Medical Biophysics Commons^™

Kl-Vs Heterozygosity Is Associated With Lower Amyloid-Dependent Tau Accumulation And Memory Impairment In Alzheimer’S Disease, Julia Neitzel, Nicolai Franzmeier, Anna Rubinski, Martin Dichgans, Matthias Brendel, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles Decarli, Bret Borowski

Medical Biophysics Publications

Klotho-VS heterozygosity (KL-VShet) is associated with reduced risk of Alzheimer’s disease (AD). However, whether KL-VShet is associated with lower levels of pathologic tau, i.e., the key AD pathology driving neurodegeneration and cognitive decline, is unknown. Here, we assessed the interaction between KL-VShet and levels of beta-amyloid, a key driver of tau pathology, on the levels of PET-assessed neurofibrillary tau in 551 controls and patients across the AD continuum. KL-VShet showed lower cross-sectional and longitudinal increase in tau-PET per unit increase in amyloid-PET when compared to that of non-carriers. This association of KL-VShet on tau-PET was stronger in Klotho mRNA-expressing brain …

Plasma Phosphorylated-Tau181 As A Predictive Biomarker For Alzheimer’S Amyloid, Tau And Fdg Pet Status, Xue Ning Shen, Yu Yuan Huang, Shi Dong Chen, Yu Guo, Lan Tan, Qiang Dong, Jin Tai Yu, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Jonathan Jackson, Eliezer Masliah, Donna Masterman, Ozioma Okonkwo

Medical Biophysics Publications

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = …

Repetitive Mild Traumatic Brain Injury In Mice Triggers A Slowly Developing Cascade Of Long-Term And Persistent Behavioral Deficits And Pathological Changes, Xiaoyun Xu, Matthew Cowan, Flavio Beraldo, Amy Schranz, Patrick Mccunn, Nicole Geremia, Zalman Brown, Maitray Patel, Karen L. Nygard, Reza Khazaee, Lihong Lu, Xingyu Liu, Michael J. Strong, Gregory A. Dekaban, Ravi Menon, Robert Bartha, Mark Daley, Haojie Mao, Vania Prado, Marco A.M. Prado, Lisa Saksida, Tim Bussey, Arthur Brown

Medical Biophysics Publications

We have previously reported long-term changes in the brains of non-concussed varsity rugby players using magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and functional magnetic imaging (fMRI). Others have reported cognitive deficits in contact sport athletes that have not met the diagnostic criteria for concussion. These results suggest that repetitive mild traumatic brain injuries (rmTBIs) that are not severe enough to meet the diagnostic threshold for concussion, produce long-term consequences. We sought to characterize the neuroimaging, cognitive, pathological and metabolomic changes in a mouse model of rmTBI. Using a closed-skull model of mTBI that when scaled to human leads …

Staging Tau Pathology With Tau Pet In Alzheimer’S Disease: A Longitudinal Study, Shi Dong Chen, Jia Ying Lu, Hong Qi Li, Yu Xiang Yang, Jie Hui Jiang, Mei Cui, Chuan Tao Zuo, Lan Tan, Qiang Dong, Jin Tai Yu, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John C. Morris, Richard J. Perrin, Leslie M. Shaw, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Jonathan Jackson, Eliezer Masliah

Medical Biophysics Publications

A biological research framework to define Alzheimer’ disease with dichotomized biomarker measurement was proposed by National Institute on Aging–Alzheimer’s Association (NIA–AA). However, it cannot characterize the hierarchy spreading pattern of tau pathology. To reflect in vivo tau progression using biomarker, we constructed a refined topographic 18F-AV-1451 tau PET staging scheme with longitudinal clinical validation. Seven hundred and thirty-four participants with baseline 18F-AV-1451 tau PET (baseline age 73.9 ± 7.7 years, 375 female) were stratified into five stages by a topographic PET staging scheme. Cognitive trajectories and clinical progression were compared across stages with or without further dichotomy of amyloid status, …

Magnetic Resonance Imaging Sequence Identification Using A Metadata Learning Approach, Shuai Liang, Derek Beaton, Stephen R. Arnott, Tom Gee, Mojdeh Zamyadi, Robert Bartha, Sean Symons, Glenda M. Macqueen, Stefanie Hassel, Jason P. Lerch, Evdokia Anagnostou, Raymond W. Lam, Benicio N. Frey, Roumen Milev, Daniel J. Müller, Sidney H. Kennedy, Christopher J.M. Scott, Stephen C. Strother

