SANJEEV CHAWLA, Ilya Kister, Tim Sinnecker, Jens Wuerfel, Friedemann Paul, Yulin Ge

To track evolution of multiple sclerosis (MS) lesions, 9 patients underwent gradient-echo-T2* and quantitative susceptibility mapping on 7T MR system at baseline and at follow-up period (mean duration=2.4years). Majority of lesions were non-iron laden at baseline and most of them remained unchanged in size, morphology and susceptibility patterns. Some of these lesions accumulated iron deposition on follow-up. A minority of iron-laden lesions underwent redistribution of iron content. Small increase in lesion count was observed at follow-up. Interestingly, majority of these lesions were iron-enriched.  This study may provide insights into pathophysiological features of MS lesions during the course of disease evolution. 

Elda Fischi-Gomez, Guillaume Bonnier, Pavel Falkowskiy, David Romascano, Myriam Schluep, Renaud Du Pasquier, Alessandro Daducci, Jean-Philippe Thiran, Gunnar Kruger, Cristina Granziera

We explored the sensitivity of a novel diffusion MRI method i.e. “Neurite orientation dispersion and density imaging”, to detect and characterize brain microstructure alterations in relapsing-remitting multiple sclerosis patients that we followed up over 2 years. Cross-sectionally, NODDI revealed that an increase in orientation dispersion and a decrease in neurite density in NAWM and in lesions of RRMS patients compared to healthy subjects. Longitudinally, NODDI measured a decreased dispersion and an increased neurite density in MS lesions at 2 years follow-up. Also, NODDI metrics at baseline were highly related to cognition at both baseline and follow-up.

Ken Sakaie, Xiapeng Zhou, Josef Debbins, Mark Lowe, Robert Fox

The lack of imaging biomarkers is a key obstacle to the development of treatment for progressive multiple sclerosis. While diffusion MRI is a promising biomarker, variability among scanners may limit its use. We examine site-related variability among multiple sclerosis patients to inform the design of multicenter trials.

Irene Vavasour, Cornelia Laule, Shannon Kolind, Roger Tam, David Li, Alex MacKay, Anthony Traboulsee

To test the potential neuroprotective and reparative properties of alemtuzumab (a highly effective disease modifying therapy for relapsing remitting MS), we used myelin water imaging to measure myelination in MS patients treated with either alemtuzumab, interferon, or no treatment. NAWM MWF showed a steady 4% increase in alemtuzumab-treated subjects whereas MWF in subjects treated with interferon or without treatment decreased by 10% over 5 years. Myelin recovery following treatment with alemtuzumab supports previous clinical trial findings, provides understanding of the biological mechanisms underlying observed clinical improvement and demonstrates that MWF is a powerful biomarker for neuroprotection and repair in MS.

Shannon Kolind, Irene Vavasour, Roger Tam, Lisa Tang, Alexander Rauscher, Robert Carruthers, Rick White, Victoria Levesque, Hideki Garren, David Clayton, David Li, Anthony Traboulsee

Conventional MRI scans cannot evaluate disease-related changes in normal-appearing white matter, and have limited sensitivity for detecting changes in chronic lesions. In this work, we employed 2 quantitative MRI measures related to myelin content, myelin water fraction and magnetization transfer ratio, to evaluate the effects a potential novel therapy for multiple sclerosis (ocrelizumab) compared to a commonly-used therapy (interferon beta-1a). Over 2 years, these myelin-related measurements increased or remained stable in all regions for patients taking ocrelizumab, while they decreased for interferon beta-1a. These results support the use of quantitative MRI measures for more efficient, biologically specific clinical trial outcomes.

Paola Valsasina, Maria Rocca, Fiammetta Pirro, Annalisa Colombi, Elisabetta Pagani, Ermelinda De Meo, Bruno Colombo, Paolo Preziosa, Vittorio Martinelli, Giancarlo Comi, Andrea Falini, Massimo Filippi

Aim of this study was to investigate the temporal evolution of resting state (RS) functional connectivity (FC) in patients with multiple sclerosis (MS) and its correlation with clinical and cognitive worsening. The predictive value of baseline functional network measures on the worsening of clinical disability/cognitive impairment was also explored. No significant RS FC changes were detected in healthy controls, while MS patients showed a complex pattern of longitudinal changes in the different networks, with a trend towards an increase (or stability) of RS FC in clinically stable MS patients, and a decrease of RS FC in clinically worsened MS patients. 

Kingkarn Aphiwatthanasumet, Olivier Mougin, Nick Geades, Nikos Evangelou, Richard Bowtell, Penny Gowland

MS lesions are known to evolve in time, many showing signs of remyelination. To investigate this, we considered the changes in the regions around existing lesions of varying ages, to test the hypothesis that there is ongoing tissue damage in the regions around white matter lesions in MS. We found that the quantitative MT measured at 7T values in the region surrounding MS lesions decreased over the period of a longitudinal 6 month study. No systematic trend was found for the lesion core. This supports the hypothesis that an MS lesion causes ongoing damage in the region surrounding the lesion. 

Adil Maarouf, Soraya Gherib, Elisabeth Soulier, Sylviane Confort-Gouny, Maxime Guye, Jean Pelletier, Jean-Philippe Ranjeva, Wafaa Zaaraoui

Longitudinal evaluation of brain sodium concentration in physiological conditions

Paola Valsasina, Maria Rocca, Mohammad Aboulwafa, Paolo Preziosa, Frederik Barkhof, Hugo Vrenken, Claudio Gobbi, Chiara Zecca, Alex Rovira, Xavier Montalban, Hugh Kearney, Olga Ciccarelli, Lucy Matthews, Jacqueline Palace, Antonio Gallo, Alvino Bisecco, Achim Gass, Philipp Eisele, Carsten Lukas, Barbara Bellenberg, Giancarlo Comi, Massimo Filippi

Aims of this large, multicenter study were to characterize baseline cervical cord atrophy in patients with multiple sclerosis (MS) compared with healthy controls, and to evaluate the modification of cervical cord cross-sectional area (CSA) over one-year of follow-up in such patients. Results indicated that baseline cord atrophy was present in MS patients vs controls, with a differential effect across phenotypes and a greater severity of atrophy in the progressive forms of the disease. Significant CSA decrease over time was found in relapsing remitting, primary progressive MS and in clinically worsened patients.

Nagesh Adluru, Hyunwoo Kim, Richard Davidson, Andrew Alexander, Sterling Johnson, Vikas Singh

This work presents novel statistical image analysis methods to characterize complex morphological brain changes using MRI data. Specifically, our procedure utilizes the fundamental representations of "longitudinal change" -- voxel-wise Jacobian matrices obtained from image registration. Currently their univariate summaries (for example determinants) are ubiquitously used in neuroimaging studies. Operating directly with representations of Jacobians namely Cauchy deformation tensors, which are elements of an abstract mathematical manifold of symmetric positive definite matrices, yields promising improvements in statistical power in detecting subtle but statistically significant effects. The key technical contributions are computational algorithms for estimating multivariate general linear models with manifold-valued response variables.

Hua CHENG, Hong ZHANG, Yang FAN, TongLi HAN, Yue LIU, Yun PENG

Quantitative Susceptibility Mapping (QSM) has been well used in evaluating the iron quantity changes in adult patients with multiple sclerosis (MS). However, it has not been tested in pediatric MS patients. In the present study, QSM was applied to assess difference of iron quantity in clinically isolated syndrome (CIS) and MS in children. It is shown that QSM provides a superior sensitivity method in the detection iron of changes of MS-related tissue in children, which suggests that QSM may serve as a potential sensitive biomarker in pediatric MS.

Loredana Storelli, Maria Rocca, Ermelinda De Meo, Elisabetta Pagani, Lucia Moiola, Angelo Ghezzi, Pierangelo Veggiotti, Ruggero Capra, Maria Pia Amato, Agnese Fiorino, Lorena Pippolo, Maria Pera, Giancarlo Comi, Andrea Falini, Massimo Filippi

In this study, diffusion tensor (DT) magnetic resonance imaging (MRI) was applied to describe brain structural network architecture and connectivity abnormalities underlying cognitive dysfunction in 53 pediatric multiple sclerosis (MS) patients in comparison to 26 age- and gender-matched healthy controls (HC). Global and local network analyses were performed to assess between-group differences of connectivity metrics and cortical hubs. Cognitive impairment in pediatric MS patients seemed to be mainly associated to a reduced strength of connections of structural hubs and loss of efficiency in information transmission.

Erin MacMillan, Julia Schubert, Irene Vavasour, Roger Tam, Alexander Rauscher, Rick White, Hideki Garren, David Clayton, Victoria Levesque, David Li, Anthony Traboulsee, Shannon Kolind

Single voxel magnetic resonance spectroscopy (MRS) was performed in thirty-seven relapsing multiple sclerosis (MS) patients, who were enrolled in a phase III clinical trial of ocrelizumab versus interferon beta-1a, at baseline, 24, 48, and 96 weeks follow-up. 24 healthy controls were also scanned. MRS demonstrated a significant interaction between visit and treatment group in the NAA/tCr ratio. The change in absolute metabolite concentrations over 96 weeks revealed that this interaction was primarily driven by increased NAA and reduced inflammation in the ocrelizumab group, while the interferon beta-1a group exhibited a smaller increase in NAA and ongoing inflammation.  

Ian Tagge, Daniel Schwartz, Katherine Powers, Rohit Bakshi, Peter Calabresi, Todd Constable, John Grinstead, Roland Henry, Govind Nair, Jiwon Oh, Li Pan, Nico Papinutto, Daniel Pelletier, Daniel Reich, Nancy Sicotte, Jack Simon, William Stern, William Rooney

The current lack of standardization in MRI protocols leads to increased variability, particularly in semi-quantitative techniques such as MTR, and makes comparisons between studies almost impossible. A single subject with clinically stable RRMS travelled to seven North American sites and underwent two distinct 3T MRI sessions following a standardized MTR and qT₁ protocol at each site. Both MTR and qT₁ mapping have been shown to have potential in elucidating tissue characteristics and underlying pathology. This work demonstrated that use of carefully standardized protocols produces consistent quantitative and semi-quantitative measurements across sites in MS brain tissue in-vivo.

Thalis Charalambous, Carmen Tur, Ferran Prados, Steven Pavert, Declan Chard, David Miller, Sebastien Ourselin, Jonathan Clayden, Claudia Gandini Wheeler-Kingshott, Alan Thompson , Ahmed Toosy

Numerous studies demonstrated structural network changes in patients with multiple sclerosis (MS). However, the predictive nature of the graph-derived metrics is not yet examined. In this longitudinal study, we constructed baseline diffusion-based structural networks and we used multiple linear regression analysis to assess the ability of the network measures to predict follow-up increased lesion load and brain atrophy in MS (n=49). Our results suggest that edge density, global and local efficiency can predict follow-up brain atrophy after adjusting for the nuisance variables, signifying that network analysis can provide new insights into disease trajectories and offer potential biomarkers for MS progression.

Alexandra Sorega, Mário João Fartaria , Guillaume Bonnier, Tobias Kober, Renaud Du Pasquier, Myriam Schluep, Gunnar Krueger, Meritxell Bach Cuadra, Cristina Granziera

Lesion load and activity in multiple sclerosis (MS) patients, as identified by conventional magnetic resonance imaging (MRI), correlate only moderately with patients clinical status and evolution. Cortical lesion number and volume measured with advanced MRI may provide better correlates to cognitive dysfunction and disability. In this work, we studied the clinical impact of  advanced MRI metrics of cortical and subcortical lesion evolution in a cohort of early relapsing-remitting MS patients. The number and volume of lesions that “shrunk”, disappeared or remained stable over time were strong determinants of changes in cognition in our patients cohort.

Rebecca Samson, Manuel Cardoso, Nils Muhlert, Varun Sethi, Özgür Yaldizli, Maria Ron, Ferran Prados , Sebastian Ourselin, David Miller, Claudia Gandini Wheeler-Kingshott, Declan Chard

Outer cortical magnetisation transfer ratio (cMTR) is potentially a sensitive measure of pathology linked to clinical disease progression in multiple sclerosis (MS). Here we aimed to investigate longitudinal outer and inner cMTR changes in healthy controls (HC) and people with MS of different clinical subtypes. Follow-up (FU) outer cMTR showed larger reductions in secondary progressive (SP)MS than other subtypes, and inner cMTR was also reduced more than in HC and relapsing-remitting (RR)MS, although cMTR was reduced in all MS patients at FU. This supports histopathological findings and suggests that cMTR measurement may be relevant to clinical disease progression in MS.

Aline Thomas, Jiadi Xu, Peter Van Zijl, Jeff Bulte

VDMP-CEST MRI can spatiotemporally monitor disease progression in a mouse model of multiple sclerosis. Lower VDMP-CEST signals corresponded to a decreased lipid and metabolite content in the peri-ventricular region of the brain, characteristic of the disease, with magnetic resonance spectroscopy used as validation.

Weidong Luo, Kelly Leyden, Aziz Ulug, Sebastian Magda, Julia Albright, Robert Haxton, Chris Airriess

Quantitative measures such as lesion volume and distribution have significant value for clinicians evaluating disease progression. Clinical standards for lesion evaluation include visual inspection of MRI images, or expert manual segmentation of lesions. These subjective measurements are often vulnerable to inter- and intra-rater variability, resulting in low reproducibility. CorTechs Labs’ LesionQuant is a fully-automated lesion segmentation tool for clinical use designed to provide accurate and reproducible lesion segmentations. This study objectively evaluates the segmentation results of LesionQuant compared to expert manual segmentation.

Esther Ruberte, Tim Sinnecker, Michael Amann, Yvonne Naegelin, Iris-Katharina Penner, Matteo Pardini, Jens Kuhle, Tobias Derfuss, Christoph Stippich, Ludwig Kappos, Jens Wuerfel, Özgür Yaldizli

As pars pro toto, lateral ventricle enlargement might give an indirect estimate of brain atrophy. In contrast to whole brain atrophy, ventricle enlargement is, however, clinically easy to assess and its quantification is robust to MR images of less than perfect quality. Here we investigate i) the applicability of an automatic lateral ventricle delineation algorithm (ALVIN) in multiple sclerosis (MS), and ii) the association between of lateral ventricle enlargement and clinical disability in MS longitudinally. We found that ALVIN reliably estimates the lateral ventricle volume in MS that is associated with whole brain atrophy and neurological as well as cognitive disability.

Ilona Lipp, Catherine Foster, Rachael Stickland, Alison Davidson, Richard Wise, Valentina Tomassini

The first aim of this study was to investigate retest-reliability of gray matter perfusion estimates in patients with multiple sclerosis. Using multi-inversion time pulsed ASL, we demonstrate good repeatability of global and local perfusion estimates over a four-week interval. The perfusion estimates were consistently lower in the patients than in a group of healthy controls. The second aim was to relate GM perfusion to disease characteristics. We could not find an effect of disease duration or stage (relapsing-remitting vs progressive) on perfusion, but we did observe a weak correlation with cognition, supporting previous studies.

Thomas Welton, Dorothee Auer, Cris Constantinescu, Rob Dineen

Knowledge of reproducibility of graph-theoretic brain network metrics in disease populations is critically important for applications in clinical studies but non-existent in published literature. We compared reproducibility of graph metrics over time in a cohort of MS patients to reported values in published studies of reproducibility in healthy volunteers. We found that reproducibility was good in MS patients but slightly lower than in healthy people. Reproducibility of graph-theoretic brain network metrics in MS patients is not greatly dissimilar to that in healthy populations, which supports their use in clinical studies.

Ahmed Elkady, Dana Cobzas, Hongfu Sun, Gregg Blevins, Alan Wilman

Purpose: To create an anatomically-interpretable framework for localized analysis of brain iron accumulation/demyelination, and apply this framework to Multiple Sclerosis (MS) Deep Gray Matter (DGM).

Materials and Methods: Quantitative Susceptibility and R2* maps were computed for 110 MS and 75 control subjects.

Results: Significant iron accumulation and insignificant demyelination were detected in MS DGM. Common MS pathological volumes and their pathological effect size progressively increased with advanced phenotypes. The developed framework offered improved statistical power and iron specificity compared to whole structure and singular analysis.

Conclusion: Using a novel localized analysis pipeline, we demonstrated the progressive iron accumulation in MS DGM.    

Eduardo Caverzasi, Christian Cordano, Alyssa Zhu, Antje Bischof, Gina Kirkish, Nico Papinutto, Michael Devereux, Nicholas Baker, Sam Arnow, Justin Inman, Hao Yiu, Carolyn Bevan, Jeffrey Gelfand, Bruce Cree, Stephen Hauser, Roland Henry, Ari Green

Fifty Multiple Sclerosis subjects were evaluated by optical coherence tomography and MRI, including multi-shell and putative myelin content imaging focused on primary visual area, thalamus and cerebellum. Predictive models of visual function performance, measured by visual evoked potentials and low contrast visual acuity were tested using a partial least square regression analysis. Combination of MRI and OCT metrics appears to strongly describe the visual function. Myelin content imaging, in particular, has a strong predictive value once there is history of optic neuritis. These preliminary results may improve the understanding of the pathological mechanisms underlying clinical dysfunction in multiple sclerosis.

Dulcie Vousden, Alexander Friesen, Lily Qiu, Rylan Allemang-Grand, Jan Scholz, Sheena Josselyn, Paul Frankland, Jason Lerch

Human and rodent imaging studies show that experience can lead to task-specific increases in brain structure, but the cellular and molecular basis of these changes is unknown. Here, we test the hypothesis that the these volume changes depend on the same signaling pathways required for learning and memory formation. We exposed mice lacking CREB (a transcription factor critical for memory) to an enriched housing environment, and imaged their brains longitudinally over two weeks. Surprisingly, enrichment altered the neuroanatomy of all mice, regardless of CREB genotype. These findings provide evidence that the volume changes are due to CREB-independent processes. 

Balasrinivasa Sajja, Aditya Bade, Mariano Uberti, Michael Boska, Howard Gendelman, Santhi Gorantla, Yutong Liu

Use of HIV-1 humanized mice allows the evaluation of brain morphology affected by disease and disease altering therapies. We posit that such studies can elucidate the pathobiology of HIV-1 associated neurological disorders. As irradiation, administered at birth, is a required step for long-term graft integrity we evaluated the effect of irradiation on mouse brain development using manganese-enhanced MRI (MEMRI) atlas-based segmentation. Brain size reductions in irradiated mice showed substantive morphological alterations. Thus, evaluation of irradiation effects on brain morphology is a requisite step in assessments of virus-induced brain pathology.

Ssu-Ju Li, Hui-Yu Wang, Hui-Ching Lin, Ting-Chun Lin, Han-Fang Wu, Chi-Wei Lee, Yu-Chun Lo, You-Yin Chen, Hsin-Yi Lai

This study demonstrates changes of functional connectivity in motor related brain areas and the motor cortex and striatum may be crucial areas for treatment and evolution of autism spectrum disorder (ASD). Our results indicate that both CT-DBS and 5-TH treatments can alter the social interaction and motor related functional connectivity VPA-induced ASD rats by modifying the motor cortico-striatal circuit. The rsfMRI has the potential to explore functional connectivity in the brain and monitor functional plasticity changes in a specific neuroanatomical pathway in vivo. 

