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Gina D'Souza^1,2, Nathan W. Churchill^2,3,4, Dylan X. Guan⁵, Marc A. Khoury^1,2, Corinne E. Fischer^1,2,6, and Tom A. Schweizer^1,2,3,7,8
1Institute of Medical Science, University of Toronto, Toronto, ON, Canada, ²Keenan Centre for Biomedical Research, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON, Canada, ³Neuroscience Research Program, St Michael's Hospital, Toronto, ON, Canada, ⁴Physics Department, Toronto Metropolitan University, Toronto, ON, Canada, ⁵Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ⁶Department of Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, ⁷Division of Neurosurgery, Department of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON, Canada, ⁸The Institute of Biomaterials & Biomedical Engineering, University of Toronto, Toronto, ON, Canada

Keywords: Alzheimer's Disease, Traumatic brain injury

Traumatic Brain Injury (TBI) is associated with an accelerated course of dementia, although biological relationships are still incompletely understood. We characterized the differences in cortical thickness, for Alzheimer’s Disease (AD) patients with and without a history of TBI. Among individuals diagnosed with AD, a history of TBI was associated with a smaller decrease in cortical thickness in frontal-temporal regions, relative to their non-AD counterparts, with analyses controlling for the effects of age, sex, and education. TBI may lower the susceptibility threshold for cognitive decline related to AD by decreasing an individuals’ ability to cope with aging and/or AD pathology.

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Jason Langley¹ and Xiaoping Hu^1,2
1Center for Advanced Neuroimaging, University of California Riverside, Riverside, CA, United States, ²Department of Bioengineering, University of California Riverside, Riverside, CA, United States

Keywords: Alzheimer's Disease, Dementia, lewy body

Up to 60% of Alzheimer's disease cases have Lewy body pathology. In Alzheimer's disease, Lewy body pathology is associated with more rapid cognitive decline, parkinsonism, and younger symptom onset. In this abstract, we examine nigral volume in Alzheimer's disease patients and patients with mild cognitive impairment with Lewy body pathology. We find that cognitively impaired patients with Lewy bodies have greater neuronal loss in substantia nigra pars compacta as well as reduced nigral volume.

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Caleb J. Han¹, Spencer Waddle¹, Maria Garza¹, L. Taylor Davis², Jarrod Eisma¹, Rohan Chitale³, Matthew Fusco³, Colin D. McKnight², Sky Jones¹, Lori C. Jordan^1,4, and Manus J. Donahue^1,2,5
1Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ²Radiology, Vanderbilt University Medical Center, Nashville, TN, United States, ³Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, United States, ⁴Pediatrics, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Psychiatry, Vanderbilt University Medical Center, Nashville, TN, United States

Keywords: Neurofluids, Stroke, Moyamoya, glymphatic, choroid plexus, cerebrovascular reactivity, CSF

This work applies hypercapnic reactivity and deep-learning techniques to evaluate choroid plexus (ChP) vascular compliance dependence on large arterial patency in intracranial vasculopathy. ChP reactivity was found to be preserved regardless of macrovascular vasculopathy, despite dependencies of resting ChP perfusion on cortical ischemia. Findings support the possibility that changes in resting ChP function in other studies in the presence of arterial vasculopathy and cerebral ischemia may be a response to circulating biochemical markers of ischemic stress, prompting the ChP to attenuate CSF production levels through feedback, rather than vascular mechanisms, to support glial health in ischemia.

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Nastaren Abad¹, Chitresh Bhushan¹, Luca Marinelli¹, Afis Ajala¹, H. Doug Morris², Ante Zhu¹, Eric Fiveland¹, Seung-Kyun Lee¹, J Kevin DeMarco^2,3, Robert Shih^2,3, Maureen Hood^2,3, Gail Kohls³, Kimbra Kenney², Vincent Ho², and Thomas K.F Foo^1,2
1GE Research, Niskayuna, NY, United States, ²Uniformed Services University of the Health Sciences, Bethesda, MD, United States, ³Walter Reed National Military Medical Center, Bethesda, MD, United States

Keywords: Traumatic brain injury, Diffusion/other diffusion imaging techniques

Diffusion MRI based microstructural evaluation of DTI, DKI, and intra-axonal radii, enabled by the ultra-high performance MAGNUS gradients, was leveraged in this study to assess differences between healthy controls and chronic mild traumatic brain injury presentations. Parcel-wise group and brain WM asymmetry analysis highlighted specific sub-region involvement differing from healthy controls in evaluated metrics. Subject specific analysis highlighted specific anatomical regions that could be more susceptible in TBI with the effect size potentially masked with central tendency analysis.