Medical Biophysics Publications

Despite the wide application of the magnetic resonance imaging (MRI) technique, there are no widely used standards on naming and describing MRI sequences. The absence of consistent naming conventions presents a major challenge in automating image processing since most MRI software require a priori knowledge of the type of the MRI sequences to be processed. This issue becomes increasingly critical with the current efforts toward open-sharing of MRI data in the neuroscience community. This manuscript reports an MRI sequence detection method using imaging metadata and a supervised machine learning technique. Three datasets from the Brain Center for Ontario Data Exploration …

Neutrophil Dynamics Affect Mycobacterium Tuberculosis Granuloma Outcomes And Dissemination, Caitlin Hult, Joshua T. Mattila, Hannah P. Gideon, Jennifer J. Linderman, Denise E. Kischner

Math Faculty Publications

Neutrophil infiltration into tuberculous granulomas is often associated with higher bacteria loads and severe disease but the basis for this relationship is not well understood. To better elucidate the connection between neutrophils and pathology in primate systems, we paired data from experimental studies with our next generation computational model GranSim to identify neutrophil-related factors, including neutrophil recruitment, lifespan, and intracellular bacteria numbers, that drive granuloma-level outcomes. We predict mechanisms underlying spatial organization of neutrophils within granulomas and identify how neutrophils contribute to granuloma dissemination. We also performed virtual deletion and depletion of neutrophils within granulomas and found that neutrophils play …

Improved Segmentation Of The Intracranial And Ventricular Volumes In Populations With Cerebrovascular Lesions And Atrophy Using 3d Cnns, Emmanuel E. Ntiri, Melissa F. Holmes, Parisa M. Forooshani, Joel Ramirez, Fuqiang Gao, Miracle Ozzoude, Sabrina Adamo, Christopher J.M. Scott, Dar Dowlatshahi, Jane M. Lawrence-Dewar, Donna Kwan, Anthony E. Lang, Sean Symons, Robert Bartha, Stephen Strother, Jean Claude Tardif, Mario Masellis, Richard H. Swartz, Alan Moody, Sandra E. Black, Maged Goubran

Medical Biophysics Publications

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with …

Nnresting State Fmri Scanner Instabilities Revealed By Longitud Inal Phantom Scans In A Multi-Center Study, Aras Kayvanrad, Stephen R. Arnott, Nathan Churchill, Stefanie Hassel, Aditi Chemparathy, Fan Dong, Mojdeh Zamyadi, Tom Gee, Robert Bartha, Sandra E. Black, Jane M. Lawrence-Dewar, Christopher J.M. Scott, Sean Symons, Andrew D. Davis, Geoffrey B. Hall, Jacqueline Harris, Nancy J. Lobaugh, Glenda Macqueen, Cindy Woo, Stephen Strother

Medical Biophysics Publications

Quality assurance (QA) is crucial in longitudinal and/or multi-site studies, which involve the collection of data from a group of subjects over time and/or at different locations. It is important to regularly monitor the performance of the scanners over time and at different locations to detect and control for intrinsic differences (e.g., due to manufacturers) and changes in scanner performance (e.g., due to gradual component aging, software and/or hardware upgrades, etc.). As part of the Ontario Neurodegenerative Disease Research Initiative (ONDRI) and the Canadian Biomarker Integration Network in Depression (CAN-BIND), QA phantom scans were conducted approximately monthly for three to …

Thermal Properties Of 18f-Fdg Uptake And Imaging In Positron Emission Tomography Scans Of Cancerous Cells, Carleigh R. Eagle

PANDION: The Osprey Journal of Research and Ideas

Positron Emission Tomography (PET) scans can utilize a radioactive tracer, in this case 2-deoxy2-[fluorine-18] fluoro-D-glucose (¹⁸F-FDG), to visualize malignant tumors in cancer patients. The uptake was compared to glucose to understand the difference in thermal properties, which contribute to the ability to image the cancerous cells. The uptake of ¹⁸F-FDG by cancer cells and the imaging process of positron emission tomography were reviewed from a thermodynamic perspective. Gastrointestinal and neurological imaging techniques were reviewed to understand the role of PET imaging in different areas of the human body.