Chul-Woong Woo, Jae Im Kwon, Sang Tae Kim, Kyung won Kim, YoonSeok Choi, Jinil Kim, Jeong Kon Kim, Su Jeong Ham, Seul I Lee, Ho-jin Kim, Jeeheon Kang, Dong-Cheol Woo

Recent evidence indicated that hydrogen sulfide is capable of attenuating ischemia/reperfusion (I/R) injury in brain. However, the influence of H₂S administration timing on its neuroprotective efficacy has not yet been assessed, thus we aimed to perform this study which used MRI and ¹H-MRS in rats with focal cerebral I/R injury. Our study demonstrated that hydrogen sulfide administration at 1 minute before reperfusion showed better neuroprotective effect than that at 30 minutes before reperfusion.

Su Xu, Wenjun Zhu, JiaBei Wang, Xi Chen, Rao Gullapalli, Edward Herskovits, Elias Melhem, Qi Cao

A mouse model of late-stage alcoholic liver fibrosis (LALF) was used to investigate changes of neurochemical levels in specific brain regions that may relate to behavioral changes at LALF. Higher glutamine levels result in osmotic/oxidative stress were found in the thalamus and hippocampus of the alcohol-treated mice than in controls. Thalamic levels of taurine and creatine were significantly diminished and were strongly correlated with the alcohol-induced depressive behavior observed in an open field test. In addition, significant elevations in hippocampal glutamate were indicative of upregulated local glutamatergic activation. These pilot findings provide novel insight into the development of alcohol-induced HE.

Jie Zhan, Tsen-Hsuan Lin, Jane Libbey, Peng Sun, Ze-Zhong Ye, Chunyu Song, Michael Wallendorf, Honghan Gong, Robert Fujinami, Sheng-Kwei Song

Hippocampal neuronal damage and inflammation are the hallmark pathologies of epilepsy. We demonstrate the capability of diffusion based spectrum imaging (DBSI) to quantify hippocampal CA1 neuronal dendritic injury/loss and inflammation in TMEV-induced epilepsy mice, followed by immunohistochemistry (IHC) validation. Results demonstrate that both DTI and DBSI metrics changed in CA1 region of TMEV-induced seizure mouse. DBSI-derived fiber fraction correlated with MAP2-positive area fraction, and DBSI-derived restricted isotropic diffusion fraction correlated with DAPI-positive nucleus density.

Yifan Zhang, Yongming Jin, Agnes Luo, Xin Yu

The current study investigated the effect of sonic hedgehog agonist (SAG) treatment in post-stroke recovery. SAG- and vehicle-treated mice were evaluated with MRI at day 2 and day 30 after middle cerebral artery occlusion (MCAO) surgery. Our results show that SAG treatment showed significantly increased cerebral perfusion in the ischemic penumbra at day 30, suggesting enhanced angiogenesis. In addition, SAG-treated mice also exhibited decreased T2, suggesting reduced neuronal damage. These results suggest that the sonic hedgehog signaling pathway can be a potential therapeutic target for stroke treatment.

Wenwen Yu, Zhe Wu, Hongjian He, Jianhui Zhong, Zheng Wang

Effects of normal aging on myelin have drawn considerable attention for decades. Previous studies hypothesized that myelin sheath degeneration could result in the reduction of the fraction of myelin water due to the inflow of intra- or extra-cellular water between myelin sheath. This study investigates aging effects on myelin degeneration in elderly macaques using a multi-echo GRE sequence. Using a three-pool model, we observed a significant decrease in the fraction of myelin water in the body of corpus callosum and a negative correlation with ages in 8 monkeys (aged 21~25), indicating heterogeneous degradation of white matter infrastructure with aging.

Hong-Chun Chou, Bor-Show Tzang, Vincent Chin-Hung Chen, Jun-Cheng Weng

Attention deficit hyperactivity disorder (ADHD) is a most common developmental disorders in both children and adult population. However, the treatment for ADHD remains limited. To investigate the effects of taurine on ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted in this study. The functional brain signals including functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) were detected by using resting-state functional magnetic resonance imaging (rs-fMRI). Our findings in FC and mALFF suggested that taurine administration probably improves the hyperactive behavior in ADHD by changing brain functional signals in SHR rats.

Joseph Guy, Robin Franklin, Kevin Brindle, Daniel Reich

Custom-built solenoid coils and 3D-printed rat brain slicers were used to identify and extract surgically placed inflammatory regions of interest within rat brains. The sequentially smaller and more sensitive coils combined with a highly-optimized gradient echo sequence, imaging setup, and registration algorithm achieved ultra high 25 µm isotropic resolution 3D MRI datasets. These images contained fully sampled k-space of the tissue pathology with preservation of the high frequency image details.

Jonathan Reinwald, Robert Becker, Claudia Falfan-Melgoza, Anne Mallien, Dragos Inta, Peter Gass, Alexander Sartorius, Wolfgang Weber-Fahr

Post-weaning social isolation rats are a widely used translational animal model for schizophrenia based on its typical schizophrenic-like behavioral alterations. Nevertheless, effects of isolation on functional brain connectivity are highly understudied. We used resting-state functional magnetic resonance imaging with seed-based and graph analyses to investigate effects of social isolation in rats on brain connectivity. Our major findings consistently demonstrated dysmodularity, hypofrontality, posterior hyperconnectivity and reorganization of the somatosensory cortex. These features resemble alterations of functional brain connectivity commonly observed in schizophrenic patients and other translational animal models, underlining the potential use of isolated rats as a translational model of schizophrenia.

Tim Luo, Peng Zhai, Olayinka Oladosu, Kahlil Rawji, Yunyan Zhang

Myelin injury and repair are associated with many neurological diseases including multiple sclerosis. We evaluated the utility of NODDI and MRI texture analysis for assessing myelin integrity using a mouse model of de- and re-myelination. Following lesion induction in mouse spinal cord, 9.4T MRI was conduced during demyelination (day 7) and ongoing remyelination (days 14, 28, and 35). With histological verification, both texture heterogeneity and neurite orientation dispersion (ODI) increased when demyelination occurs. But the latter showed persistent recovery with remyelination, similar to lesion size. These findings suggest the utility of ODI and texture heterogeneity as measures of myelin integrity.

Laetitia Degiorgis, Meltem Karatas, Marion Sourty, Chrystelle Po, Thomas Bienert, Hsu Lei Lee, Dominik von Elverfeldt, Chantal Mathis, Anne-Laurence Boutillier, Frédéric Blanc, Jean-Paul Armspach, Laura-Adela Harsan

Resting state functional magnetic resonance imaging (rsfMRI) has opened a new window into the brain and its connectome, proposing abnormal functional connectivity as a candidate biomarker of brain pathologies¹. We explored this pathway and performed rsfMRI and network analysis in the Thy-Tau22 transgenic mouse model of Alzheimer’s disease, evaluating possible network signatures of early pathological states. We mapped the brain functional connectivity patterns and found overactive resting state BOLD signal in core players of the memory and learning systems, including the hippocampal network. This correlates with subtle memory deficits characterizing a very early pathological phenotype of the Thy-Tau22 mouse model.

Ben Duffy, ManKin Choy, Jin Hyung Lee

The kindling model of epilepsy is associated with a permanent form of synaptic potentiation, which is considered to be pathological. In this study we used optogenetic fMRI to observe changes in plasticity that occur following a kindling regime. Upon stimulation of the ventral hippocampus, post-kindling fMRI data displayed significantly more widespread activation, particularly in pre-frontal regions compared to pre-kindling acquisitions. Simultaneous LFP measurements were used to confirm the absence of epileptic activity that would confound the interpretation. This represents a powerful technique which can be used for understanding cognitive impairments or understanding the mechanism of anti-epileptogenic therapies.

Audrey Bouchet, Marine Potez, Nicolas Coquery , Claire Rome, Benjamin Lemasson, Elke Bräuer-Krisch, Chantal Rémy, Jean Laissue, Emmanuel Barbier, Valentin Djonov, Raphael Serduc

Synchrotron microbeam radiation therapy (MRT), a spatially fractionated preclinical radiotherapy, is more efficient than broad beam irradiation (BB) at opening the blood-brain tumor barrier of intracranial rodent glioblastomas. MRT-induced increase of tumor vascular permeability is significantly greater, earlier and more prolonged than in the BB alone group, especially in highly proliferative areas. MRT targeted all tumor regions, including areas not impacted by BB. High dose microbeams might be used to facilitate the delivery of intravenously injected drugs to tumoral tissue: Adjuvant chemotherapy might thus be more effective when coupled with MRT than with homogeneous radiation fields used in conventional radiotherapy.

Alexandra Wright, Rebecca Theilmann, Sam Ridgway, Miriam Scadeng

Brain enlargement is associated with concomitant growth of interneuronal distance, increased conduction time, and reduced neuronal interconnectivity. Recognition of these functional constraints led to the hypothesis that large-brained mammals should exhibit greater structural and functional brain lateralization. As a taxon with the largest brains in the animal kingdom, Cetacea (whales, dolphins, and porpoises) provide a unique opportunity to examine asymmetries of brain structure and function. In the present study, diffusion tensor imaging (DTI) and tractography were used to investigate cerebral white matter asymmetry in the bottlenose dolphin.

Nicola Bertolino, Yegor Sinelnikov, Dhaval Shah, Robert Zivadinov, Ferdinand Schweser

Simultaneous Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) in small animals would enable entirely new approaches to drug development and yield to a better functional understanding of living organisms. However, preclinical systems that allow truly simultaneous PET and MRI are not yet commercially available. We present the integration of an optimized microPET camera with ultra-high magnetic field strength MRI.

Laura-Adela Harsan, Meltem Karatas, Thu Lan NGUYEN, Anna Mechling, Tanzil Arefin , Thomas Bienert, Hsu-Lei Lee, Dominik von Elverfeldt, Yann Herault

Resting state functional MRI (rsfMRI) is currently the only non-invasive approach capable of giving insight into the large-scale cerebral networks architecture and its dynamic changes in pathology or following therapeutic interventions. With the aim of deciphering specific network signatures underlying memory and cognitive impairments in Down Syndrome pathology, we performed rsfMRI and network analysis in the Dp(16)1yey mouse model. We found perturbed synchrony of BOLD-signal in the hippocampal network of Dp(16)1yey mice. We further modulated this memory specific cerebral circuitry via therapeutic treatment with a DYRK1A kinase inhibitor, aimed at rescuing the memory and cognitive dysfunctions characterizing this mouse model.

Nicola Bertolino, Suyog Pol, Robert Zivadinov, Natan Babek, Michelle Sudyn, Michele Sveinsson, Danielle Siebert, Marilena Preda, Dhaval Shah, Ferdinand Schweser

Persistent clusters of inflammatory cells in the leptomeningeal compartment  are thought to contribute directly to subpial cortical demyelination and neurodegeneration in MS patients. In human patients, post-contrast 3D T2-FLAIR allows the detection of leakage of contrast agent into inflammatory foci and the subarachnoid space. We propose a pulse sequence for LMI imaging in rodents and demonstrate its applicability in the EAE-MOG model of MS at 9.4T. 

Julie Hamaide, Kristina Lukacova, Lubica Kubikova, Marleen Verhoye, Annemie Van der Linden

In vivo diffusion tensor neuroimaging of adult male zebra finches was used to longitudinally monitor the effects of bilateral neurotoxic lesioning of a striatal component of the song control network and to explore possible causal relationships between the observed neuroplastic changes and specific alterations in song performance.

Manon Simard, James Larkin, Alexandre Khrapitchev, Kevin Ray, Michael Chappell, Nicola Sibson

Arterial spin labelling (ASL) MRI is a useful clinical method of measuring blood flow in brain disorders such as tumours. This work presents a pre-clinical assessment of cerebral blood flow (CBF) by pseudo-continuous ASL in progressing rat breast cancer brain metastases. A statistically significant decrease in CBF of brain metastases was readily observed when tumours had grown sufficiently to breach the blood brain barrier, allowing gadolinium enhancement in T₁-weighted images. Upon histological analysis, the brain metastases proved to be hypoxic, consistent with a reduction in CBF in those regions.

Heather Decot, Sung-Ho Lee, Han Zhang, Fei Fei Wang, Regina Carelli, Yen-Yu Ian Shih, Garret Stuber

Several different neural systems are likely to be dysregulated to promote maladaptive behaviors associated with drug addiction.  Here, we investigate changes in global functional connectivity across the brain following self-administration of cocaine and a period of abstinence in rats.  We found whole brain enhancement in synchronized activity immediately following cocaine self-administration compared to pre-cocaine.  Furthermore, whole brain network connectivity continued to strengthen following a period of abstinence.  These data suggest that the dynamic shifts in functional connectivity following cocaine exposure persist during periods of abstinence and may provide a critical mechanistic link to relapse susceptibility.

Niels Schwaderlapp, Philipp Janz, Jochen Leupold, Dominik von Elverfeldt, Jan Korvink, Jürgen Hennig, Carola Haas, Pierre LeVan

Hippocampal sclerosis involves neuronal loss in hippocampal subfields and is a common characteristic of temporal lobe epilepsy (TLE). Investigation of the metabolic alterations following a status epilepticus may lead to a better understanding of epileptogenesis and can reveal biomarkers for TLE. Overcoming the major disadvantages of single voxel ¹H MR spectroscopy, namely a low spatial and temporal resolution, this study investigates the capability of the glutamate chemical exchange saturation transfer (GluCEST) method to map endogenous glutamate alterations in a mouse model of TLE.

Esben Hansen, Kasper Lipsø, Rasmus Tougaard, Christoffer Laustsen, Jan Henrik Ardenkjær-Larsen

Dynamic Contrast-Enhanced MR (DCE-MR) perfusion assessment with gadolinium contrast agents is currently the most widely used cerebral perfusion MR method. Hyperpolarized water has recently been shown to succeed 13C probes as angiography probe. In this study, we demonstrate the feasibility of hyperpolarized water for visualizing the brain vasculature of a large animal in a clinically relevant setting. In detail, reference perfusion values were obtained and large to small arteries could be identified.

Emer Hughes, Olivia Carney, Nora Tusor, Kelly Pegoretti, Sophie Arulkumaran, Lucilio Cordeo-Grande, Christopher Kelly, Madeline Barnett, Michelle Krishnan, Johannes Steinweg, Joanna Allsop, Ana Dos Santos Gomes, Julia Wurie, Jose Bueno-Conde, Matthew Fox, Amber Strang, Maryanne Sharma, Suresh Victor, Counsell Serena, David Edwards, Joseph Hajnal, Mary Rutherford

The aim of this study was to ascertain the prevalence and type of incidental findings present in the low risk term brain using MRI. Out of 200 infants, 105 had incidental findings, with 8 requiring follow-up assessment.  Common findings included subdural haemorrhage, punctate and cystic lesions and hyperintense signal of the basal ganglia. Findings requiring further assessment included subarachnoid, cerebellar, and germinal matrix haemorrhages, ectopic posterior pituitary lobe, subepenymal heterotopia and venous infarcts. Prevalence of incidental findings in this cohort is significant. Communicating to parents the possibility of detecting abnormalities and referral pathways are important considerations in neonatal research. 

Xianjun Li, Miaomiao Wang, Heng Liu, Jie Gao, Xiaocheng Wei, Jian Yang

White matter in human brain undergoes a complex and long lasting process. It is not likely that conventional diffusion parameters are specific enough to distinguish axon-related and myelin-related processes. This study investigates directional diffusivities in intra-axonal and extra-axonal compartments on preterm neonates, term neonates, infants, and adults. Two change patterns of extra-axonal axial and radial diffusivities are found during development. This may be related to premyelination and myelination. Developmental changes of the fiber dispersion and intra-axonal diffusivities are observed in both pre-myelination and myelination periods. Directional diffusivities in intra-axonal and extra-axonal compartments provide more detailed information to evaluate axonal development.

Congcong Liu, Zhijie Jian, Xianjun Li, Chao Jin, Miaomiao Wang, Heng Liu, Jian Yang

Assessment of WM myelination is important to diagnose WM disorders in infants and children. We retrospectively evaluated 109 subjects (age of 6-48 months) using modified Cecilia Parazzini’s scoring method based on T2WI visual evaluation. A significantly positive correlation was found between age and total scores of WM myelination with non-linear correlation coefficient of 0.948 (p<0.01). TBSS results demonstrated WM myelination progressed rapidly during age of 6-20 months and relatively stable during age of 21-48 months. The modified scoring method was more applicable to assess the WM myelination in infant with age of 6-20 months.

Douglas Dean III, Elizabeth Planalp, William Wooten, Nagesh Adluru, H Goldsmith, Richard Davidson, Andrew Alexander

Quantitative MRI affords a unique opportunity to map dynamic patterns of neurodevelopment and provide insight into relations between brain maturation and emerging cognition. Using a data-driven technique, we investigated underlying patterns of white matter microstructure and subsequently examined the relationships of these microstructural correlations with respect to gestation-corrected age. We demonstrate that patterns of white matter development may be informative to studies of early brain development.

Paola Scifo, Pasquale Della Rosa, Elisa Marchetta, Silvia Pontesilli, Roberta Scotti, Antonella Poloniato, Andrea Falini, Cristina Baldoli

  Aim of this study is to investigate, through DTI, structural white matter (WM) asymmetries in newborns and compare these differences in control and in preterm newborns scanned at term. Both controls and preterms show multiple regions of asymmetries in all the DTI indices. A small area localised in the talamic radiations was found to have a significant difference of WM brain asymmetries between the two groups of subjects.

Claire Kelly, Alicia Spittle, Jeanie Cheong, Jian Chen, Joy Olsen, Abbey Eeles, Jennifer Walsh, Marc Seal, Peter Anderson, Lex Doyle, Deanne Thompson

The neonatal period is critical for brain development, however relationships between the brain and behaviour early in life are poorly understood. This study investigated relationships between whole brain, multimodal, quantitative magnetic resonance imaging (MRI) measures and neurobehavioural function in 257 preterm infants at term-equivalent age. Voxel-based morphometry and tract-based spatial statistics identified regions where grey and white matter volume and white matter microstructure were associated with various aspects of neurobehavioural function, with regions varying depending on the function. Thus, this study improves knowledge of brain-behaviour relationships early in life, which may help with predicting long-term outcomes and assessing early interventions to improve outcomes. 

Serafeim Loukas, Lara Lordier, Frédéric Grouiller, Didier Grandjean, François Lazeyras, Dimitri Van de Ville, Petra S. Hüppi

In this study we examined the impact of the environmental enrichment of preterm newborns with music on auditory cortex functional connectivity. A group of preterm infants listened to music from 33 weeks gestational age until term equivalent age. Two control groups were used: preterm and full-term infants without music. Auditory cortex functional connectivity with cerebral regions known to be implicated in tempo and familiarity processing were identified for preterm newborns that had music training during their stay in the NICU using Psychophysiological Interaction (PPI) analyses. Our results suggest that music training during hospitalization can modify functional connectivity in the newborn brain.

