Medicine and Health Sciences Commons^™

A Macaque Connectome For Large-Scale Network Simulations In Thevirtualbrain, Kelly Shen, Gleb Bezgin, Michael Schirner, Petra Ritter, Stefan Everling, Anthony R. Mcintosh

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Models of large-scale brain networks that are informed by the underlying anatomical connectivity contribute to our understanding of the mapping between the structure of the brain and its dynamical function. Connectome-based modelling is a promising approach to a more comprehensive understanding of brain function across spatial and temporal scales, but it must be constrained by multi-scale empirical data from animal models. Here we describe the construction of a macaque (Macaca mulatta and Macaca fascicularis) connectome for whole-cortex simulations in TheVirtualBrain, an open-source simulation platform. We take advantage of available axonal tract-tracing datasets and enhance the existing …

Predator-Induced Fear Causes Ptsd-Like Changes In The Brains And Behaviour Of Wild Animals, Liana Y. Zanette, Emma C. Hobbs, Lauren E. Witterick, Scott A. Macdougall-Shackleton, Michael Clinchy

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Predator-induced fear is both, one of the most common stressors employed in animal model studies of post-traumatic stress disorder (PTSD), and a major focus of research in ecology. There has been a growing discourse between these disciplines but no direct empirical linkage. We endeavoured to provide this empirical linkage by conducting experiments drawing upon the strengths of both disciplines. Exposure to a natural cue of predator danger (predator vocalizations), had enduring effects of at least 7 days duration involving both, a heightened sensitivity to predator danger (indicative of an enduring memory of fear), and elevated neuronal …

Consciousness-Specific Dynamic Interactions Of Brain Integration And Functional Diversity, Andrea I. Luppi, Michael M. Craig, Ioannis Pappas, Paola Finoia, Guy B. Williams, Judith Allanson, John D. Pickard, Adrian M. Owen, Lorina Naci, David K. Menon, Emmanuel A. Stamatakis

Brain and Mind Institute Researchers' Publications

Prominent theories of consciousness emphasise different aspects of neurobiology, such as the integration and diversity of information processing within the brain. Here, we combine graph theory and dynamic functional connectivity to compare resting-state functional MRI data from awake volunteers, propofol-anaesthetised volunteers, and patients with disorders of consciousness, in order to identify consciousness-specific patterns of brain function. We demonstrate that cortical networks are especially affected by loss of consciousness during temporal states of high integration, exhibiting reduced functional diversity and compromised informational capacity, whereas thalamo-cortical functional disconnections emerge during states of higher segregation. Spatially, posterior regions of the brain’s default mode …

Altered Motor, Anxiety-Related And Attentional Task Performance At Baseline Associate With Multiple Gene Copies Of The Vesicular Acetylcholine Transporter And Related Protein Overexpression In Chat::Cre+ Rats, Craig P. Mantanona, Johan Alsiö, Joanna L. Elson, Beth M. Fisher, Jeffrey W. Dalley, Timothy Bussey, Ilse S. Pienaar

Brain and Mind Institute Researchers' Publications

© 2019, The Author(s). Transgenic rodents expressing Cre recombinase cell specifically are used for exploring mechanisms regulating behavior, including those mediated by cholinergic signaling. However, it was recently reported that transgenic mice overexpressing a bacterial artificial chromosome containing choline acetyltransferase (ChAT) gene, for synthesizing the neurotransmitter acetylcholine, present with multiple vesicular acetylcholine transporter (VAChT) gene copies, resulting in altered cholinergic tone and accompanying behavioral abnormalities. Since ChAT::Cre+ rats, used increasingly for understanding the biological basis of CNS disorders, utilize the mouse ChAT promotor to control Cre recombinase expression, we assessed for similar genotypical and phenotypical differences in such rats compared …

Are Specific Learning Disorders Truly Specific, And Are They Disorders?, Lien Peters, Daniel Ansari

Brain and Mind Institute Researchers' Publications

© 2019 The Authors Specific learning disorders, such as dyslexia and dyscalculia, are frequently studied to inform our understanding of cognitive development, genetic mechanisms and brain function. In this Opinion Paper, we discuss limitations of this research approach, including the use of arbitrary criteria to select groups of children, heterogeneity within groups and overlap between domains of learning. By drawing on evidence from cognitive science, neuroscience and genetics, we propose an alternative, dimensional framework. We argue that we need to overcome the problems associated with a categorical approach by taking into account interacting factors at multiple levels of analysis that …