Development Of Quantitative Molecular Photoacoustic Imaging For Noninvasive Cancer Diagnostics, Cayla Zandbergen

Dissertations and Theses (Open Access)

Traditional diagnostic imaging provides clinicians with anatomical information that guides both diagnosis and treatment planning; however, once a tumor has progressed enough to be visible, it has often reached an advanced stage. Molecular imaging techniques allow for real-time visualization of chemical and biological processes via imaging of specific biomarkers, which can facilitate detection of malignancies before they become visible. One biomarker of interest is blood oxygen saturation (SO₂) due to its correlation with hypoxia, which is associated with increased tumor malignancy; some studies have also established SO₂ as an independent biomarker of disease progression. Additionally, because cancerous …

Advancement Of A 3d Computational Phantom And Its Age Scaling Methodologies For Retrospective Dose Reconstruction Studies, Aashish Gupta

Dissertations and Theses (Open Access)

We have used a 3D age-scalable computational phantom for over two decades for retrospective dose reconstruction studies of childhood cancer survivors (CCS) treated with 2D historic radiotherapy (RT). However, our phantom and its age scaling functions (ASF) must be updated so that it can be used in studies that include survivors treated with contemporary RT. We aimed to implement our phantom and its age scaling functions in DICOM format and determine the feasibility of applying our ASFs to accurately scale the whole-body CT-based anatomies.

In the implementation study, we developed Python scripts that model the phantom and ASFs in a …

Medical Schools Ignore The Nature Of Consciousness At Great Cost, Anoop Kumar

Journal of Wellness

The essential question of the relationship between consciousness and matter is ignored in medical school curricula, leading to a machine-like view of the human being that contributes to physician burnout and intellectual dissatisfaction. The evidence suggesting that the brain may not be the seat of consciousness is generally ignored to preserve the worldview of the primacy of matter. By investigating new frameworks detailing the nature of consciousness at different levels of hierarchy, we can bring intellectual rigor to a once opaque subject that supports a fundamental reality about our experience: We are human beings, not only human bodies.

Rapid Microscopic Fractional Anisotropy Imaging Via An Optimized Linear Regression Formulation., N J J Arezza, D H Y Tse, C A Baron

Medical Biophysics Publications

Water diffusion anisotropy in the human brain is affected by disease, trauma, and development. Microscopic fractional anisotropy (μFA) is a diffusion MRI (dMRI) metric that can quantify water diffusion anisotropy independent of neuron fiber orientation dispersion. However, there are several different techniques to estimate μFA and few have demonstrated full brain imaging capabilities within clinically viable scan times and resolutions. Here, we present an optimized spherical tensor encoding (STE) technique to acquire μFA directly from the 2nd order cumulant expansion of the powder averaged dMRI signal obtained from direct linear regression (i.e. diffusion kurtosis) which requires fewer powder-averaged signals than …

Current State Of Lgbtqia+ Healthcare, Jessica Vadas

Conference Presentation Abstracts

No abstract provided.

Implications Of The Quantum Dna Model For Information Sciences, F. Matthew Mihelic

Faculty Publications

The DNA molecule can be modeled as a quantum logic processor, and this model has been supported by pilot research that experimentally demonstrated non-local communication between cells in separated cell cultures. This modeling and pilot research have important implications for information sciences, providing a potential architecture for quantum computing that operates at room temperature and is scalable to millions of qubits, and including the potential for an entanglement communication system based upon the quantum DNA architecture. Such a system could be used to provide non-local quantum key distribution that could not be blocked by any shielding or water depth, would …

Magnetic Vector Potential Manipulation Of Majorana Fermions In Dna Quantum Logic, F. Matthew Mihelic

Faculty Publications

In the quantum logic of the DNA molecule, electrons are held and conducted coherently as spinless Cooper pairs and are shielded from electromagnetic energy by a Faraday cage effect of the double lipid bilayer of the nuclear membrane. The magnetic vector potential generated by cellular depolarization can synchronize logical activity in portions of the DNA molecule by affecting spin directions of appropriately oriented spinless electrons via the Aharonov-Bohm effect, but is not blocked by that Faraday cage effect. Within the logically and thermodynamically reversible chiral enantiomeric symmetry of the deoxyribose moieties the decoherent transition of Cooper pair to Dirac pair …

Therapeutic Potential Of Trp Channels In The Targeting Of Rheumatoid Arthritis Synovial Fibroblasts, Brittany Isabella Schwam

Theses and Dissertations (ETD)

Rheumatoid arthritis is a chronic inflammatory disease primarily affecting the synovium, articular cartilage, and bone within a joint, but it is a unique form of arthritis wherein effects are systemic. The cause of this autoimmune disease remains unknown, but there are many environmental and genetic factors that play into susceptibility. Research is still far from drug-free remission despite great advancements over the past few decades. The majority of therapies developed rely on immunosuppressant or immunomodulator molecules and come with risk of infection, high costs, and toxic, uncontrolled side effects. Those diagnosed maintain a significant unmet need for targeted therapies.