David Price, Cristina Uria-Avellanal , Magdalena Sokolska, Subhabrata Mitra, Alan Bainbridge, Xavier Golay, Nicola Robertson

31P image selected in vivo spectroscopy was used to measure deep grey matter intracellular pH in 43 neonates with hypoxic-ischaemic encephalopathy.  All neonates had previously received therapeutic hypothermia, the current standard of care.  Brain alkalosis was associated with poor outcomes reproducing what was found from whole-brain pH measurements in the pre-cooling era. Brain alkalosis was associated with increased seizure burden, the first time this has been shown in babies.  Avoiding brain alkalosis could be a new objective for treating seizures and for neuroprotection in neonatal encephalopathy.

Joseph Yang, Richard Beare, Belinda Stojanovski, Wirginia Maixner, Marc Seal, Mark Mackay

Imaging markers that can infer microstructural changes occurring in childhood arterial ischemic stroke (CAIS) may lead to a better understanding of the disease’s neurobiological substrates. We applied both the Neurite Orientation Dispersion and Density Imaging (NODDI) and the Spherical Mean Technique (SMT) diffusion compartment models to two-shell diffusion data acquired in four acute CAIS patients. We demonstrate that parameter estimates derived from the stroke-affected regions were consistent with known microstructural changes described in acute stroke histopathology. The magnitudes of parameter changes were associated with stroke severity, and the motor outcomes at follow-up.

Claire Kelly, Jeanie Cheong, Alicia Spittle, Jian Chen, Marc Seal, Peter Anderson, Lex Doyle, Deanne Thompson

Infants born preterm are at risk of neurodevelopmental delays in childhood, and MRI may improve knowledge of underlying cerebral changes. Relationships were investigated between whole brain volumes and microstructure in 256 preterm infants and neurodevelopmental outcomes at age 2 years using voxel-based morphometry and tract-based spatial statistics. Lower grey and white matter volumes and altered white matter microstructure were associated with poorer outcomes. In general, relatively widespread brain regions were associated with cognition, more central regions with cerebral palsy, and more peripheral regions with language. This study provides further understanding of how brain structure in preterm infants is related to longer-term outcomes. 

Xianjun Li, Jie Gao, Miaomiao Wang, Edward Hui, Xiaocheng Wei, Jian Yang

Punctate white matter lesions (PWML) are common in preterm neonates. Neurodevelopmental outcome of the neonates is related to the lesion extensions. This study aimed to characterize the extent of microstructural variations for different PWML grades. White matter microstructural variations were different across PWML grades. The severe PWML were associated with extensive microstructural changes. Pattern of increased AD, increased RD, and reduced/unchanged FA was found proximal to the PWML. Unchanged AD, increased RD, and reduced/unchanged FA were observed in the vast regions distal from the PWML. These findings may help in determining outcomes of PWML and treatment strategies.

Hyun Gi Kim, Jin Wook Choi, Sung-Min Gho, Young Ju Lee, Ha Young Shin

Clinical usage of myelination quantification is wide in children. With multi-parametric quantitative MRI, it is possible to acquire T1-weighted or T2-weighted contrast image simultaneously with absolute values of R1 and R2 relaxation rates and proton density. Using the absolute values, myelination water fraction (MWF) can be calculated. 

Yang Zheng, Xiaoming Wang, Xuna Zhao

The environment of the brain dynamically changes with neonatal brain development, and the topic of whether the application of magnetic resonance imaging (MRI) can reflect these brain environment changes is a recent one. In recent years, a new magnetic resonance contrast technology called amide proton transfer (APT) imaging has emerged which can detect protein and peptides through the signal from water (1), reflecting in vivo pH and protein concentration at the cellular and molecular level. The so-called amide proton mainly refers to the amide proton from the free protein and the polypeptide backbones.

Takuya Hinoda, Yasutaka Fushimi, Tomohisa Okada, Akira Yamamoto, Tsutomu Okada, Kaori Togashi

To assess the susceptibility changes in early childhood (0 45 months) and these consistencies with previous reports. In our study, 35 children were enrolled and QSM was calculated from 3D gradient-echo images. Susceptibility values in deep gray matter structures showed positive correlation with the subjects’ age and theoretical iron contents, and these in white matter structures showed negative correlation in posterior peduncle of internal capsule and optic radiation. These results reflect the normal neural development in the early childhood and QSM can provide us quantitative methods to evaluate brain development.

Ahmed Serag, Emma Telford, Scott Semple, James Boardman

Preterm birth is a major cause of neuropsychiatric impairment in childhood and leads to significant long-term clinical, educational and social problems. A major issue confronting clinicians who work with preterm infants and their families is the identification of infants who are most at risk for subsequent neurodevelopmental disability and who may benefit from early intervention services. We designed a system for the identification of preterm infants at high risk of developmental disorders using convolutional neural networks (CNN). The designed network yields an accuracy of 83.33%, and is applicable to the automated analysis of larger study cohorts.

Cindy Xue, Lin Shi, Steve Hui, Tsz-ping Lam, Bobby Ng, Jack Cheng, Winnie Chu

Adolescent Idiopathic Scoliosis (AIS) is a 3-dimensional spinal deformity which occurs predominantly in adolescent girls. Impaired postural balance and tonsillar ectopia are reported findings in AIS. This study sought to investigate and compare white matter integrity of the cerebellar pathways in AIS with matched controls. Anatomically-guided deterministic tractography was used to reconstruct the cerebellar pathways. Lower FA value was found in spinocerebellar tract and in intracerebellar tract in AIS, suggestive of, reduced white matter integrity of the cerebellar pathway, which is in agreement with similar changes in other white matter pathways within the brain of AIS patients.  

Deanne Thompson, Claire Kelly, Jian Chen, Richard Beare, Marc Seal, Peter Anderson, Lex Doyle, Alicia Spittle, Jeanie Cheong

Many early life factors contribute to how well a preterm child will develop, and these affect the brain differently based on how early the infant is born. The current study found that earlier gestational age is related to smaller brain volumes and less mature white matter at term-equivalent age. Correlated with these brain measures were lower birthweight SD score, multiple birth or high social risk. We show that infants born moderate and late preterm have altered brain development, not just those born very preterm, and there is a differential effect of early life predictors based on gestational age. 

Jeong-Won Jeong, Harry Chugani, Michael Behen, Senthil Sundaram

This study is to investigate if different types of genetic mutations observed in children with global developmental delay (GD) are associated with white matter dysmorphologies and neuropsychological assessments. Eight children with GD having different mutations underwent a 3T MRI including diffusion tensor imaging with topological whole brain connectome analysis. Four of eight GD-associated mutations having high gene expression level in frontal and hippocampal regions showed apparently increased connectivity strengths in frontal and hippocampal regions which were significantly correlated with three behavioral phenotypes (IQ, memory, communication) suggesting that white matter abnormalities in different regions are perhaps driven by different genetic mutations.  
 

Vishal Patel, Noriko Salamon

We demonstrate a novel technique for studying white matter pathology by examining the statistical properties of the DWI signal. We apply a sparse coding method, K-SVD, to decompose a diffusion-weighted series. We then quantify the efficiency of the resulting encoding by computing the Gini coefficient.  We show that this measure is abnormally decreased in a cohort of lissencephaly patients compared to age-matched control subjects.  Our results support the hypotheses that more organized white matter can be more sparsely encoded and that the sparsity of the encoding may thus be used to infer pathological white matter states.

PhuaHwee TANG, HsiaoPiau NG

Retrospective study of MRI brains with volumetric measurements done using voxel based morphology was conducted for children with seizures imaged in KK Women’s and Children’s Hospital since 2006.  There was decreased cerebral volume and increased ventricular volume in children with hippocampal abnormalities compared to children with structurally normal brain, the difference in volumes exceeding 1 standard deviation, not statistically significant likely on account of the small sample sizes.  Relative reduced grey matter to white matter is seen in children with hippocampal abnormalities as well as in children with neuronal migration abnormalities, reaching statistical significance in both groups. 

YISHAN LUO, LIN SHI, DANTONG MIAO, XIN ZHANG, Queenie Chan, Winnie CW CHU, BING ZHANG, DEFENG WANG

In this paper, we proposed a set of fetal brain MRI analysis methods to quantify the fetal brain tissue volume. We used deep learning-based brain mask extraction method to obtain brain mask and reconstructed 3D fetal brain volumes using registration-based reconstruction method. Then an age-specific atlas-based segmentation method was applied to segment three major tissues (White Matter, cortical Gray Matter, cerebrospinal fluid). The changes of intracranial volume and the three brain tissue volumes across different gestational ages were calculated and fitted with both linear and quadratic curves. The results demonstrated the effectiveness of the automatic 3D fetal MRI quantification methods.  

Wenjing Zhang, Yaxin Zhu, Di Yang, Peining Liu, Zhihan Yan, Su Lui

To investigate the impact of hormone maturation on brain function and psychological development, seventy-three girls aged 6-11 years were enrolled. Using the global voxel-wise functional connectivity, we found that girls with hormonal maturation showed significantly greater functional connectivity strength mainly in the default mode network and limbic system, relative to girls who were not hormonally maturated. While these two networks contribute substantially to the social cognition, cognitive processing and emotion regulation, our finding suggested that the hormonal maturation manifested its effects greatly on regions which are crucial to the social, self-referencial, and emotional cognition development.

Yanrong Guo, Pei Dong, Guorong Wu, Weili Lin, Dinggang Shen

Automatic and consistent hippocampus segmentation from longitudinal infant brain MR image sequences is crucial for the measurement and analysis of its growth trajectory during early brain developing stage. To achieve this goal, we propose to use the longitudinal hypergraph method for joint learning the MR images from multiple acquisition time-points. We apply the proposed method to segment hippocampus from infant brain MR dataset which contains five time-points from 2 weeks to 12 months of age. According to the experimental results, our method outperforms other state-of-the-art label fusion methods in terms of both segmentation accuracy and consistency. 

Lili He, Nehal Parikh

By school age, 30-50% of very preterm infants exhibit cognitive deficits. Unfortunately, cognitive deficits cannot be reliably diagnosed until 3 to 5 years of age. These early years are now recognized as critical for neuroplasticity when early intervention therapies can enhance infants’ ability to reach their full cognitive potential. Diffuse white matter abnormality (DWMA) is seen on term-equivalent age MRI in 50-75% of very preterm infants and is predictive of cognitive deficits. In this study, we examined features of DWMA and conducted personalized prediction in very preterm infants, soon after birth, using machine learning algorithms.

Tianyi Qian, Zhigang Qi, Kuncheng Li

Resting-state fMRI has been widely used to investigate the functional deficits of Alzheimer's disease (AD) and mild cognitive impairment (MCI). In this study, we applied this method to investigate the differences in tissue perfusion deficits between MCI, AD, and normal control (NC) groups. The results show that the AD and MCI groups have areas with less fast perfusion than normal controls. While the MCI group has more perfusion deficits in the frontal lobe, the AD group has more perfusion deficits in the parietal and occipital lobe.

Hao Shu, Gang Chen, Zan Wang, Duan Liu, Guangyu Chen, B. Douglas Ward, Chunxian Yue, Fan Su, Lihua Gu, Feng Bai, Shi-Jiang Li, Zhijun Zhang

We reported distinct EM neural correlates among APOE alleles in elderly subjects but still unclear whether and how the APOE ε4 carriers’ distinct EM neural correlates contribute to an increased risk of AD onset. This study found that higher HFC strength in the EM neural correlates correlated with better longitudinal EM performance in the APOE ε3ε3 subjects but associated with inferior longitudinal EM performance in the ε4 carriers. These findings indicate that the degeneracy of EM function advance differential AD onset risk among APOE alleles, and provide a potential tool to predict APOE ε4 carriers with impending cognitive decline.

Jens Goettler, Isabelle Riederer, Lorenzo Pasquini, Stephan Kaczmarz, Claus Zimmer, Christine Preibisch, Christian Sorg

BOLD-functional connectivity (BOLD-FC) is decreased in Alzheimer’s disease (AD), and suggested to reflect reduced coherence of neural activity. However, the BOLD signal is based on vascular hemodynamics, therefore, impaired perfusion might also contribute to reduced BOLD-FC. Here, 32 AD patients and 22 controls underwent a simultaneous MR/PET, assessing BOLD-FC by resting-state fMRI, baseline CBF by pASL, and neuronal activity by FDG-uptake. Patients’ BOLD-FC, CBF, and FDG-uptake were reduced within the same precuneal regions. BOLD-FC was positively associated with mean CBF, specifically in patients and independently from FDG-uptake. Data indicate that impaired vascular hemodynamics contribute to reduced BOLD-FC in AD.

Remika Mito, David Raffelt, Thijs Dhollander, David Vaughan, Olivier Salvado, Amy Brodtmann, Christopher Rowe, Victor Villemagne, Alan Connelly

Alzheimer’s disease (AD) is characterised by extensive white matter disruption, however voxel-based studies have been unable to provide fibre-specific insight into how this alters brain connectivity. Here, we applied fixel-based analysis (FBA) to diffusion MRI data to investigate changes in AD and mild cognitive impairment (MCI) patients. AD patients exhibited significant reductions in both fibre density and cross-section across multiple fibre tracts, while significant decreases in MCI were only evident in the posterior cingulum and uncinate, upon tract-of-interest analysis. This work demonstrates the value of FBA in identifying both macroscopic and microscopic changes to specific fibre pathways in the investigation of AD.

Soo Hyun Cho, Geon-Ho Jahng, Jang-Hoon Oh, Hyug-Gi Kim, Hak Young Rhee, Chang Woo Ryu, Key-Chung Park, Dal Mo Yang, Eui Jong Kim, Wook Jin

To measure temporal changes of the metabolite level during a memory task, proton functional MRS (fMRS) data with a single-voxel PRESS sequence were acquired at the precuneus and posterior cingulate brain region during a face-name association task using a 3 Tesla MRI scanner for the 28 cognitive normal elderly, 16 amnestic mild cognitive impairment, and 12 Alzheimer’s disease individuals. We measured the fMRS data three times at the eight-month interval. All of the acquired data were analyzed using LCModel software. Glx at the second trial increased significantly compared to that of the first trial in the novel condition.

Gloria Castellazzi, Letizia Casiraghi, Giovanni Savini, Fulvia Palesi, Paolo Vitali, Nicoletta Anzalone, Elena Sinforiani, Giovanni Magenes, Cristina Cereda, Claudia Gandini Wheeler-Kingshott, Giuseppe Micieli, Egidio D'Angelo

Evidence from recent studies suggests that machine learning applied on MRI can be used to reliably differentiate Alzheimer disease from other major dementia diseases, e.g. Vascular Dementia (VD). In this work we used a machine learning approach applied on features derived from resting state fMRI (rs-fMRI) to build a model that is able not only to differentiate AD from VD, but also to classify the prevalent underlying disease (AD or VD) in a group of early dementia patients for whom clinical profile presented major overlap between symptoms of AD and symptoms of VD (i.e. mixed dementia subjects, MXD).

Bénédicte Maréchal, Sophie Espinoza, Wadie Ben Hassen, Tobias Kober, Christophe Habas, Alexis Roche

We investigate the potential of an automated method to provide hippocampal volume estimates using T1-weighted images obtained from the MP2RAGE sequence. Scheltens visual medial temporal atrophy scores from 27 patients undergoing clinical brain MRI for workup of cognitive decline were compared to automated volumetric measures using multinomial logistic regression. Strong correlation was observed which suggests that the employed hippocampal volumetry method may help supporting diagnosis of neurodegenerative diseases.

Jeam Barbosa, Silvio Bernardes da Silva Filho, Carlo Rondinoni, Antonio Santos, Carlos Salmon, Nereida Costa Lima, Eduardo Ferriolli, Júlio Moriguti

Constant atrophy in Alzheimer's disease is observed until the later DAD stages.

Alexis Roche, Daniel Damian, Frédéric Pedron, Bénédicte Maréchal, Patric Hagmann, Philippe Maeder, Reto Meuli, Tobias Kober, Jean-François Démonet

We implemented an automated classifier using T1-weighted magnetic resonance imaging-based brain volumetry and the Montreal Cognitive Assessment test to predict whether patients of a University Memory Clinic with suspected neurocognitive disorders have subjective complaints, or suffer from either typical or mixed forms of Alzheimer's disease. The classifier achieved an accuracy of 80.8% and was found to require both psychometric and brain morphometric data to perform best.

Kristof Govaerts, Jessica Sternisa, Tom Dresselaers, Fred Van Leuven, Uwe Himmelreich

Alzheimer's Disease (AD) is the most common neurodegenerative disease, and is influenced by various environmental factors. In this study, we evaluate the effect of a high-fat, high-sugar ‘Western-type’ diet on the on the vascular response capacity to hypercapnia in a double transgenic (APP/PS1) mouse model of AD. We make use of Arterial Spin Labelling to investigate basal perfusion and cerebrovascular response to hypercapnia (CVR) in the hippocampus, cortex and thalamus. 

Keith S Cover, Ronald A van Schijndel, Adriaan Versteeg, Alberto Redolfi, Paolo Bosco, Soheil Damangi, Bob W van Dijk, Hugo Vrenken, Giovanni B Frisoni, Frederik Barkhof

The segmentation noise of hippocampal atrophy measurement methods can be measured using the  back-to-back (BTB) reproducibility with the ADNI1 data set. Previous studies have only measured the segmentation noise over a one year interval. In the current study, two methods are shown to be substantially less noisy than manual hippocampal atrophy measurements over both 1 and 3 years - MAPS-HBSI and the recent FreeSurfer 6.0 Beta B (Build 20161008). Scatter plots of the 1 year versus 3 year BTB differences were found to be a particularly simple and effective way to display the segmentation noise of a method.

Zhao Qing, Weiping Li, Wenbo Wu, Fangfang Wang, Renyuan Liu, Zuzana Nedelska, Jakub Hort, Hui Zhao, Weibo Chen, Queenie Chan, Bin Zhu, Yun Xu, Bing Zhang

Loss of spatial navigation skills is a typical feature in mild cognitive impairment. Here we investigate intrinsic activity using resting-stat functional magnetic resonance imaging within the subcortical regions, which is previously reported to be important in spatial navigation. Right hippocampus, pallidum and thalamus showed significant decreased regional homogeneity of local intrinsic activity in the patients, and the correlational trend between regional homogeneity and allocentric navigation performance showed significantly difference between patients and normal aging controls. These results showed evidences for the intrinsic subcortical activity damage and a possible compensatory mechanism of spatial navigation in the early mild cognitive impairment.

Matteo Mancini, Mara Cercignani, Sonia Bonnì, Silvia Picazio, Viviana Ponzo, Maria Concetta Pellicciari, Elias Casula, Laura Serra, Carlo Caltagirone, Giacomo Koch, Marco Bozzali

We present a double-blind randomized cross-over clinical study that aims to investigate the efficacy of two weeks of repetitive transcranial magnetic stimulation (TMS) in modulating cognitive performances in patients with mild cognitive impairment (MCI) and to characterize in vivo brain connectivity changes in MCI patients after rTMS. We used a multi-modal approach based on behavioural tests, TMS-EEG, DWI and fMRI. The behavioural and neurophysiological results support the role of medial parietal region in memory process. Moreover, our findings suggest that TMS may be a potential effective strategy in treatment of MCI patients for whom, currently, there is no available therapy. 

