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Estimation Of Free Water-Corrected Microscopic Fractional Anisotropy., Nico J J Arezza, Tales Santini, Mohammad Omer, Corey A Baron Jan 2023

Estimation Of Free Water-Corrected Microscopic Fractional Anisotropy., Nico J J Arezza, Tales Santini, Mohammad Omer, Corey A Baron

Medical Biophysics Publications

Water diffusion anisotropy MRI is sensitive to microstructural changes in the brain that are hallmarks of various neurological conditions. However, conventional metrics like fractional anisotropy are confounded by neuron fiber orientation dispersion, and the relatively low resolution of diffusion-weighted MRI gives rise to significant free water partial volume effects in many brain regions that are adjacent to cerebrospinal fluid. Microscopic fractional anisotropy is a recent metric that can report water diffusion anisotropy independent of neuron fiber orientation dispersion but is still susceptible to free water contamination. In this paper, we present a free water elimination (FWE) technique to estimate microscopic …


Putative Concussion Biomarkers Identified In Adolescent Male Athletes Using Targeted Plasma Proteomics, Michael R. Miller, Michael Robinson, Lisa Fischer, Alicia Dibattista, Maitray A. Patel, Mark Daley, Robert Bartha, Gregory A. Dekaban, Ravi S. Menon, J. Kevin Shoemaker, Eleftherios P. Diamandis, Ioannis Prassas, Douglas D. Fraser Dec 2021

Putative Concussion Biomarkers Identified In Adolescent Male Athletes Using Targeted Plasma Proteomics, Michael R. Miller, Michael Robinson, Lisa Fischer, Alicia Dibattista, Maitray A. Patel, Mark Daley, Robert Bartha, Gregory A. Dekaban, Ravi S. Menon, J. Kevin Shoemaker, Eleftherios P. Diamandis, Ioannis Prassas, Douglas D. Fraser

Medical Biophysics Publications

Sport concussions can be difficult to diagnose and if missed, they can expose athletes to greater injury risk and long-lasting neurological disabilities. Discovery of objective biomarkers to aid concussion diagnosis is critical to protecting athlete brain health. To this end, we performed targeted proteomics on plasma obtained from adolescent athletes suffering a sports concussion. A total of 11 concussed male athletes were enrolled at our academic Sport Medicine Concussion Clinic, as well as 24 sex-, age- and activity-matched healthy control subjects. Clinical evaluation was performed and blood was drawn within 72 h of injury. Proximity extension assays were performed for …


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 Dec 2021

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 …


Higher Csf Stnfr1-Related Proteins Associate With Better Prognosis In Very Early Alzheimer’S Disease, William T. Hu, Tugba Ozturk, Alexander Kollhoff, Whitney Wharton, J. Christina Howell, 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, Richard J. Perrin, Leslie M. Shaw, Zaven Kachaturian, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Eliezer Masliah, Donna Masterman, Ozioma Okonkwo, Laurie Ryan, Nina Silverberg, Adam Fleisher Dec 2021

Higher Csf Stnfr1-Related Proteins Associate With Better Prognosis In Very Early Alzheimer’S Disease, William T. Hu, Tugba Ozturk, Alexander Kollhoff, Whitney Wharton, J. Christina Howell, 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, Richard J. Perrin, Leslie M. Shaw, Zaven Kachaturian, Maria Carrillo, William Potter, Lisa Barnes, Marie Bernard, Hector González, Carole Ho, John K. Hsiao, Eliezer Masliah, Donna Masterman, Ozioma Okonkwo, Laurie Ryan, Nina Silverberg, Adam Fleisher

Medical Biophysics Publications

Neuroinflammation is associated with Alzheimer’s disease, but the application of cerebrospinal fluid measures of inflammatory proteins may be limited by overlapping pathways and relationships between them. In this work, we measure 15 cerebrospinal proteins related to microglial and T-cell functions, and show them to reproducibly form functionally-related groups within and across diagnostic categories in 382 participants from the Alzheimer’s Disease Neuro-imaging Initiative as well participants from two independent cohorts. We further show higher levels of proteins related to soluble tumor necrosis factor receptor 1 are associated with reduced risk of conversion to dementia in the multi-centered (p = 0.027) and …


Correlation Between Alzheimer’S Disease And Type 2 Diabetes Using Non-Negative Matrix Factorization, Yeonwoo Chung, Hyunju Lee, Michael W. Weiner, Paul Aisen, Ronald Petersen, Cliford R. Jack, 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, Ronald G. Thomas, Michael Donohue, Sarah Walter, Tamie Sather Dec 2021

