Lester Melie-Garcia^1,2,3, Muhamed Barakovic^1,2,3, Matthias Weigel^1,2,3,4, Reza Rahmanzadeh^1,2,3, Riccardo Galbusera^1,2,4, Po-Jui Lu^1,2,3, Alessandro Cagol^1,2,3, Antoine Lutti⁵, Sabine Schaedelin⁶, Pascal Benkert⁶, Alexandra Todea^1,2,3,7,8, Esther Ruberte^1,9, Ernst-Wilhelm Radue¹, Ludwig Kappos^1,2,3, Jens Kuhle³, and Cristina Granziera^1,2,3
1Translational Imaging in Neurology (ThINK), Biomedical Engineering Department, University of Basel, Basel, Switzerland, ²Department of Medicine, University Hospital Basel, Basel, Switzerland, ³Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, Basel, Switzerland, ⁴Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland, ⁵Laboratory for Research in Neuroimaging (LREN), Department of Clinical Neurosciences, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland, ⁶Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, Basel, Switzerland, ⁷Division of Neuroradiology, Department of Radiology, University Hospital Basel, Basel, Switzerland, ⁸Translational Imaging in Neurology (ThINK) Basel, Biomedical Engineering Department, University of Basel, Basel, Switzerland, ⁹Medical Image Analysis Center (MIAC), Basel, Switzerland

A scarce body of literature studies the Corpus Callosum (CC) normal-appearing white matter (NAWM) in Relapsing-Remitting Multiple Sclerosis (RRMS). This work aimed to characterize the degree of the alterations in different CC segments by assessing the extent of damage to myelin and axon, as measured with myelin volume fraction, axonal volume fraction, and g-ratio. These microstructural measures correlated with disease duration, EDSS, number, and volume of the lesions in other white matter regions. In sum, this work shows that CC pathology in RRMS patients is related to focal damage and/or diffuse neurodegeneration, which is clinically relevant.

Jannis Müller^1,2, Po-Jui Lu^1,2, Hyeong-Geol Shin³, Reza Rahmanzadeh^1,2, Charidimos Tsagkas^1,2, Muhamed Barakovic^1,2, Riccardo Galbusera^1,2, Özgür Yaldizli^1,2, Matthias Weigel^1,4, Yi Wang⁵, Thanh Nguyen⁵, Jens Kuhle², Jongho Lee³, and Cristina Granziera^1,2
1Department of Biomedical Engineering, Faculty of Medicine, University Hospital Basel and University of Basel, Translational Imaging in Neurology (ThINk) Basel, Basel, Switzerland, ²University Hospital Basel and University of Basel, Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Basel, Switzerland, ³Department of Electrical and Computer Engineering, Seoul National University, Laboratory for Imaging Science and Technology, Seoul, Korea, Republic of, ⁴Division of Radiological Physics, Department of Radiology, University Hospital Basel and University of Basel, Basel, Switzerland, ⁵Department of Radiology, Weill Medical College of Cornell University, New York, NY, United States

The visualization and characterization of cortical MS lesions is challenging on conventional MRI. In the present study, we used a susceptibility source separation algorithm to divide the positive and negative susceptibility of quantitative susceptibility mapping (QSM) MRI, so that we could disentangle signal alterations due to myelin loss or iron accumulation. In 19 MS patient with 123 cortical lesions, we found that the major part of QSM susceptibility of cortical lesions is driven by myelin and iron loss, while only a small proportion of lesions (12/123, 9.8%) showed an increment of susceptibility that is caused by iron accumulation.

Lukas Pirpamer¹, Andrej Vovk², Anna Damulina³, Michael Khalil³, Reinhold Schmidt¹, Christian Enzinger^4,5, and Stefan Ropele^3
1Department of Neurology, Division of Neurogeriatrics, Medical University of Graz, Graz, Austria, ²Medicinska fakulteta, Univerza v Ljubljani, Ljubljana, Slovenia, ³Department of Neurology, Division of General Neurology, Medical University of Graz, Graz, Austria, ⁴Neurology, Medical University of Graz, Graz, Austria, ⁵Department of Radiology, Division of Neuroradiology, Medical University of Graz, Graz, Austria