FIRAT KARA, Michael Belloy, Garima Yadav, An Langbeen, Jules Jacobs, Disha Shah, Steffen Roßner, Peter Ponsaerts, Marleen Verhoye, Annemie Van Der Linden

Dysregulation of hypothalamic pituitary gonadal (HPG) axis signaling  with  menopause is considered as a risk factor for Alzheimer’s disease (AD). Menopause leads to decreased sex steroid signaling and increased luteinizing hormone signaling which may have profound effects on many cellular processes that predispose to neurodegeneration and impairment in cognitive function. The effects of amyloid production on resting state BOLD fMRI using functional connectivity analysis in a mouse model of AD have been previously published. However how HPG axis dysregulation affect resting state functional connectivity in a mouse model of AD has not been studied. Here we show that ovariectomized AD mice, a commonly used animal model to study menopause related hormonal changes in the  HPG axis, exhibit alterations in resting state connectivity in the mouse default mode network connectivity. These findings  establish a causal link between AD and HPG axis dysregulation.

Marjolein Bulk, Boyd Kenkhuis, Linda van der Graaf, Ingrid Hegeman, Mark van Buchem, Remco Natté, Louise van der Weerd

Changes in susceptibility-based MRI contrast and histological correlates of post-mortem brain tissue have been used to distinguish differences in spreading patterns of AD pathology over the cortex between AD subtypes. Susceptibility-based MRI allowed us to clearly distinguish early-onset and late-onset AD patients. The MRI contrast in the different regions closely reflected the overall severity of pathology. This study confirms iron deposition as the underlying source of MRI contrast in all cortical regions, and demonstrates that iron deposition is a putative biomarker for disease progression, with a spatial and temporal spreading pattern independent of amyloid and tau.

Udunna Anazodo, Elizabeth Finger, Claes Ladefoged, Frank Prato, Jonathan Thiessen, Keith St Lawrence

This study examined regional associations of hypoperfusion to hypometabolism in frontotemporal dementia patients using simultaneous PET/MRI acquisitions. Concordance between modalities was observed across regions. In general ASL-CBF appears to complement PET-FDG measurements

Kristian Mortensen, Simon Sanggaard, Hedok Lee, Palle Koch, Maiken Nedergaard, Bjørn Quistorff, Helene Benveniste

The link between hypertension and cerebral small vessel disease is key to understanding pathobiology of certain types of dementia. We studied the effects of mild hypertension on a newly discovered pathway for clearance of solutes from the brain parenchyma in young spontaneously hypertensive rats using DCE-MRI after intrathecal infusion of a paramagnetic contrast agent. We found normal-to-increased tracer influx and decreased efflux to and from the brain parenchyma, consistent with a lowered efficiency of brain solute clearance. This suggests that a compromised brain waste transport system may be implicated in the development of cerebral small vessel disease and dementia. 

Qing Wang, Yong Wang, Jon Christensen, Yi Su, Lisa Cash, John Morris, Mark Mintun, Tammie Benzinger

Accumulation of amyloid beta (Aβ) plaques and neurofibrillary tau tangles are the neuropathological hallmarks of Alzheimer disease (AD). However, increasing evidence points to the involvement of neuroinflammation in early AD and disease progression. Diffusion basis spectrum imaging (DBSI) is a novel non-invasive and non-radioactive multi-parametric diffusion MRI technique to quantify neuroinflammation in AD. We demonstrated that DBSI derived neuroinflammation marker significantly correlated with 11C-PK11195 PET imaging, a marker for microglia activation and neuroinflammation, suggesting DBSI as a promising endogenous, non-radioactive method to quantify neuroinflammation in AD.

Leon Munting, Lydiane Hirschler, Ernst Suidgeest, Emmanuel Barbier, Matthias van Osch, Louise van der Weerd

Cerebral Blood Flow (CBF) as measured with ASL-MRI is an emerging Alzheimer’s Disease (AD) biomarker. However, vascular pathology may delay the arterial transit time (ATT) of the magnetic label and influence the measurement. Thus, ATT estimation can potentially reveal vascular pathology and benefit CBF quantification. To evaluate CBF and ATT as read-out markers in AD mouse models, time-encoded ASL was used to measure ATT and CBF in the APPswe/PS1ΔE9 AD model. No major CBF difference was found when ATT was taken into account. However, AD mice showed increased ATT in the thalamus and decreased CBF in the cortex and striatum. 

Jiaying Zhang, Catherine Slattery, Ross Paterson, Alexander Foulkes, Laura Mancini, David Thomas, Marc Modat, Nicolas Toussaint, David Cash, John Thornton, Daniel Alexander, Sebastien Ourselin, Nick Fox, Jonathan Schott, Hui Zhang

Young Onset Alzheimer's disease (YOAD) is characterised by its syndromic diversity, which may be underpinned by different patterns of white matter (WM) network breakdown. This prompts considerable interest in studying WM. We have previously shown that NODDI, a multi-shell diffusion MRI technique, is more sensitive at detecting WM changes in YOAD than standard DTI and demonstrated unique profiles of WM deficits in its syndromic variants. Here we investigated longitudinal WM changes in YOAD patients using NODDI, and explored the patterns of longitudinal WM changes associated with syndromic variants using tract-based spatial statistics (TBSS). 

Joseph Helpern, George Glenn, Andreana Benitez, Fatima Falangola, Rachael Deardorff, Jens Jensen

Automated fiber quantification with white matter tract integrity metrics identified subtle changes in brain microstructure occurring in the early stages of Alzheimer’s pathology. These metrics were found to be significantly different in the posterior section of the parahippocampal white matter in cognitively normal older adults with hippocampal atrophy as compared to those without. Axonal water fraction distinguished those with hippocampal atrophy versus those without with the largest effect size (Cohen’s d = 0.86, p = 0.004). As expected, the metrics for these two groups did not differ in the arcuate fasciculus, a tract typically unaffected in Alzheimer’s disease.

Gloria Chiang, Xiangling Mao, Guoxin Kang, Eileen Chang, Sneha Pandya, Shankar Vallabhajosula, Richard Isaacson, Lisa Ravdin, Dikoma Shungu

Oxidative stress has been implicated as an important pathological mechanism in the development of Alzheimer’s disease (AD). The purpose of this study was to assess whether J-edited ¹H MRS levels of glutathione (GSH) –  the primary antioxidant in living tissue – are associated with brain amyloidosis, as assessed with PET, and memory in a community-dwelling cohort of nondemented older adults. The results showed an inverse association relating GSH, a sensitive marker of oxidative stress, and amyloidosis, one of the pathological hallmarks of AD, and a weaker association with memory, thereby collectively further implicating oxidative stress in AD pathophysiology.

 

Eo-Jin Hwang, Hyun Seok Choi , Jinhee Jang, Seung Eun Jung, So-Lyung Jung, Kook-Jin Ahn, Bum-soo Kim, Joong-Seok Kim

The purpose of this study was to differentiate Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) by evaluating deep gray matter regions of the three subject groups. The 3D T1 weighted images and quantitative susceptibility maps (QSM) were segmented into 15 deep gray matter structures to estimate volumes and mean susceptibility values, and differences among the three groups were evaluated using a one-way analysis of covariance (ANCOVA) with age and gender as covariates. A multivariate logistic regression and receiver operating characteristic curve analyses were performed to determine associated imaging features and diagnostic performance.

Geon-Ho Jahng, Sang-Tae Kim, Peter Verwilst, Hyug-Gi Kim, Jee-Hyun Cho, Kwan Soo Hong, Ki Woong Kim, Jong Seung Kim, Wook Jin, Eui Jong Kim, Dal Mo Yang

A new T1 molecular MRI contrast agent specifically designed to be specific for oligomeric Aβ was developed by combining the commercially available gadolinium (Gd)-Dota with an oligomeric Aβ-specific DNA aptamer. We confirmed the protein size with Aβ polymerization in aspect of molecular masses when polymers were formed. We performed the following experiment in the cell level and AD-model mice. We identified a particular region with a significantly distinct T1 MRI signal, allowing for distinguishing Alzheimer's disease model mice from non-Tg mice.

Xiaowei Zhuang (co-first), Ryan R Walsh (co-first), Zhengshi Yang, Virendra Mishra, Karthik Sreenivasan, Dietmar Cordes

In this study, we explored the dynamics of Parkinson’s disease (PD) brain network function utilizing the co-activation pattern (CAP) analysis emphasizing sensorimotor network (SM) function during resting-state. We modified the routine to calculate group dominant CAPs (d-CAPs) and proposed a novel way to obtain within-subject CAP switching-rate. Reduced dynamics of the SM network in PD was demonstrated by both decreased number of d-CAPs and decreased switching-rate, which corroborates electrophysiologic data.

Paula Trujillo, Paul Summers, Alex Smith, Seth Smith, Antonella Costa, Daniel Claassen

Parkinson’s disease (PD) is characterized by the loss of pigmented dopaminergic neurons in the substantia nigra pars compacta (SNc). The aim of the study was to evaluate the feasibility of rapid magnetization pool size ratio (PSR) mapping as a subset of the magnetization transfer (MT) properties of the SNc in healthy subjects and patients with PD. These results demonstrated the feasibility of performing quantitative PSR mapping in human SN within reasonable scan times, and that PSR is likely the quantitative MT parameter most relevant for PD.

Dinesh Selvarajah, Joseph Harding, Shillo Pallai, Solomon tesfaye, Iain Wilkinson

This study for the first time has shown alterations in white matter MD in patients with DSPN. Increased MD in the primary somatosensory cortex in patients with diabetic neuropathy (DN) is suggestive of white matter microarchitecture degeneration, and supports the evidence of neuronal loss in the somatosensory cortex in patients with . Furthermore, these results also support the previous evidence of thalamic neuronal dysfunction in DN on MR spectroscopy. Changes in the degree of white matter structure might provide a pathophysiological underpinning of spinal cord atrophy and brain volume reduction in DN. 

Jie Gao, Min Tang, Xin Zhang, Xiaoling Zhang, Kaining Shi, Xiaohong Wu

This study aims to use a two-compartment diffusion model of white matter based on diffusional kurtosis imaging (DKI) to explore early white matter alternations in middle-aged type 2 diabetes mellitus (T2DM) . 33 T2DM patients and 13 healthy control were enrolled. All diffusion parameters (FA=fractional anisotropy, MD=mean diffusivity, AD=axial diffusivity, RD=radial diffusivity, MK=mean kurtosis, AK=axial kurtosis, RK=radial kurtosis, D_a=intra-axonal diffusivity, D_e?=axial extra-axonal space diffusivity, D_e⊥= radial extra-axonal space diffusivity) were compared. D_e⊥ was demonstrated to be the most sensitive in detecting the diffusion changes. These increased D_e⊥ (extra-axonal diffusivity) and unchanged D_a (intra-axonal diffusivity) reflected the increased water and/or demyelination.

Rifeng Jiang, Wenzhen Zhu, Qing Duan, Yunjing Xue, Yihao Yao, Jingjing Shi, Linying Guo

This study uses NODDI, a novel tool, to quantify changes of white matter (WM) skeleton in patients with ALS. By TBSS analysis, significant FA reductions were demonstrated within the (pre)frontal WM, partial parietal WM, corpus callosum and partial corticospinal tract. Similarly, significant Ficvf reductions were found within almost all the WM skeleton, which was more extensive than that of FA. In contrast, ODI showed no significant changes in all the WM skeleton. Therefore, NODDI is a more potential tool to demonstrating the neurite density reductions for ALS patients, which will help lead to earlier diagnosis and treatment for ALS.

Xiaojun Guan, Peiyu Huang, Qiaoling Zeng, Chunlei Liu, Min Xuan, Quanquan Gu, Xiaojun Xu, Nian Wang, Nian Wang, Xinfeng Yu, Xiao Luo, Jingjing Xu, Wei Luo, Yong Zhang, Minming Zhang

Myelinated white matter showing diamagnetic susceptibility is important for information transfer in the brain. In Parkinson’s disease, the white matter is damaged secondary to nigral degeneration. Quantitative susceptibility mapping is a novel technique for noninvasive assessment of regional white matter ultrastructure, and provides different information to standard diffusion tensor imaging.

Tsung-Yuan Li, Vincent Chin-Hung Chen, Shu-Ling Huang, Dah-Cherng Yeh, Jyh-Wen Chai, Clayton Chi-Chang Chen, Jun-Cheng Weng

Neuroimaging studies suggest that white matter and cognitive function changes were affected by breast cancer and its treatments. Our study interested in the early effect of the brain by chemotherapy. This study included 19 breast cancer survivors who had completed their chemotherapy and 20 healthy control group. Generalized q-sampling imaging (GQI) with voxel-based analysis was performed to show the brain structural differences between two groups. Multiple regression was also used to detect the correlation between Mini-Mental State Examination (MMSE) and the indices of GQI. Our results provided further evidence that breast cancer and adjuvant chemotherapy are associated with adverse effects on white matter.

Apurva Shah, Shivali Wagle, Jitendra Saini, Pramod Pal, Madhura Ingalhalikar

This study aims at assessing the large scale structural network changes in Parkinson’s disease. The structural connectome is computed using probabilistic fiber tracking on diffusion MRI between 95 regions of interest. Graph theoretic analysis on the connectome is carried out at several levels of granularity: global, local (nodal) and lobar. We find that patients with PD demonstrate lower network clustering capability and lower neural connectivity as well as significantly reduced nodal influence of the hippocampus. Additionally, widespread patterns of reduced connectivity are observed in the temporal and occipital areas. These deficits could potentially mark the non-motor symptoms indicated in PD.

lin lin, Guangyao wu

To our knowledge, this is the first whole-brain VBM meta-analysis showing a reduced volume of whole and regional gray matter (GM) in the brains of type 2 diabetes mellitus (T2DM) patients. we used a new meta-analytic tool, signed differential mapping to identify consistent results about global and regional abnormalities in T2DM, and explore the relationship between cognitive and GM alternations. We showed educed volume of whole and regional GM in T2DM patients, particularly in the temporal lobe, the GM volumes of the right insula were positively correlated with MMSE scores, and those changes may indicate a risk of dementia.

Chao-Yu Shen, Shu-Li Wang, Jeng-Dau Tasi, Ju-Chien Wu, Jun-Cheng Weng

The current study was to explore the relationship between prenatal exposure to PFASs, determined in maternal blood collected during the third trimester of pregnancy and the children’s brain volume difference at the age of 13-15 years old. The results showed a signi?cant negative correlation between the maternal blood PFASs concentrations and the children's brain MRI in multiple different brain areas, including both gray matter and white matter.

Chae Won Shin, Sun-Won Park, Jee-Young Lee, Jongho Lee, Seon Lee, Jae Myung Kim, Jung Hyo Lhim

This study is to evaluate the impact of quantitative susceptibility mapping (QSM) on regional distribution of iron deposition and its correlations with non-motor symptoms in patients with early Parkinson disease (PD). The QSM values of deep nuclei and clinical data using validated scales were obtained from patients. There were no differences in regional QSM values between patients and controls, and the QSM values were not correlated with any of motor or non-motor symptoms in PD patients. This study suggests that the QSM may not be a sensitive tool enough to use in patients with early PD.

Jessica Livingston-Thomas, Greg Cron, Therese Gagnon, Anthony Carter, Matthew Jeffers, Dale Corbett

Vascular cognitive impairment (VCI) arises from chronic cerebral hypoperfusion and is characterized by executive dysfunction, memory problems, and motor impairments.  In countries where people eat highly processed, energy-dense food, there are high rates of VCI.  Poor diet is also linked to metabolic syndrome, which is also associated with cognitive dysfunction.  Metabolic syndrome and VCI commonly coexist within cardiovascular patients.  Due to the translational failure of many promising preclinical treatments for cardiovascular disease, researchers are trying to incorporate human comorbidities within animal disease models.  Here, we develop a rat model which combines cerebral hypoperfusion with an unhealthy diet.

Virendra Mishra, Karthik Sreenivasan, Christopher Bird, Dietmar Cordes, Ryan Walsh

In vivo imaging that reliably captures the impact of the spreading pathology of Parkinson’s disease (PD), including its impact on both white and gray matter, remains elusive. In this study, we applied graph-theoretical techniques to multi-site diffusion-MRI data from a cohort of early PD-subjects in Parkinson’s Progressive Markers Initiative (PPMI) database. A distinctive structural backbone-network was revealed in early PD-subjects without any a-priori assumptions involving cortical and subcortical regions that are known to be involved in various stages of PD, including early PD (Olfactory-cortex, globus-pallidum, and striatum). Our study opens new avenues to understanding progression of PD from a graph-theoretical approach.

Xueling Suo, Du Lei, Nannan Li, Lan Cheng, Lei Li, Fuqin Chen, Meiyun Wang, Rong Peng, Qiyong Gong

To use diffusion tensor imaging (DTI) and graph theory approaches to explore the brain structural connectome in patients with early-stage drug-naive Parkinson's disease (PD). The structural connectome was constructed by using deterministic tractography and thresholding the mean fractional anisotropy of 90 brain regions to yield 90*90 partial correlation matrixes. The decreased characteristic path length L_p and increased global efficiency E_glob in the PD patients relative to healthy controls indicated that structural networks are closer to randomization, providing a structural basis for functional alterations of PD.

Matteo Paoletti, Eduardo Caverzasi, Maria Luisa Mandelli, Jesse Brown, William Seeley, Roland Henry, Howard Rosen, Bruce Miller, Maria Gorno-Tempini, Stefano Bastianello, Michael Geschwind

Diffusion restriction on MRI is an important diagnostic finding in sporadic Jakob-Creutzfeld disease. We performed group-wise quantitative cortical and subcortical grey matter mean diffusivity analysis at 3.0 T and tested feasibility of single-subject diffusivity restriction maps, that, compared to group-wise analysis, can better describe variable patterns of involvement in sJCD. DMN-related regions demonstrated prominent diffusion restriction; thus DMN functional connectivity was evaluated. DMN showed a increased connectivity in sJCD, that based on cross-sectional analysis seems to decrease along with clinical worsening. Resting-state fMRI may be a promising candidate to evaluate involvement in sJCD especially during the preclinical phase.

Guangyu Chen, Andrew Nencka, Hao Shu, Shekar Kurpad, Shi-Jiang Li, Peter Pahapill

Chronic pain is an important and growing problem in aging populations. A key challenge to treating chronic pain is the absence of effective, objective methods of assessment. This study,  from a homogeneous group of chronic pain patients with failed back surgery syndrome, demonstrated that the functional interaction strength between the limbic striatum and neocortex were very tightly correlated with the patients’ pain scores. We believe this index may form the basis for an objective, non-invasive biomarker for chronic lower back pain, and may be generalizable to other types of chronic pain.

Maria Luisa Mandelli, Christa Watson, Eduard Vilaplana, Jesse Brown, Zachary Miller, Isabel Honey, Ariane Welch, Miguel Santos-Santos, Howard Rosen, Bruce Miller, William Seeley, Maria Luisa Gorno-Tempini

Graph theory analysis is a method recently introduced to study the brain as a network. In this study we investigate the topological distribution of the speech and language functional network in nfvPPA patients characterized by isolated and progressive language impairments. We identified the hubs of the speech and language network in healthy controls and nfvPPA. In patients, the network  presented an abnormal topological distribution where right-sided brain regions were recruited. These findings suggest that in nfvPPA this network reorganizes in the presence of localized gray matter volume loss.

