hypothesis that T2* weighted signal change following oxygen challenge could be used as an improved biomarker for penumbra. We tested this hypothesis on transient (45 mins) focal ischemia to determine.

Qiang Shen^1,2, Virendra Desai¹, and Timothy Q Duong^1,2
1Research Imaging Institute, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States, ²Ophthalmology/Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States

Acute diffusion data has been used to predict ischemic tissues fate on a pixel-by-pixel basis. Predictions however were made based on acute MRI data from a single time point. This study proposes a novel approach to incorporate the temporal characteristics of acute ADC (apparent diffusion coefficient) changes to characterize tissue fate based on a pixel by pixel basis. This approach was tested on rat stroke models subjected to permanent and 60-min middle cerebral artery occlusion (MCAO). We concluded that there were distinct temporal patterns that determined tissue salvageability and incorporating temporal information should improve prediction accuracy.

Andreas Lemke¹, Saskia Grudzenski², Jörg Döpfert¹, Frederik Bernd Laun³, Tristan Kuder³, Marc Fatar², and Lothar Rudi Schad^1
1Computer Assisted Clinical Medicine, Heidelberg University, Mannheim, Germany, ²Experimental Neurology, Heidelberg University, Mannheim, Germany, ³Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany

Diffusion kurtosis imaging of eight mice with induced middle cerebral artery occlusion (MCAo) was performed 24 h after MCAo using a cryo probe and a 9.4 T animal scanner. The apparent diffusion coefficient (D_app=0.49±0.09 µm²/ms vs. 0.75±0.05 µm²/ms, P=0.0078), and the fractional anisotropy (FA=0.07±0.02 vs. 0.10±0.02, P=0.039) are significantly decreased in the ischemic tissue compared to the healthy contralateral tissue, whereas the kurtosis is significantly increased in the ipsilateral region (K_app=1.15±0.10 vs. 0.66±0.09, P=0.0078).

Sanneke van Rooden¹, Maarten J. Versluis¹, Julien R. Milles², Andrew G. Webb¹, Mark A. van Buchem¹, and J. van der Grond^1
1C.J. Gorter Center for High-field MRI, department of Radiology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands, ²LKEB, department of Radiology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands

We previously demonstrated that distinct hypointense foci in the cerebral cortex and the presence of a so-called inhomogeneous cortex can be visualized post mortem with 7T MRI in human brain specimens with cerebral Aâ deposition. Our aim is to reproduce these findings in living Alzheimer‘s Disease (AD) patients using 7T MRI. Seven AD patients and 13 memory complainers were scanned using a high resolution T2*-weighted scan including the frontal and parietal regions of the brain. The results show an inhomogeneous aspect of the cortex and an increased phase difference between gray and white matter in AD patients on phase images.

Dae-Hyuk Kwon¹, Jong-Min Kim², Se-Hong Oh¹, Hye-Jin Jeong¹, Sung-Yeon Park¹, Je-Geun Chi^1,3, Young-Bo Kim¹, Beom-Seok Jeon², and Zang-Hee Cho^1
1Neuroscience Research Institute, Gachon University of Medicine and Science, Kuwol-dong Namdong-gu, Incheon, Korea, Republic of, ²Departments of Neurology, Seoul National University, Seoul, Korea, Republic of, ³Departments of Pathology, Seoul National University, Seoul, Korea, Republic of

We investigated 3D structural deformations of the substantia nigra (SN) in Parkinson¡¯s disease (PD). To achieve this, we obtained 3D fast gradient echo image with 7T MRI in order to understand entire structure of the SN and performed quantitative surface analysis. High-resolution 7T 3D MR images showed the inner structures of the SN in normal controls. We found a striking similarity between our results and the patterns of subdivisions of the SN as observed using calbindin D28K immunostaining. These findings strongly suggest that two different contrasts in the SN observed with 7T MRI could be due to the nigrosomes, since these structures were scarcely seen in the patient group. Accordingly, this 3D imaging study demonstrates the potential of the 7T MRI for quantification of the structural changes in the SN, especially for the purposes of research and diagnosis of PD.