Genome-Wide Association Analysis Of Hippocampal Volume Identifies Enrichment Of Neurogenesis-Related Pathways, Emrin Horgusluoglu-Moloch, Shannon L. Risacher, Paul K. Crane, Derrek Hibar, Paul M. Thompson, Andrew J. Saykin, Kwangsik Nho, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Jeffrey Kaye, Joseph Quinn, Lisa Silbert, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher

Medical Biophysics Publications

© 2019, The Author(s). Adult neurogenesis occurs in the dentate gyrus of the hippocampus during adulthood and contributes to sustaining the hippocampal formation. To investigate whether neurogenesis-related pathways are associated with hippocampal volume, we performed gene-set enrichment analysis using summary statistics from a large-scale genome-wide association study (N = 13,163) of hippocampal volume from the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium and two year hippocampal volume changes from baseline in cognitively normal individuals from Alzheimer’s Disease Neuroimaging Initiative Cohort (ADNI). Gene-set enrichment analysis of hippocampal volume identified 44 significantly enriched biological pathways (FDR corrected p-value < 0.05), of which 38 pathways were related to neurogenesis-related processes including neurogenesis, generation of new neurons, neuronal development, and neuronal migration and differentiation. For genes highly represented in the significantly enriched neurogenesis-related pathways, gene-based association analysis identified TESC, ACVR1, MSRB3, and DPP4 as significantly associated with hippocampal volume. Furthermore, co-expression network-based functional analysis of gene expression data in the hippocampal subfields, CA1 and CA3, from 32 normal controls showed that distinct co-expression modules were mostly enriched in neurogenesis related pathways. Our results suggest that neurogenesis-related pathways may be enriched for hippocampal volume and that hippocampal volume may serve as a potential phenotype for the investigation of human adult neurogenesis.

Multimodal Hippocampal Subfield Grading For Alzheimer’S Disease Classification, Kilian Hett, Vinh Thong Ta, Gwenaëlle Catheline, Thomas Tourdias, José V. Manjón, Pierrick Coupé, 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 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

© 2019, The Author(s). Numerous studies have proposed biomarkers based on magnetic resonance imaging (MRI) to detect and predict the risk of evolution toward Alzheimer’s disease (AD). Most of these methods have focused on the hippocampus, which is known to be one of the earliest structures impacted by the disease. To date, patch-based grading approaches provide among the best biomarkers based on the hippocampus. However, this structure is complex and is divided into different subfields, not equally impacted by AD. Former in-vivo imaging studies mainly investigated structural alterations of these subfields using volumetric measurements and microstructural modifications with mean diffusivity …

Mousebytes, An Open-Access High-Throughput Pipeline And Database For Rodent Touchscreen-Based Cognitive Assessment, Flavio H. Beraldo, Daniel Palmer, Sara Memar, David I. Wasserman, Wai Jane V. Lee, Shuai Liang, Samantha D. Creighton, Benjamin Kolisnyk, Matthew F. Cowan, Justin Mels, Talal S. Masood, Chris Fodor, Mohammed A. Al-Onaizi, Robert Bartha, Tom Gee, Lisa M. Saksida, Timothy J. Bussey, Stephen S. Strother, Vania F. Prado, Boyer D. Winters, Marco A.M. Prado

Medical Biophysics Publications

© 2019, eLife Sciences Publications Ltd. All rights reserved. Open Science has changed research by making data accessible and shareable, contributing to replicability to accelerate and disseminate knowledge. However, for rodent cognitive studies the availability of tools to share and disseminate data is scarce. Automated touchscreen-based tests enable systematic cognitive assessment with easily standardised outputs that can facilitate data dissemination. Here we present an integration of touchscreen cognitive testing with an open-access database public repository (mousebytes.ca), as well as a Web platform for knowledge dissemination (https://touchscreencognition.org). We complement these resources with the largest dataset of age-dependent high-level cognitive assessment of …

3d Vessel-Wall Virtual Histology Of Whole-Body Perfused Mice Using A Novel Heavy Element Stain, P. Joy Dunmore-Buyze, Charmainne Cruje, Zengxuan Nong, Jason J. Lee, John A. Kiernan, J. Geoffrey Pickering, Maria Drangova