Chun-Qiang Lu, Yun Jiao, Shenghong Ju

Altered brain structure in cirrhotic patients have been seen in previously reported studies. Many studies focus on the grey matter change of the caudate putamen, while few study investigate the relationship of thalamus grey matter change and cirrhotic symptoms. Our study reveal that the grey matter density of thalamus is closely correlated with the clinical makers of the cirrhosis, which may help to clarify the mechanism of the thalamus structural change.

Quan Jiang, Li Zhang, Guangliang Ding, Esmaeil Davoodi-Bojd, Qingjiang Li, Lian Li, David Hearshen, Michael Chopp, Zhenggang Zhang

The recently discovered glymphatic system has fundamentally altered the traditional model of cerebrospinal fluid (CSF) hydrodynamics and shown promising results in applications for understanding neurological diseases1, 2. However, little is known how diabetes affects the glymphatic system. The current study is the first investigation of the effect of diabetes on the glymphatic system and the relationship between glymphatic system and cognitive impairment in diabetic rats using MRI and fluorescence imaging.

Dibashree Tamuli, Tavpritesh Sethi, Anup Singh, S. Senthil Kumaran, Ashok Jaryal, Achal Srivastava, Kishore Deepak

Brain volumetric analysis of SCA 1, 2 and 3 shows differential measurements with reference to cortical thinning and volumes of brain stem and cerebellum. Therefore, to find a solution to classify SCA1, 2 and 3, we have applied machine learning approach for feature selection followed by random forest modeling using volumetric features of the brain.

Mohammed Goryawala, Elizabeth Willen, Anai Cuadra, Varan Govind

Milder forms of HIV-associated neurocognitive disorders (HAND) are frequently observed in approximately half of the HIV-infected individuals, even with treatment for HIV infection. Cognitive deficits observed in them can be associated with injury to the frontal and temporal lobes of their brains. The goal of this study was to assess the impact of HIV infection on vulnerable structural connections in these lobar regions in adults perinatally-infected with HIV. Our results indicate that altered connectivity in frontal lobe regions with differentiated modularity and significant alterations in hub patterns at the temporo-parietal junction occurred in the HIV group. 

Hansol Lee, Minkyeong Kim, HyungJoon Cho, Se Young Chun, Gi Yeong Huh, Eun-Joo Kim, Jae-Hyeok Lee

 To investigate the origin of susceptibility-weighted imaging (SWI) contrast in frontal white matters of adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP), we performed a combined post-mortem magnetic resonance imaging (MRI) and histological study of ALSP pathology. The myelin architectural changes, marked central myelin loss with preserved U-fibers beneath cortical gray matter, mainly contributed to the susceptibility contrast.

Naying He, Shiyang Chen, Jason Langley, Yong Zhang, Fuhua Yan, Xiaoping Hu

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by nigral-striatal dopamine deficiency and motor symptoms. Neuroimaging studies have shown that functional connectivity within cortical-striatal networks and related connections are disturbed in PD. But these are based on conventional static resting-state analyses which assume functional connectivity being static over time. Recent studies have demonstrated that resting state brain activity is highly dynamic. In this work, we applied Gaussian Hidden Markov Model to investigate dynamic functional connectivity in PD and compared it with that in normal controls. Our results show alterations in sensorimotor, DMN, and visual networks in PD.

Xiang-An Zhao, Lin Sung-Han, Tsai Chih-Chien, Wu Yi-Ming, Lin Wey-Yil, Weng Yi-Hsin, Lu Chin-Song, Wang Jiun-Jie

Progressive Supranuclear Palsy (PSP) is an atypical Parkinsonism, which shared similar symptoms with Parkinson’s disease (PD) and PSP progressed typically much faster than PD and the prognosis is often poor. The linear regression analysis demonstrated the capability of diffusion MRI indices as measured from multiple brain regions in the prediction of two-year clinical severity. Strong predictive power can be observed in mHY, motor subscale of UPDRS and PIGD. The two-year clinical decay in patients with PSP can be accurately predicted by using diffusion tensor derived parameters as measured from distinct brain regions.

Lin-Feng Yan, Xin Zhang, Yu Han, Yu-Chuan Hu, Hai-Yan Nan, Ying-Zhi Sun, Zhi-Cheng Liu, Yang Yang, Wen Wang, Guang-Bin Cui

To find the early biomarkers for predicting the histological grading and prognosis of glioma, the study compared the discriminating efficiency of multiple metrics from DCE, Multi-b DWI and 3D-ASL with a histogram analysis approach, and further evaluated the combined accuracy and the survival association. The accuracy of assessing glioma grading and survival would not significantly improved by a univariate parameter, but highly promoted by combining the multiple parameters of histogram analysis from various MRI modality. We will further utilize the machine learning to evaluate the classifying accuracy.

Urspeter Knecht, Nicole Porz, Beate Sick, Elvis Murina, Nuno Miguel Pedrosa de Barros, Philippe Schucht, Evelyn Herrmann, Jan Gralla, Roland Wiest, Marwan El-Koussy, Johannes Slotboom

The diagnosis of brain tumors using visual criteria is very challenging. A novel computational method for computer aided radiologic diagnostics (CARD) is described based on quantitative textural features from ADC-maps, and a machine learning algorithm (Random-Forest classification). The reproducibility of the method was examined with 3 human raters was performed, and the Fleiss'-Kappa-test revealed high inter-rater agreement of κ=0.821 (p-value<<0.001) and an intra-rater agreement of κ =0.822 (p-value<<0.001). The method significantly improves the differential diagnosis of medulloblastoma versus pilocytic-astrocytomas.

Ka-Loh Li, Natale Quartuccio, Xiaoping Zhu, Samantha Mills, Alan Jackson

Histogram Analysis of v_e was used for quantification of heterogeneity in glioblastomas and to study whether heterogeneity is related to survival. 27 patients with GBM were imaged. v_ehistograms were processed by using a 4-mixture Gaussian distribution. Patients with short survival show an increasing proportion of the third Gaussian distribution.  The mean of the 2nd Gaussian component, μ2,  (p = 0.00015) and the weight of the 3rd components, w3 (p = 0.0066) were the most predictive for survival.  The identification of tissue components, characterized by Gaussian fitting of v_e values suggests that these represent, in some way, separate tissue subpopulations.

Yiping Lu, Bo Yin, Shihai Luan, Li Liu, Ji Xiong, Jianbo Wen, Jianxun Qu, Daoying Geng

In this research, territorial Arterial Spin Labelling (t-ASL) and unenhanced 3D-TOF-MRA were used to evaluate the usage in identification of the feeding vasculature of meningiomas in 20 consecutive patients. Results showed that the inter-observer agreement was excellent for the identification of the origin of the feeding arteries by t-ASL, which was better than the inter-observer agreement of 3D-TOF-MRA. The inter-modality agreement between t-ASL and 3D-TOF-MRA for the feeding arteries was moderate. The information about feeding arteries was potentially related to patients’ symptoms and pathology, making it crucial for neurosurgeons in planning surgery and evaluating prognosis.

Yuelei Lyu, Bo Hou , Shuai Liu , Hui You, Yu Wang, Wenbin Ma , Feng Feng

This study investigates the role of 3D-pcASL in discriminating between glioma progression(TP)and treatment related changes(TRC). We found that the maximum CBF (absolute value and its normalized values) in the lesion from 3D-pcASL were significantly higher in the TP group than in the TRC group. The ROC curve analysis showed the maximum CBF has an excellent performance in differentiating TP from TRC in patients with newly diagnosed glioma who have undertaken radiotherapy or chemoradiotherapy.

Ashley Stokes, Jack Skinner, Laura Bell, Adrienne Dula, Thomas Yankeelov, C. Quarles

The purpose of this study is to establish thresholds for parametric response mapping (PRM) using apparent diffusion coefficients (ADC) and intra-voxel incoherent motion (IVIM) parameters in healthy controls and to apply these thresholds in a cohort of brain tumor patients to study regional treatment-induced changes in diffusion and perfusion. We obtained thresholds (95% confidence intervals) of 0.38 and 0.32 x10^-3 mm²/s for ADC and IVIM-D, respectively. For the perfusion-related distributions, the thresholds were 10 ml/100g (IVIM-f_p) and 54 ml/100g/min (IVIM-f_pD*). This multi-parametric sensitivity to local tumor changes could be useful to simultaneously evaluate treatment-induced changes in perfusion and cellularity.

Andrew Beers, Yi-Fen Yen, Kyrre Emblem, Elizabeth Gerstner, Bruce Rosen, Jayashree Kalpathy-Cramer

We evaluate the reproducibility of ktrans values derived from dynamic contrast MRI images in patients with newly diagnosed glioblastoma. Particular focus is put on the reproducibility across choices of T1 values and arterial input functions (AIFs) to the Tofts-Kermode model. Reproducibility is assessed across multiple pre-therapy baseline visits in a 45 patient cohort. Our model based on static population AIFs and static global T1 values had excellent reproducibility compared to other models including unique individual AIFs and T1 maps. There is relatively little concordance between all tested models, but individual AIFs led to higher mean ktrans values.

Laura Bell, Leland Hu, Ashley Stokes, Samuel McGee, Leslie Baxter, C. Quarles

With DSC-MRI, contrast agent leakage effects in high-grade gliomas must be resolved for accurate CBV measurements. Our aim is to compare CBV values across 1) varying preload doses, 2) two different previously published leakage correction methods, 3) normalized to either the AIF or normal appearing white matter (NAWM), and 4) different CBV integration limits. This was accomplished by acquiring six consecutive DSC-MRI with varying preloads in 14 glioma patients. We found that leakage corrected CBV measurements exhibit high consistency across variable preload doses, particularly when data is integrated under the “First Pass Only” and normalized to the AIF.

Qian Xu, Kai Xu, Qi Liu, Hong Ma, Jiangfen Wu, Jianxun Qu

Differentiation of treatment-related radiation necrosis from recurrent neoplasm is often difficult and dynamic susceptibility contrast perfusion MR imaging (DSC-MRI) is reported to be a surrogate marker for distinguishing them. However, DSC technique is invasive and has its disadvantage. Three dimensional pseudo-continuous ASL (3D-pcASL) can provide noninvasive absolute cerebral blood ?ow (CBF) measurement with insensitivity to permeability, and it is especially necessary for the evaluation of the postoperative gliomas patients where the blood-brain barrier (BBB) is completely broken with much more leakage effects. This study aimed to differentiate true progression from radiation necrosis of gliomas by using 3D-pcASL and DSC-MRI.

Lei Qin, Xiang Li, Jinrong Qu, Katherine Leung, Angie Li, Geoffrey Young

Gaussian normalization generates more consistent nCBV maps than the gold standard, manual NAWM normalization. The ease of implementation and automated aspect of Gaussian normalization makes it an appealing method that could be successfully implemented in the clinical setting.

Jing Zhao, Jian-ping Chu, Jing-yan Wang, Xu Yan

Neurite orientation dispersion and density imaging (NODDI) was an advanced DWI. Our study is to quantitatively evaluate the diagnostic efficiency of NODDI in grading gliomas. 29 patients were recruited and they underwent whole-brain DWI which were collected at three b value (0, 1000 and 2000 s/mm2) and 1000 and 2000 s/mm2 with 30 directions. Compared with LGG, ficvf and ODI are significantly higher in HGG and the mean value of ficvf showed the highest diagnostic value. Quantitative parameters from NODDI can aid in gliomas grading and the mean value of ficvf showed the highest diagnostic power.

Rifeng Jiang, Wenzhen Zhu, Lingyun Zhao, Qing Duan, Yunjing Xue, Jingjing Jiang

DKI is a promising tool to predict the survival of glioma patients. MK, MD and ADC were significantly correlated with overall survival (OS) of patients with astrocytic tumor. By univariate Kaplan-Meier survival analyses, OS of the patients was related to tumor grade, Ki-67 LI, resection status, enhancement degree, edge, edema degree, lesion number, MK, MD and ADC (log rank p < 0.05 for all).  Multivariate Cox regression analysis indicated that MK is an independent predictor of OS in these patients, and it is a risk factor (P = 0.006, HR=2.142 and 95%CI=1.247-3.679 for MK increasing every 0.1). These results are helpful to clinic.

Yuankui Wu, Shukun Liao, Danni Wang, Lichao Ma, Jun Hua, Yingjie Mei, Jun Wang, Jun Zhou, Yikai Xu

The purpose of this study is to investigate the feasibility of grading primary brain gliomas with inflow-based vascular-space-occupancy (iVASO) MRI. The iVASO MRI perfusion approach enables the quantitative analysis of physiological information of tumor without using exogenous contrast agent. The measured arteriolar cerebral blood volume (CBVa) showed a significant association with tumor grades as well as the capability to predict tumors grades. When exogenous contrast agent administration is difficult or contraindicated in certain patient populations, iVASO MRI may used as an option for the clinical management of brain tumors.

Louis-Olivier Bouchard, Christian Berthelot, Maxime Villeneuve

Diffusion MRI can be helpful in pre-operative brain tumor evaluation to assess white matter tracts involved. It is however a time-consuming sequence, a problem that Simultaneous Multi-slice Imaging was designed to solve, although it has to demonstrate its quality non-inferiority. We compared in five patients tractographic data (using HARDI), acquired with and without SMS techniques, to evaluate the quality of imaging data as measured by the number of fibers between two regions of interest. We found that SMS-factor 2, cut time down by 37%, which is clinically relevant. We also found that SMS-2 is indeed non-inferior (alpha=0,03125) and can be used without quality compromise. 

Haopeng Pang, Ningning Di, Chengjun Yao, Yan Ren, Jingsong Wu , Yong Zhang, Jianxun Qu , Zhenwei Yao

This study was designed to determine if CBF derived from ASL perfusion imaging could be used to quantitatively evaluate the MVD of brain gliomas on a “point-to-point” basis. The study enrolled 47 patients with treatment-naive brain gliomas who underwent preoperative ASL before stereotactic surgery. We histologically quantified MVD from CD34-stained sections of stereotactic biopsies and co-registered biopsy locations with localized CBF measurements. CBF showed a statistically significant positive correlation with MVD. ASL can be a quantitative and noninvasive perfusion MR method for evaluating the MVD of brain gliomas, and may reflect the microvascularity of gliomas.

Jalal Andre, S Kristie McKown, Swati Rane

Assessment of cerebral and tumor perfusion has frequently been advocated for initial prognostication, and evaluation for possible progression, of primary brain tumors, historically accomplished via intravenous injection of a gadolinium-based contrast agent (GBCA).  The potential for intracranial and corporeal deposition of GBCA invites the development and optimization of non-invasive, contrast-exempt (NICE) methods to assess cerebral perfusion.  We sought to develop and implement NICE spin-label-based methods incorporating cerebral blood flow (CBF) and volume (CBV) assessment, applied in treated GBM patients.

Thomas Lindner, Isabel Lübbing, Christian von der Brelie, Michael Helle, Olav Jansen, Michael Synowitz, Stephan Ulmer

Performing MRI studies in an intraoperative setting is generally limited due to hardware and patient positioning restrictions. Structural imaging alone might not be sufficient to gather all required information. The goal of this study was to implement pseudo-continuous ASL in the intraoperative neurosurgical setting with limited hardware available and compare the images with measurements obtained pre-, and postoperatively on different clinical MRI scanners. The first application in a patient shows the potential of intraoperative ASL imaging with regards to visualizing residual tumor mass already during the surgical intervention in similar image quality.

Kiyohisa Kamimura, Masanori Nakajo, Yoshihiko Fukukura, Shingo Fujio, Takashi Iwanaga, Tomoyuki Okuaki , Takashi Yoshiura

Our purpose was to evaluate the intravoxel incoherent motion (IVIM) in the pituitary adenoma using turbo spin-echo diffusion-weighted imaging (TSE-DWI). The f (perfusion fraction) in the pituitary adenoma was significantly lower than that in the normal pituitary gland, which is consistent with histopathologically known lower microvascular density in adenomas compared to normal pituitary tissue. There was no significant correlation between the f and the volume in pituitary adenomas. TSE-DWI-based IVIM imaging is a viable imaging technique for assessment of vascularity in skull base lesions including pituitary adenoma.

Kazuhiro Murayama, Takashi Fukuba, Shigeharu Ohyu, Ayako Ninomiya, Kazuhiro Katada, Hiroshi Toyama

Additional benefits of quantitative analysis of peritumoral edema for distinguishing between brain tumors by diffusion weighted image or dynamic susceptibility contrast MRI has been described. Our aim was to investigate the hypothesis that quantitative analysis of intravoxel incoherent motion (IVIM) in peritumoral edema may be a useful parameter for distinguishing between central nervous system lymphoma (CNSL) and other brain tumors. Quantitative analysis of IVIM indicates that D* and f maps of CNSL visually showed increase values in peritumoral edema. Our results indicate that these IVIM parameters have been successfully applied to obtain quantitative estimates of the vascularity and perfusion in peritumoral edema for differenciating CNSL and others without gadolinium contrast agent.

AI-LING HSU, Ping-Ni Wang, Jyh-Horng Chen, Ho-Ling Liu

Cerebrovascular reactivity (CVR) with hypercapnia challenges, such as a breath-hold (BH) task, has been proposed to indicate areas with neurovascular uncoupling potentials for presurgical fMRI. Previous studies have shown that BH response correlated with resting-state fluctuation of amplitude (RSFA) in healthy adults. This study explores the use of RSFA for indicating sites with neurovascular uncoupling potentials in presurgical fMRI of patients with gliomas. The RSFA with ICA-based denoising approaches was found to perform superior to the traditional approaches. Unlike BH, RS-fMRI is less dependent on patient performance thus can be widely applied in clinical practice. 

Chen Niu, Xiao Ling, Pan Lin, Kun Zhang, Xin Liu, Liping Guo, Wenfei Li, Hao Song, Ming Zhang, Maode Wang

The aim of this study is to investigate whether there is consistency between active and passive movement in patients with brain tumors. Two motor tasks (active and passive hand movement) were applied to brain tumor patients. Our results demonstrate that there is no statistical difference of activation intensity between active hand movement and passive hand movement in patients with brain tumors. Our results suggest that passive movement fMRI provides a potential method for presurgical mapping in cases where patients are unable to comply with task instructions.

Bradford Moffat, Sarah Kalus, Christopher Steward, Chris Kokkinos, Patricia Desmond, Pramit Phal

We present a quantitative resting state fMRI method for determining the laterality of language processing in patients undergoing neurosurgical procedures. The results show that laterality indices based on the resting state fMRI can predict a patient’s laterality based on a language task fMRI. This has potential for guiding neurosurgical interventions in patients unable to perform task fMRI exams or during surgery with an interventional MRI scanner.

Junyu Guo, John Glass, JungWon Hyun, Yimei Li, Heather Conklin, Lisa Jacola, Ching-Hon Pui, Sima Jeha, Wilbrun Reddick

Acute lymphoblastic leukemia survivors may have significant deficits in processing speed and working memory even when treated with only chemotherapy. We investigate the relationship of diffusion tensor imaging metrics in an a priori brain structural network with neurocognitive functions such as processing speed and working memory. We found that fractional anisotropy values in the structural network were significantly positively associated with processing speed performance in two MR exams two years apart, and axial diffusivity values were negatively associated with working memory in the MR exam at the end of therapy.  These findings may provide potential evidence for a structural neurocognitive network.