Se-Hong Oh¹, Jong-Min Kim², Sung-Yeon Park¹, Dae-Hyuk Kwon¹, Hye-Jin Jeong¹, Myung-Kyun Woo¹, Young-Bo Kim¹, John Huston III³, Kendall H. Lee⁴, Beom S. Jeon², and Zang-Hee Cho^1
1Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea, Republic of, ²Departments of Neurology, College of Medicine, Seoul National University, Seoul, Korea, Republic of, ³Department of Radiology, Mayo Clinic, Rochester, United States, ⁴4Department of Neurosurgery and Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, United States

Parkinson¡¯s disease (PD) is a neurodegenerative disorder resulting from progressive loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Therefore, imaging of the SN has been regarded to hold greatest potential for use in the diagnosis of PD. At the 7.0T magnetic resonance imaging (MRI), it is now possible to delineate clearly the shapes and boundaries of the SN. We scanned eight early and two advanced PD patients, along with nine age-matched control subjects, using a 7.0T MRI in an attempt to directly visualize the SN and quantify the differences in shape and boundaries of SN between PD subjects in comparison with the normal control subjects. In the normal controls, the boundaries between the SN and crus cerebri appear smooth, and clean ¡®¡®arch¡¯¡¯ shapes that stretch ventrally from posterior to anterior. In contrast, these smooth and clean arch-like boundaries were lost in PD subjects. The measured correlation analyses show that, in PD patients, there is age-dependent correlation and substantially stronger UPDRS motor score-dependent correlation. These results suggest that, by using 7.0T MRI, it appears possible to use these visible and distinctive changes in morphology as a diagnostic marker of PD.

Hye-Jin Jeong¹, Se-Hong Oh¹, Jong-Min Kim², Dae-Hyuk Kwon¹, Sung-Yeon Park¹, Joshua H. Park¹, Young-Bo Kim¹, Je-Geun Chi^1,3, Chan-Woong Park¹, Beom S Jeon², and Zang-Hee Cho^1
1Neuroscience Research Institute, Gachon University of Medicine and Science, Incheon, Korea, Republic of, ²Department of Neurology,College of Medicine, Seoul National University, Seoul, Korea, Republic of, ³Departments of Pathology,College of Medicine, Seoul National University, Seoul, Korea, Republic of

Using 3D T2*-weighted images obtained with 7.0T MRI, we were able to observe definition of entire structure of the substantia nigra (SN) in Parkinson¡¯s disease (PD). Especially, change of inner structure of the SN which is believed to be the nigrosomes was shown. These findings appear in correlation analysis. The measured correlation analyses show that there is age dependent correlation and substantially UPDRS motor score dependent correlation in PD patients. These results suggest 7.0T 3D T2*-weighted MR imaging could provide quantitative estimation of the SN in PD.

JiunJie Wang¹, WeyYil Lin², ChinSung Lu³, Ali Tabesh⁴, YiHsin Weng⁵, and YauYau Wai^5
1ChangGung University, TaoYuan county, Taiwan, Taiwan, ²ChangGung Memorial Hospital, TaoYuan county, Taiwan, Taiwan, ³ChangGung memorial hospital, ⁴NewYor University Medical School,⁵ChangGung Memorial Hospital

The mean diffusion kurtosis was measured from 30 patient of idiopathic Parkinson¡¦s Disease. Compared with diffusion tensor derived indices, such as Fractional Anisotropy and mean/axial/radial diffusivity, the mean kurtosis in the basal ganglia has significantly improved diagnostic performance in differentiating from normal controls. The receiver operative curve analysis showed the best performance in substantia nigra, which has a sensitivity and specificity of approximately 0.87 and 0.92.

Federica Agosta¹, Vladimir S. Kostic², Michela Pievani¹, Milica Jecmenica-Lukic², Elka Stefanova², Antonio Scarale¹, and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy, ²Department of Neurology, University of Belgrade School of Medicine, Belgrade, Yugoslavia

Using voxel-based morphometry, this study investigated whether a specific pattern of gray matter (GM) loss is associated with freezing-of-gait (FOG) in Parkinson’s disease (PD). Compared with controls (HC), PD patients showed bilateral frontoparietal GM atrophy. The pattern of GM atrophy was similarly widespread when considering PD-FOG patients only vs. HC. On the contrary, PD-noFOG vs. HC showed only small regions of left fronto-temporal GM atrophy. FOG score was associated with left frontal GM atrophyvolume. Such a relationship was independent of executive deficits. This finding suggests that the frontostriatal system may be involved in the pathophysiology of FOG in PD.

