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Yi-Chen Lin¹, Ssu-Ju Li¹, Yu-Chun Lo², Ting-Chieh Chen¹, Ching-Wen Chang¹, Tsai-Yu Cho¹, Mu-Hua Wang¹, Ching-Te Chen³, Sheng-Huang Lin^4,5, and You-Yin Chen^1,2
1Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, Taiwan, ²PhD Program in Medical Neuroscience, Taipei Medical University, Taipei, Taiwan, ³Abbott Neuromodulation, Austin, TX, United States, ⁴Department of Neurology, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan, ⁵Department of Neurology, Tzu Chi University, Hualien, Taiwan

Keywords: Alzheimer's Disease, fMRI, Intermittent theta-burst stimulation (iTBS)

Intermittent theta-burst stimulation (iTBS) has been hypothesized to be a more effective paradigm for deep brain stimulation (DBS) in treating various neurological disorders by altering neuronal circuits. However, the effect of iTBS in improving memory deficits in AD patients remains unknown. Combining iTBS in central thalamus (CT-iTBS) with functional magnetic resonance imaging, our results demonstrated the restoration of brain functional connectivity (FC) in corticolimbic circuit of AD mice model, accompanied with enhancing memory cognitive function in novel object recognition test and T-maze test. These results revealed that CT-iTBS could be an effective treatment for improving symptoms of individuals with AD.

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Youssef Z Wadghiri¹, Jelle Veerart¹, Sean Murray¹, Jakub Szabo¹, Carolyn Akers¹, Thomas Genovese¹, Hannah Goldman¹, Jonathan Leung¹, Charles V Kingsley ², Henry Rusinek¹, Stanton Gray², William Donald Hopkins², Thomas Wisniewski¹, and Henrieta Scholtzova^1
1NYU Grossman School of Medicine, New York, NY, United States, ²UT - MD Anderson Cancer Center, Houston, TX, United States

Keywords: Alzheimer's Disease, Aging, Non human primate

The current study seeks to identify neuroimaging biomarkers in a unique squirrel monkey (SQM) as a spontaneous model of cerebral amyloid angiopathy both in vivo and ex vivo using conventional MRI metrics in young and geriatric SQM cohorts and demonstrate the utility of quantitative R2* to map age-related differences in SQM neuropathology cross-sectionally and longitudinally. 

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Devin Raine Everalo Cortes^1,2,3,4, Margaret C. Stapleton^2,4, Samuel Wyman^2,4, Kristina E. Schwab^5,6, Noah W. Coulson^2,7, Dalton R West^2,4, Thomas Becker-Szurszewski^5,6, Sean Hartwick^5,6, Anthony G. Christodoulou⁸, and Yijen L Wu^2,3,4,9
1Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States, ²Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States, ³Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, United States, ⁴Rangos Research Center Small Animal Imaging Core, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁵Rangos Research Center Animal Imaging Core, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States, ⁶Department of Pediatrics, University of Pittsburgh, School of Medicine, Pittsburgh, PA, United States, ⁷Rangos Research Center Small Animal Imaging Core, University of Pittsburgh, Pittsburgh, PA, United States, ⁸Biomedical Imaging Research Institue, Cedars-Sinai Medical Center, Los Angeles, CA, United States, ⁹Department of Pediatrics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States

Keywords: Alzheimer's Disease, Brain Connectivity, Metabolism, fMRI

Apolipoprotein E (APOE) alleles are strong genetic risk factors for the Late-Onset-Alzheimer’s Disease (LOAD). In this study we utilize our novel 4D Oxy-wavelet functional MRI to study the bioenergetic footprint of APOE knockout (KO) mice compared to wild type (WT) mice. We have created neuronal networks in mice defined by bioenergetic dispersion throughout the whole brain, and demonstrated key differences between APOE KO and WT. We further validate our oxywavelet index for probing mitochondrial function non-invasively and present new signal processing methods for relevant biomarker extraction.