Naeim Bahrami, Tyler Seibert , Roshan Karunamuni, Jona Hattangadi-Gluth, Nikdokht Farid, Anders Dale, Carrie McDonald

The purpose of this study is to determine whether brain structural network properties change in brain tumor patients following fractionated, partial brain radiotherapy(RT). We applied graph theory to MRI-derived cortical thickness estimates in 54 patients pre and post-RT and examine global and local changes in network topology. Increases in global efficiency, transitivity, and modularity were observed post-RT compared to pre-RT. Decreases in local efficiency and clustering coefficient were seen in regions receiving higher doses of RT. Our findings demonstrate alterations in global and local network topology following RT in patients with primary brain tumors.

Masaaki Hori, Kouhei Kamiya, Yuichi Suzuki, Ryuji Nojiri, Yasuaki Turushima, Ryo Ueda, Issei Fukunaga, Misaki Nakazawa, Akifumi Hagiwara, Christina Andica, Koji Kamagata, Keiichi Ishigame, Kanako Kumamaru, Shigeki Aoki

The purpose of this exhibit is to present the pitfalls of generating MR fiber g-ratio mapping in neurological disease patients, and to propose possible solutions. While the g-ratio maps can help to make comprehensive diagnosis together with clinical information (i.e. symptoms), probable differential diagnosis and conventional MR imaging findings can help to avoid the misuse of MR fiber g-ratio maps in the clinical setting.

Olivier Clerk-Lamalice, John Chen

This work will review key concepts of our current understanding of stroke pathophysiology, imaging protocol with an interest on specific MRI sequences. This review will also introduce important concepts regarding stroke-related neuroinflammation.

Michael Chappell, Iris Asllani, Xavier Golay, Matthias Günther, Juan Hernández-Tamames, Matthias van Osch

Partial Volume Effects have a profound influence on the perfusion images generated using Arterial Spin Labelling. We are only starting to appreciate how this influences our interpretation of the images and what we can discover when using perfusion imaging in studies. This e-poster seeks to outline the key issues, underlying theory about what effects PVE might have, methods to correct for them, and when correction may or may not be a good idea.

Julie Harreld, Muhammad Ayaz, Claudia Hillenbrand, Ralf Loeffler, Scott Hwang, Junyu Guo, Zoltan Patay

MRI has assumed a central role in the detection of leptomeningeal metastasis for risk stratification of pediatric CNS tumors, but not all sequences are created equal for detection of tumor in CSF.  In this presentation, we describe the strengths, weaknesses and tradeoffs of sequences commonly used for this purpose, and suggest guidelines for a targeted imaging protocol with increased sensitivity for leptomeningeal tumor, in less scan time. 

Maria Arango-White, Diego Herrera, Sergio Vargas

Cortical development malformations are relatively uncommon conditions but have an enormous impact in children with neuro-developmental delay, disability and epilepsy. We aim to present cases from our clinical practice to illustrate the pathology spectrum and review the existing literature about these malformations. We emphasize the importance of an MRI approach to elaborate a differential diagnosis which can be useful to focus genetic tests, and to establish prognosis in these patients.

Cory Pfeifer, Amber Pokorney, Patricia Cornejo

The Image Gently campaign has resulted in increased awareness of radiation risks in the pediatric population. A major effect of this is a reduction in computed tomography in pediatric hospitals. While MRI may be able to achieve many of the goals of CT, risks related to sedation and the need for increased resources to perform sedated MRI must also be considered for children with conditions known to require follow-up imaging. In cases where children have external ventricular shunts in place over a long term, rapid sequence MRI has been well-described in its role to assess ventricular size while avoiding both ionizing radiation and sedation. Here we describe the use of our version of the rapid sequence MRI to assess additional indications, as more than half of the patients undergoing this study in our facility do not have indwelling ventricular shunt catheters at the time of imaging. Limitations of this technique are also discussed.

Cornelia Laule, Irene Vavasour, Shannon Kolind, Thorarin Bjarnason, Jing Zhang, Donna Lang, Hanwen Liu, Emil Ljungberg, Roger Tam, Erin MacMillan, John Kramer, Sandra Sirrs, Piotr Kozlowski, Alexander Rauscher, Lara Boyd, G.R. Wayne Moore, Anthony Traboulsee, David Li, Alexander MacKay

Myelin water imaging (MWI) provides quantitative and specific mapping of myelin content in-vivo. Water trapped between myelin bilayers have a short T₂ relaxation time; the fractional proportion of this myelin water signal correlates strongly with histological staining for myelin. MWI has successfully been used to study both the brain and spinal cord where it can increase our understanding of development, aging and disease processes, and may also improve accuracy of diagnosis, prognosis and assessment of therapeutic response. Moving forward, MWI is expected to play an important role in the development and monitoring of new treatments targeted at remyelination and neuroprotection.

Marina Salluzzi, Nicole Blenkin, Richard Frayne

As institutions, agencies and governing bodies move toward increased value for invested research funds, core laboratory facilities have been found to be an effective solution to researcher needs. The Calgary Image Processing and Analysis Centre was envisioned as a core lab to support the local research community, and today it provides an evolving suite of services to facilitate the translation efforts in medical imaging research. CIPAC's evolution has been possible due to the synergy with local researchers striving for a quality solution to research image data management needs.

Shunrou Fujiwara, Takaaki Beppu, Kuniaki Ogasawara, Yoshichika Yoshioka

Brain temperature (BT) had traditionally been discussed whether it may be a simple parameter depending on body (core) temperature or it may regulate the neural activities; however, recent reports with magnetic resonance imaging (MRI) system demonstrated BT was strongly associated with the cerebral perfusion and metabolism in patients with ischemic change. Here, we reviewed BT measurement techniques with a MRI system and discussed the pathologic conditions causing BT alteration relating to the cerebral perfusion and metabolism.

Christina Andica, Akifumi Hagiwara, Misaki Nakazawa, Masaaki Hori, Shigeki Aoki

Synthetic MRI is a method of imaging based on the quantification of T1, T2, PD and B1 field by a single scan. The features of synthetic MRI such as; quantitative maps, tailored contrast-weighted imaging, brain tissue and myelin segmentation and volumetry show some advantages in the evaluation of brain disorders. However, some limitations were also noted.

Daiji Uchiyama, Katsumi Nakamura, Takehisa Tsuji

We herein report the 4 cases of brain abscess secondary to odontogenic infection due to an untreated tooth decay.  In all cases, there were no abnormalities on physical and intraoral examinations, nor overt trismus or facial swelling. Dental CT showed a periapical radiolucency around the root tips of a decayed tooth, which revealed periodontal abscess. After the multidisciplinary therapy including antibiotics, abscess drainage, and dental treatments, all the patients recovered and discharged.

Manu Singh, Bernard Chow, Kai Kinder

This educational exhibit provides an up-to-date, practical approach for MRI evaluation of the brachial plexus.

Dewen Yang

Age-related white matter changes (ARWMC) are prevalent brain imaging findings and important substrates for cognitive impairment in the elderly. The true pathogenesis of ARWMC is not well understood. Previous studies verified that ARWMC also associate with cognitive decline. In Alzheimer’s disease, ARWMC is also common findings on MRI images. The clinical importance of ARWMC in AD trials is reviewed.

Chunyan Zhang, Jingliang Cheng, Yong Zhang, Kangkang Xue, Shaoyu Wang

This study aimed to explore the diagnostic points of myoepithelial carcinoma(MEC)in the nasopharynx analyze through analysing the imaging features.11 patients with MEC in the nasopharynx and paranasal sinus confirmed by pathology were analyzed retrospectively. CT and MRI appearances can localize the tumors,show tumors’size, and delineate the relationship of the 1esions with the surrounding tissue.On CT findings, MEC easily has osteolytic destruction and on MR and ADC vuale it owns certain characteristic features.These characteristics are conducive to the early diagnosis and rational treatment in clinics.

Xueying Ma, Dun Ding, Fengli Liang, Zhuonan Wang, Haining Li, Yingxiang Sun, Ming Zhang

The purpose of this study was to provide a deeper knowledge of clinical presentation, imaging diagnosis, differential diagnosis and the management of the intraspinal bronchiogenic cysts. We retrospectively studied three cases of SBCs which were registered in our department and analyzed eight case reports which were all published in English. The SBCs can occur anywhere in the spinal canal, but they are more likely to present at the cervical canal and might be along with some developmental malformations of spine. We emphasize the role of MRI findings in the diagnosis before surgery. It is recommended that the lesion should be removed as completely as possible on the premise of protecting the spinal cord from being injured.

Lixia Yang, Yu Cheng

Both Susceptibility Weighted Imaging (SWI) and T2 star (T2*) imaging can measure the brain iron deposition. However, the two ways by which the brain iron is measured are not compared. This study measured the brain iron of healthy volunteers and Parkinson’s disease patients by SWI and T2* imaging. we found that SWI and T2* imaging could estimate the brain iron, and the SWI radiant values of SNr and RN were significance difference between healthy volunteers and Parkinson’s disease patients, suggesting the SWI had better reliability to diagnose the Parkinson’s disease than the T2* imaging.

Ozden Kilinc, Sara Dastmalchian, Michael Coffey, Mark Cohen, Jeffrey Sunshine, Andrew Sloan, Chaitra Badve

Neuroimaging plays critical diagnostic and prognostic role in the management of brain tumors. However, there can be a significant overlap in the imaging features between neoplastic and various non-neoplastic pathological processes in the brain. The knowledge of key differentiating features of such non-neoplastic entities is essential for a radiologist to facilitate accurate and timely diagnosis. Additionally, in such settings, judicious use of advanced imaging techniques such as perfusion imaging and spectroscopy can help the radiologist as problem-solving tools. In this exhibit, we review the conventional and advanced imaging features of different disease processes that are encountered in day-to-day clinical practice and can mimic brain neoplasms on imaging. 

Warren Chang, Michael Loecher, Daniel Ennis, Aichi Chien, J. Pablo Villablanca

In this study, image quality of high resolution PC-MRA (4D Flow) and 3D-TOF was compared. Ten healthy volunteers were scanned with high resolution 4D-Flow and 3D-TOF angiograms at 0.5 mm isotropic spatial resolution in clinically-useful scan times of 7 and 12 minutes.  There was no significant difference in image quality between 4D Flow and 3D-TOF in both source images and MIPs.  4D Flow acquisitions were velocity encoded, allowing hemodynamic evaluation of intracranial structures.   This study demonstrated that phase-contrast techniques such as 4D-Flow have comparable image quality to 3D-TOF while obtaining velocity measurements, showing promise as a viable alternative to 3D-TOF. 

Antoine Cherix, Thomas Larrieu, Arantxa Duque Moreno, Hongxia Lei, Santiago Moléon, Carmen Sandi, Rolf Gruetter

¹H-MRS was used to study metabolic changes associated with basal anxiety levels in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of naive mice. Results indicate some neuroenergetic differences specific to the NAc, which supports the idea that this structure plays a critical role in the etiology of anxiety.

Sang-Young Kim, Marc Kaufman, Bruce Cohen, Joseph Coyle, Fei Du, Dost Öngür

In this work, we present the advantage of TE-averaged PRESS approach to reliably quantify brain glutamate and glycine levels in vivo in patients with psychosis. Since glutamtergic dysregulation and NMDA receptor hypofunction are implicated in the pathophysiology of major psychiatric conditions, non-invasive in vivo assessments of glutamate and its NMDA receptor modulator, glycine, would be of great importance. We found significantly elevated glutamate and glycine levels in the anterior cingulate cortex and parieto-occipital cortex of patients with first-episode psychosis as compared to healthy controls, suggesting increased brain glutamatergic activity with compensatory attempts to correct for NMDA receptor hypofunction.  

Cecile Bordier, Carlo Nicolini, Angelo Bifone

Graph theoretical methods have been widely applied to study the modular organization of functional connectivity networks in neuropsychiatric disorders like Schizophrenia. However, current methods are affected by a resolution limit that prevents detection of modules that are smaller than a scale determined by the size of the entire network. We have developed a resolution-limit-free method, dubbed Surprise, and applied it to study resting state functional connectivity networks in a large cohort of Schizophrenia patients and matched controls. Improved resolution reveals substantial reorganization of resting state connectivity structure in patients, with previously undetected fragmentation and merging of sensory and associative modules.

Young-Hoon Sung, Xian-Feng Shi, Perry Renshaw, Douglas Kondo

Converging evidence implicates mitochondrial dysfunction in bipolar disorder (BPD). Treatments of adolescent BPD have limited efficacy, and are associated with significant toxicity. Phosphorus magnetic spectroscopy imaging (³¹P MRSI) may shed light on the pathophysiology and neural markers of adolescent BPD. In the present study, nicotinamide adenine dinucleotide (NAD) levels were measured using ³¹P MRSI in 15 adolescents with BPD and 23 healthy controls (HC). BPD adolescents had significantly decreased NAD levels compared to HC. Clinical trials of NAD precursors are required to determine whether restoration of NAD levels is feasible, and can serve as a treatment for adolescent BPD.

Wenbin Li, Huaiqiang Sun, Su Lui, Qiyong Gong

We analyzed the white matter (WM) asymmetry in a relatively large sample of drug-naïve schizophrenia patients under different genetic load. Based on this method, our findings demonstrated similar overall WM brain torque in sporadic and familial schizophrenia patients and healthy controls. Furthermore, our observation that familial illness was associated with more abnormal brain asymmetry compared to sporadic patients and that these specific changes were mainly located in a functional network associated with auditory hallucinations suggesting genetic factors may play critical roles in impacting risk for the most common form of hallucinations in schizophrenia.

Masaya Misaki, Raquel Phillips, Vadim Zotev, Chung Ki Wong, Frank Krueger, Matthew Feldner, Jerzy Bodurka

In combat veterans with and without PTSD diagnosis, we performed connectome-wide exploration of the whole-brain voxel-by-voxel fMRI connectivity using multivariate distance-based matrix regression (MDMR) analysis to determine connectivity abnormalities without a priori hypothesis. PTSD veterans showed increased connectivity across sensory motor areas and the superior temporal to default mode network (DMN) areas compared to non-trauma-exposed control. Veterans without PTSD also showed altered connectivity in the bilateral insula compared to control. This abnormal connectivity pattern was normalized after real-time fMRI neurofeedback training focused on learning to control left amygdala activity with positive autobiographical memory recall.

Natalie Zahr, Manojkumar Saranathan

Volumes of the thalamus and 4 thalamic substructures (i.e., anterior (AT), mediodorsal (MD), ventrolateral (VL), pulvinar (Pul)) were quantified using a novel automated segmentation algorithm in 18 individuals meeting criteria for Alcohol Use Disorders (AUD) and 28 healthy controls (Con). Multiple regressions considered contributions of diagnosis (i.e., Con vs. AUD), age, sex, and intracranial volume on substructural volumes. Volumes of AT, VL, and Pul were smaller with increasing age. Volumes of MD and Pul were affected by diagnosis: both were smaller in the AUD relative to the Con group. These results suggest that thalamic substructures have differential vulnerability to pathological processes.

Xinyu Hu, Ming Zhou, Lu Lu, Lianqing Zhang, Xiaoxiao Hu, Xuan Bu, Hailong Li, Yanchun Yang, Qiyong Gong, Xiaoqi Huang

The current study, for the first time, integrated voxel-wise univariate analysis and multivariate pattern classification approach to evaluate the alterations of localized neural connectivity in a relatively large sample of drug-naive patients with obsessive-compulsive disorder (OCD). Our findings (i) suggested the disequilibrium between the fronto-parietal circuit and the cerebellum might be associated with the pathophysiology of OCD, (ii) indicated the translational role of the localized neural connectivity as a potential discriminative pattern to identify OCD at the individual level and (iii) highlighted the hyperactivation of the prefrontal cortex in the pathophysiologic process of OCD.

Jennifer Evans, Niall Lally, Li An, Allison Nugent, Carlos Zarate

This study investigates the feasibility of measuring glutamate and glutamine metabolites by 7T 1H-MRS after a ketamine infusion in a double blind placebo cross-over study in major depression. MRS data was acquired from the pre-genual anterior cingulate in 15 depressed and 13 healthy controls. Glutamate levels, but not glutamine, were found to be significantly different between groups.

D Rangaprakash, Nathan Hutcheson, Katherine Lawrence, Teena Moody, Sarah Madsen, Sahib Khalsa, Michael Strober, Cara Bohon, Jamie Feusner

Anorexia nervosa (AN) and body dysmorphic disorder (BDD) share distorted perception of appearance, anxiety, and depression, yet their common and distinguishing neural phenotypes of emotion processing remain unknown. To address this, we studied fronto-limbic connectivity using functional MRI data obtained while participants (N=94) viewed fearful faces and rated their own subjectively experienced fearfulness. Healthy controls exhibited, as predicted, significant bidirectional medial prefrontal (mPFC)-amygdala connectivity, which increased across blocks. However, BDD participants exhibited significant mPFC-to-amygdala but not amygdala-to-mPFC connectivity (indicating limbic hypo-responsiveness), while AN exhibited no significant prefrontal-amygdala connectivity. This study suggests distinct, aberrant fronto-limbic modulatory connectivity in AN and BDD.

Lijing Xin, Philipp S Baumann, Raoul Jenni, Luis Alameda, Carina Ferrari, Philippe Conus, Rolf Gruetter, Kim Q Do

Mitochondrial dysfunction including altered brain energy metabolism has been implicated in the pathophysiology of schizophrenia. The aim of this study was to investigate prefrontal lactate(Lac) levels in patients with chronic schizophrenia. An increase of [Lac_mPFC] was observed in patients with chronic schizophrenia relative to healthy controls. This may be associated with glucose metabolism impairment and mitochondrial dysfunction resulting from oxidative stress. Indeed, oxidative damages can impair mitochondrial oxidative phosphorylation and enzyme activities of pyruvate dehydrogenase, leading to Lac production. Therefore, this study provides in vivo evidence supporting that oxidative stress and mitochondrial dysfunction may be involved in schizophrenia. 

Bharath Holla, Rajanikanth Panda, Ganesan Venkatasubramanian, Rose Bharath, Vivek Benegal

Adolescents with high familial-loading of alcoholism exhibit altered premorbid subcortical and cerebellar brain-volumes compared to their peers. They also differ in brain-activity during executive-functioning, reward, and emotion-processing tasks. However, the changes in the maturation of the cortical thickness during the adolescence in these high-risk (HR) individuals and their relationship with the externalizing-behaviors have never been examined. Our findings reveal wide-spread delays in cortical maturation in HR subjects, which may ultimately contribute to their addiction vulnerability. More importantly, these effects reduce with age by late-adolescence in the absence of substance-misuse. Additionally, cortical thinning was associated with better behavioral control across groups

Weina Wang, Xiaorui Su, Qiyong Gong, Qiang Yue

PTSD is associated with a variety of structural and functional brain abnormalities, but the molecular pathophysiological mechanisms are unknown. 25 pediatric PTSD and 24 matched healthy control subjects underwent single voxel 1H-MRS. Right amygdala NAA was significantly increased in pediatric PTSD subjects than in controls, and the other metabolites did not differ significantly between the groups. We hypothesis that long-term excessive activation in amygdala after traumatic events may lead to increase density and activity of the neurons in pediatric PTSD patients with increased NAA concentration, which may be an adaptive response to traumatic stimulation in the human brain. Our findings add the neurochemical abnormality evidence in pediatric PTSD.

