Roy AM Haast¹, Dimo Ivanov², Ali R Khan^1,3, Irenaeus FM de Coo⁴, Elia Formisano^2,5, and Kamil Uludag^6,7
1Robarts Research Institute, Western University, London, ON, Canada, ²Department of Cognitive Neuroscience, Maastricht University, Maastricht, Netherlands, ³Department of Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, ⁴Department of Genetics and Cell Biology, Maastricht University, Maastricht, Netherlands, ⁵Maastricht Center for Systems Biology, Maastricht University, Maastricht, Netherlands, ⁶Institute for Basic Science, Center for Neuroscience Imaging Research, Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Republic of Korea, ⁷University Health Network, Toronto, ON, Canada

The m.3243A>G mutation is the most commonly observed mitochondrial mutation in humans. It causes a wide range of phenotypes, ranging from normal healthy aging to a severely affected quality of life through neuroradiological changes and cognitive impairment. Here, we studied the cerebellar changes in these patients and showed significant local reductions in gray matter tissue volume and functional connectivity using 7T MRI. Interestingly, its white matter remains relatively intact. Taken together, the current results contributes to the still limited understanding of brain pathologies in m.3243A>G patients.

Riccardo Pascuzzo¹, Vikram Venkatraghavan², Marco Moscatelli¹, Marina Grisoli¹, Esther E. Bron², Stefan Klein², Janis Blevins³, Gianmarco Castelli¹, Lawrence B. Schonberger⁴, Pierluigi Gambetti⁵, Brian S. Appleby³, and Alberto Bizzi^1
1Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy, ²Biomedical Imaging Group Rotterdam, Departments of Medical Informatics & Radiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands, ³National Prion Disease Pathology Surveillance Center, Case Western Reserve University, School of Medicine, Cleveland, OH, United States, ⁴National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, United States, ⁵Department of Pathology, Case Western Reserve University, School of Medicine, Cleveland, OH, United States

The subtypes of sporadic Creutzfeldt-Jakob disease (sCJD), determined only at autopsy, may have different abnormality patterns in diffusion-weighted magnetic resonance imaging (DW-MRI) according to few reports. For the first time, we provide temporal cascades of the DW-MRI abnormalities in seven distinct sCJD subtypes using a data-driven technique named “discriminative event-based model”. Based on these cascades, we propose a novel procedure to identify the subtype of a patient. We found that sCJD subtypes have either initial cortical (MM/MV1, MM/MV2C, VV1 subtypes) or subcortical involvement (MV2K and VV2) with specific orderings of DW-MRI abnormalities, allowing a correct subtype prediction in most cases.

Laura W.M. Vergoossen^1,2, Jacobus F.A. Jansen^1,2,3, Thomas T. van Sloten^4,5, Miranda T. Schram^2,4,5, Walter H. Backes^1,2, and on behalf of The Maastricht Study^4
1Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, ³Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, ⁴Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ⁵School for Cardiovascular Disease, Maastricht University, Maastricht, Netherlands

White matter hyperintensities interfere with the course of white matter tracts, and disrupt connections between gray matter regions. This process might potentially underlie cognitive decline. In the large population-based Maastricht Study (n=5083), we found an association of lower processing speed scores with larger white matter hyperintensities and smaller total tract volumes in important processing speed related white matter tracts. These findings provide more insight into how white matter hyperintensities seem to influence the cognition-sensitive organization of white matter tracts.

Ji Won Bang¹, Anna M Chen^1,2, Carlos Parra¹, Gadi Wollstein¹, Joel S Schuman¹, and Kevin Chan^1,3
1Department of Ophthalmology, New York University, New York, NY, United States, ²Sackler Institute of Graduate Biomedical Sciences, New York University, New York, NY, United States, ³Department of Radiology, New York University, New York, NY, United States

Glaucoma is considered to involve neurochemical alterations in the visual system. While the role of excitotoxicity in glaucoma remains controversial, we showed that the balance between glutamate, a main excitatory signal, and gamma-aminobutyric acid (GABA), a main inhibitory signal, is involved in glaucoma pathogenesis. We demonstrated that the visual cortex of glaucoma patients changes to an excitatory-dominant state and that this change is driven by reduced GABA. Additionally, we showed that visual field loss is associated with reduced N-acetyl-aspartate, a marker for neuronal integrity. Taken together, these findings suggest that neurochemical alterations may serve as informative markers for glaucoma.

Jean-Baptiste Perot^1,2, Clement M. Garin^1,2, Salma Bougacha^1,2,3,4, Alexandra Durr^5,6, Marc Dhenain^1,2, Sandrine Humbert⁷, Emmanuel Brouillet^1,2, and Julien Flament^1,2
1Molecular Imaging Research Center (MIRCen), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Fontenay-aux-Roses, France, ²UMR 9199, Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France, ³Inserm UMR-S U1237, Normandie University, UNICAEN, GIP Cyceron, Caen, France, ⁴Inserm U1077 Neuropsychologie et Imagerie de la mémoire Humaine, Normandie University, UNICAEN, EPHE, CHU de Caen, Caen, France, ⁵Inserm UMR-S U1127, Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, Paris, France, ⁶Département de génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP, Paris, France, ⁷Inserm U1216, Grenoble Institut des Neurosciences (GIN), Univ. Grenoble Alpes, Grenoble, France

Huntington’s disease (HD) is an inherited neurodegenerative disease characterized by cognitive, motor and psychiatric symptoms. Despite tremendous efforts made during past years, there is a need for more predictive and functional biomarkers of disease pathogenesis and progression. In the present study, we developed a longitudinal and multimodal imaging protocol to elucidate HD pathogenesis in a mouse model of HD and to evaluate the potential of different biomarkers. Our approach combining volume, gluCEST and magnetization transfer imaging and automated brain segmentation revealed a brain network particularly vulnerable in this model.