There …

Remotely Controlled Enzyme Behavior Using Localized Thermal Gradients, Sarah Brown

UNO Student Research and Creative Activity Fair

No existing model describes an identified special case of enzyme behavior when directly stimulated with thermal energy via an RF field.

The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Nano-medicine and biotechnology are the future of medical diagnostics and treatment. The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Direct heating of an enzyme vs bulk heating changes the enzyme activity.

I tested how direct transfer of thermal energy changes rates of enzyme reactions. We created samples of enzymes, attached to ferrous (magnetic) nano-particles, and …

Multisite Comparison Of Mri Defacing Software Across Multiple Cohorts, Athena E. Theyers, Mojdeh Zamyadi, Mark O'Reilly, Robert Bartha, Sean Symons, Glenda M. Macqueen, Stefanie Hassel, Jason P. Lerch, Evdokia Anagnostou, Raymond W. Lam, Benicio N. Frey, Roumen Milev, Daniel J. Müller, Sidney H. Kennedy, Christopher J.M. Scott, Stephen C. Strother, Stephen R. Arnott

Medical Biophysics Publications

With improvements to both scan quality and facial recognition software, there is an increased risk of participants being identified by a 3D render of their structural neuroimaging scans, even when all other personal information has been removed. To prevent this, facial features should be removed before data are shared or openly released, but while there are several publicly available software algorithms to do this, there has been no comprehensive review of their accuracy within the general population. To address this, we tested multiple algorithms on 300 scans from three neuroscience research projects, funded in part by the Ontario Brain Institute, …

Kinetic Analysis Of Dominant Intraprostatic Lesion Of Prostate Cancer Using Quantitative Dynamic [18F]Dcfpyl-Pet: Comparison To [18F]Fluorocholine-Pet, Dae Myoung Yang, Fiona Li, Glenn Bauman, Joseph Chin, Stephen Pautler, Madeleine Moussa, Irina Rachinsky, John Valliant, Ting Yim Lee

Medical Biophysics Publications

Purpose: Identification of the dominant intraprostatic lesion(s) (DILs) can facilitate diagnosis and treatment by targeting biologically significant intra-prostatic foci. A PSMA ligand, [ F]DCFPyL (2-(3-{1-carboxy-5-[(6-[ F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid), is better than choline-based [ F]FCH (fluorocholine) in detecting and localizing DIL because of higher tumour contrast, particularly when imaging is delayed to 1 h post-injection. The goal of this study was to investigate whether the different imaging performance of [ F]FCH and [ F]DCFPyL can be explained by their kinetic behaviour in prostate cancer (PCa) and to evaluate whether DIL can be accurately detected and localized using a short duration dynamic positron …

Utilization Of Salvage And Systemic Therapies For Recurrent Prostate Cancer As A Result Of 18F-Dcfpyl Pet/Ct Restaging, Wei Liu, Katherine Zukotynski, Louise Emmett, Hans T. Chung, Peter Chung, Robert Wolfson, Irina Rachinsky, Anil Kapoor, Ur Metser, Andrew Loblaw, Gerard Morton, Tracy Sexton, Michael Lock, Joelle Helou, Alejandro Berlin, Colm Boylan, Susan Archer, Gregory R. Pond, Glenn Bauman

Medical Biophysics Publications

Purpose: Our purpose was to investigate the effect of the addition of prostate-specific membrane antigen (PSMA)-targeted positron emission tomography/computed tomography (PET/CT) in patients with recurrent prostate cancer post-primary radiation therapy. Methods and Materials: A prospective, multi-institutional clinical trial evaluated 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid ( F-DCFPyL) PET/CT restaging in 79 men with recurrent prostate cancer post-primary radiation therapy. We report actual patient management and compare this with proposed management both before and after PSMA-targeted PET/CT. Results: Most patients (59%) had a major change in actual management compared with pre-PET/CT proposed management. The rate of major change was underestimated by immediately post-PET/CT surveys (32%). …