Christopher Rowley, Manpreet Sehmbi, Luciano Minuzzi, Benicio Frey, Nicholas Bock

T₁-weighted signal is known to be correlated with age and myelin content. T₁-weighted images with optimized intracortical contrast were taken in subjects aged 17-45. The half cortical depth signal was mapped in 67 healthy controls and 43 individuals diagnosed with bipolar disorder type-1. We investigated the trajectory of the signal with age in each group and it was found that healthy signal trajectory follows a quadratic form with age, while no correlation with age was found in bipolar disorder. We have shown that it is possible to map signal trajectory changes in clinical populations across the cortex. 

Lei Li, Xinyu Hu, Xiaoqi Huang, Qiyong Gong

Previous studies have clarified that differentiating the disease- and traumatic stress-related brain changes may elucidate the core neural mechanism of PTSD. This study is to investigate brain functional alterations in PTSD and the traumatic exposed controls (TEC) relative to the non-traumatized healthy controls (HC) separately, using a data-driven graph theoretical approach--whole-brain functional connectivity strength (FCS) mapping. The current study provided the preliminary evidence of common and separate abnormalities of neural correlates at whole-brain level associated with PTSD and traumatic stress. The disequilibrium between the DMN and the SN might be associated with the pathophysiology of PTSD.

Huaiqiang Sun, Ying Chen, Haoyang Xing, Su Lui, Qiyong Gong

A multivariable analysis framework for schizophrenia prediction with quantitative cortical morphology features features extracted at individual level.

Bart Ferguson, Natalia Petridou, Alessio Fracasso, Martijn Van den Heuvel, Rachel Brouwer, Hilleke Hulshoff Pol, Rene Kahn, Rene Mandl

Patients with schizophrenia show cortical gray matter thinning but it is unknown whether all six cortical layers are implicated or that specific layers are affected. Knowing which layers are involved gives more insight in the underlying pathophysiological processes of schizophrenia. Here we present a method to compute detailed laminar profiles per brain area from conventional 3T T1-weighted scans, which can be used to obtain information on relative layer organization. We validate this method by comparing average profiles computed from conventional 3T scans to profiles computed from high resolution scans, acquired at ultra-high field MRI (7T).

Michelle Solleveld, Anouk Schrantee, Henk-Jan Mutsaerts, Paul Lucassen, Liesbeth Reneman

Preclinical studies have shown that selective serotonin reuptake inhibitor (SSRI) treatment, when applied to the developing brain, is associated with long-term changes in the adult serotonergic system. Using pharmacological MRI (phMRI), we here investigated whether SSRIs can also induce such age-dependent changes in the human serotonergic system. We found that the phMRI response to citalopram was decreased in the amygdala only in adult female subjects who had been first exposed to SSRIs early in life, whereas a blunted response was found in subjects first exposed at a later age.

Sakthivel Sekar, Joanes Grandjean , Joanne Garnell, Sankar Seramani, Marc Ceuster, Hilde Lavreysen, Kishore Bhakoo

MR-Spectroscopy offers a unique potential to characterize underlying neuronal mechanisms of psychiatric dysfunctions and the effects of psychoactive drugs, at a fundamental neuro-metabolite level in-vivo. We studied two preclinical disease models: the chronic mild unpredictable stress (CMUS) model, a putative model for depression, and a sub-chronic memantine (NMDA antagonist) model, a putative model for psychosis using single voxel spectroscopy (SVS). Our results represents metabolic fingerprinting of dysfunctions utilising live metabolic flux profiling; documenting neuro-metabolic effects of novel psycho-active drugs, presenting novel insights in-vivo. Our results and unique approach, exemplifies the potential value of SVS in early stage drug discovery and its potential translation to clinical research.

Fei Li, Su Lui, Li Yao, Xiaoqi Huang, Yanchun Yang, Qiyong Gong

In order to explore the role of anterior cingulate cortex (ACC) in the pathophysiology of obsessive-compulsive disorder (OCD), we used the resting-state functional magnetic resonance imaging (rfMRI) and Granger causality analysis (GCA) and found that the left pregenual ACC of OCD showed decreased amplitude of low-frequency fluctuation (ALFF) than controls. The areas with altered ALFF exhibited decreased driving effect to right dorsal superior frontal gyrus (dSFG) and left precuneus, and a significant increase in the causal influence from left ventral SFG (vSFG) to the left pregenual ACC in OCD compared to controls.

Kung-Te Chu, Vincent Chin-Hung Chen, Te-Wei Kao, Jun-Cheng Weng

Major depressive disorder (MDD) is a significant brain dysfunction that might cause self-harm behavior. The abnormal brain structures between MDD and healthy control have been investigated by using diffusion tensor imaging (DTI) in several studies. However, few studies discussed the brain structure changes in MDD patients with self-harm behavior. Moreover, there were some limitations in DTI. Therefore, our study aimed to find the abnormalities of neurological structure of white matter among MDD without self-harm behavior (MDD_N), MDD with self-harm behavior (MDD_S), and healthy control (HC), using generalized q-sampling imaging (GQI). We found the significant differences in the corpus callosum, superior longitudinal fasciculus (SLF), cingulum, and frontal lobe of GQI indices in individual groups.

Mariana Lazar, Maia Boudzinskaia, Emma Meyer, Dolores Malaspina, James Babb, Oded Gonen

Diffusional Kurtosis Imaging (DKI) and Magnetic Resonance Spectroscopy Imaging were employed to assess microstructural changes of hippocampus in patients with schizophrenia. Increased mean kurtosis and mean diffusivity were observed for both left and right hippocampi in patient compared to the control group. In patients, mean kurtosis showed a strong negative correlation with N-acetylaspartate concentration. These results suggest disorganized hippocampal microstructure, likely due to neuroinflammatory processes such as micro- and astrogliosis and/or disorganized neuronal domains. DKI’s apparent sensitivity to microstructural deficits may ultimately be employed to identify individuals with microscopic hippocampal impairment.

Adrienne Lee, Luke Wang, Benjamin Rowland, Vicky Liao, Elisabetta Del Re, Robert McCarley, Alexander Lin

Degree of schizophrenia (SZ) was determined by phase-locking factor (PLF) acquired through an electroencephalogram (EEG). Correlation spectroscopy (COSY) spectra of the chronic SZ patients and age-matched healthy controls were then compared. A significant difference (p < 0.05) between SZ and controls was found in the concentrations of alanine supported by a strong correlation between PLF and alanine levels.  These results suggest further studies to examine alanine as a potential biomarker for schizophrenia. 

Xiaowei Zou, Timothy Durazzo, Dieter Meyerhoff

The general goal of this study is to determine the volume changes of cortical and subcortical brain regions in smoking and currently non-smoking alcohol-dependent individuals during short-term and long-term abstinence from alcohol, compared with non-/light-drinking controls. Preliminary results from paired t-tests within each group show that the anterior cingulate cortex, dorsolateral prefrontal cortex, orbitofrontal cortex, insula, and hippocampus have different recovery patterns, which suggest potentially different neuropathological changes and/or injuries. More statistical analyses will test for cross-sectional and longitudinal differences between the groups for a better interpretation of the regional volume changes and their cognitive and behavioral correlates.

Harri Merisaari, Ivan Jambor, Marko Pesola, Maria Gardberg, Janek Frantzén, Pekka Jokinen, Hannu Aronen, Timo Liimatainen, Heikki Minn, Aida Kiviniemi

Our aim was to study the feasibility of quantitative RAFF, T1ρ_cw, T1ρ_adiab and T2ρ_adiab imaging for the first time in human gliomas and to assess their ability to differentiate gliomas with specific genetic profile. FLAIR lesion segmentation and histogram analysis from parametric maps were applied. Both IDH mutated and 1p19q codeleted gliomas demonstrated a tendency for lower relaxation values compared to IDH wild-type and 1p19q intact gliomas, respectively. Additionally, T2ρ, adiab significantly correlated to Ki-67 and tumor aggressiveness. We conclude that RAFF, T1ρ_cw, T1ρ_adiab and T2ρ_adiab imaging of gliomas is feasible and carry a potential for improving non-invasive glioma characterization.

Runze Yang, Susobhan Sarkar, V. Wee Yong, Jeff Dunn

Glioblastoma Multiforme (GBM) is an aggressive brain cancer. Immunotherapy is a promising avenue of exploration for treatment of GBM. We discovered a new drug capable of stimulating innate immunity and showed that it is able of reducing tumor growth in a mouse model of GBM. We used ultrasmall iron oxide nanoparticles (USPIO) to track the migration of stimulated immune cells and showed that this drug related response can be detected with as little as 7 days of treatment. MRI tracking of immune cells using USPIO is a promising tool that can be easily translated into the clinical setting.

Yan Li, Spencer Behr, Susan Chang, Sarah Nelson, Michael Evans

This study evaluated the feasibility of using combined metabolic imaging methodologies, namely 3D lactate-edited proton magnetic resonance spectroscopic imaging and Gallium-68 citrate PET, in patients with glioma using a PET/MR scanner. 

Huimin Yang, Chaohsiung Hsu, Yung-Ya Lin

Application of MR imaging is very limited in imaging sensitivity and contrast in regards to the detection of brain tumor at an early stage because of tiny variations between healthy tissue and early-stage tumor. The radiation damping effect provides insight about the nonlinear spin evolution. Taking advantage of nonlinear spin evolution, we confirmed theoretically and experimentally that MR imaging provides a more stable and significant contrast in comparison to conventional methods. 

Ramon Barajas Jr, Bronwyn Hamilton, David Pettersson, Daniel Schwartz, Jenny Firkins, Prakash Ambady, Andrea Horvath, Heather McConnell, Joao Prola-Netto, Csanad Varallyay, Jerry Jaboin, Charlotte Kubicky, Ahmed Raslan, Aclan Dogan, Jeremy Ciporen, Leslie Muldoon, William Rooney, Edward Neuwelt

Ferumoxytol iron nanoparticles are used as an off label molecular MR imaging contrast agent in patients with reduced renal function precluding gadolinium administration.  Glioblastoma molecular features are now recognized as an integral component of glioma pathogenetic classification and clinical outcome.  IDH1 mutation accounts for approximately 10% of glioblastoma.  The absence of a reliable noninvasive biomarker of glioblastoma IDH mutation prompted this retrospective study to determine if Ferumoxytol MR Imaging is diagnostic of IDH mutational status.  We observed that the presence of increased Ferumoxytol to Gadolinum enhancing ratio was a significant 3T MR imaging biomarker for IDH mutational status in recurrent glioblastoma and the differentiation of pseudoprogression. 

Marram Olson, Jason Crane, Janine Lupo, Marisa Lafontaine, Sarah Nelson

Quantitative analysis of metabolic and dynamic imaging data produces maps of parameters that show promise for improving medical diagnosis and therapeutic monitoring for patients with brain tumors. Statistical ROI analysis of these maps can be used to quantitatively summarize multi-modality imaging metrics and longitudinal changes. In this work we demonstrate a standards-based mechanism for generating and communicating minable, quantitative Region of Interest (ROI)  analysis results that can easily be integrated into clinical workflows and radiomic studies.

Esin Ozturk-Isik, Sevim Cengiz, Koray Ozduman, Alpay Ozcan, Cengiz Yakicier, M. Necmettin Pamir, Alp Dincer

The tumor biology of diffuse-gliomas is best reflected by their molecular profile. Isocitrate dehydrogenase (IDH) mutation status has the strongest correlation to treatment response and patient survival among all molecular markers. The aim of this study is to predict IDH mutation status of gliomas based on short-echo time MR spectroscopic (MRS) biomarkers by using machine learning algorithms at 3T. Our results indicated that MRS based biomarkers were able to discriminate between IDH-mutant and IDH-wild type patients with up to 91% sensitivity, %78 specificity, and 86.9% accuracy by using an ensemble of bootstrap-aggregated decision trees classification with a three-fold cross validation.

Csanad Varallyay, Andrea Horvath, Gerda Toth, Laszlo Szidonya, Emily Youngers, Edward Neuwelt

Ferumoxytol as an MRI contrast agent has the advantage of long intravascular phase and strong transverse relaxivity, allowing high resolution depiction of abnormal vasculature and steady state blood volume (SS-CBV) mapping. In clinical studies it would be beneficial to use ferumoxytol as an immediate extension of standard of care gadolinium enhanced MRI, instead of imaging on two separate days. This study concludes that the 3D T2* weighted acquisition has substantial T1 weighting, while the 2D acquisition does not, therefore the latter one is preferable for ferumoxytol vascular imaging if gadolinium is on board.

Kenneth Maravilla, Daniel San Juan Orta, Sang Joon Kim, Guillermo Elizondo Riojas

This double-blind randomized cross-over study was conducted to demonstrate non-inferiority of gadoterate meglumine vs. gadobutrol in MRI diagnosis of brain tumors. Images from two identical MRIs with each agent were evaluated by three independent off-site readers. Overall lesion visualization and characterization was scored as “good” or “excellent” in >90% of patients by all readers. Despite a small difference in signal intensity measurements in favor of gadobutrol, similar results were observed with the two agents regarding overall lesion visualization and characterization or qualitative efficacy criteria. Non-inferiority of gadoterate meglumine vs. gadobutrol in diagnosis of brain tumors by MRI was demonstrated. 

Fulvio Zaccagna, Frank Riemer, Mary McLean, James Grist, Joshua Kaggie, Rolf Schulte, Sarah Hilborne, Tomasz Matys, Jonathan Gillard, Colin Watts, Stephen Price, Martin Graves, Ferdia Gallagher

Glioma grade and the extent of local infiltration are important factors for guiding management. Imaging tumor heterogeneity may also improve diagnosis and therapy planning. ²³Na-MRI has been used here to demonstrate a gradient in sodium concentration across gliomas: necrosis greater than viable tissue greater than edema. This gradient was evident in all 17 tumors analyzed and is consistent with the expected underlying histopathology; concentration is increasing throughout the evolution from edema, dominated by the extracellular compartment, to the necrotic core, dominated by dead cells and broken sodium pumps. ²³Na-MRI may therefore represent an imaging biomarker of tumor heterogeneity in glioma.

Mitsuharu Miyoshi, Masafumi Harada, Yuki Kanazawa, Hiroyuki Kabasawa

Although MTR asymmetry is often used as a CEST parameter, it is not quantitative. In this study, CEST Peak Extraction (CPE) method was used to separate CEST and MT parameters. CEST peaks in brain tumor could be fitted with Lorentzian function on CPE spectrum. Each fitted parameter had a quantitative meaning in multi pool model, which includes CEST pool, binding water MT pool and free water pool.

Gaurav Verma, Sanjeev Chawla, Harish Poptani, MacLean Nasrallah, Michael Thomas, Arati Desai, Steven Brem, Suyash Mohan

Mutations in isocitrate dehydrogenase (IDH) play an increasing role in clinical assessment of human gliomas and determination of treatment. The performance of Chemical Shift Imaging (CSI) to detect 2-hydroxyglutarate (2HG) in mutant-IDH gliomas was assessed in the routine clinical environment. Specificity of 80% and sensitivity of 63% was achieved in a cohort of 15 patients scanned with the technique at 3T. Greater sensitivity, through longer acqusition or more sensitive equipment could result in reliable non-invasive detection of this putative biomarker present in a majority of Grade II/III gliomas.

Hatef Mehrabian, Hany Soliman, Arjun Sahgal, Greg Stanisz

Radiation necrosis is the most common side-effect of stereotactic radiosurgery (SRS) and has similar characteristics to tumor progression on standard anatomical MRI. Differentiating these two conditions is a major long standing clinical challenge.  In this study the potential of chemical exchange saturation transfer (CEST) in differentiating the two conditions in patient with brain metastases is investigated. The results showed that the magnetization transfer ratio (MTR) of amide and NOE peaks provided the best separation of radiation necrosis cases from tumor progression cases. However, the commonly used amide proton transfer (APT) was unable to differentiate the two conditions. 

Gilbert Hangel, Eva Heckova, Bernhard Strasser, Michal Považan, Stephan Gruber, Elisabeth Springer, Georg Widhalm, Matthias Preusser, Siegfried Trattnig, Wolfgang Bogner

We present the application of single-slice high-resolution FID-MRSI with short acquisition delay at 7T that provides whole-slice metabolite maps in eight patients with different types of glioma. With six minutes measurement time, it could be easily integrated into a standard imaging protocol. The results show that it is possible to resolve metabolic deviations in an extended number of biochemical compounds in tumors with unprecedented spatial details, thereby offering deeper insight into the neurochemical profiles of different glioma types. This suggests that the demonstrated method has a high potential for the research of glioma.

Vivek TIWARI, Sandeep Ganji, ZhongXu An, Changho Choi

Gliomas harboring mutations in Isocitrate-Dehydrogenase (IDH) 1/2 exhibits a neomorphic-activity resulting in production of 2-hydroxyglutarate (2HG) by 2-3 orders of magnitude. Non-invasive detection of 2HG using conventional 1H Magnetic Resonance Spectroscopy (MRS) is challenging due to extensive overlap with the resonances of neighboring metabolites. Here we have designed a TE-Averaged PRESS 1H-MRS that reduces the spectral-overlaps of GABA, Gln, Glu and glutathione signals on 2HG-2.25ppm-resonance that provides a reliable-detection of 2HG. We have also estimated T2 in each brain-tumor by taking the advantage of multiple-TEs used in TE-averaging acquisitions, and used patient-specific T2 for estimation of 2HG. 

Melanie Morrison, Erin Felton, Angela Jakary, Andrew Leynes, Peder Larson, Sabine Mueller, Janine Lupo

In the treatment of pediatric medulloblastomas, cranial radiation therapy (CRT) may induce long-term effects including CRT-induced vascular injury and cognitive impairments. 7T Susceptibility-weighted MRI was used to characterize CRT-induced injury in the form of cerebral microbleeds (CMBs) as potential markers of cognitive deficits. The majority of CMBs were located in the frontal lobe, which develop late in the adolescent brain. CMB density was associated with deficits in working and visual memory as a function of time since CRT. This work supports a modification of future standards for defining radiation target volumes, with evidence for early intervention with cognitive rehabilitation strategies.  

Yang Yang, Lin-Feng Yan, Xin Zhang, Hai-Yan Nan, Yu-Chuan Hu, Yu Han, Jin Zhang, Wen Wang, Guang-Bin Cui

Texture analysis is a powerful image analysis method to assess the heterogeneous distribution of tumor quantitatively. Different statistical models have been applied in texture analysis to classify glioma grade and level. It has not been evaluated that which model is the most efficient. The aim of this study is to compare four texture models in glioma grading. Texture features were extracted from multimodality MR images in 3D ROIs. After machine learning and leave-one-out cross validation, the gray-level run-length matrix was found as the best model while gray-level was set as 256. 