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Zhiliang Wei^1,2, Yuguo Li^1,2, Lin Chen³, Hongshuai Liu⁴, Minmin Yao⁴, Jiadi Xu^1,2, Angeliki Louvi⁵, Wenzhen Duan^4,6, and Hanzhang Lu^1,2,7
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Electronic Science, Xiamen University, Xiamen, China, ⁴Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵Departments of Neurosurgery and Neuroscience, Yale School of Medicine, New Haven, CT, United States, ⁶The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁷Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Dementia, Animals

Vascular cognitive impairment and dementia (VCID) is the second leading cause of dementia and is often mixed with other pathologies. Related mouse models with relatively pure vascular pathologies are used for mechanistic studies or therapeutic trials. CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a monogenic condition causing lacunar strokes and vascular dementia. Using the established mouse model of CADASIL, we aimed to investigate potential microvascular dysfunctions with advanced non-contrast MRI techniques. We found that CADASIL mice displayed elevated oxygen consumption and impaired cerebrovascular reactivity, suggesting simultaneous metabolic and vascular stress.

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Dustin Loren Velasco Almanza^1,2, Wilfred Lam², Margaret Koletar², Mary Hill³, JoAnne McLaurin^3,4, Greg Stanisz^1,2, and Bojana Stefanovic^1,2
1Medical Biophysics, University of Toronto, Toronto, ON, Canada, ²Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ³Biological Sciences, Sunnybrook Research Institute, Toronto, ON, Canada, ⁴Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada

Keywords: Alzheimer's Disease, CEST & MT

Our study characterized the hippocampal glucose uptake in an Alzheimer’s Disease rat model (TgF344AD) comorbid with metabolic syndrome modeled by cafeteria (CAF) diet. Glucose uptake was evaluated by detecting 2-deoxy-D-glucose (2DG) using chemical exchange saturation transfer (CEST) MRI in 6- and 12-month-old cohorts, reflecting pre-clinical and established disease stages, respectively. CAF diet attenuated glucose uptake of both non-transgenic and transgenic-AD at 6 months of age; whereas at 12 months of age, CAF diet enhanced the hippocampal glucose uptake of TgAD but attenuated it in chow-fed TgAD, when compared to that in correspondingly fed nTg littermates.

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Kexin Wang^1,2, Jianpan Huang³, Ziqin Zhang^1,2, Kannie W. Y. Chan^3,4, and Jiadi Xu^2,4
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, China, ⁴Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Alzheimer's Disease, CEST & MT, pH mapping

Guanidinium CEST (GuanCEST) and amideCEST are highly sensitive to pH change, while their correlations with pH are opposite. Thus taking (unitless) difference of GuanCEST and amideCEST provides a reliable indicator for pH. Polynomial and Lorentzian line-shape fitting (PLOF) method helps extract the two CEST signals precisely, and the (unitless) difference shows a significant increase (p=0.008, n=10) in Alzheimer’s disease (AD) mouse brain compared with that of wild type mouse at 3T. Our results light up a novel and promising method to detect the onset of AD noninvasively, bringing the recent breakthrough in AD mechanism to further clinical application.

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Jing Li¹, Renyuan Liu¹, Pin Lv¹, and Bing Zhang^1
1The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Keywords: Alzheimer's Disease, fMRI, neurovascular coupling

Neurovascular uncoupling can be found in the early stage of AD continuum. The effect of AQP4 content on neurovascular coupling (NVC) in AD mice is unclear. Adult 5xFAD mice and wild-type mice were employed in this study.  Mice received TGN-020, an AQP4 inhibitor, intraperitoneally. The results showed that 20 min after the injection of TGN-020, reduced ReHo in the basal area of the frontal lobe, a trend of reduced functional connectivities and disordered network properties were found among the AQP4-inhibited WT and 5xFAD mice. Therefore, Inhibition of AQP4 may reduce the NVC, and disorder the functional network.