Periventricular tissue damage in multiple sclerosis has been suggested to be mediated by toxic soluble factors in the cerebrospinal-fluid. Magnetization transfer imaging has shown great potential to reveal microstructural tissue changes and has been used to study the association of periventricular normal-appearing white matter (NAWM) changes to the distance from the ventricle. We assessed high-resolution magnetization transfer saturation imaging (MTsat) in equidistant bands around the ventricle of MS patients and compared the resulting MTsat gradient of the thalamus and NAWM. While PV-MTsat values in NAWM are consistent to the literature, MTsat values in the outer thalamic bands were higher than controls, likely caused by increased iron levels.

Riccardo Galbusera^1,2,3, Erik Bahn⁴, Matthias Weigel^1,2,3, Po-Jui Lu^1,2,3, Jonas Franz⁴, Muhamed Barakovic^1,2,3, Sabine Schaedelin⁵, Lester Melie-Garcia^1,2,3, Reza Rahmanzadeh^1,2,3, Peter Dechent⁶, Antoine Lutti⁷, Govind Bhagavatheeshwaran⁸, Wolfgang Brück⁴, Ludwig Kappos^2,3, Christine Stadelmann⁴, and Cristina Granziera^1,2
1Neurology Clinic and Policlinic, Departments of Medicine, Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ²Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ³Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB) Basel, University Hospital Basel and University of Basel, Basel, Switzerland, ⁴Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany, ⁵Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland, ⁶Department of Cognitive Neurology, MR-Research in Neurosciences, University Medical Center Göttingen, Göttingen, Germany, ⁷Centre for Research in Neuroscience - Department of Clinical Neurosciences, Laboratoire de recherche en neuroimagerie (LREN) University Hospital and University of Lausanne, Lausanne, Switzerland, ⁸National Institute of Neurological Disorders and Stroke, Bethesda, MD, Bethesda, MD, United States

We have characterized the imaging correlates of subpial demyelination in the cerebral cortex of  MS patients by exploiting multiparametric postmortem qMRI and histopathology. MTsat, qT1 and AD were the measures that best captured subpial lesions pathology. Additionally, we found that some subpial lesions exhibit a juxta-cortical rim of increased susceptibility and show lower MWF than the ones without rim.

Jinhee Jang¹, Hyeong-Geol Shin², Hyebin Lee¹, Dohoon Park¹, Junghwa Kang³, Yoonho Nam³, Jongho Lee², and Woojun Kim^4
1Radiology, Seoul St. Mary's Hospital, Seoul, Korea, Republic of, ²Department of Electrical and Computer Engineering, Seoul National University, Seoul, Korea, Republic of, ³Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, Korea, Republic of, ⁴Neurology, Seoul St. Mary's Hospital, Seoul, Korea, Republic of

Using χ-separation, detailed characterization of MS and NMOSD lesions were possible. Majority (490/611, 80%) of MS lesions were hypo-diamagnetic on χ_neg maps, suggesting loss of diamagnetic myelin. On the contrary, only 14.2% (32/225) of NMOSD lesions were hypo-diamagnetic. On χ_pos maps, some MS and a few NMOSD lesions showed paramagnetic rim round the lesion, which was identical to paramagnetic rim sign on SWI or QSM. The proportion of hypo-diamagnetic lesions showed excellent diagnostic performances (AUROC 0.961, 95%CI 0.907-1), as compared to central vein sign and paramagnetic rim lesion sign. 

Zilin CHEN¹, Jianpan HUANG¹, Joseph H.C. LAI¹, Kai-Hei TSE², and Kannie W.Y. CHAN^1,3,4,5
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China, ²Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China, ³Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴City University of Hong Kong Shenzhen Research Institute, Shenzhen, China, ⁵Hong Kong Centre for Cerebro-Cardiovascular Health Engineering (COCHE), Hong Kong, China

Multiple sclerosis (MS) is a common demyelinating disease that heavily relies on differential diagnosis. Specific CEST contrast is known to be sensitive to alterations in proteins and lipids, the major components of myelin. This includes amide protons at 3.5 ppm and relayed nuclear Overhauser effect (rNOE) at -1.6~-3.5 ppm. Here, we study these CEST contrasts and their uniqueness towards myelin changes in a cuprizone model, which recapitulates remyelination and demyelination in MS. We observed substantial changes of rNOE and amide, during demyelination (P<0.05) and remyelination, indicating great potential of CEST MRI in monitoring myelin change and MS identification at 3T.

