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Franklyn A Howe¹, Daniel Richardson², Lauren Binnie³, Uzma Khan⁴, Philip Rich⁴, Daniel HJ Davis⁵, Atticus H Hainsworth², and Jeremy Isaacs^3
1Neurosciences Research Section, St George's, University of London, London, United Kingdom, ²Neurosciences Research Section, St George's, University of London, LONDON, United Kingdom, ³Dept Neurology, St George's University Hospital Foundation Trust, LONDON, United Kingdom, ⁴Neuroradiology, St George's University Hospital Foundation Trust, LONDON, United Kingdom, ⁵MRC Unit for Lifelong Health and Ageing, University College London, LONDON, United Kingdom

Myo-Inositol is sometimes considered a marker of brain inflammation and studies indicate mI (mI/tCr) increases with age up to the 6th decade. We performed 1H MRS in four brain regions of very elderly hospitalised patients (n=25, aged 67-90 yrs) of which 12 had delirium. Elevated mI/tCr was associated with increasing Fazekas score for white matter damage (p<0.001) in all regions. In addition mI/tCr and mI/NAA showed negative correlation with age (p<0.001). There were no significant differences between patients with or without delirium. Decreased mI/tCr due to reduced glial cell numbers or dysfunction may coincide with increased mI/tCr associated with inflammation.

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In this study, we showed that structural disconnectivity due to T2 FLAIR lesions in the ventral attention and subcortical networks, in particular within the supramarginal and putamen, occurs earlier in the sequence of disability (i.e., mild to severe) in multiple sclerosis. We also showed that paramagnetic rim lesion (PRL)-based structural disconnectivity in motor-related regions occurs earlier in the disability event sequence, followed by non-PRL-based structural disconnectivity in the caudate and postcentral gyrus. T2 FLAIR lesion-based structural disconnectivity in subcortical regions, including the thalamus, occurs earliest in the sequence of cognitive impairment (i.e. preserved to impaired).

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Alzheimer’s Disease (AD) is characterized by increased inflammation and increased glucose utilization as detected by FDG-PET. Using a new deuterium MRI method based on a [D₇]glucose tracer, we can image the brain of a mouse model of AD with in plane resolution approaching 1 mm. Mass spectrometry imaging of the same brains shows characteristic changes in protein associated glycans that correlate well with immunohistochemical staining for inflammation. We believe this new research pipeline can provide powerful new insights into AD pathophysiology.  

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This study focused on the slight quantitative changes of brain structures based on the high-resolution brain MRI and automatic segmentation with neural fingerprint technology for whole-brain of depressive patients. We found the volume changes of specific regional sub-structures, which were related to emotion and spirit, such as the cingulate gyrus, cuneiform lobe, hippocampus, et al before clinical diagnosis. Depression revealed the gender difference. The male depressions were more sensitive to hippocampus, while female’s were more sensitive to entorhinal cortex. It might indicate ovarian hormone fluctuations modulate women’s susceptibility to stress, brain structure/function, and inflammatory activity and reactivity.  

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T₂w imaging could assist in the early diagnosis of multiple sclerosis (MS). However, these scans are inherently qualitative, and variable intensities in the images depend on hardware and acquisition parameters. On the other hand, standardized quantitative T₂ maps can serve as a sensitive biomarker of MS and the longitudinal assessment of the disease progression. In this abstract, we present the first results demonstrating that calculating T₂ maps from vendor T₂w sequence is feasible, which could allow for an earlier diagnosis of MS disease.

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Eva Periche-Thomas¹, Itamar Ronen², Claire MacIver¹, Dmitri Sastin¹, Jonathan Underwood¹, James Coulson¹, Helena Leach¹, Francesca Branzoli³, Mara Cercignani¹, and Neil Harrison^1
1CUBRIC, Cardiff University, Cardiff, United Kingdom, ²CISC, Brighton and Sussex Medical School, Brighton, United Kingdom, ³ICM-Paris Brain Institute, Paris, France

Age-associated cognitive decline and neurodegenerative disorders have been linked to altered immune function and inflammation, and particularly to the role of microglia. Current methods for imaging (micro)glia in humans are limited to TSPO-PET, a costly and invasive technique with poor cellular specificity. Here we acquired diffusion weighted (DW) MRS in 15 young and 15 older participants, each scanned twice, after Interferon-1beta or placebo. Results supported our prior hypotheses of selective effects of Interferon-1beta on the apparent diffusion coefficient of thalamic Choline (p<0.040), providing support for DW-MRS as a novel in-vivo method for quantifying glial morphology.