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Jenna M. Radovich^1,2, Jordan Ogg³, Zachary Baty^1,2, Aaron Wilber³, and Samuel Colles Grant^1,2
1National High Magnetic Field Laboratory, Florida State University, Tallahassee, FL, United States, ²Chemical & Biomedical Engineering, FAMU-FSU College of Engineering, Tallahassee, FL, United States, ³Psychology, Florida State University, Tallahassee, FL, United States

Keywords: Alzheimer's Disease, Brain Connectivity, Graph theory, Progressive Degeneration

A hallmark of Alzheimer's Disease (AD) is spatial disorientation, such as getting lost in new locations. A potential cause is disrupted exchange between egocentric and allocentric reference frames, in which the parietal and retrosplenial cortex have roles. This study aimed to examine rs-fMRI and DTI in relationship with coordination between reference frames in a transgenic AD rat model. Behavioral and DTI data suggest that both age and genotype lead to declines in action-orientation performance with alterations appearing at 5 mon, and at 6 mon structurally with profound changes developing longitudinally across multiple ROI. 

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Maria-Eleni Dounavi¹, Elijah Mak¹, Audrey Low¹, Guy B Williams², Katie Wells³, Graciela Muniz-Terrera^3,4, Brian Lawlor⁵, Lorina Naci⁵, Paresh Malhotra⁶, Ivan Koychev⁷, Karen Ritchie⁸, Li Su^1,9, Craig W Ritchie³, and John T O'Brien^1
1Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom, ²Department of Clinical Neurosciences and Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom, ³Centre for Dementia Prevention, University of Edinburgh, Edinburgh, United Kingdom, ⁴Ohio University, Athens, OH, United States, ⁵Institute of Neuroscience, Trinity College Dublin, University of Dublin, Dublin, United Kingdom, ⁶Division of Brain Science, Imperial College Healthcare NHS Trust, London, United Kingdom, ⁷Department of Psychiatry, University of Oxford, Oxford, United Kingdom, ⁸INSERM, Montpellier, France, ⁹University of Sheffield, Sheffield, United Kingdom

Keywords: Alzheimer's Disease, Arterial spin labelling

Extensive brain hypoperfusion is well-established in people with Alzheimer’s disease (AD). However, mixed findings have emerged during the pre-symptomatic disease stage. In this study, we used arterial spin labelling (ASL) MRI in middle-aged, cognitively normal participants from the PREVENT-Dementia study to evaluate cerebral perfusion differences between carriers and non-carriers of the apolipoprotein ε4 (APOE4) allele. The ASL spatial coefficient of variation (CoV) was used as a proxy for arterial transit time (ATT) delays. We found hyperperfusion in APOE4 carriers which was not accompanied by increased spatial CoV, suggesting that the observed hyperperfusion is not driven by ATT delays. 

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Tony Zhou¹, Zongpai Zhang², Arvind Balachandrasekaran³, Cyrus A. Raji⁴, James T. Becker⁵, Lewis H. Kuller⁶, Yulin Ge⁷, Oscar L. Lopez⁸, Weiying Dai², and H. Michael Gach^1,9
1Radiation Oncology, Washington University School of Medicine, Saint Louis, MO, United States, ²Computer Science, State University of New York at Binghamton, Binghamton, NY, United States, ³Boston Children's Hospital, Boston, MA, United States, ⁴Radiology and Neurology, Washington University School of Medicine, Saint Louis, MO, United States, ⁵Psychiatry, Psychology, and Neurology, University of Pittsburgh, Pittsburgh, PA, United States, ⁶Epidemiology, University of Pittsburgh, Pittsburgh, PA, United States, ⁷Radiology, New York University School of Medicine, New York City, NY, United States, ⁸Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States, ⁹Radiology and Biomedical Engineering, Washington University School of Medicine, Saint Louis, MO, United States

Keywords: Alzheimer's Disease, Arterial spin labelling

We conducted a longitudinal study to determine if reduced temporoparietal and frontal cerebral blood flow (CBF) in elderly population leads to reduced gray matter volumes (GMVs) in the temporal lobe, or vice versa. We observed smaller GMVs in the temporal pole (TP) region in Alzheimer’s disease (AD) patients. We also found associations of: (1) the TP GMVs with subsequent temporoparietal CBF declines; (2) the TP CBF with its own subsequent GMV changes; and (3) the hippocampal GMVs with longitudinal frontal CBF declines. Hypoperfusion in the temporal lobe may be an early event driving atrophy, followed by temporoparietal and frontal hypoperfusion.