Saadiya Rashid Ismail^1,2, Sarah Mustafa², Samantha Miller², Tim Rasmussen², David J Lurie¹, and Peter Teismann^2
1ABIC, University of Aberdeen, Aberdeen, Aberdeenshire, United Kingdom, ²IMS, University of Aberdeen, Aberdeen, Aberdeenshire, United Kingdom

Aggregated proteins are central to several diseases. The aim of this research is to investigate the possibility of detecting and quantifying aggregated protein alpha-synuclein which is implicated in Parkinson’s disease, using fast field-cycling (FFC) nuclear magnetic resonance relaxometry. This technique detects aggregation through the 14N1H quadrupolar relaxation process exhibited as characteristic peaks in the R1 spectrum of water 1H, called quadrupolar peaks. Preliminary results suggest that it may be feasible to produce a quadrupolar signal from aggregated protein alpha-synuclein and further work is being carried out to quantify the protein. This may lead to more information about the disease model.

Mélanie Craveiro¹, Philippe Coune², Bernard Schneider², Patrick Aebischer², and Rolf Gruetter^1,3
1Laboratory for Functional and Metabolic Imaging, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ²Neurodegenerative Studies Laboratory, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, ³Universities of Lausanne and Geneva, Departments of Radiology, Switzerland

Animal models of Parkinson’s disease (PD) provide an experimental means to define early markers of pathological changes that may affect the nigrostriatal pathway prior to overt neurodegeneration. Only a few toxin-based PD animal models have been investigated by MR spectroscopy (MRS) yet. In this study, the neurochemical profile of two PD rat models, a toxin-based model and a model expected to more faithfully replicate early pathological alterations leading to PD in humans, were acquired by MRS in the striatum. The use of these two models provided a powerful means to detect proper markers of the pathology.

Tracy Robert Melzer^1,2, Richard Watts^1,3, Michael R MacAskill^1,2, Ross J Keenan⁴, Ajit Shankaranarayanan⁵, David C Alsop⁶, Leslie Livingston^1,2, John C Dalrymple-Alford^1,7, and Tim J Anderson^1,2
1Van der Veer Institute for Parkinson's and Brain Research, Christchurch, New Zealand, ²Medicine, University of Otago, Christchurch, New Zealand, ³Physics and Astronomy, University of Canterbury, Christchurch, New Zealand, ⁴Christchurch Radiology Group, Christchurch, New Zealand, ⁵GE Healthcare, Menlo Park, CA, United States, ⁶Beth Israel Deaconess Medical Center, Boston, MA, United States, ⁷Psychology, University of Canterbury, Christchurch, New Zealand

We used structural MRI and pseudo-continuous ASL to characterize brain changes associated with cognitive status in Parkinson’s disease (PD). PD patients were classified as cognitively normal (PD-N), with mild cognitive impairment (PD-MCI), or with dementia (PD-D). PD-MCI and PD-D showed decreased cortical perfusion relative to controls and PD-N. Only PD-D exhibited widespread grey matter atrophy. The structure-function dissociation in PD-MCI suggests that functional blood flow changes occurred before detectable structural changes in cognitive decline associated with PD. This dissociation provides a promising biomarker sensitive to cognitive status in PD.

Mohit Saxena¹, S Senthil Kumaran², Vinay Goyal¹, and Madhuri Behari^1
1Department of Neurology, All India Institute of Medical Sciences, New Delhi, India, ²Department of N.M.R, All India Institute of Medical Sciences, New Delhi, India

Parkinson’s disease is characterized by motor dysfunction. In this functional MRI study, we attempt to study the BOLD activation pattern with respect to the progression of the disease and the dopamine therapy. The enhanced activation of primary motor cortex in PD in the off state could be normalized to an extent by dopaminergic therapy. Compensatory mechanisms involving cerebellum and areas other than sensorimotor cortex are observed with the progression of the disease.

