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Caroline Guglielmetti^1,2, Christian Cordano³, Chloe Najac⁴, Ari Green³, and Myriam Chaumeil^1,2
1Department of Physical Therapy and Rehabilitation Science, University of California San Francisco, San Francisco, CA, United States, ²Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ³Department of Neurology, University of California San Francisco, San Francisco, CA, United States, ⁴Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, Leiden, Netherlands

Keywords: Multiple Sclerosis, Hyperpolarized MR (Non-Gas)

We used hyperpolarized ¹³C MR spectroscopy imaging (MRSI) in a multiple sclerosis model and showed that we could monitor immune cell activation by measuring hyperpolarized [1-¹³C]pyruvate conversion to lactate. We further demonstrated that this approach detected response to two existing treatments, fingolimod and dimethyl fumarate. We observed a reduction of pyruvate-to-lactate flux after treatment, that can be explained by increased pyruvate dehydrogenase activity and decrease of immune cells. In addition, we evaluated brain perfusion using hyperpolarized [¹³C]urea, but saw no therapy effect. Altogether, we demonstrated that hyperpolarized ¹³C MRSI has potential to monitor immunomodulatory therapies within the central nervous system.

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Ryn Flaherty¹, Yu Sui¹, and Mariana Lazar^1
1Radiology, New York University Grossman School of Medicine, New York, NY, United States

Keywords: Alzheimer's Disease, Neuroinflammation

Evidence suggests subjective cognitive decline (SCD) is an early risk factor for Alzheimer’s disease.  We analyzed the associations between memory and diffusion microstructure in the lower cingulum white matter bundle in SCD with DTI and NODDI. Better memory performance was associated with decreased free water volume fraction (FWVF) in the SCD group but not the control group. To the best of our knowledge, this is the first study to find differences in the associations between NODDI FWVF and memory in SCD in the lower cingulum. This finding supports prior findings of increased neuroinflammation in the earliest stages of Alzheimer’s Disease.

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Paul Condron^1,2, Haribalan Kumar ^1,3,4, Samantha Holdsworth^1,2, Daniel Cornfeld^1,2, and Graeme Bydder^1,5
1Mātai Medical Research Institute, Gisborne, New Zealand, ²Univeristy of Auckland, Auckland, New Zealand, ³Auckland Bioengineering Institute, Auckland, New Zealand, ⁴GE Healthcare, Victoria, Australia, ⁵University of California San Diego, San Diego, CA, United States

Keywords: Neuroinflammation, Multiple Sclerosis, neurodegeneration, MASDIR, Inversion Recovery (IR) sequences, tissue property filters

Keywords; Neuroinflammation, Multiple Sclerosis, Neuro, Drugs.

MASDIR sequences can show up to 15 times the contrast of T1-weighted MP-RAGE sequences. This is a consequence of using changes in T1 synergistically 3-4 times in the same sequence to detect subtle changes due to neuroinflammation and lesions. Extensive high contrast focal and diffuse abnormalities in white matter were demonstrated in areas that showed no abnormality with state-of-the-art T2-weighted spin echo and T2-FLAIR sequences in patients with multiple sclerosis. This demonstrated good correlation with advanced sequences such as T1 and myelin maps.

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Chunwei Ying¹, Peter Kang², Michael M. Binkley², Andria L. Ford^1,2, Yasheng Chen², Jason Hassenstab^2,3, Qing Wang^1,3, Jeremy Strain², John C. Morris³, Jin-Moo Lee^1,2, Tammie L. S. Benzinger^1,3,4, and Hongyu An^1,2
1Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, MO, United States, ²Department of Neurology, Washington University School of Medicine, St Louis, MO, United States, ³Knight Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, MO, United States, ⁴Department of Neurosurgery, Washington University School of Medicine, St Louis, MO, United States

Keywords: Dementia, Dementia

Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) pathologies commonly coexist in community-dwelling elderly. It is not discernible whether neuroinflammation and amyloid beta (Aβ) deposition are distinct or entangled pathophysiological mechanisms in patients with mixed AD and VCID pathologies. In this study, we found that neuroinflammation (measured by ¹¹C-PK11195 uptake) but not Aβ deposition (measured by ¹¹C-PiB binding), contributes to white matter hyperintensities baseline volume and progression. Both neuroinflammation and Aβ deposition independently contribute to cognitive impairment progression. Neuroinflammation and Aβ deposition represent two distinct pathophysiological pathways in elderly participants with mixed AD and VCID pathologies.