Correlation Between Alzheimer’S Disease And Type 2 Diabetes Using Non-Negative Matrix Factorization, Yeonwoo Chung, Hyunju Lee, Michael W. Weiner, Paul Aisen, Ronald Petersen, Cliford R. Jack, 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, Ronald G. Thomas, Michael Donohue, Sarah Walter, Tamie Sather

Medical Biophysics Publications

Alzheimer’s disease (AD) is a complex and heterogeneous disease that can be affected by various genetic factors. Although the cause of AD is not yet known and there is no treatment to cure this disease, its progression can be delayed. AD has recently been recognized as a brain-specific type of diabetes called type 3 diabetes. Several studies have shown that people with type 2 diabetes (T2D) have a higher risk of developing AD. Therefore, it is important to identify subgroups of patients with AD that may be more likely to be associated with T2D. We here describe a new approach …


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 Dec 2021

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, …


Author Correction: Spread Of Pathological Tau Proteins Through Communicating Neurons In Human Alzheimer’S Disease (Nature Communications, (2020), 11, 1, (2612), 10.1038/S41467-020-15701-2), Jacob W. Vogel, Yasser Iturria-Medina, Olof T. Strandberg, Ruben Smith, Elizabeth Levitis, Alan C. Evans, Oskar Hansson, 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, Michael Donohue, Matthew Bernstein, Nick Fox, Paul Thompson Dec 2021

Author Correction: Spread Of Pathological Tau Proteins Through Communicating Neurons In Human Alzheimer’S Disease (Nature Communications, (2020), 11, 1, (2612), 10.1038/S41467-020-15701-2), Jacob W. Vogel, Yasser Iturria-Medina, Olof T. Strandberg, Ruben Smith, Elizabeth Levitis, Alan C. Evans, Oskar Hansson, 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, Michael Donohue, Matthew Bernstein, Nick Fox, Paul Thompson

Medical Biophysics Publications

The original version of the Supplementary information associated with this Article inadvertently omitted Supplementary Table S1. The HTML has been updated to include a corrected version of the Supplementary information.


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 Dec 2021

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 = …


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 Nov 2021

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 …


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 Oct 2021

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 Aug 2021

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 …


Rapid Microscopic Fractional Anisotropy Imaging Via An Optimized Linear Regression Formulation., N J J Arezza, D H Y Tse, C A Baron Jul 2021

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 …


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 Feb 2021

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 Jan 2021

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 Jan 2021

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 Jan 2021

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 Dec 2020

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 Dec 2020

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 Dec 2020

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 Dec 2020

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 Dec 2020

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 Dec 2020

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 Dec 2020

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 …


Optimization Of Multi-Electrode Implant Configurations And Programming For The Delivery Of Non-Ablative Electric Fields In Intratumoral Modulation Therapy., Erin Iredale, Andrew Deweyert, Douglas A Hoover, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong Nov 2020

Optimization Of Multi-Electrode Implant Configurations And Programming For The Delivery Of Non-Ablative Electric Fields In Intratumoral Modulation Therapy., Erin Iredale, Andrew Deweyert, Douglas A Hoover, Jeff Z Chen, Susanne Schmid, Matthew O Hebb, Terry M Peters, Eugene Wong

Medical Biophysics Publications

PURPOSE: Application of low intensity electric fields to interfere with tumor growth is being increasingly recognized as a promising new cancer treatment modality. Intratumoral modulation therapy (IMT) is a developing technology that uses multiple electrodes implanted within or adjacent tumor regions to deliver electric fields to treat cancer. In this study, the determination of optimal IMT parameters was cast as a mathematical optimization problem, and electrode configurations, programming, optimization, and maximum treatable tumor size were evaluated in the simplest and easiest to understand spherical tumor model. The establishment of electrode placement and programming rules to maximize electric field tumor coverage …


Brain Metabolite Levels In Sedentary Women And Non-Contact Athletes Differ From Contact Athletes, Amy L. Schranz, Gregory A. Dekaban, Lisa Fischer, Kevin Blackney, Christy Barreira, Timothy J. Doherty, Douglas D. Fraser, Arthur Brown, Jeff Holmes, Ravi S. Menon, Robert Bartha Nov 2020

Brain Metabolite Levels In Sedentary Women And Non-Contact Athletes Differ From Contact Athletes, Amy L. Schranz, Gregory A. Dekaban, Lisa Fischer, Kevin Blackney, Christy Barreira, Timothy J. Doherty, Douglas D. Fraser, Arthur Brown, Jeff Holmes, Ravi S. Menon, Robert Bartha