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Jianing Tang^1,2, Elizabeth Joe³, Helena Chui³, and Lirong Yan^2,3
1Biomedical Engineering, Northwestern University, Evanston, IL, United States, ²Radiology, Northwestern University, Evanston, IL, United States, ³Department of Neurology, University of Southern California, Los Angeles, CA, United States

Keywords: Alzheimer's Disease, Blood vessels

Increasing evidence suggests that vascular compliance could offer valuable insights into the pathology of Alzheimer’s diseases. Recently, carotid pulse wave velocity (cPWV) between internal carotid artery and common carotid artery has been successfully measured by a fast single-slice oblique-sagittal PC-MRI technique. In this study, we evaluated the role of cPWV in brain amyloid deposition and cognitive decline in an aged cohort. The results showed that greater cPWV was associated with cognitive decline and amyloid pathology. Our findings suggest elevated cPWV may affect amyloid clearance in brain, leading to cognitive impairment. cPWV could be a potential sensitive imaging marker of AD.

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Ken Sakaie¹, Katherine Koenig², Jian Lin², Alan Lerner³, James Leverenz⁴, and Mark J. Lowe^2
1The Cleveland Clinic, Cleveland, OH, United States, ²Imaging Institute, The Cleveland Clinic, Cleveland, OH, United States, ³Brain Health and Memory Center, Neurological Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States, ⁴Lou Ruvo Center for Brain Health, The Cleveland Clinic, Cleveland, OH, United States

Keywords: Alzheimer's Disease, Dementia

Imaging measures of tissue microstructure of the fornix are are potential biomarkers for cognitive decline in Alzheimer’s disease (AD). However, partial volume averaging (PVA) between the fornix and cerobrospinal fluid can be substantial. As a result, measured changes may reflect atrophy, not changes in tissue microstructure. Neurite Orientation Dispersion and Direction Imaging and Free Water Elimination diffusion tensor imaging account for PVA. We present results from a cohort of AD patients, patients with mild cognitive impairment (MCI) and cognitively normal (CN) subjects, showing that NODDI and DTI measures correlate with specific scores cognitive status.

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Wen Zhang¹ and Bing Zhang^2
1Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, ²The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Keywords: Alzheimer's Disease, Diabetes

Subcortical atrophy and increased cerebral β-amyloid and tau deposition are linked to cognitive decline in type 2 diabetes. However, whether and how subcortical atrophy is related to Alzheimer’s pathology in diabetes remains unclear. We investigated the subcortical structural alterations induced by diabetes and the relationship between subcortical alteration, Alzheimer’s pathology and cognition. Our results suggested that although both type 2 diabetes and AD are correlated with subcortical neurodegeneration, type 2 diabetes have no direct or indirect effect on the cerebral amyloid deposition and CSF p-tau.

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Ning Hua¹, Olga Minaeva¹, Juliet Moncaster¹, Hernan Jara¹, and Lee Goldstein^1
1Boston University, Boston, MA, United States

Keywords: Alzheimer's Disease, DSC & DCE Perfusion

The goal of the project is to explore the possibility of using dynamic contrast-enhanced (DCE)-MRI for detecting subtle blood-brain barrier leakage in a transgenic mouse model of Alzheimer’s disease. The washout slope of Gd concentration was used to assess microvascular integrity. We observed different washout patterns in transgenic relative to control mice. Our findings demonstrated that the washout slope could be used to assess status of blood-brain barrier permeability in AD mice.