Medical Biophysics Publications

Virtual histology – utilizing high-resolution three-dimensional imaging – is becoming readily available. Micro-computed tomography (micro-CT) is widely available and is often coupled with x-ray attenuating histological stains that mark specific tissue components for 3D virtual histology. In this study we describe a new tri-element x-ray attenuating stain and perfusion protocol that provides micro-CT contrast of the entire vasculature of an intact mouse. The stain – derived from an established histology stain (Verhoeff’s) – is modified to enable perfusion through the vasculature; the attenuating elements of the stain are iodine, aluminum, and iron. After a 30-minute perfusion through the vasculature (10-minute …

Comparison Of Quality Control Methods For Automated Diffusion Tensor Imaging Analysis Pipelines, Seyyed M.H. Haddad, Christopher J.M. Scott, Miracle Ozzoude, Melissa F. Holmes, Stephen R. Arnott, Nuwan D. Nanayakkara, Joel Ramirez, Sandra E. Black, Dar Dowlatshahi, Stephen C. Strother, Richard H. Swartz, Sean Symons, Manuel Montero-Odasso, Robert Bartha

Medical Biophysics Publications

© 2019 Haddad et al. The processing of brain diffusion tensor imaging (DTI) data for large cohort studies requires fully automatic pipelines to perform quality control (QC) and artifact/outlier removal procedures on the raw DTI data prior to calculation of diffusion parameters. In this study, three automatic DTI processing pipelines, each complying with the general ENIGMA framework, were designed by uniquely combining multiple image processing software tools. Different QC procedures based on the RESTORE algorithm, the DTIPrep protocol, and a combination of both methods were compared using simulated ground truth and artifact containing DTI datasets modeling eddy current induced distortions, …

The Bin1 Rs744373 Snp Is Associated With Increased Tau-Pet Levels And Impaired Memory, Nicolai Franzmeier, Anna Rubinski, Julia Neitzel, Michael Ewers, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowski, Arthur W. Toga, Laurel Beckett, Robert C. Green, Andrew J. Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Lew Kuller, Marcus Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, Marek M. Mesulam, William Potter, Peter Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue

Medical Biophysics Publications

© 2019, The Author(s). The single nucleotide polymorphism (SNP) rs744373 in the bridging integrator-1 gene (BIN1) is a risk factor for Alzheimer’s disease (AD). In the brain, BIN1 is involved in endocytosis and sustaining cytoskeleton integrity. Post-mortem and in vitro studies suggest that BIN1-associated AD risk is mediated by increased tau pathology but whether rs744373 is associated with increased tau pathology in vivo is unknown. Here we find in 89 older individuals without dementia, that BIN1 rs744373 risk-allele carriers show higher AV1451 tau-PET across brain regions corresponding to Braak stages II–VI. In contrast, the BIN1 rs744373 SNP was not associated …

Accelerated 129xe Mri Morphometry Of Terminal Airspace Enlargement: Feasibility In Volunteers And Those With Alpha-1 Antitrypsin Deficiency, Alexei Ouriadov, Fumin Guo, David G Mccormack, Grace Parraga

Medical Biophysics Publications

PURPOSE: Multi-b diffusion-weighted hyperpolarized inhaled-gas MRI provides imaging biomarkers of terminal airspace enlargement including ADC and mean linear intercept (L

METHODS: We evaluated multi-b (0, 12, 20, 30, and 45.5 s/cm

RESULTS: For the HV subgroup, mean differences of 5%, 2%, and 8% were observed between fully sampled and undersampled k-space for ADC, L

CONCLUSIONS: Accelerated multi-b diffusion-weighted

Functional Localization Of The Frontal Eye Fields In The Common Marmoset Using Microstimulation, Janahan Selvanayagam, Kevin D. Johnston, David J. Schaeffer, Lauren K. Hayrynen, Stefan Everling

Brain and Mind Institute Researchers' Publications

Copyright © 2019 the authors. The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. Although investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus, the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (Callithrix jacchus) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity; however, physiological investigation …

Synergistic Toxicity In An In Vivo Model Of Neurodegeneration Through The Co-Expression Of Human Tdp-43M337v And TauT175d Protein, Alexander J. Moszczynski, Madeline Harvey, Niveen Fulcher, Cleusa De Oliveira, Patrick Mccunn, Neil Donison, Robert Bartha, Susanne Schmid, Michael J. Strong, Kathryn Volkening