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Mariem Hamzaoui¹, Jeanne Garcia^1,2, Giacomo Boffa^1,3, Andrea Lazzarotto^1,2,4, Vito A G Ricigliano², Arya Yazdan Panah¹, Théodore Soulier¹, Celine Louapre¹, Benedetta Bodini^1,2, and Bruno Stankoff^1,2
1Sorbonne Université, Paris Brain Institute, ICM, CNRS, Inserm, Paris, France, paris, France, ²Department of Neurology, Saint- Antoine Hospital, APHP, Paris, France, paris, France, ³Department of Neurology, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy, genoa, Italy, ⁴Padova Neuroscience Center, University of Padua, Padua, Italy, padua, Italy

Keywords: Multiple Sclerosis, Neuroinflammation, [¹⁸F]-DPA-714, TSPO, Lesion individualization and phenotyping, disease progression

Positron emission tomography with18kDa-translocator (TSPO) tracers opens the perspective to image innate immune cells underlying the smoldering component of multiple sclerosis (MS), that currently mostly escape from MRI evaluation. Using [¹⁸F]-DPA-714-PET, we developed a novel lesion TSPO based classification of MS lesions and showed that an unexpectedly high proportion have a persistent neuroinflammatory content. A longitudinal follow up of subjects unraveled that this lesional smoldering component predicted atrophy and clinical progression. Following the acute phase, most lesions may therefore develop a chronic inflammatory component which can persist for several years, subsequently promoting neurodegeneration and clinical progression in MS.

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Jun Wang^1,2, Guangyao Liu^2,3, Kai Ai⁴, Pengfei Zhang¹, Wenjing Huang¹, and Jing Zhang^2,3
1Second Clinical School, Lanzhou University, Lanzhou, China, ²Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China, ³Gansu Province Clinical Research Center for Functional and Molecular Imaging, Lanzhou University Second Hospital, Lanzhou, China, ⁴Department of clinical science, Philips Healthcare, Xi’an, China

Keywords: Neuroinflammation, fMRI

The etiology of IBD complicated with anxiety, depression and other psychological comorbidities is still unclear. The purpose of this study was to quantify neurotransmitter (GABA and Glx) in the medial prefrontal cortex (mPFC) of IBD patients with MEGA-PRESS spectroscopy and explore its relationship with clinical scores. We found that mPFC GABA+ and Glx concentration were significantly decreased in IBD patients and were associated with abdominal pain and depressive symptoms separately, suggesting psychological comorbidities in IBD patients were related to mPFC neurotransmitter dysregulation. It provides a new explanation for the neuropsychological mechanism of IBD in the development of the disease.

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Osman Hatipoglu^1,2,3, Tsagkas Charidimos ^1,2,3,4, Mario Ocampo-Pineda^1,2,3, Lester Melie-Garcia^1,2,3, Matthias Weigel^1,2,3,5, Po-Jui Lu^1,2,3, Muhamed Barakovic^1,2,3, Julien Cohen-Adad^6,7,8, Ludwig Kappos^2,3, Jens Kuhle^2,3, and Cristina Granziera^1,2,3
1Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland, ²Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland, ³Neurologic Clinic and Policlinic, Departments of Head, Spine and Neuromedicine, University Hospital Basel, Basel, Switzerland, ⁴Translational Neuroradiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH), Bethesda, MD, United States, ⁵Division of Radiological Physics,Department of Radiology, University Hospital Basel, Basel, Switzerland, ⁶Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montreal, QC, Canada, ⁷NeuroPoly Lab, Institute of Biomedical Engineering, Polytechnique Montreal, Montreal, QC, Canada, ⁸Mila, Quebec AI Institute, Montreal, QC, Canada

Keywords: Multiple Sclerosis, Spinal Cord

The utility of advanced quantitative MRI for assessment of spinal cord tissue damage in multiple sclerosis has not yet been established. In this work, we used T1-mapping as well as quantitative magnetization transfer saturation and echo-planar imaging to quantify the extent of pathologic changes in the cervical cord of multiple sclerosis patients. Our results point to extensive demyelination and axonal loss both in the normal-appearing and lesional cervical cord, as well as to and chronic inflammation of cSCWM lesions in secondary progressive multiple sclerosis. Hence, quantitative spinal cord MRI may provide valuable information about the pathologic substrate of this disease.