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Feng Han¹, Xufu Liu¹, Richard Mailman², Xuemei Huang², and Xiao Liu^1
1the Pennsylvania State University, State College, PA, United States, ²Pennsylvania State University College of Medicine and Milton S. Hershey Medical Center, Hershey, PA, United States

Keywords: Alzheimer's Disease, fMRI (resting state), cerebrospinal fluid

The β-amyloid (Aβ) plaque, an Alzheimer’s disease (AD) hallmark, accumulates first in the default mode network (DMN) regions years before AD diagnosis. The underlying mechanisms remain elusive. Low-frequency (<0.1 Hz) resting-state global brain activity was recently found coupled by cerebrospinal fluid (CSF) movements, and this coupling has been linked to AD pathologies, including Aβ accumulations, presumably due to its role in glymphatic clearance. Here we showed the preferential Aβ accumulation in DMN was related to the reduced engagement of the global brain activity in these regions, partly explained by its failure to reach these regions as cortical propagating waves.

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Silvie Suriany¹, Clio Gonzalez-Zacarias², Chau Vu², Sharon ONeil³, Gagan C Mathur⁴, Dawn C Ward⁵, Alyssa Ziman⁵, Ellen B Klapper⁶, Lefan Zhuang⁷, and John C Wood^1
1Pediatrics, Children's Hospital of Los Angeles-USC KSOM, Los Angeles, CA, United States, ²University of Southern California, Los Angeles, CA, United States, ³Neuropsychology, Children's Hospital of Los Angeles-USC KSOM, Los Angeles, CA, United States, ⁴Transfusion Medicine, Children's Hospital of Los Angeles-USC KSOM, Los Angeles, CA, United States, ⁵Transfusion Medicine, University of California, Los Angeles, Los Angeles, CA, United States, ⁶Transfusion Medicine, Cedar Sinai Medical Center, Los Angeles, CA, United States, ⁷Transfusion Medicine, City of Hope Medical Center, Duarte, CA, United States

Keywords: Dementia, Metabolism, Iron Deficiency

Iron deficiency is the predominant cause of anemia in adults, typically occurring in women with heavy menses, endometriosis or fibroids. We study cerebral metabolic rate of oxygen (CMRO₂), blood brain barrier (BBB) permeability to water, and neurocognitive function in 34 women with iron deficiency anemia (IDA). We observed striking deficits in verbal and spatial memory, perceptual reasoning, and crystalized intelligence that were strongly correlated with hemoglobin level. CMRO₂ was lower than predicted by anemia alone, correlated to BBB permeability to water, and associated with poorer neurocognitive performance, suggesting decreased brain capillary surface area for oxygen and water diffusion.

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Anita Monteverdi¹, Fulvia Palesi², Michael Schirner^3,4,5,6,7, Francesca Argentino², Mariateresa Merante², Alberto Redolfi⁸, Francesca Conca⁹, Laura Mazzocchi¹⁰, Matteo Cotta Ramusino^2,11, Alfredo Costa^2,11, Anna Pichiecchio^2,10, Lisa Maria Farina⁹, Stefano Cappa^9,12, Viktor Jirsa¹³, Petra Ritter^3,4,5,6,7, Claudia A.M. Gandini Wheeler-Kingshott^1,2,14, and Egidio D’Angelo^1,2
1Brain Connectivity Center, IRCCS Mondino Foundation, Pavia, Italy, ²Dept of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy, ³Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Berlin, Germany, ⁴Department of Neurology with Experimental Neurology, Charité, Universitätsmedizin Berlin, Berlin, Germany, ⁵Bernstein Focus State Dependencies of Learning and Bernstein Center for Computational Neuroscience, Berlin, Germany, ⁶Einstein Center for Neuroscience Berlin, Berlin, Germany, ⁷Einstein Center Digital Future, Berlin, Germany, ⁸Laboratory of Neuroinformatics, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, ⁹IRCCS Mondino Foundation, Pavia, Italy, ¹⁰Advanced Imaging and Radiomics Center, IRCCS Mondino Foundation, Pavia, Italy, ¹¹Unit of Behavioral Neurology, IRCCS Mondino Foundation, Pavia, Italy, ¹²University Institute of Advanced Studies (IUSS), Pavia, Italy, ¹³Institut de Neurosciences des Systèmes, INSERM, INS, Aix Marseille University, Marseille, France, ¹⁴NMR Research Unit, Queen Square MS Centre, UCL Queen Square Institute of Neurology, Department of Neuroinflammation, University College London, London, United Kingdom