Medical Biophysics Publications

Although it has been suggested that the co-expression of multiple pathological proteins associated with neurodegeneration may act synergistically to induce more widespread neuropathology, experimental evidence of this is sparse. We have previously shown that the expression of Thr175Asp-tau (tauT175D) using somatic gene transfer with a stereotaxically-injected recombinant adeno-associated virus (rAAV9) vector induces tau pathology in rat hippocampus. In this study, we have examined whether the co-expression of human tauT175D with mutant human TDP-43 (TDP-43M337V) will act synergistically. Transgenic female Sprague-Dawley rats that inducibly express mutant human TDP-43M337V using the choline acetyltransferase (ChAT) tetracycline response element (TRE) driver with activity modulating …

Sign And Speech Share Partially Overlapping Conceptual Representations, Samuel Evans, Cathy J. Price, Jörn Diedrichsen, Eva Gutierrez-Sigut, Mairéad Macsweeney

Brain and Mind Institute Researchers' Publications

© 2019 The Author(s) Conceptual knowledge is fundamental to human cognition. Yet, the extent to which it is influenced by language is unclear. Studies of semantic processing show that similar neural patterns are evoked by the same concepts presented in different modalities (e.g., spoken words and pictures or text) [1–3]. This suggests that conceptual representations are “modality independent.” However, an alternative possibility is that the similarity reflects retrieval of common spoken language representations. Indeed, in hearing spoken language users, text and spoken language are co-dependent [4, 5], and pictures are encoded via visual and verbal routes [6]. A parallel approach …

Variational Representational Similarity Analysis, Karl J. Friston, Jörn Diedrichsen, Emma Holmes, Peter Zeidman

Brain and Mind Institute Researchers' Publications

© 2019 The Authors This technical note describes a variational or Bayesian implementation of representational similarity analysis (RSA) and pattern component modelling (PCM). It considers RSA and PCM as Bayesian model comparison procedures that assess the evidence for stimulus or condition-specific patterns of responses distributed over voxels or channels. On this view, one can use standard variational inference procedures to quantify the contributions of particular patterns to the data, by evaluating second-order parameters or hyperparameters. Crucially, this allows one to use parametric empirical Bayes (PEB) to infer which patterns are consistent among subjects. At the between-subject level, one can then …

Normalisation Of Mri Ventilation Heterogeneity In Severe Asthma By Dupilumab, Sarah Svenningsen, Ehsan Ahmed Haider, Rachel L Eddy, Grace Parraga, Parameswaran Nair

Medical Biophysics Publications

Ventilation heterogeneity in asthma could be due to many reasons. Luminal obstruction due to inflammatory cells or mucus, smooth muscle constriction and airway wall thickness could all contribute individually or collectively to ventilation heterogeneity. Interleukin-4 and interleukin-13, acting through the common interleukin-4 receptor, have the potential to modulate all of these features of asthma.1 Inhaled hyperpolarised gas MRI provides a way to regionally visualise and quantify the functional consequence of these features.2 Dupilumab is a fully human monoclonal antibody directed against the alpha-subunit of the interleukin-4 receptor.3 Here, we report a severe asthmatic who showed significant improvement and normalisation of …

Postnatal Catch-Up Growth Leads To Higher P66shc And Mitochondrial Dysfunction., Shelby Oke, Gurjeev Sohi, Daniel Barry Hardy

Physiology and Pharmacology Publications

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet …

A Sound-Sensitive Source Of Alpha Oscillations In Human Non-Primary Auditory Cortex, Alexander J. Billig, Björn Herrmann, Ariane E. Rhone, Phillip E. Gander, Kirill V. Nourski, Beau F. Snoad, Christopher K. Kovach, Hiroto Kawasaki, Matthew A. Howard, Ingrid S. Johnsrude

Brain and Mind Institute Researchers' Publications

Copyright © 2019 Billig, Herrmann et al. The functional organization of human auditory cortex can be probed by characterizing responses to various classes of sound at different anatomical locations. Along with histological studies this approach has revealed a primary field in posteromedial Heschl's gyrus (HG) with pronounced induced high-frequency (70-150 Hz) activity and short-latency responses that phase-lock to rapid transient sounds. Low-frequency neural oscillations are also relevant to stimulus processing and information flow, however, their distribution within auditory cortex has not been established. Alpha activity (7-14 Hz) in particular has been associated with processes that may differentially engage earlier versus …