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Evgeniya Kirilina¹, Luke Edwards¹, Carsten Jäger^1,2, Tilo Reinert¹, Anna Jauch¹, Malte Brammerloh^1,3, Karl-Heinz Herrmann⁴, Patrick Scheibe¹, Felix Büttner^1,3, Dennis Brückner⁵, Gerald Falkenberg⁵, Jürgen R. Reichenbach⁴, and Nikolaus Weiskopf^1
1Neurophysics, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Paul Flechsig Institute - Center of Neuropathology and Brain Research, Leipzig, Germany, ³Faculty of Physics and Earth Sciences, Leipzig University, Leipzig, Germany, ⁴Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany, ⁵PETRA III, Deutsches Elektronen-Synchrotron DESY, Hamburg, Germany

Keywords: Alzheimer's Disease, Contrast Mechanisms, iron, plaques, posterior cortical atrophy, cortex

We combined ultra-high resolution quantitative MRI, X-ray fluorescence, and biophysical modeling to study iron-induced MRI contrast in the visual cortex of patients with Alzheimer’s disease (AD) and its variant posterior cortical atrophy (PCA). The iron content of amyloid plaques in patients with PCA and AD exceeded the iron concentration in the surrounding tissue by less than 15%, constituting only a minor contribution to the intracortical T2* contrast. The elevated levels of brain iron detected by iron-sensitive MRI contrasts are not indicative of plaques but may reflect other processes, such as inflammation or leakage in the blood-brain barrier.

Ling Fang¹, Matthew C. Murphy², Sha Tan³, Qiuxia Luo¹, Jingbiao Chen¹, Bingjun He¹, Jun Chen², Jonathan M. Scott², Kevin J. Glaser², Richard L. Murphy², Wei Qiu³, and Jin Wang^1
1Department of Radiology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, ²Department of Radiology, Mayo Clinic, Rochester, MN, United States, ³Department of Neurology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Keywords: Multiple Sclerosis, Elastography

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. MR Elastography (MRE) can quantitatively assess biomechanical tissue properties in vivo noninvasively. We investigated the potential value of MRE to reveal changes in tissue viscoelasticity in regions and the whole brain in MS patients and to analyze the relevance to clinical manifestations. Our results suggest that the damping ratio and loss modulus are promising quantitative biomarkers for evaluating tissue damage in MS.

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Keywords: Neuroinflammation, Infectious disease, Alcohol Use

Chronic alcohol use and HIV infection can have synergistic effects that negatively impact the brain leading to abnormalities such as neuro-inflammation. Free-water eliminated DTI (FWE-DTI) has been suggested as a biomarker of neuro-inflammation. This study compare DTI and FWE-DTI derived metrics in the brains of HIV+/HIV- chronic drinkers to determine whether HIV infection or drinking behavior is a more significant factor contributing to brain microstructural abnormalities and neuro-inflammation. Our results suggest that HIV is a more significant factor than drinking level contributing to elevated free water in the brain as a sign of neuro-inflammation.

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Mada Hashem^1,2,3, A. Max Hamilton^1,2,3, and Jeff F. Dunn^1,2,3
1Department of Radiology, University of Calgary, Calgary, AB, Canada, ²Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada, ³Experimental Imaging Centre, University of Calgary, Calgary, AB, Canada

Keywords: Multiple Sclerosis, Animals, arterial spin labeling, high field MRI

While multiple sclerosis (MS) is typically considered a white matter disease, there is prominent evidence that gray matter pathology, such as hypoxia, disruptions in metabolic rate and mitochondrial dysfunction are involved as well. We are applying a novel multimodal technique combining near-infrared spectroscopy and high-field MRI to study the mitochondrial status as well as oxygen delivery and consumption in the cortex of the EAE mouse model of MS. Reduced perfusion, and consequent hypoxia, with abnormal mitochondrial regulation and no change in consumption rate were found in EAE mice. Hypoxia and mitochondrial damage are likely to exacerbate the pathology in MS.