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Emine Can¹, Baby Martin-McNulty¹, Ganesh Kolumam¹, and Johannes Riegler^1
1Calico Life Sciences LLC, South San Francisco, CA, United States

Keywords: Neurodegeneration, Aging, Lifespan, Stroke, metabolism, Spectroscopy, Brain

NAD⁺ is required for vital cellular processes such as redox regulation, DNA damage repair and cell signaling. There has been a growing interest in modifying NAD⁺ concentrations in the hope that it might increase longevity. However, there is no clear consensus on changes in NAD⁺ concentration due to healthy aging. Commonly used in vitro assays for NAD quantification are not suitable for longitudinal studies. We therefore implemented an in vivo downfield ¹H MRS method to characterize NAD⁺ concentrations during aging in mice and showed that ¹H MRS can detect hypoxia induced changes in brain NAD⁺ concentrations.

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Thomas Hagan¹, Jia Ying¹, Chuan Huang^1,2, Minos Kritikos³, Sean Clouston³, and Benjamin Luft^4
1Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States, ²Department of Radiology, Stony Brook Medicine, Stony Brook, NY, United States, ³Program in Public Health and Department of Family, Population, and Preventative Medicine, Stony Brook Medicine, Stony Brook, NY, United States, ⁴Department of Medicine, Stony Brook Medicine, Stony Brook, NY, United States

Keywords: Neurodegeneration, Degenerative

Mounting evidence has shown that first responders to the 9/11 terrorist attack on the World Trade Center(WTC) are developing early-onset dementia but the underlying pathology driving this remains to be understood. Our team assessed the relationship between cognitive impairment and susceptibility differences in the brains of responders for the first time using quantitative susceptibility mapping(QSM). While research on Alzheimer’s disease has reported changes in QSM across several regions, we found elevated susceptibility located in the amygdala of responders with CI. Our findings bolster evidence suggesting that WTC responders are experiencing unique pathology which could point to a novel neurodegenerative disease.

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Marta Lancione¹, Graziella Donatelli^2,3, Matteo Cencini¹, Paolo Bosco¹, Mauro Costagli^1,4, Mirco Cosottini⁵, Laura Biagi¹, and Michela Tosetti^1
1IRCCS Stella Maris, Pisa, Italy, ²IMAGO7 Foundation, Pisa, Italy, ³Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy, ⁴University of Genoa, Genoa, Italy, ⁵University of Pisa, Pisa, Italy

Keywords: Neurodegeneration, Neurodegeneration, Atlas, Nigrosome

Iron accumulation in Nigrosome 1 (N1) may represent an important biomarker in neurodegenerative disorders but its small dimension and the vanishing swallow tail sign in patients make the segmentation of this region challenging. We propose a probabilistic atlas of N1 created on a multimodal (T1-w and T2*-w) template using ROIs that were manually drawn on 0.6mm-isotropic T2*-weighted images of twenty healthy subjects. Its usability and accuracy were tested on four additional subjects by comparing the mean N1 susceptibility and T2* obtained using the atlas to those obtained from manual ROIs and by measuring their geometrical proximity.