Medical Biophysics Publications

White matter tracts are known to be susceptible to injury following concussion. The objective of this study was to determine whether contact play in sport could alter white matter metabolite levels in female varsity athletes independent of changes induced by long-term exercise. Metabolite levels were measured by single voxel proton magnetic resonance spectroscopy (MRS) in the prefrontal white matter at the beginning (In-Season) and end (Off-Season) of season in contact (N = 54, rugby players) and non-contact (N = 23, swimmers and rowers) varsity athletes. Sedentary women (N = 23) were scanned once, at a time equivalent to the Off-Season …


Neural Effects Of Oxytocin And Mimicry In Frontotemporal Dementia: A Randomized Crossover Study, Lindsay D. Oliver, Chloe Stewart, Kristy Coleman, James H. Kryklywy, Robert Bartha, Derek G.V. Mitchell, Elizabeth C. Finger Nov 2020

Neural Effects Of Oxytocin And Mimicry In Frontotemporal Dementia: A Randomized Crossover Study, Lindsay D. Oliver, Chloe Stewart, Kristy Coleman, James H. Kryklywy, Robert Bartha, Derek G.V. Mitchell, Elizabeth C. Finger

Medical Biophysics Publications

OBJECTIVE: To determine whether intranasal oxytocin, alone or in combination with instructed mimicry of facial expressions, would augment neural activity in patients with frontotemporal dementia (FTD) in brain regions associated with empathy, emotion processing, and the simulation network, as indexed by blood oxygen-level dependent (BOLD) signal during fMRI. METHODS: In a placebo-controlled, randomized crossover design, 28 patients with FTD received 72 IU intranasal oxytocin or placebo and then completed an fMRI facial expression mimicry task. RESULTS: Oxytocin alone and in combination with instructed mimicry increased activity in regions of the simulation network and in limbic regions associated with emotional expression …


Higher Csf Strem2 Attenuates Apoe4-Related Risk For Cognitive Decline And Neurodegeneration, Nicolai Franzmeier, M. Suárez-Calvet, Lukas Frontzkowski, Annah Moore, Timothy J. Hohman, Estrella Morenas-Rodriguez, Brigitte Nuscher, Leslie Shaw, John Q. Trojanowski, Martin Dichgans, Gernot Kleinberger, Christian Haass, Michael Ewers, Michael Weiner, Paul Aisen, Gerald Novak, Robert C. Green, Tom Montine, Ronald Petersen, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Laurel Beckett, Danielle Harvey, John Kornak, Clifford R. Jack, Anders Dale, Matthew Bernstein, Joel Felmlee Oct 2020

Higher Csf Strem2 Attenuates Apoe4-Related Risk For Cognitive Decline And Neurodegeneration, Nicolai Franzmeier, M. Suárez-Calvet, Lukas Frontzkowski, Annah Moore, Timothy J. Hohman, Estrella Morenas-Rodriguez, Brigitte Nuscher, Leslie Shaw, John Q. Trojanowski, Martin Dichgans, Gernot Kleinberger, Christian Haass, Michael Ewers, Michael Weiner, Paul Aisen, Gerald Novak, Robert C. Green, Tom Montine, Ronald Petersen, Anthony Gamst, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Laurel Beckett, Danielle Harvey, John Kornak, Clifford R. Jack, Anders Dale, Matthew Bernstein, Joel Felmlee

Medical Biophysics Publications

Background: The Apolipoprotein E ϵ4 allele (i.e. ApoE4) is the strongest genetic risk factor for sporadic Alzheimer's disease (AD). TREM2 (i.e. Triggering receptor expressed on myeloid cells 2) is a microglial transmembrane protein brain that plays a central role in microglia activation in response to AD brain pathologies. Whether higher TREM2-related microglia activity modulates the risk to develop clinical AD is an open question. Thus, the aim of the current study was to assess whether higher sTREM2 attenuates the effects of ApoE4-effects on future cognitive decline and neurodegeneration. Methods: We included 708 subjects ranging from cognitively normal (CN, n = …


A Novel Salvage Option For Local Failure In Prostate Cancer, Reirradiation Using External Beam Or Stereotactic Radiation Therapy: Systematic Review And Meta-Analysis, Mark T. Corkum, Lucas C. Mendez, Joseph Chin, David D'Souza, R. Gabriel Boldt, Glenn S. Bauman Sep 2020

A Novel Salvage Option For Local Failure In Prostate Cancer, Reirradiation Using External Beam Or Stereotactic Radiation Therapy: Systematic Review And Meta-Analysis, Mark T. Corkum, Lucas C. Mendez, Joseph Chin, David D'Souza, R. Gabriel Boldt, Glenn S. Bauman