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Cristiana Fiscone¹, Leonardo Rundo², Alessandra Lugaresi^1,3, David Neil Manners¹, Kieren Allinson⁴, Elisa Baldin⁵, Raffaele Lodi^1,6, Caterina Tonon^1,6, Claudia Testa^6,7, Mauro Castelli⁸, and Fulvio Zaccagna^9,10,11
1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, ²Department of Information and Electrical Engineering and Applied Mathematics, University of Salerno, Salerno, Italy, ³UOSI Riabilitazione Sclerosi Multipla, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, ⁴Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, ⁵Epidemiology and Statistics Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, ⁶Functional and Molecular Neuroimaging Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, ⁷Department of Physics and Astronomy, University of Bologna, Bologna, Italy, ⁸NOVA Information Management School, Universidade NOVA de Lisboa, Lisbon, Portugal, ⁹Department of Imaging, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom, ¹⁰Department of Radiology, University of Cambridge, Cambridge, United Kingdom, ¹¹Radcliffe Department of Medicine, Investigative Medicine Division, University of Oxford, Oxford, United Kingdom

This work evaluates the reliability of radiomic features in healthy controls and patients with multiple sclerosis using MR Quantitative Susceptibility Mapping (QSM), to guide the identification of future potential biomarkers. To ensure reproducibility, we assessed the non-lesioned parenchyma. Feature robustness was evaluated against the number of grey levels and echo times, measuring the Intraclass Correlation Coefficient (ICC). More than 65% of features were robust; different outcomes between regions were interpreted considering their anatomical characteristics (e.g. fibres’ orientation), confirmed by radiomic measurements (e.g. entropy). In future work, we are going to assess characterization and classification potential of those measurements.

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Clinically relevant non-invasive blood-brain barrier (BBB) function imaging techniques are needed to monitor the role of neuroinflammation and endothelial cell dysfunction, particularly in small vessel disease (SVD). Diffusion-weighted ASL measures water exchange rate (k_w), a promising endogenous BBB function metric, but has not been assessed in sporadic SVD. We measured k_w in SVD patients to explore associations with established Gadolinium-based contrast agent (GBCA) BBB permeability measures and SVD severity. We found only limited associations between k_w and GBCA metrics, although patients with more severe SVD tended to have higher k_w, reflecting that the methods may probe different mechanisms.

Rui Shen¹, Jiachen Liu¹, Chenyang Zhao², Ning Xu¹, Shuwan Yu¹, Huiyu Qiao¹, Zihan Ning¹, Hualu Han¹, Zixuan Lin³, Hanzhang Lu⁴, Haiyan Ding¹, and Xihai Zhao^1
1Center for Biomedical Imaging Research, Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China, ²Department of Radiology, the Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, China, ³College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China, ⁴Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baldimore, MD, United States

We investigated the short-term changes in brain structure, perfusion and oxygen metabolism in young adult patients infected with SARS-COV-2 Omicron but with mild symptoms in China using multimodal MRI. The clinical and brain MR imaging characteristics were compared between patient group (n=98) and healthy control group（n=50). Our findings suggest that there are no significant short-term changes in brain structure, perfusion and oxygen metabolism determined by multimodal MR imaging in young adult patients infected with SARS-CoV-2 Omicron. The potential trend of decline in the volume of cerebral nucleus in the patient group needs further investigation.

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The Diffusion Bubble Model (DBM) is a new method for detecting neuroinflammation in the brains of mice with Sanfilippo Syndrome. This rare and debilitating disorder primarily affects children and causes progressive neurodegeneration. DBM utilizes diffusion spectrum derived from dMRI to detect brain injuries such as inflammation. It can work in both white and gray matter with limited number of diffusion directions. The study found that brain injuries with inflammation  had reduced the fraction of the slow diffusion component and increasing the fraction of the fast diffusion component. The findings may establish non-invasive biomarkers for detecting and evaluating neuroinflammation diseases.