Yaoyu Zhang¹, Jialin Hu¹, Miao Zhang², Rong Guo^3,4, Yudu Li^3,4, Yibo Zhao^3,4, Ziyu Meng¹, Danni Wang¹, Wenli Li¹, Biao Li², Jun Liu⁵, Binyin Li⁵, Zhi-Pei Liang^3,4, and Yao Li^1
1School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China, ²Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ³Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁵Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Early and accurate diagnosis of AD is clinically important. Neurometabolic signals measured noninvasively by MRSI showed potential. Previous MRSI studies, limited to single voxel/slice techniques, could only examine neurometabolite concentration from limited brain regions. Using a high-resolution 3D MRSI technique, we assessed neurometabolic signature in AD by integrating neurometabolite concentrations from multiple brain regions. The discriminative power of global neurometabolic signature was evaluated in comparison with that of Aβ PET for both AD detection and predicting cognitive decline, showing promising results. The study provides a good foundation for further investigation using neurometabolic signature for early and accurate diagnosis of AD.

Zhihan Chen^1,2, Keliang Chen², Yuxin Li^1,2, Qianhua Zhao^1,2, and Liqin Yang^1,2
1Fudan University, Shanghai, China, ²Huashan Hospital, Shanghai, China

In this study, based on rs-fMRI, we analyzed the dynamic characteristics of 3 groups: MCI convert to AD within one-year follow-up (1Y_AD), stable in MCI within one-year follow-up (1Y_MCI) and revision from MCI within one-year follow-up (1Y_HC), including nodal entropy and measurements of dynamic brain functional network. We found that with the disease progression, the brain functional network was reconfigured into a highly-integrated/segregated pattern, and dwell time of highly-integrated pattern is associated with executive function in 1Y_AD. These findings provide the evidence for developing dynamic measurements as potential biomarkers for tracking mechanism of AD.

Yao Wang¹, Fuqing Zhou¹, Yaou Liu², and Qian Long ^3
1Department of Radiology, The First Affiliated Hospital of Nanchang University, Nanchang, China, ²Department of Radiology, Beijing Tiantan Hospital, Beijing, China, ³MR Research, GE Healthcare, Beijing, China

The study investigated gender-related differences in patients with multiple sclerosis by assessing static and dynamic functional connectivity within large scale functional networks. Our results observed that MS could eliminate the effect of gender on static and dynamic functional connectivity in healthy controls, and affect static connectivity in male patients and dynamic connectivty in female patients. Correlation analyses suggested these characteristics of static and dynamic connectivity were related to disability and gray matter volume. Thus, our findings underline the importance of gender in founctional impairment and reorganization in MS

Fuyan Li¹, Wei Zong¹, Fuxin Ren¹, Ning Li¹, Xiao Li¹, Zongrui Dai², Weibo Chen³, Muwei Li⁴, and Fei Gao^1
1Department of Radiology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China, ²Westa College, Southwest University, Chongqing, China, ³Philips Healthcare, Shanghai, China, ⁴Vanderbilt University Institute of Imaging Science, Nashville, TN, United States

Cognitive impairment is a common symptom of MS. GSH and Glu, keeping a homeostasis in the stable stage, were considered as key players in oxidative stress defending and synaptic plasticity, respectively. We aim to explore the changes of GSH and Glu levels and GSH-Glu couplings in RRMS and their association with cognitive impairment. Our findings indicate that oxidative stress and glutamatergic dysfunction may contribute to cognitive impairment of MS in a regional specificity manner. Hippocampal GSH-Glu decoupling may offer a crucial noninvasive measure of early cognitive impairment and provide a new strategy for the treatment of MS patients.