Yingqiu Liuyang, Jin Shang, Yanwei Miao, Shesnia Salim Padikkalakandy Cheriyath, Yan Guo

The objective of this study, was to differentiate low from high grade glioma using texture analysis of quantitative ADC maps, and further aimed at revealing the microscopic changes of glioma in the evolution of low grade to high grade.Conclusion that texture analysis of ADC signal value based on entire tumor could provide more information in differentiation of low and high grade glioma. Through logistic regression analysis we obtain skewness, entropy,long run emphasis are the independent influence  factors, and joint application of them showed superior diagnostic value.

Jing Liu, Kannie Chan, Bin Zhang, Guan Liu, Shui Zhang

A preliminary classification of primary central nervous system lymphoma (PCNSL) was reported based on the MRI radiographical features. We classified the 90 PCNSL patients based on the T1 contrast-enhanced MRI findings and assessed treatment responses. The goal is to provide some guidelines and additional information for diagnosis and treatment planning. We categorized these patients into four distinctive types of PCNSL according to the T1 findings and observed the treatment response rate, which we found the highest in type Ia. This could potentially facilitate the diagnosis and treatment plan of PCNSL in a routine clinical setting.  

Niha Beig, Ramon Correa, Prateek Prasanna, Jhimli Mitra, Ameya Nayate, Anant Madabhushi, Pallavi Tiwari

The recent categorization of low-grade Glioma (LGG) has been modified based on the molecular aberrations associated with IDH mutations (IDHmut or IDH-WT) and 1p19q co-deletions (codel or non-codel). We explored the utility of radiogenomic analysis to identify radiomics signatures (computer extracted features from MRI) that distinguish IDHmut codel, IDHmut noncodel, and IDH-WT LGG tumors on T2 and FLAIR sequences.  Initial results indicate that radiomic features from non-enhancing regions on T2 and infiltrative edges on FLAIR can segregate the 3 subgroups. A non-invasive means of discerning molecular subtypes on MRI may allow clinicians to determine prognosis, and inform treatment strategy.

Yihao Yao, Ilhami Kovanlikaya, Ramin Jafari, Yi Wang, Wenzhen Zhu

The accuracy of grading astrocytic brain tumors using texture analysis (TA) on quantitative susceptibility mapping (QSM) was studied. For texture analysis training data set, most discriminant factor (MDF1) values were significantly different for low grade and high grade astrocytomas (p<0.01), as well as Grade II and III, Grade II and IV, Grade III and IV (p<0.01). For texture analysis test data set, 19/20 cases in differentiating low grade from high grade astrocytomas, 16/20 cases in Grade II, III and IV differentiation were correctly classified. TA promises to be a useful tool for grading astrocytoma on QSM.

Ra Gyoung Yoon, Ho Sung Kim, Myeong Ju Koh, Sang Joon Kim

We evaluated a volume-weighted voxel-based multiparametric (MP) clustering method as an imaging biomarker for differentiating recurrent glioblastoma from delayed radiation necrosis, comparing to the single imaging parameters of DWI, DSC and DCE perfusion MR. In an area under the receiver operating characteristic curve analysis, volume-weighted voxel-based MP clustering demonstrated better diagnostic accuracy for discriminating these two conditions than single imaging parameters. When performed with use of an optimal cutoff, volume-weighted voxel-based MP clustering improved the overall sensitivity. Therefore, quantitative analysis using volume-weighted voxel-based MP clustering is superior to single imaging parameter measurements for differentiating recurrent glioblastoma from delayed radiation necrosis.

Vera Keil, Monika Warmuth-Metz, Christina Reh, Jonas Enkirch, Torsten Pietsch, Hans Schild, Elke Hattingen, Peter Hau

Medulloblastoma in adults is very rare and shows prognostically relevant histological and genetic subtypes. Within a nation-wide multicenter study, pre-surgical MRIs of 28 cases were analysed to identify imaging biomarkers, which may be used to non-invasively predict these subtypes based on a radiophenotype. Molecular genetic subtypes SHH p53wt, WNT and non-WNT/non-SHH (Group 4) were significantly distinct in their relation to the 4th ventricle and lower rhombic limb, and extent of edema. Further imaging biomarkers could be identified that differentiate histological subtypes and nuclear-ß-catenin expression patterns. Imaging biomarkers were not congruent to markers identified in pediatric patients implying possible age-related differences.

Edgar Rios Piedra, Benjamin Ellingson, Suzie El-Saden, Ricky Taira, Alex Bui, William Hsu

We present an automated brain tumor segmentation framework to measure the variability associated to the tumor boundary that is observed on multimodal MRI; this is a vital task to accomplish as quantitative and automated tumor measurements and assessment become the standard in neuro-oncology for disease diagnosis, treatment planning, and clinical monitoring.

Mustapha Bouhrara, Michael Maring, David Reiter, Jean-Marie Bonny, Richard Spencer

 Changes in myelin water fraction (MWF) represent a biomarker for central nervous system disease. However, high quality mapping of MWF is challenging, requiring very high signal-to-noise ratio for accurate and stable results. In this work, we demonstrate the potential of a new multispectral filter to permit high quality MWF mapping using in-vivo GRASE brain imaging datasets. Indeed, unlike conventional averaging filters, our filter permits substantial reduction of the random variation in derived MWF estimates while preserving edges and small structures. Finally, our results regarding patterns of MWF as a function of age are consistent with recent literature.  

Minghui Tang, Keigo Nishi, Toru Yamamoto

Cerebral arteriolar vasomotor function would be a biomarker for early diagnosis of dementia. We developed a quantitative mapping technique for cerebral arteriolar vasomotor function without administrating any agents. The natural respiratory fluctuation of CO₂ in arterial blood was used, which alters cerebral blood flow and venous blood oxygenation, and hence modulates the MRI signal. This new technique is based on our finding of a strong correlation in MR signals between the cardiac fluctuation in brain parenchyma and the respiratory fluctuation at the sagittal sinus. Using this new mapping technique, the degeneration of arteriolar vasomotor function associated with aging was observed.

Xin Hong, Sei Hwan Oh, Ying Hwey Nai, Saima Hilal, Suz-Chieh Sung, Mohammad Ikram, Christopher Chen, Kai-Hsiang Chuang

Cerebral blood flow (CBF) is an important biomarker of the brain function and has been shown to correlate with cognitive performance in diseases. Since cardiovascular and metabolic complications are common in elders, to understand the influence of vascular confound in cognitive correlation, we investigated how cardiovascular risk factors may affect the relationship between cognitive functions and CBF in non-demented elders. We found that mean arterial blood pressure, haematocrit, blood cholesterol and glucose levels had significant negative effects on CBF. This suggests that cardiovascular risk factors shall be taken into consideration when analyzing CBF in aging, cognitive impairment, and neurodegenerative diseases.

Pascal Tétreault, Diana Valdés Cabrera, Robert Stobbe, Corey Baron, Christian Beaulieu

This study compared short diffusion time (4 ms) oscillating gradient spin echo (OGSE) relative to regular long diffusion time (40 ms) pulsed gradient spin echo (PGSE) DTI in healthy individuals over a 40 year age span (n=12, 24 to 67 years old) to identify unique microstructure organization and reveal potential age related changes in three portions of the corpus callosum. Diffusivity and anisotropy were shown to depend on the diffusion time, mostly in the splenium, and these changed with age possibly reflecting alterations of restrictive dimensions such as the loss of specific axon diameters with aging.

Gwang-Won Kim, Chung-Man Moon, Gwang-Woo Jeong

The aging process and menopausal transition are important factors in sexual dysfunction of menopausal women. Until now, it has been unknown how menopause synchronously influences brain morphology and brain function during visually stimulated sexual arousal in menopausal women. We used structural and functional magnetic resonance imaging (fMRI) in parallel to evaluate menopause-related brain morphological and functional alterations during visually stimulated sexual arousal in menopausal women.

Christopher O'Neill, Cheryl McCreary, Richard Frayne

R2* relaxation and susceptibility measurements are both candidate biomarkers for studying brain change. The relative variability of R2* and quantitative susceptibility mapping (QSM) approaches was studied in six deep brain regions in 182 normal subjects (18-89 years). The variability of R2* measures (average coefficient of variation, CoV: 0.33, mean ± standard deviation over regions) was found to be significantly less than QSM measurements (average CoV: 5.72). The variability in R2* measurements was found to vary with age, unlike QSM which showed no age effects. The increased variability observed in QSM measurements, however, may obscure smaller age effects.

Toshiharu Nakai, Noriko Ogama, Takashi Sakurai, Mika Ueno, Sachiko Kiyama, Ayuko Tanaka

The relationship between the history of participation in community based physical exercise activity and the volume of white matter hyperintensity was evaluated in order to investigate the long-term effects of physical exercises on the neurophysiological status of brain to support cognitive processing in older adults. The FLAIR MR images obtained from 54 community dwelling older adults were segmented semi-automatically and the WMH volumes were quantified. It was suggested that long-term physical exercises more than 5 years for 90 minutes once per week may potentially reduce the progress of WMH lesions as well as the risk of fall.

Arturo Cardenas-Blanco, Matthew Betts, Peter Nestor, Emrah Düzel, Julio Acosta-Cabronero

To date, several studies have shown the value of quantitative susceptibility mapping (QSM) and R2* to detect aging-associated neurobiological mechanisms often based on single parametric features, either mean or median values, to characterise QSM/R2* behaviours in regions of interest (ROIs). In this study we propose the use of Haralick texture features to probe regional distribution characteristics of voxel intensities in R2*/QSM images. The results demonstrate that Haralick texture features add value to study the aging brain since they increase significantly the accuracy in subcortical R2*/QSM differentiation between elderly and young subjects.

Andrew Carradus, Benjamin Hunt, Prejaas Tewarie, Nicolas Geades, Simon Shah, Olivier Mougin, Matthew Brookes, Penny Gowland

This study explores the relationships that cortical myelination and cortical thickness have with age, and expands on existing literature by investigating whether the previously reported trends are still present when only looking at individual lobes of the brain. We find that quadratic variations occur in all four lobes of the brain in regards to myelination, and that cortical thickness declines linearly with age in all lobes except the temporal. We also find that myelination levels and cortical thickness appear to change independently of each other.

Maíra Pinto, Antônio dos Santos, Carlos Salmon

The human brain is a complex structure that undergoes continuous, non-linear changes over the lifespan. We used anatomic and diffusion data from 165 healthy subjects, collected retrospectively from CCIFM/HC-FMRP. T1-weighted images were used for cortical parcellation, thus 102 of 148 cortical regions had statistically significant decrease with age. Three fiber tracts were selected: Corpus Callosum, Uncinate Faciculus and Corticospinal Tract, their diffusion parameters, FA and MD, showed significant relationship with cortical thickness of the biggest cortical area in the ending of each tract. Despite these correlations, it was possible to verify that age is the pivotal variable in this relationship.

Daniele Mascali, Emily Kittelson, Keith Jamison, Kâmil Ugurbil, Essa Yacoub, Shalom Michaeli, Lynn Eberly, Melissa Terpstra, Federico Giove, Silvia Mangia

Age-courses of multiple MRI outcomes were here characterized with a specific focus to default mode network (DMN) regions. Data were collected with unprecedented sensitivity and spatial resolution using the Human Connectome Project Lifespan Pilot protocol from 65 subjects divided in 4 age-groups (teen, young, middle-age and older adults). Age-related decreases of grey matter volumes, mean diffusivity, amplitude of resting-state oscillations and regional homogeneity were observed in both anterior and posterior DMN, and were more pronounced in anterior than in posterior DMN.  Connectivity between posterior and anterior DMN regions remained relatively stable during the lifespan.

Andrew Hale, Penny Gowland, Paul Greenhaff, Susan Francis

Age-related alterations in cerebral vascular function may be better understood by investigating cerebral response to exercise. We performed a MR study involving low/moderate intensity exercise in healthy young and older subjects. We assess the effect of exercise on CBF response, cerebral oxygenation, and CMRO₂. We also investigate the relationship of GM-volume and physical fitness with ageing. At rest, there was no difference between CBF and CMRO₂ but an increase in oxygen extraction with age. On exercise the age-related increase in OEF remained, however CBF and CMRO₂ were blunted in older subjects. GM-volume was found to be associated with VO_2max.

Kiarash Ghassaban, Sean K Sethi, Shuang Xia, E. Mark Haacke

In this work, 81 healthy subjects were recruited to assess iron deposition as a function of age in eight major brain nuclei using quantitative susceptibility mapping. By thresholding out high iron content region for each structure, seven basal ganglia and midbrain structures were evaluated locally and compared with the literature. Global (the entire structure) and regional (high iron content) susceptibility changes versus age were also analyzed for the dentate nucleus. In addition to the global analysis being consistent with the literature, regional analysis showed more sensitivity and precision as well as the left hemisphere dominance in terms of iron deposition.

Alexandra Badea, Nian Wang, Gary Cofer, Simon Davis, John Ervin, Dianne Cruz, G Allan Johnson

Detecting early brain changes in neurodegenerative diseases such as Alzheimer’s disease (AD) is essential for enabling interventions. We thus need to increase our ability to accurately localize areas that change, and to quantifying changes. The temporal lobe is essential for memory function. This is where AD hallmarks such as plaques, tangles, and neuronal death happen first. White matter has been proposed to have a role in early AD. We use high resolution magnetic resonance histology and diffusion tensor imaging to characterize the temporal lobe and its tracts. A compressed sensing acquisition with cluster based reconstruction increased efficiency four-fold.

Chad Otoshi, Thomas Ernst, Kenichi Oishi, Hua Jun Liang, David Greenstein, Linda Chang

Microstructural brain changes before, 1-month and 6-months and after working Memory Training was evaluated in both HIV-positive and seronegative individuals.  While working memory training improved performance in both trained and non-trained working memory tasks, brain diffusivities increased in most brain regions after training in both groups, more in HIV than controls in some regions. These findings suggest ongoing brain inflammation associated with normal aging or HIV may mask the training-related changes in DTI measures.

Qinmu Peng, King Kevin, Minhui Ouyang, Hanzhang Lu, Hao Huang

Numerous studies have revealed that DTI-derived metrics are sensitive to the microstructural changes of the aging white matter tracts. However, microstructural changes associated with non-Gaussian water diffusion cannot be quantified by DTI-derived metrics, but uniquely quantified by DKI-derived metrics. Little is known on the progressive white matter microstructural changes measured by DKI-derived metric during aging. In this study, we found that the measurements of DKI-derived mean kurtosis (MK) decrease heterogeneously across white matter tracts, characterized with significant MK decreases in limbic tracts including fornix and cingulum and insignificant MK decreases in the association tracts.

Lindsay Hill, Dung Minh Hoang, Willis Chen, Youssef Wadghiri

Here we study normal brain aging in wild type C57BL/6 mice and have detected a decline in cerebrovasculature over the two year aging process

Muzamil Arshad, Jeffrey Stanley, Naftali Raz

Multi-echo T₂ imaging (ME-T₂) enables the investigation of multiple white matter compartments. The short T₂ compartment has been the focus of recent investigations due to its specificity for the myelin water compartment. However, the much larger intra/extra cellular (IE) compartment has been relatively less explored. Here we investigate age differences in the geometric mean T₂(geomT_2IEW) of the IE compartment in subcortical white matter tracts. We demonstrate that the effects of age on geomT_2IEW are not uniform across white matter tracts and suggest that this index may offer additional value in the characterization of age differences of white matter microstructure. 

Pui Wai Chiu, Hui Zhang, Savio Wai Ho Wong, Tianyin Liu, Gloria Hoi Yan Wong, Queenie Chan, Henry Ka Fung Mak

Rostral ACC displays a characteristic task-induced deactivation, while dorsal ACC displays positive BOLD responses in cognitive tasks. Nevertheless, the effect of age on the rostral ACC and dorsal ACC has never been investigated within the same cohort. In this study, quantitative proton magnetic resonance spectroscopy was used to investigate the metabolic changes in the rostral ACC and dorsal ACC in a local Chinese cohort at 3.0T. Both rostral ACC and dorsal ACC showed age-related metabolic changes. Rostral ACC may reveal greater degree of compensation compared to dorsal ACC. 

Hyeon-Man Baek, Yeong-Jae Jeon

In this study, in vivo quantification of brain metabolites measured on the dorsolateral prefrontal cortex (DLPFC) was carried out with LCModel using a priori knowledge based on experiment metabolite basis set signals. The main observation in this work was the significant reduction of tCho and Ins, and increase of GSH and Glx concentrations in the left DLPFC of alcohol dependent patients compared to healthy control subjects.

Michele Guerreri, Alessandra Caporale, Marco Palombo, Emiliano Macaluso, Marco Bozzali, Silvia Capuani

The intent of this study was to test the potential of parameters extracted by the so-called anomalous diffusion (AD) stretched exponential γ-imaging model, to detect microstructural modifications occurring in brain during normal aging. Conventional DTI metrics was also considered. 27 healthy volunteers with age range 21-77y underwent DW acquisitions. Parametric maps of Mean γ (Mγ) and γ Anisotropy (γA) were obtained and a quantitative analysis was carried in different regions of White and Deep Grey Matter. We found that AD and DTI parameters correlations with age indicate changes in different brain regions diversifying thus aging patterns.

William Cottam, Diane Reckziegel, Marianne Drabek, Dorothee Auer

Arterial spin labelling is a powerful, non-invasive tool to map cerebral blood flow (CBF) in the study of neural activity patterns underpinning spontaneous behaviour or personality traits. In this study we sought to directly investigate the effects of negative affect, specifically trait anxiety on local cerebral blood flow in a group of patients with chronic pain known to have mildly elevated anxiety scores. This study found widespread cerebral blood flow in osteoarthritis subjects with chronic pain that correlate significantly with trait anxiety, overlapping with regions previously reported to relate to autonomic functions. fMRI studies should account for increased physiological arousal.  

João Santos Silva, Ícaro Oliveira, André Paschoal, Renata Leoni

Recently, the effects of aging on human brain tissue, mainly how structural changes may be related to functional changes, have been extensively discussed. However, there is still no agreement on which brain regions have altered perfusion and how it is related with dementia. Therefore, in the present study, we investigated regional changes in perfusion and gray matter concentration in healthy aging, Mild Cognitive Impairment and Alzheimer’s disease. The results indicate a significant age- and disease-related reduction of regional cerebral perfusion associated with brain atrophy. Therefore, these alterations may be important biomarkers for neurodegeneration.

Pui Wai Chiu, Hui Zhang, Savio Wai Ho Wong, Tianyin Liu, Gloria Hoi Yan Wong, Queenie Chan, Henry Ka Fung Mak

Memory for face–name associations is an important type of memory in our daily lives, and often declines in older adults, but the neural mechanisms underlying such decline are still unknown. In this study, quantitative proton magnetic resonance spectroscopy was used to investigate the metabolic changes in the bilateral hippocampi in a local Chinese cohort at 3.0T. The relationship between metabolite concentrations and memory recall accuracy from a face-name recognition task was also assessed. Right hippocampus revealed the plausibility of compensation activity during aging, and the memory recall accuracy was associated with alterations in glutamatergic neurotransmission.