Ventricular Volume Expansion In Presymptomatic Genetic Frontotemporal Dementia, Tamara P. Tavares, Derek G.V. Mitchell, Kristy Coleman, Christen Shoesmith, Robert Bartha, David M. Cash, Katrina M. Moore, John Van Swieten, Barbara Borroni, Daniela Galimberti, Maria Carmela Tartaglia, James Rowe, Caroline Graff, Fabrizio Tagliavini, Giovanni Frisoni, Stefano Cappa, Robert Laforce, Alexandre De Mendonça, Sandro Sorbi, Garrick Wallstrom, Mario Masellis, Jonathan D. Rohrer, Elizabeth C. Finger

Medical Biophysics Publications

Copyright © 2019 American Academy of Neurology. ObjectiveTo characterize the time course of ventricular volume expansion in genetic frontotemporal dementia (FTD) and identify the onset time and rates of ventricular expansion in presymptomatic FTD mutation carriers.MethodsParticipants included patients with a mutation in MAPT, PGRN, or C9orf72, or first-degree relatives of mutation carriers from the GENFI study with MRI scans at study baseline and at 1 year follow-up. Ventricular volumes were obtained from MRI scans using FreeSurfer, with manual editing of segmentation and comparison to fully automated segmentation to establish reliability. Linear mixed models were used to identify differences in ventricular …

Chronic Obstructive Pulmonary Disease: Thoracic Ct Texture Analysis And Machine Learning To Predict Pulmonary Ventilation, Andrew Westcott, Dante P I Capaldi, David G Mccormack, Aaron D Ward, Aaron Fenster, Grace Parraga

Medical Biophysics Publications

Background Fixed airflow limitation and ventilation heterogeneity are common in chronic obstructive pulmonary disease (COPD). Conventional noncontrast CT provides airway and parenchymal measurements but cannot be used to directly determine lung function. Purpose To develop, train, and test a CT texture analysis and machine-learning algorithm to predict lung ventilation heterogeneity in participants with COPD. Materials and Methods In this prospective study (

An Accurate Registration Of The Bigbrain Dataset With The Mni Pd25 And Icbm152 Atlases., Yiming Xiao, Jonathan C Lau, Taylor Anderson, Jordan Dekraker, D Louis Collins, Terry Peters, Ali R Khan

Brain and Mind Institute Researchers' Publications

Brain atlases that encompass detailed anatomical or physiological features are instrumental in the research and surgical planning of various neurological conditions. Magnetic resonance imaging (MRI) has played important roles in neuro-image analysis while histological data remain crucial as a gold standard to guide and validate such analyses. With cellular-scale resolution, the BigBrain atlas offers 3D histology of a complete human brain, and is highly valuable to the research and clinical community. To bridge the insights at macro- and micro-levels, accurate mapping of BigBrain and established MRI brain atlases is necessary, but the existing registration is unsatisfactory. The described dataset includes …

Visualization Of The Small Airways:What It Is And Why It Matters, Mark L Schiebler, Grace Parraga

Medical Biophysics Publications

When the earth transitioned to an oxygen-containing atmosphere, many bacterial species were killed by the free radicals that developed in their cytoplasm. New life forms took advantage of this change by evolving to use oxygen as the final resting place for electrons involved in the Krebs cycle. Animals today rely on getting oxygen into the blood stream and getting carbon dioxide out by ventilation through sequentially smaller and smaller tubes until diffusion takes over, finally reaching the terminal respiratory bronchiole and its associated alveoli for gas exchange. All animals are obligate aerobes. One group has estimated that there are 274 …

Exposure To The Rxr Agonist Sr11237 In Early Life Causes Disturbed Skeletal Morphogenesis In A Rat Model, Holly Dupuis, Michael Andrew Pest, Ermina Hadzic, Thin Xuan Vo, Daniel B. Hardy, Frank Beier

Physiology and Pharmacology Publications

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Longitudinal bone growth occurs through endochondral ossification (EO), controlled by various signaling molecules. Retinoid X Receptor (RXR) is a nuclear receptor with important roles in cell death, development, and metabolism. However, little is known about its role in EO. In this study, the agonist SR11237 was used to evaluate RXR activation in EO. Rats given SR11237 from post-natal day 5 to post-natal day 15 were harvested for micro-computed tomography (microCT) scanning and histology. In parallel, newborn CD1 mouse tibiae were cultured with increasing concentrations of SR11237 for histological and whole-mount evaluation. …

A Framework For Evaluating Correspondence Between Brain Images Using Anatomical Fiducials., Jonathan C Lau, Andrew G Parrent, John Demarco, Geetika Gupta, Jason Kai, Olivia W Stanley, Tristan Kuehn, Patrick J Park, Kayla Ferko, Ali R Khan, Terry M Peters