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Valeria Elisa Contarino¹, Francesco Maria Lo Russo¹, Giorgio Conte¹, Claudia Morelli², Francesca Trogu², Silvia Casale¹, Sara Sbaraini³, Luca Caschera¹, Valentina Genovese¹, Chunlei Liu⁴, Claudia Maria Cinnante², Vincenzo Silani², and Fabio Maria Triulzi^1
1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Milano, Italy, ²Auxologico, Milano, Italy, ³ASST Santi Paolo e Carlo, San Carlo Borromeo Hospital, milano, Italy, ⁴UC Berkeley, Milano, Italy

Keywords: Neurodegeneration, Brain, motor cortex; quantitative susceptibility mapping; amyotrophic lateral sclerosis

vVisual SWI-based and automatic QSM-based assessments show high diagnostic accuracy in UMN- predominant ALS

Jia-Hui Lin¹, Jia-Hui Lin¹, Qiu-Yi Dong¹, Yun-Bin Cao¹, and Hua-Jun Chen^1
1Fujian Medical University Union Hospital, Fuzhou, China

Keywords: Neurodegeneration, fMRI (resting state)

This is the first study on alterations in the patterns of dynamic functional connection density (dFCD) involving ALS. We obtained resting-state fMRI data from ALS and healthy controls (HCs). We calculated the functional connectivity (FC) and the functional connection density (FCD) value. dFCD was assessed by sliding-window correlation method. The standard deviation of dFCD can measure dFCD variability. The dFCD variability was reduced in some brain region in HC group, whereas increase was observed in some brain region of ALS patients. dFCD variability can distinguish two groups. ALS patients exhibit aberrant dynamic property in brain functional architecture.

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Mackenzie Langan^1,2, Em Rose Triolo³, Oleksandr Khegai^1,2, Carolina Ferreira-Atuesta⁴, Johnathan Sutkowski⁴, Trey Hedden⁴, Mehmet Kurt³, and Priti Balchandani^2,5,6
1Icahn School of Medicine at Mount Sinai, New York, NY, United States, ²Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ³Department of Mechanical Engineering, University of Washington, Seattle, WA, United States, ⁴Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁵Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States, ⁶Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, United States

Keywords: Neurodegeneration, Diffusion Tensor Imaging, High-Field MRI

Here we outline a preliminary method using a novel method which leverages UHF neuroimaging to measure detectable correlations in two measures: microstructural (mean diffusivity and fractional anisotropy) acquired at 7T and amyloid beta (β-amyloid) accumulation, acquired using 3T PET-MR.The combination of these methods aids in the ability to map tissue structure and achieve unprecedented visualization of the consequences of β-amyloid accumulation as it relates to neurodegenerative disorders. We show the feasibility of leveraging high resolution diffusion to advance out understand of the relationship between fractional anisotropy and mean diffusivity within brain regions that may be affected by β-amyloid deposition. 

KIRAN THAPALIYA¹, Sonya Marshall-Gradisnik¹, Markus Barth², Natalie Eaton-Fitch¹, and Leighton Barnden^1
1Griffith University, Gold coast, Australia, ²The University of Queensland, Brisbane, Australia

Keywords: Neurodegeneration, Brain

COVID -19 caused by the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected more than 600 million and caused the deaths of over six million people worldwide.  The majority of the infected patients do not recover fully from the COVID-19 infections and develop post-COVID conditions also known as long-COVID has similar symptoms compared to Myalgic Encephalomyelitis/Chronic fatigue syndrome. In this study, we evaluated the volumetric changes in the brainstem regions in ME/CFS, long-COVID patients compared to healthy controls.  Our study showed that brainstem volumes higher in ME/CFS and long-COVID patients compared to healthy controls.

Jia-Hui Lin¹, Yun-Bin Cao¹, Qiu-Yi Dong¹, and Hua-Jun Chen^1
1Fujian Medical University Union Hospital, Fuzhou, China

Keywords: Neurodegeneration, fMRI (resting state)

Amplitude of low-frequency fluctuation (ALFF) can identify abnormal regional neural activity in minimal hepatic encephalopathy (MHE). This work sought to evaluate the temporal variability of ALFF to reveal MHE-related alterations in the dynamics of spontaneous neural activity. Healthy controls and patients with cirrhosis [including MHE and without MHE (NHE)] were enrolled in this investigation. Utilizing a sliding-window approach to calculate the dynamic ALFF (dALFF) variability. The dALFF variability in some brain region progressively decreased from NHE to MHE group and it can distinguish NHE and MHE patients. Our findings highlight aberrant dynamic brain function in MHE.