Disease-Related Cortical Thinning In Presymptomatic Granulin Mutation Carriers, Sergi Borrego-Écija, Roser Sala-Llonch, John Van Swieten, Barbara Borroni, Fermín Moreno, Mario Masellis, Carmela Tartaglia, Caroline Graff, Daniela Galimberti, Robert Laforce, James B. Rowe, Elizabeth Finger, Rik Vandenberghe, Fabrizio Tagliavini, Alexandre De Mendonça, Isabel Santana, Matthis Synofzik, Simon Ducharme, Johannes Levin, Adrian Danek, Alex Gerhard, Markus Otto, Chris Butler, Giovanni Frisoni, Sandro Sorbi, Carolin Heller, Martina Bocchetta, David M. Cash, Rhian S. Convery, Katrina M. Moore, Jonathan D. Rohrer, Raquel Sanchez-Valle

Medical Biophysics Publications

Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years …

Case – 18F-Dcfpyl-Positron Emission Tomography/Computed Tomography (Pet/Ct) Time Of Imaging, Golmehr Sistani, Ur Metser, Glenn S. Bauman, David T. Laidley, Stephen E. Pautler, Katherine A. Zukotynski

Medical Biophysics Publications

No abstract provided.

Cortical Thickness Estimation In Individuals With Cerebral Small Vessel Disease, Focal Atrophy, And Chronic Stroke Lesions, Miracle Ozzoude, Joel Ramirez, Pradeep Reddy Raamana, Melissa F. Holmes, Kirstin Walker, Christopher J.M. Scott, Fuqiang Gao, Maged Goubran, Donna Kwan, Maria C. Tartaglia, Derek Beaton, Gustavo Saposnik, Ayman Hassan, Jane Lawrence-Dewar, Dariush Dowlatshahi, Stephen C. Strother, Sean Symons, Robert Bartha, Richard H. Swartz, Sandra E. Black

Medical Biophysics Publications

Background: Regional changes to cortical thickness in individuals with neurodegenerative and cerebrovascular diseases (CVD) can be estimated using specialized neuroimaging software. However, the presence of cerebral small vessel disease, focal atrophy, and cortico-subcortical stroke lesions, pose significant challenges that increase the likelihood of misclassification errors and segmentation failures. Purpose: The main goal of this study was to examine a correction procedure developed for enhancing FreeSurfer’s (FS’s) cortical thickness estimation tool, particularly when applied to the most challenging MRI obtained from participants with chronic stroke and CVD, with varying degrees of neurovascular lesions and brain atrophy. Methods: In 155 CVD participants …

Histologic Tissue Components Provide Major Cues For Machine Learning-Based Prostate Cancer Detection And Grading On Prostatectomy Specimens, Wenchao Han, Carol Johnson, Mena Gaed, José A. Gómez, Madeleine Moussa, Joseph L. Chin, Stephen Pautler, Glenn S. Bauman, Aaron D. Ward

Medical Biophysics Publications

Automatically detecting and grading cancerous regions on radical prostatectomy (RP) sections facilitates graphical and quantitative pathology reporting, potentially benefitting post-surgery prognosis, recurrence prediction, and treatment planning after RP. Promising results for detecting and grading prostate cancer on digital histopathology images have been reported using machine learning techniques. However, the importance and applicability of those methods have not been fully investigated. We computed three-class tissue component maps (TCMs) from the images, where each pixel was labeled as nuclei, lumina, or other. We applied seven different machine learning approaches: three non-deep learning classifiers with features extracted from TCMs, and four deep learning, …

A Telescope Gwas Analysis Strategy, Based On Snps-Genes-Pathways Ensamble And On Multivariate Algorithms, To Characterize Late Onset Alzheimer’S Disease, Margherita Squillario, Giulia Abate, Federico Tomasi, Veronica Tozzo, Annalisa Barla, Daniela Uberti, Michael W. Weiner, Paul Aisen, Ronald Petersen, Jack R. Clifford, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Tom Montine