Erik B Beall¹, Anneke M Frankemolle², Jay L Alberts³, Michael D Phillips¹, and Mark J Lowe^1
1Imaging Institute, Cleveland Clinic, Cleveland, OH, United States, ²Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States, ³Center for Neurological Restoration, Cleveland Clinic, Cleveland, OH, United States

Parkinson’s Disease (PD) is a progressive neurologic disorder primarily characterized by altered motor function. Assisted exercise has been shown to produce dramatic improvement in PD patients’ motor symptoms in the absence of medication, comparable to the effects of medication alone. Functional connectivity MRI has been used to show network effects of medication. Here we present connectivity results of the complementary effects of 1) assisted exercise and 2) medication, both referenced to the off-medication state of the same subjects. Our main findings include largely similar changes in connectivity with both meds and exercise.

Hong Yang¹, Xu-ning Zheng², Yi-lei Zhao³, Jue Wang⁴, and Min-ming Zhang^5
1Department of Radiology, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhengjiang, China, People's Republic of, ²Department of Neurology, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhejiang, China, People's Republic of, ³Department of Radiology, First Affiliated Hospital of College of Medical Science, Zhejiang University, Hangzhou, Zhejiang, China, People's Republic of, ⁴State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China, People's Republic of,⁵Department of Radiology, The Second Affiliated Hospital of College of Medical Sciences, Zhejiang University, Hangzhou, Zhejiang, China, People's Republic of

Using regional homogeneity (ReHo) method, the current study explore the abnormal spontaneous neural activity of resting state in early PD patients. Ten early PD patients were compared with eleven controls. After data preprocessing, ReHo analysis was performed using software REST. The increased ReHo was showed in bilateral frontal lobe, left parietal lobe, left cerebellum, right parietal Lobe and precuneus; Meanwhile, the decreased ReHo was showed in left frontal Lob, left occipital lobe and calcarine. These results revealed the pathophysiological mechanisms underlying early PD and demonstrate the feasibility of using ReHo as a useful tool to monitor cerebral dysfunction in PD

Xiaojun Xu¹, Hengyi Cao¹, Dan Long¹, and Minming Zhang^1
1Department of Radiology, No.2 Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China, People's Republic of

PD is characterized by a large number of non-motor clinical features, among them the somatosensory deficit is a significant part. However, the exact neural mechanism of this impaired somatosensory function is still scarcely known. We used a method based on the graph theory to measure the functional connectivity of the somatosensory network activated by passively tactile stimulation. We found that SMA is the most important ¡°node¡± of the abnormal tactile network for PD patients, which indicated that the dysfunction of SMA might be the key point of abnormal function of somatosensory networks in Parkinsonian brain.

Wenjun Li¹, Gang Chen¹, Xiaolin Liu¹, Chunming Xie^1,2, Guanyu Chen¹, Barney Douglas Ward¹, Joseph Goveas³, Jennifer Jones⁴, Malgorzta Franczak⁴, Piero Antuono⁴, and Shi-jiang Li^1,3
1Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ²School of Clinical Medicine, Southeast University, Nanjing, Jiangsu, China, People's Republic of, ³Psychiatry and Behavior Medicine, Medical College of Wisconsin, Milwaukee, WI, United States, ⁴Neurology, Medical College of Wisconsin, Milwaukee, WI, United States

Although atrophy is one of the hallmarks of Alzheimer’s disease (AD), the relationship between brain atrophy and system level dysfunction in functional connectivity networks is not well understood. While severe neurodegeneration in late stage of AD are likely to result in functional alterations, the extent to whether the morphological changes lead the functional changes or vice-versa in mild stage of the disease is still unclear. Our current study is aimed to investigate how functional networks evolve among brain regions involving atrophy in patients with mild cognitive impairment (MCI) and AD.

guangyu chen¹, chunming xie¹, gang chen¹, Barney Douglas Ward¹, wenjun li¹, Piero Antuono², and shi-jiang li^3
1biophysics, Medical College of Wisconsin, milwaukee, wisconsin, United States, ²Neurology, Medical College of Wisconsin, milwaukee, wisconsin, United States, ³Psychiatry and Behavioral Medicine, Medical College of Wisconsin, milwaukee, wisconsin, United States

The correlation between global signal and all brain voxel's time series which are not regressed out the global signal can reveal the distribution pattern of global signal in brain. The significant correlation between global signal distribution and behavior score such as Geriatric Depression Scale (GDS) and Rey Auditory Verbal Learning Test (RAVLT) indicates that global signal has biological significance. And we found that the different distribution pattern between healthy and mild cognitively impaired brain is primary overlapped with default mode network.