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Bing LIU^1,2, Linwei Zhang³, Aocai Yang¹, Jixin Luan¹, Kuan Lv¹, and Guolin Ma^1
1Department of Radiology, China Japan Friendship Hospital, Beijing, China, ²Graduate School of Peking Union Medical College, Beijing, China, ³Department of Neurology, China Japan Friendship Hospital, Beijing, China

Keywords: Neurodegeneration, Brain Connectivity, functional MRI, independent component analysis, spinocerebellar ataxia type 3, large-scale brain networks, functional connectivity

Large-scale resting-state functional network connectivity changes in spinocerebellar ataxia type 3 patients were found in both inter- and intranetwork functional connectivity. Especially, the increased intranetwork functional connectivity within the lateral visual network may potentially be a compensatory mechanism of visual-related symptoms in SCA3.

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Pankaj Pankaj¹, S Senthil Kumaran¹, Achal Kumar Srivastava², Ramesh Kumar Agrawal³, Ajay Garg⁴, Ashima Nehra⁵, and Roopa Rajan^2
1Nuclear Magnetic Resonance, All India Institute of Medical Sciences, New Delhi, New Delhi, India, ²Neurology, All India Institute of Medical Sciences, New Delhi, New Delhi, India, ³School of Computer & Systems Sciences, Jawaharlal Nehru University, New Delhi- 110 067, New Delhi, India, ⁴Neuro-radiology, All India Institute of Medical Sciences, New Delhi, New Delhi, India, ⁵Neuropsychology, All India Institute of Medical Sciences, New Delhi, New Delhi, India

Keywords: Neurodegeneration, Diffusion Tensor Imaging

The study assessed changes in brain tissue microstructures in SCA type 1, 2 and 12 patients using diffusion tensor imaging. Our findings exhibited widespread reduced fractional anisotropy (FA), increased radial (RD) and axial diffusivity (AD) in SCA with respect to that in healthy subjects. FA was decreased in SCA1 and SCA2 in the superior and inferior longitudinal fasciculus, anterior thalamic radiation, inferior fronto-occipital fasiculus, forceps minor, corticospinal tract, cingulum, uncinate fasciculus as compared to controls. Abnormal white matter structure may be linked to cognitive and behavioural impairment in SCA 1 and SCA 2 patients.

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Cristiana Fiscone¹, Fiorina Bartiromo², Luca Baldelli¹, Luisa Sambati³, Serena D'Aniello⁴, Stefania Evangelisti¹, Micaela Mitolo^2,5, Claudia Testa^2,6, Pietro Cortelli^1,3, Raffaele Lodi^1,2, Federica Provini^1,3, and Caterina Tonon^1,2
1Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy, ²Functional and Molecular Neuroimaging Unit, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, ³Clinica Neurologica Rete Metropolitana, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy, ⁴Department of Advanced Biomedical Sciences, University of Naples Federico II, Napoli, Italy, ⁵Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy, ⁶Department of Physics and Astronomy, University of Bologna, Bologna, Italy

Keywords: Neurodegeneration, Brain, RBD

REM sleep Behavior Disoder (RBD) is a parasomnia, possibly converting in a neurodegenerative α-synucleinopathy. We explored to role of iron accumulation in this condition exploiting Quantitative Susceptibility Mapping (QSM), a quantitative imaging technique returning susceptibility values voxel-per-voxel. RBD patients were compared to healthy controls; cortical and sub-cortical areas were segmented with automatic and semi-automatic methods and susceptibility distributions were compared. Significant increase of iron deposition resulted in multiple cortical areas, in the brainstem and in the gray matter nuclei of the limbic system, suggesting that QSM may help in identifying biomarkers that predict the conversion from RBD to neurodegeneration.