Keywords: Alzheimer's Disease, Modelling, Frontotemporal Dementia

This work provides the first personalized and non-invasive assessment of resting-state networks connectivity and excitatory/inhibitory balance in health and in neurodegenerative diseases (Alzheimer’s disease, Frontotemporal Dementia). Multiple networks were characterized at single-subject level performing brain dynamics simulations with The Virtual Brain (TVB). TVB-derived parameters identified specific network properties (at single network and inter-network level) and their disruption in neurodegeneration, underlined the relationship between neurophysiology and neuropsychology, and outlined a personalized fingerprint sensitive to clinical severity. This model-based simulation of brain networks functional dynamics lay the groundwork for customized biomarkers research and defines new trajectories for designing novel tailored interventional workflows. 

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Mackenzie L Carlson¹, Phillip DiGiacomo¹, Brian Burns², Nicole Mouchawar¹, Julian Maclaren¹, Murat Aksoy¹, Pascal Spincemaille³, Alexey Dimov³, Yi Wang³, Brian Rutt¹, and Michael Zeineh^1
1Stanford University, Stanford, CA, United States, ²GE Healthcare, Seattle, WA, United States, ³Weill Cornell Medical College, New York, NY, United States

Keywords: Alzheimer's Disease, Motion Correction

Abnormal accumulation of iron has been found in the subiculum of Alzheimer’s Disease (AD) patients postmortem. This motivated us to push MRI resolution to observe iron accumulation in vivo in AD patients. Using optical prospective motion correction to enable higher resolution at 7T, we imaged 4 healthy controls, 3 mild cognitive impairment, and 1 Alzheimer’s Disease patient with a 60-minute research brain MRI protocol. Hippocampal iron deposits were detected by a neuroradiologist aware of diagnosis in 2 out of 4 MCI/AD subjects despite that mean R2* quantification in the subiculum was not significantly different between healthy control and MCI/AD subjects.

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Khalid Saifullah¹, Nazanin Makkinejad¹, Arnold M. Evia², David A. Bennett², Julie A. Schneider², and Konstantinos Arfanakis^1,2
1Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, United States, ²Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, United States

Keywords: Alzheimer's Disease, Neurodegeneration, Aging, Atherosclerosis

Multiple age-related neuropathologies lead to atrophy of subcortical brain structures. However, definitive diagnosis of most of these pathologies is only possible at autopsy, complicating investigations into the effects of age-related neuropathologies on the shape of subcortical brain structures. The present work combined ex-vivo MRI and detailed pathologic assessment in a large number (N=842) of community-based older adults to study the relationship between age-related neuropathologies and the shape of subcortical brain structures. The resulting deformation patterns may be used as features in in-vivo classifiers of age-related neuropathologies.

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Rashed Sobhan¹, David R. Willis², Rachel Gillings², Michael J. Thrippleton³, Joanna M. Wardlaw³, Anne-Marie Minihane², Narelle M. Berry², and Donnie Cameron^1,4
1Norwich Medical School, University of East Anglia, Norwich, United Kingdom, ²University of East Anglia, Norwich, United Kingdom, ³University of Edinburgh, Edinburgh, United Kingdom, ⁴Department of Radiology, C.J. Gorter Centre for High Field MRI, Leiden University Medical Centre, Leiden, Netherlands

Keywords: Alzheimer's Disease, Permeability, DCE-MRI, Low-level Blood-brain-barrier Leakage, Mild cognitive impairment

We implemented recent developments in DCE-MRI pre-processing and analysis techniques to compare local differences in blood brain barrier (BBB) integrity in subjective memory impairment (SMI) and mild cognitive impairment (MCI), two early indicators of Alzheimer’s disease. Also, as part of the CANN trial, we explored the impact of a combined flavanol and omega-3 fatty acid-based nutritional intervention on BBB leakage. The results show that BBB leakage in memory processing regions can distinguish between SMI and MCI, and thus can be used to quantitatively assess the progress of cSVD towards onset of MCI and/or early indication of Alzheimer’s disease.