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Myrte Strik¹, Warda T Syeda¹, Yasmin Blunck^1,2, Vivien Li^3,4,5, Rebecca Glarin¹, Scott C Kolbe⁶, Bradford A Moffat¹, Leigh A Johnston^1,2, Elaine Lui^1,7,8, and Trevor J Kilpatrick^3,4,5
1Radiology, Melbourne Brain Centre Imaging Unit, University of Melbourne, Melbourne, Australia, ²Biomedical Engineering, University of Melbourne, Melbourne, Australia, ³Neuroimmunology and Remyelination Laboratory, Florey Institute for Neuroscience and Mental Health, Melbourne, Australia, ⁴Florey Department of Neuroscience and Mental Health, University of Melbourne, Melbourne, Australia, ⁵Neurology, Royal Melbourne Hospital, Melbourne, Australia, ⁶Research Partnerships & Translation, RMIT University, Melbourne, Australia, ⁷Radiology, University of Melbourne, Melbourne, Australia, ⁸Radiology, Royal Melbourne Hospital, Melbourne, Australia

Multiple sclerosis patients may need to switch disease modifying treatments due to various reasons, with risk of recurrent disease activity during transition period. Identifying patients at risk is challenging. In this pilot study we used a non-conventional quantitative multi-modal 7T MRI approach to assess evolution of lesions when switching medication. We observed altered diffusion, susceptibility and T1 values three months after stopping, and these metrics returning to baseline values three months after starting new medication. Multi-modal quantitative MR techniques at ultra-high field MRI may be more sensitive to detect subtle changes over time to potentially better inform underlying disease activity.

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Anna Stölting¹, Colin Vanden Bulcke^1,2, Benoit Macq², and Pietro Maggi^1
1Neuroinflammation Imaging Lab, Université catholique de Louvain, Brussels, Belgium, ²ICTEAM Institute, Université catholique de Louvain, Louvain-la-Neuve, Belgium

Paramagnetic Rim Lesions (PRL) in Multiple Sclerosis (MS) are associated with increased disability and axonal damage. We examined PRL microstructure using Track Density Imaging (TDI) and four diffusion MRI (dMRI) models, including Microstructure Fingerprinting (MF). When compared to non-PRL, PRL showed larger size, higher T1-values, lower neurite density index and fibre volume fraction on dMRI (p < 0.001) and reduced track density on TDI (p < 0.0001), suggesting impaired axonal density/integrity in PRL. Results obtained with the novel MF model are in line with those obtained with other dMRI models, indicating its potential for studying MS lesion pathology.

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Sebastian Endt^1,2,3,4, Carolin M Pirkl³, Marco Palombo⁴, and Marion I Menzel^1,2,3
1AImotion Bavaria, Technische Hochschule Ingolstadt, Ingolstadt, Germany, ²Technical University of Munich, Munich, Germany, ³GE HealthCare, Munich, Germany, ⁴Cardiff University Brain Research Imaging Center (CUBRIC), Cardiff University, Cardiff, United Kingdom

We present MicroCoP, a flexible tool for the generation of digital Microstructure Correlation Phantoms that can be used to benchmark multicomponent MRI reconstruction methods. The phantoms provide ground-truth distributions for the MR tissue parameters of your choice. These can be fed into forward simulations and thus provide a pair of ground-truth distributions and resulting signal evolutions to thoroughly evaluate multicomponent MRI reconstruction methods.

Jack Reeves¹, Fahad Salman¹, Michael G Dwyer^1,2, Niels Bergsland¹, Bianca Weinstock-Guttman³, Sarah Muldoon⁴, Robert Zivadinov^1,2, and Ferdinand Schweser^1,2
1Buffalo Neuroimaging Analysis Center, Buffalo, NY, United States, ²Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, Buffalo, NY, United States, ³Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Buffalo, NY, United States, ⁴Department of Mathematics, University at Buffalo, Buffalo, NY, United States

Deep gray matter (DGM) iron dyshomeostasis has been linked to neuroinflammation in multiple sclerosis (MS). In the present work, we hypothesized that a novel correlation analysis of magnetic susceptibility co-fluctuations between DGM regions reveals short-term (<1 year) MS-related iron dyshomeostasis that is undetectable with conventional ROI-based methods. Our results showed the correlations-based analysis was more sensitive to MS vs HC group differences than the standard ROI-based approach. A simulation indicated that the MS-related differences may be due to neuroinflammatory-based disruption to normal aging-related iron accumulation. Our methodology may be applied to study neuroinflammatory diseases at short timescales not previously possible.

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Quantitative brain atlases can be combined in multiparametric characterisations of the same template voxel with a number of microstructure-sensitive quantities, potentially enabling earlier and more specific characterisation of changes caused by disease. We combine in this study two quantitative atlases, absolute water content and myelin water fraction, to generate a novel atlas describing absolute myelin water content. This is relevant as a baseline for investigating changes in inflammatory diseases involving both demyelination and brain edema. The accompanying relaxometric parameters R2* and R2 are combined in an atlas of the reversible relaxation rate R2’. Fibre tract-specific distributions and correlations are found.