Medical Biophysics Publications

Genome–wide association studies (GWAS) have revealed a plethora of putative susceptibility genes for Alzheimer’s disease (AD), with the sole exception of APOE gene unequivocally validated in independent study. Considering that the etiology of complex diseases like AD could depend on functional multiple genes interaction network, here we proposed an alternative GWAS analysis strategy based on (i) multivariate methods and on a (ii) telescope approach, in order to guarantee the identification of correlated variables, and reveal their connections at three biological connected levels. Specifically as multivariate methods, we employed two machine learning algorithms and a genetic association test and we considered …

Challenges And Opportunities With Causal Discovery Algorithms: Application To Alzheimer’S Pathophysiology, Xinpeng Shen, Sisi Ma, Prashanthi Vemuri, Gyorgy Simon, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, Andrew J. Saykin, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, M. Marcel Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas

Medical Biophysics Publications

Causal Structure Discovery (CSD) is the problem of identifying causal relationships from large quantities of data through computational methods. With the limited ability of traditional association-based computational methods to discover causal relationships, CSD methodologies are gaining popularity. The goal of the study was to systematically examine whether (i) CSD methods can discover the known causal relationships from observational clinical data and (ii) to offer guidance to accurately discover known causal relationships. We used Alzheimer’s disease (AD), a complex progressive disease, as a model because the well-established evidence provides a “gold-standard” causal graph for evaluation. We evaluated two CSD methods, Fast …

Fam222a Encodes A Protein Which Accumulates In Plaques In Alzheimer’S Disease, Tingxiang Yan, Jingjing Liang, Ju Gao, Luwen Wang, Hisashi Fujioka, Michael W. Weiner, Norbert Schuff, Howard J. Rosen, Bruce L. Miller, David Perry, Paul Aisen, Paul Aisen, Arthur W. Toga, Gustavo Jimenez, Michael Donohue, Devon Gessert, Kelly Harless, Jennifer Salazar, Yuliana Cabrera, Sarah Walter, Lindsey Hergesheimer, Arthur W. Toga, Karen Crawford, Scott Neu, Lon S. Schneider, Sonia Pawluczyk, Mauricio Becerra, Liberty Teodoro, Bryan M. Spann, Ronald Petersen, Clifford R. Jack, Matthew Bernstein

Medical Biophysics Publications

Alzheimer’s disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction …

Social Cognition Impairment In Genetic Frontotemporal Dementia Within The Genfi Cohort, Lucy L. Russell, Caroline V. Greaves, Martina Bocchetta, Jennifer Nicholas, Rhian S. Convery, Katrina Moore, David M. Cash, John Van Swieten, Lize Jiskoot, Fermin Moreno, Raquel Sanchez-Valle, Barbara Borroni, Robert Laforce, Mario Masellis, Maria Carmela Tartaglia, Caroline Graff, Emanuela Rotondo, Daniela Galimberti, James B. Rowe, Elizabeth Finger, Matthis Synofzik, Rik Vandenberghe, Alexandre De Mendonça, Fabrizio Tagliavini, Isabel Santana, Simon Ducharme, Chris Butler, Alex Gerhard, Johannes Levin, Adrian Danek, Markus Otto, Jason D. Warren

Medical Biophysics Publications

A key symptom of frontotemporal dementia (FTD) is difficulty interacting socially with others. Social cognition problems in FTD include impaired emotion processing and theory of mind difficulties, and whilst these have been studied extensively in sporadic FTD, few studies have investigated them in familial FTD. Facial Emotion Recognition (FER) and Faux Pas (FP) recognition tests were used to study social cognition within the Genetic Frontotemporal Dementia Initiative (GENFI), a large familial FTD cohort of C9orf72, GRN, and MAPT mutation carriers. 627 participants undertook at least one of the tasks, and were separated into mutation-negative healthy controls, presymptomatic mutation carriers (split …

Hyperpolarized Carbon-13 Magnetic Resonance Measurements Of Tissue Perfusion And Metabolism, Keith Michel

Dissertations and Theses (Open Access)

Hyperpolarized Magnetic Resonance Imaging (HP MRI) is an emerging modality that enables non-invasive interrogation of cells and tissues with unprecedented biochemical detail. This technology provides rapid imaging measurements of the activity of a small quantity of molecules with a strongly polarized nuclear magnetic moment. This polarization is created in a polarizer separate from the imaging magnet, and decays continuously towards a non-detectable thermal equilibrium once the imaging agent is removed from the polarizer and administered by intravenous injection. Specialized imaging strategies are therefore needed to extract as much information as possible from the HP signal during its limited lifetime.

In …