Medical Biophysics Publications

Purpose: Reirradiation (re-RT) using external beam radiation therapy (EBRT) is a novel salvage strategy for local failure in prostate cancer. We performed a systematic review describing oncologic and toxicity outcomes for salvage EBRT/stereotactic radiation therapy (SBRT) re-RT. Methods and Materials: A International Prospective Register of Systematic Reviews registered (#141466) systematic review, meta-analysis, and meta-regression was conducted using preferred reporting items for systematic reviews and meta-analyses guidelines. PubMed and EMBASE were searched from inception through September 2019. Outcome measures included local control (LC), biochemical relapse free survival (BRFS), and ≥grade 3 genitourinary (GU)/gastrointestinal (GI) toxicity. EBRT and SBRT data were collected …


Ontario Neurodegenerative Disease Research Initiative (Ondri): Structural Mri Methods And Outcome Measures, Joel Ramirez, Melissa F. Holmes, Christopher J.M. Scott, Miracle Ozzoude, Miracle Ozzoude, Sabrina Adamo, Gregory M. Szilagyi, Maged Goubran, Fuqiang Gao, Stephen R. Arnott, Jane M. Lawrence-Dewar, Jane M. Lawrence-Dewar, Derek Beaton, Stephen C. Strother, Douglas P. Munoz, Mario Masellis, Richard H. Swartz, Robert Bartha, Sean P. Symons, Sandra E. Black, Michael Strong, Peter Kleinstiver, Natalie Rashkovan, Susan Bronskill, Sandra E. Black, Michael Borrie, Elizabeth Finger, Corinne Fischer, Andrew Frank, Morris Freedman, Sanjeev Kumar, Stephen Pasternak Aug 2020

Ontario Neurodegenerative Disease Research Initiative (Ondri): Structural Mri Methods And Outcome Measures, Joel Ramirez, Melissa F. Holmes, Christopher J.M. Scott, Miracle Ozzoude, Miracle Ozzoude, Sabrina Adamo, Gregory M. Szilagyi, Maged Goubran, Fuqiang Gao, Stephen R. Arnott, Jane M. Lawrence-Dewar, Jane M. Lawrence-Dewar, Derek Beaton, Stephen C. Strother, Douglas P. Munoz, Mario Masellis, Richard H. Swartz, Robert Bartha, Sean P. Symons, Sandra E. Black, Michael Strong, Peter Kleinstiver, Natalie Rashkovan, Susan Bronskill, Sandra E. Black, Michael Borrie, Elizabeth Finger, Corinne Fischer, Andrew Frank, Morris Freedman, Sanjeev Kumar, Stephen Pasternak

Medical Biophysics Publications

The Ontario Neurodegenerative Research Initiative (ONDRI) is a 3 years multi-site prospective cohort study that has acquired comprehensive multiple assessment platform data, including 3T structural MRI, from neurodegenerative patients with Alzheimer's disease, mild cognitive impairment, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and cerebrovascular disease. This heterogeneous cross-section of patients with complex neurodegenerative and neurovascular pathologies pose significant challenges for standard neuroimaging tools. To effectively quantify regional measures of normal and pathological brain tissue volumes, the ONDRI neuroimaging platform implemented a semi-automated MRI processing pipeline that was able to address many of the challenges resulting from this heterogeneity. The purpose …


Glutamate And Dysconnection In The Salience Network: Neurochemical, Effective Connectivity, And Computational Evidence In Schizophrenia, Roberto Limongi, Peter Jeon, Michael Mackinley, Tushar Das, Kara Dempster, Jean Théberge, Robert Bartha, Dickson Wong, Lena Palaniyappan Aug 2020

Glutamate And Dysconnection In The Salience Network: Neurochemical, Effective Connectivity, And Computational Evidence In Schizophrenia, Roberto Limongi, Peter Jeon, Michael Mackinley, Tushar Das, Kara Dempster, Jean Théberge, Robert Bartha, Dickson Wong, Lena Palaniyappan

Medical Biophysics Publications

Background: Functional dysconnection in schizophrenia is underwritten by a pathophysiology of the glutamate neurotransmission that affects the excitation-inhibition balance in key nodes of the salience network. Physiologically, this manifests as aberrant effective connectivity in intrinsic connections involving inhibitory interneurons. In computational terms, this produces a pathology of evidence accumulation and ensuing inference in the brain. Finally, the pathophysiology and aberrant inference would partially account for the psychopathology of schizophrenia as measured in terms of symptoms and signs. We refer to this formulation as the 3-level hypothesis. Methods: We tested the hypothesis in core nodes of the salience network (the dorsal …