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Xiao-Zhong Jing¹, Gai-Ying Li², Yu-Peng Wu³, Xiang-Zhen Yuan⁴, Jia-Lin Chen², Reyisha Taximaimaiti¹, Jian-Qi Li², and Xiao-Ping Wang^5
1Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, ²Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, China, ³East China Normal University, Shanghai, China, ⁴Department of Neurology, Weifang People's Hospital, Weifang, China, ⁵Department of Neurology, Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Keywords: Neurodegeneration, Diffusion/other diffusion imaging techniques, Wilson’s disease; free water imaging; quantitative susceptibility mapping.

This is the first study to use a bi-tensor free water imaging to evaluate microstructural changes in deep gray matter (DGM) nuclei of Wilson’s disease (WD). Despite the shortcomings our study manifested that free water imaging detects microstructural alterations in both normal and abnormal appearing DGM nuclei of WD patients. Correlations between free water imaging indices and neurological impairment in WD patients were also noticed. Therefore, as a promising tool, free water imaging deserves further investigation in longitudinal studies to evaluate its role in monitoring disease onset, progression, and treatment efficacy in WD patients.

Yang Yang¹, Bingsheng Huang², Yingqian Chen³, Yingtong Wu², Chuxuan Lin², Zhiyun Yang³, and Xia Liu^4
1Department of Radiology, Suining Central Hospital, Suining, China, ²Medical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, China, ³Department of Radiology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, ⁴Department of Radiology, Shenzhen Kangning Hospital, Shenzhen, China

Keywords: Neurodegeneration, Neurodegeneration, Brain age, Partition modeling

This study aimed to develop and construct a MRI-based full-age-range brain age prediction model that can be applied in the Chinese health care system. We proposed a brain age prediction method based on transfer learning and partition modeling , which was using Atlas attention enhancement. The performance of models with different image masks were compared and the model constructed based on top60% image mask achieved the best prediction performance. The brain age prediction method proposed in this study can provide objective brain age for assessing brain health status in Chinese population. 

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Jingli Chen^1,2, Yarui Wei^1,2, Kangkang Xue^1,2, and Jingliang Cheng^1,2
1Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China, ²Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Magnetic Resonance Imaging, Zhengzhou, China

Keywords: Neurodegeneration, fMRI (resting state), Auditory verbal hallucinations /effective connectivity/ reward network/ dopamine

Our study employs the dynamic causal modeling (DCM) approach to perform effective connectivity (EC) analysis of the reward network to investigate the mechanisms underlying schizophrenia patients with auditory verbal hallucinations (AVHs). This study enrolled 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 normal controls (NC), undergoing resting-state functional magnetic resonance. Our findings suggest that there are some common and different EC abnormalities in the reward network of AVH and NAVH. Particularly, the abnormalities of mesolimbic and mesocortex pathways in AVH may provide guidance for understanding the neurobiological mechanisms of AVHs and treatment.

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Merel M. van der Thiel^1,2,3, Kilian Hett⁴, Nathalie A. Roos^1,5, Colin D. Mcknight⁶, Melanie K. Leguizamon⁴, Sofia Venturini^1,7, Inez H.G.B. Ramakers^3,8, Walter H. Backes^1,2,9, and Jacobus F.A. Jansen^1,2,10
1Department of Radiology & Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ²School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, ³Department of Psychiatry & Neuropsychology, Maastricht University, Maastricht, Netherlands, ⁴Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States, ⁵Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands, ⁶Department of Radiology and Radiological sciences, Vanderbilt University Medical Center, Nashville, TN, United States, ⁷Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands, ⁸School for Mental Health & Neuroscience, Maastricht University, Maastricht, Netherlands, ⁹Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands, ¹⁰Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

Keywords: Neurodegeneration, Neurofluids, Sex differences, Perivascular spaces, Waste clearance

Cerebral waste clearance reduces with healthy aging and occurs in various neurodegenerative diseases. Both perivascular spaces (PVS) and the parasagittal dural (PSD) space play important roles in waste clearance, where the former transports waste products through the parenchyma, the latter is associated with cerebrospinal fluid efflux from the cranial compartment. The current 7T MRI study investigated sex differences in the relation between PVS and PSD volume in an elderly sample. By identifying a relationship between PVS and PSD solely in females, this study illustrates the possibility of a different impairment mechanism of the clearance system between elderly men and women.