Joseph Goveas¹, Chunming Xie^2,3, Gang Chen², Wenjun Li², B. Douglas Ward², Guangyu Chen², Jennifer Jones⁴, Malgorzata Franczak⁴, Piero Antuono⁴, and Shi-Jiang Li^2
1Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, United States, ²Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States,³Neurology, School of Clinical Medicine, Southeast University, Nanjing, Jiangsu, China, People's Republic of, ⁴Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Apolipoprotein E-&4 (ApoE-&4) carriers are at an increased risk for incident late-onset Alzheimer’s disease (AD). While diminished default mode network (DMN) functional connectivity is observed in AD, increased DMN connections to medial and dorsolateral prefrontal cortices and medal temporal lobe regions, and decreased connectivity to precuneus are reported in ApoE-&4 carriers. We examined if ApoE-&4 carriers will show alterations in the DMN, executive control (ECN) and salience networks (SN), relative to ApoE-&4 non-carriers.

Gang Chen¹, Barney Douglas Ward¹, Chunming Xie¹, Wenjun Li¹, Guangyu Chen¹, Jennifer L Jones², Malgorzata Franczak², Piero Antuono², and Shi-Jiang Li^1,3
1Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, United States, ²Department of Neurology, Medical College of Wisconsin, Milwaukee, WI, United States, ³Department of Psychiatry and Behavioral Medicine, Medical College of Wisconsin, Milwaukee, WI, United States

It has been demonstrated that Alzheimer’s disease (AD) targets the brain’s specific large-scale networks (LSN). However, it is not known if AD, in different disease phases, targets different brain networks during disease progression. To address this question, the LSN analysis method was employed to identify the LSNs in the whole brain targeted by either the dementia phase or prodromal phase of the disease.

Federica Agosta¹, Michela Pievani^1,2, Cristina Geroldi², Giovanni B. Frisoni², and Massimo Filippi^1
1Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Hospital San Raffaele, Milan, Italy, ²IRCCS Centro San Giovanni di Dio - Fatebenefratelli, Brescia, Italy

Using resting-state (RS) fMRI, the coactivation patterns of the default mode network (DMN) and frontal networks were explored in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients. AD was associated with opposing coactivation effects in the DMN (decreased) and frontal networks (enhanced). The only RS abnormality in aMCI patients was a precuneus coactivation reduction in the DMN. The limited resources of the parieto-temporal cortex of AD patients may be paralleled, in an attempt to maintain cognitive efficiency, by an increased prefrontal coactivation. A medial parietal RS fMRI change seems to be present since the early phase of AD.

Beatriz Martínez-Granados¹, M. Carmen Martinez-Bisbal^1,2, Vicente Belloch³, J M Lainez⁴, Begoña López⁴, Miquel Baquero⁵, Joaquin Escudero⁶, Carol Guillem⁶, and Bernardo Celda^1,2
1Physical Chemistry, University of Valencia, Burjassot, Valencia, Spain, ²CIBER Bioengineering, Biomaterials and Nanomedicine. ISC III, Spain, ³MRI service, Hospital Universitario La Fe - ERESA, Valencia, Valencia, Spain, ⁴Neurology Service, Hospital Clínico Universitario, Valencia, Spain, ⁵Neurology Service, Hospital Universitario La Fe, Valencia, Valencia, Spain, ⁶Neurology Service, Hospital Universitario General, Valencia, Valencia, Spain

Metabolic differences between patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) by 3D CSI in small regions of parietal gray matter have been studied. 3D CSI (TE=31 ms) in a 3 T unit was performed in 54 MCI patients, 11 AD patients and 9 controls. Eight small voxels (0.75 cc) representatives of parietal gray matter were selected in two slices. NAA/Cr value was lower for AD patients than for DCL and controls in all voxels. NAA/Cr ratios were lower in the lower slice than in the upper slice. Cho/Cr ratios values also showed statistical differences between groups.