Alena Svatkova¹, Lenka Minarikova², Petr Bednarik², Verena Rosenmayr³, Gilbert Hangel², Bernhard Strasser⁴, Lukas Hingerl², Thomas Stulnig³, and Stephan Gruber^2
1Department of Medicine III, Medical University of Vienna, Vienna, Austria, ²High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ³Clinical Division for Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, Vienna, Austria, ⁴Athinoula A. Martinos Center for Biomedical Imaging, Boston, MA, United States

While glycosaminoglycan deposition in Mucopolysaccharidosis type II, a rare X-linked lysosomal storage disorder, unquestionably alters the brain, metabolic and microstructural MR markers have not been yet established. Thus, we utilized 3T diffusion MRI and fine-tuned semi-LASER MR spectroscopy as well as in-house developed 7T 3D-FID-MRS imaging to examine differences between seven MPSII and eight age-matched healthy males. Analyses revealed profound deficit in the supratentorial white matter consistent with de/dysmyelination on both diffusion and spectroscopy as well as decrease of neuronal population or hypometabolism measured as glutamate deficit in the posterior cingulate cortex, which is a critical hub of neurocognitive networks.

Radjiv Goulabchand^1,2,3, Veronica Ravano^4,5,6, Mário João Fartaria^4,5,6, Ricardo Corredor-Jerez^4,5,6, Elodie Castille^1,3, Sophie Navucet⁷, Alexandre Maria^1,2,8, Alain Le Quellec^1,2, Emmanuelle Le Bars^9,10,11, Audrey Gabelle^2,7,12, Philippe Guilpain^1,3,8, Nicolas Menjot de Champfleur^9,10, and Bénédicte Maréchal^4,5,6
1Département de médecine interne et maladies multi-organiques, Hôpital Saint Eloi, CHRU Montpellier, Montpellier, France, ²Médecine interne, CHU de Nîmes, Nîmes, France, ³Faculté de médecine, Université de Montpellier, Montpellier, France, ⁴Advanced Clinical Imaging Technology, Siemens Healthcare AG, Lausanne, Switzerland, ⁵Department of Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland, ⁶LTS 5, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland, ⁷Centre Mémoire de Ressources et de Recherche, Hôpital Gui De Chauliac, CHRU Montpellier, Montpellier, France, ⁸IRMB, INSERM, CHU Montpellier, Montpellier, France, ⁹Département d’imagerie médicale, Hôpital Gui de Chauliac, CHRU Montpellier, Montpellier, France, ¹⁰Institut d'Imagerie Fonctionnelle Humaine (I2FH), Hôpital Gui de Chauliac, Centre Hospitalier Régional Universitaire de Montpellier, Montpellier, France, ¹¹Laboratoire Charles Coulomb, CNRS UMR 5221, Université de Montpellier, Montpellier, France, ¹²Laboratoire de Biochimie-Protéomique Clinique - IRMB - CCBHM - Inserm U1183, CHU Montpellier, Hôpital St-Eloi - Université Montpellier, Montpellier, France

To date, neuropsychiatric profiles in Sjögren’s syndrome patients are not explained by the immunological profile or clinical symptoms. Consequently, there is a lack of biomarkers potentially characterizing such profiles for this rare autoimmune disease. Our goal was to investigate the potential of MRI-based features to objectively explain fatigue, depression and cognitive complaints in twenty-nine patients with primary Sjögren’s syndrome. Specifically, we explored features from automated brain morphometry and brain lesion segmentation as potential imaging biomarkers. Z-score differences in certain brain structures (thalamus, corpus callosum, ventricles, and insula) were found, suggesting an association between MRI-based biomarkers and patient’s neuropsychiatric profiles.

shuai xu¹, ye yao², jing ding³, and he wang*^4,5
1Fudan University, Shanghai, China, ²School of Public Health, Fudan University, Shanghai, China, ³Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China, ⁴Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, ⁵Human Phenome Institute, Fudan University, shanghai, China

Grouping based on white matter hyperactivities (WMH) of each white matter tract, 15 idiopathic normal pressure hydrocephalus (iNPH) patients’ 10 gait index were compared by double sample t test. The results showed some white matter tracts with strongest gait index relationships located in motor and sensory pathways including middle cerebellar peduncle (MCP), left medial lemniscus, left posterior limb of internal capsule and right posterior limb of internal capsule.

Sicong Tu^1,2, Matthew Kiernan¹, and Martin Turner^2
1Brain and Mind Centre, The University of Sydney, Sydney, Australia, ²Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom

Amyorophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition affecting the motor system, but increasingly recognised as a multi-system disease. We present two studies that highlight disease specific patterns of abnormality in the thalamus and corpus callosum that suggest regional variation in neural relay structures may be promising markers of disease progression in ALS.

Teddy Salan¹, Sameer Vyas², Paramjeet Singh², Mahendra Kumar³, Sulaiman Sheriff¹, and Varan Govind^1
1Radiology, University of Miami, Miami, FL, United States, ²Postgraduate Institute for Medical Education & Research, Chandigarh, India, ³Psychiatry and Behavioral Sciences, University of Miami, Miami, FL, United States

Several studies have focused on diffusion tensor imaging (DTI) as marker for structural damage in the brain due to infection from human immunodeficiency virus (HIV). However, few have associated the findings from diffusion kurtosis imaging (DKI) and magnetic resonance spectroscopic imaging (MRSI) measures. In this work, we correlate measures of DTI and DKI with MRSI in order to evaluate  associations between structural alterations and changes in metabolite concentrations within the brain of HIV individuals.