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Kelly M Gillen¹, Thanh D Nguyen¹, Alexey Dimov¹, Emily Demmon², Ilhami Kovanlikaya¹, Francesca Bagnato^3,4, Dominick Romano¹, David Pitt⁵, Susan Gauthier², and Yi Wang^1
1Department of Radiology, Weill Cornell Medicine, New York, NY, United States, ²Department of Neurology, Weill Cornell Medicine, New York, NY, United States, ³Department of Neurology, TN Valley HealthCare VA Medical System, Nashville, TN, United States, ⁴4Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Department of Neurology, Yale School of Medicine, New Haven, CT, United States

Keywords: Multiple Sclerosis, Quantitative Susceptibility mapping, Phase, iron

Multiple Sclerosis (MS) is an autoimmune disorder characterized by focal inflammatory demyelination. Chronic MS lesions can contain chronically activated, iron-laden microglia and macrophages. By comparing rim status on quantitative susceptibility mapping (QSM) and phase imaging with histopathology that identifies iron, we demonstrate that QSM is a more reliable indicator of iron status than phase. QSM is a valuable clinical tool to identify iron positive smoldering lesions not visible using conventional MRI techniques.

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Olivia Jones^1,2, Saffwan Mohamed³, Rainer Hinz^2,4, Ben Dickie^2,4, Laura Parkes^1,2, and Adrian Parry-Jones^2,3,5
1Division of Psychology, Communication and Human Neuroscience, University of Manchester, Manchester, United Kingdom, ²Geoffrey Jefferson Brain Research Centre, Manchester, United Kingdom, ³Division of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom, ⁴Division of Informatics, Imaging & Data Sciences, University of Manchester, Manchester, United Kingdom, ⁵Manchester Centre for Clinical Neurosciences, Northern Care Alliance NHS Foundation Trust, Manchester, United Kingdom

Keywords: Neuroinflammation, PET/MR

Intracerebral hemorrhage is a severe form of stroke. Secondary injury involves a cascade of pathophysiological changes thought to begin with microglial activation and result in blood-brain barrier(BBB) breakdown and edema formation. In this study, patients underwent dynamic contrast-enhanced MRI and [¹¹C](R)-PK11195 PET, which measure BBB leakage and binding to the translocator protein 18kDa (TSPO) expressed on activated microglia, respectively. BBB leakage and TSPO binding were elevated in the edema.  Mean co-localisation of BBB leakage and TSPO binding was 5.6%; drugs targeting inflammation may cross the BBB into 0-28% of target tissue. Modified Rankin Scale scores negatively correlated with BBB leakage.

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Keywords: Infectious disease, Spectroscopy

With the advent of antiretroviral therapy (ART), perinatally HIV-infected children have been able to transition into adulthood. However, the long term impact of HIV infection and the potential toxic effects of long term use of antiretroviral therapeutics on brain metabolites are not completely characterized. In this study, a whole-brain MRSI method is used to quantitate changes in brain metabolites, N-acetyl aspartate (NAA), total-creatine (Cr) and total-choline (Cho), in PHIV+ adults compared to matched controls. Results show significant alterations of proton MRS-observed metabolites in the whole brain of PHIV+ as they reach adulthood despite their adherence to ART.

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Anna Caroli¹, Serena Capelli¹, Angela Napolitano², Giulia Cabrini³, Alberto Arrigoni¹, Giulio Pezzetti², Mattia Previtali¹, Luca Giovanni Longhi⁴, Rosalia Zangari⁵, Ferdinando Luca Lorini⁶, Maria Sessa⁷, Andrea Remuzzi³, and Simonetta Gerevini^2
1Bioengineering Department, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Ranica (BG), Italy, ²Department of Neuroradiology, ASST Papa Giovanni XXIII, Bergamo, Italy, ³University of Bergamo, Bergamo, Italy, ⁴Neurosurgical Intensive Care Unit, Department of Anesthesia and Critical Care Medicine, ASST Papa Giovanni XXIII, Bergamo, Italy, ⁵FROM Research Foundation, ASST Papa Giovanni XXIII, Bergamo, Italy, ⁶Department of Emergency and Critical Care Area, ASST Papa Giovanni XXIII, Bergamo, Italy, ⁷Department of Neurology, ASST Papa Giovanni XXIII, Bergamo, Italy

Keywords: Infectious disease, COVID-19

This study aimed at quantifying brain diffusion alterations on DWI scans in 215 COVID-19 patients with neurological manifestations as compared with 36 normal controls. The Apparent Diffusion Coefficient (ADC) was quantified in brain tissues and regions, using an in-house MRI processing procedure. In COVID-19 patients, a widespread significant increase in ADC was found in white matter. ADC values were significantly correlated with MRI time from disease onset. ADC alteration was highest in hospitalized patients. Patients with neurological disorders showed significantly higher ADC than those with olfactory loss only. DWI shows potential as a non-invasive marker of neuroinflammation in COVID-19.