Thao Thanh Tran¹, Napapon Sailasuta¹, Martin Watterson², Louis Brenes³, and Brian D Ross^1
1MRS, Huntington Medical Research Institutes, Pasadena, CA, United States, ²Feinberg School of Medicine, Northwestern University, Chicago, IL, United States, ³Imaging Specialists of Pasadena

Drug development for treatment of Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI) has been both expensive and unsuccessful, using currently recognized clinical endpoints (MMSE, etc). While drug discovery needs additional thought, FDA, NIA and Pharma now recommend use of objective disease end points (“biomarkers”) in place of clinical diagnosis as a means of reducing group size and therefore cost of trials. Short echo time MRS, with standard operating procedure (SOP, biomarker NAA/mI should be added to ADNI protocols for diagnosis of AD and MCI.

Ileana Hancu¹, Robert Gillen², John Cowan³, and Earl Zimmerman^3
1GE Global Research Center, Niskayuna, NY, United States, ²Sunnyview Rehabilitation Hospital, Schenectady, NY, United States, ³Albany Medical Center, Albany, NY, United States

A small study is presented, aimed at understanding the relationship between brain function, as illustrated by performance on neuro-psychological (NP) tests, and 1H MRS data acquired from the posterior cingulate gyrus of normal control (NC) and mild cognitive impairment (MCI) subjects. The CPRESS mI/NAA ratio was shown to be a strong correlate of verbal memory, visuo-construction performance and visual motor integration. The same CPRESS mI/NAA ratio was also shown to improve the capability to separate NC’s from MCI subjects compared to NP tests alone.

Youngkyoo Jung¹, Thomas T Liu¹, and Christina E Wierenga^2,3
1Radiology, University of California, San Diego, La Jolla, CA, United States, ²Psychiatry, University of California, San Diego, La Jolla, CA, United States, ³Veterans Affairs San Diego Healthcare System, San Diego, CA, United States

Alzheimer's disease (AD) is a neurodegenerative brain condition with no effective treatment. Although traditionally viewed as a disease of gray matter, increasing evidence indicates that white matter (WM) alteration precedes the medial temporal lobe atrophy seen in the earliest stages of the disease. Here we investigated the potential of arterial spin labeling to detect differences in white matter perfusion between cognitively intact adults, adults with mild cognitive impairment (MCI), and AD. The AD group showed reductions of WM perfusion in posterior regions compared to the MCI and normal control groups.

Yinan Liu^1,2, Howard Rosen³, Bruce Miller³, Michael Weiner^1,2, and Norbert Schuff^1,2
1Center for Imaging of Neurodegenerative Diseases, Department of Veterans Affairs Medical Center, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, United States, ³Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA, United States

Reductions in regional cerebral blood flow(rCBF) and volume(rCBV) in Alzheimer’s disease(AD) and mild cognitive impairment(MCI), are generally interpreted as a consequence of diminished brain function, but vascular factors, restricting blood supply could be a secondary factor. Using a four phase discrete ASL model, we found bolus arrival time(BAT), arterial-arteriole transit time(aaTT), and time-to-peak(TP) are prolonged in AD and MCI relative to cognitively normal elders. The findings demonstrate that vascular aspects contribute to rCBF and rCBV reductions and should improve the classification of in AD and MCI.

Todd B Harshbarger¹, Jeff Browndyke², Allen W Song¹, and Joseph Mathews^2
1BIAC, Duke University, Durham, NC, United States, ²ADRC, Duke University, Durham, NC, United States

Patients who have undergone cardiac surgery often develop cognitive impairments. In this study, we collected perfusion data in patients pre- and post-surgery while performing a working memory task. Quantitative maps of cerebral blood flow were created, and measures of both global and local changes after surgery were made. Although the global level of perfusion does not change, localized areas in regions known to be active during the task display increased perfusion. Further research is needed to determine if these are neuronal compensatory effects or vascular changes in the brain.

Kejia Cai¹, Mohammad Haris¹, Anup Singh¹, Adam Shore¹, Rachelle Berger¹, Ari Borthakur¹, and Ravinder Reddy^1
1CMROI, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Affecting 10% of the world’s population, Alzheimer’s disease (AD) is one of the most common forms of dementia in the elderly. Recently, it was hypothesized that AD may be an angiogenesis-dependent disorder and anti-angiogenic drugs might be able to prevent and treat this disease. Here we present the first MRI demonstration of AD associated angiogenesis by using a technique based on endogenous blood oxygenation level dependent (BOLD) effect. With further development, MRI of angiogenesis and vasculature alternations could serve as a sensitive tool for investigation of AD pathology, early diagnosis and testing therapeutic efficacy of novel drugs.