Sicong Tu¹, Arkiev D'Souza^1,2, Chenyu Wang^1,2, Christina Maher¹, Colin Mahoney¹, William Huynh¹, Michael Barnett^1,2,3, and Matthew Kiernan^1,3
1Brain and Mind Centre; The University of Sydney, Sydney, Australia, ²Sydney Neuroimaging and Analysis Centre, Sydney, Australia, ³Department of Neurology, Royal Prince Alfred Hospital, Sydney, Australia

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disorder with a widespread cortical disease signature. ALS patients demonstrate global network alterations in the white matter connectome in the early stage of disease. Selective disruption of cortical motor associated nodes with the thalamus and contralateral motor cortices is present at disease onset. Disease duration is associated with reduced structural interhemispheric cortical motor connectivity. Focal motor abnormalities present in the white matter connectome may be a sensitive marker in the earliest stages of ALS prior to functional decline.

Ziming Xu¹, Zhichao Chen², Lingyun Ma², Yajie Wang¹, Hao Wu³, Hao Lu⁴, Yong Ji², and Huijun Chen^1
1Center for Biomedical Imaging Research, School of Medicine, Tsinghua University, Beijing, China, ²Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing, China, ³Department of Neurology, Tianjin Huanhu Hospital, Tianjin, China, ⁴Department of Radiology, Tianjin Huanhu Hospital, Tianjin, China

Previous in vivo studies have shown that dysfunction of blood-brain barrier is highly associated with the process of Alzheimer’s disease (AD), but similar studies in dementia with Lewy bodies (DLB) have rarely been reported. In this study, for the first time, differences of BBB leakage among patients with AD, DLB and age-matched healthy control in different brain regions had been demonstrated, which may serve as one potential tool for diagnosis of different neurodegenerative diseases and contribute to our understanding of their pathophysiological basis.

Zhiyi Zhang¹, Haoru Jiang¹, Xiangru Sun¹, Xiaochun Wang¹, Bin Wang¹, Qiao Niu¹, Huaxing Meng¹, Jiangfeng Du¹, Guoqiang Yang¹, Bo Liu¹, Hui Zhang¹, and Yan Tan^1
1Shanxi Medical University, Taiyuan, China

In this work, we presented a study which investigated the diagnostic value of quantitative susceptibility mapping (QSM) in mild cognitive impairment (MCI) of occupational aluminum (Al) workers, we found that QSM might be a reliable neuroimaging marker for the diagnosis of MCI.

Anna Kiryanova¹, Andrei Manzhurtsev^1,2,3, Olga Bozhko^2,4, Yana Fedorova⁴, and Natalia Semenova ^1,2,3,5
1Lomonosov Moscow State University, Moscow, Russian Federation, ²Clinical and Research Institute of Emergency Pediatric Surgery and Trauma, Moscow, Russian Federation, ³Emanuel Institute of Biochemical Physics of RAS, Moscow, Russian Federation, ⁴Mental Health Research Center, Moscow, Russian Federation, ⁵Semenov Federal Research Center of Chemical Physics of the Russian Academy of Sciences., Moscow, Russian Federation

This study aims to identify possible biomarkers of minimal cognitive impairment (MCI) in the posterior cingulate cortex using MR spectroscopy. Absolute concentrations of metabolites such as Cr, NAA, Cho, Glx, Ins were determined in subjects with MCI and in subjects from the normal group. Our study revealed a statistically significant increase in the absolute concentration of choline-containing compounds, as well as the Cho/Cr value in PCC in the MCI group, what may indicate the destruction of cell membranes. The results expand our knowledge in understanding the causes of MCI and are promising for the study of Cho as biomarkers.

Yang Yang¹, Qiuyu Yu¹, Peng Wu², Hui Dai¹, Xiaojuan Wu¹, Shuting Han¹, and Yonggang Li^1
1The First Affiliated Hospital of Soochow University, Suzhou, China, ²Philips Healthcare, Shanghai, China

Cognitive impairment is a symptom present in part of patients with neuromyelitis optica spectrum disorder (NMOSD). We demonstrated decreased GABA levels in the medial prefrontal cortex (mPFC) in NMOSD participants compared to healthy controls. The mPFC GABA levels showed significant associations with cognitive performance in patients with NMOSD. This study suggested that the changes in regional GABA levels might be a potential metabolic feature of cognitive decline in patients with NMOSD.