Brain and Mind Institute Researchers' Publications

Accurate spatial correspondence between template and subject images is a crucial step in neuroimaging studies and clinical applications like stereotactic neurosurgery. In the absence of a robust quantitative approach, we sought to propose and validate a set of point landmarks, anatomical fiducials (AFIDs), that could be quickly, accurately, and reliably placed on magnetic resonance images of the human brain. Using several publicly available brain templates and individual participant datasets, novice users could be trained to place a set of 32 AFIDs with millimetric accuracy. Furthermore, the utility of the AFIDs protocol is demonstrated for evaluating subject-to-template and template-to-template registration. Specifically, …

Cardiovascular Risk Scoring And Magnetic Resonance Imaging Detected Subclinical Cerebrovascular Disease, Sonia S Anand, Jack V Tu, Dipika Desai, Phillip Awadalla, Paula Robson, Sébastien Jacquemont, Trevor Dummer, Nhu Le, Louise Parker, Paul Poirier, Koon Teo, Scott A Lear, Salim Yusuf, Jean-Claude Tardif, Francois Marcotte, David Busseuil, Jean-Pierre Després, Sandra E Black, Anish Kirpalani, Grace Parraga, Michael D Noseworthy, Alexander Dick, Jonathan Leipsic, David Kelton, Jennifer Vena, Melissa Thomas, Karleen M Schulze, Eric Larose, Alan R Moody, Eric E Smith, Matthias G Friedrich

Medical Biophysics Publications

AIMS: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI).

METHODS AND RESULTS: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the …

Drug Interactions And Pharmacogenetic Factors Contribute To Variation In Apixaban Concentration In Atrial Fibrillation Patients In Routine Care, Markus Gulilat, Denise Keller, Bradley Linton, A. Demetri Pananos, Daniel Lizotte, George K. Dresser, Jeffrey Alfonsi, Rommel G. Tirona, Richard B. Kim, Ute I. Schwarz

Physiology and Pharmacology Publications

Factor Xa-inhibitor apixaban is an oral anticoagulant prescribed in atrial fibrillation (AF) for stroke prevention. Its pharmacokinetic profile is known to be affected by cytochrome P450 (CYP)3A metabolism, while it is also a substrate of the efflux transporters ATP-binding cassette (ABC)B1 (P-glycoprotein) and ABCG2 (breast cancer resistance protein, BCRP). In this study, we assessed the impact of interacting medication and pharmacogenetic variation to better explain apixaban concentration differences among 358 Caucasian AF patients. Genotyping (ABCG2, ABCB1, CYP3A4*22, CYP3A5*3) was performed by TaqMan assays, and apixaban quantified by mass spectrometry. The typical patient was on average …

Thirty-Five Years Of Computerized Cognitive Assessment Of Aging — Where Are We Now?, Avital Sternin, Alistair Burns, Adrian M. Owen

Brain and Mind Institute Researchers' Publications

Over the past 35 years, the proliferation of technology and the advent of the internet have resulted in many reliable and easy to administer batteries for assessing cognitive function. These approaches have great potential for affecting how the health care system monitors and screens for cognitive changes in the aging population. Here, we review these new technologies with a specific emphasis on what they offer over and above traditional ‘paper-and-pencil’ approaches to assessing cognitive function. Key advantages include fully automated administration and scoring, the interpretation of individual scores within the context of thousands of normative data points, the inclusion of …

Eliminating The Effects Of Motion During Radiofrequency Lesion Delivery Using A Novel Contact-Force Controller., Daniel Gelman, Allan C Skanes, Douglas L Jones, Michael Timofeyev, Tal Bar-On, Maria Drangova

Medical Biophysics Publications

INTRODUCTION: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo.

METHODS AND RESULTS: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average …

Development Of A Stand-Alone Dcs System For Monitoring Absolute Cerebral Blood Flow, Mahro Khalid, Daniel Milej, Ajay Rajaram, Androu Abdalmalak, Laura Morrison, Mamadou Diop, Keith S.T. Lawrence

Medical Biophysics Publications

© 2019 Optical Society of America. Diffuse correlation spectroscopy (DCS) is a noninvasive optical technique for monitoring cerebral blood flow (CBF). This work presents a stand-alone DCS system capable of monitoring absolute CBF by incorporating a quantitative dynamic contrast-enhanced (DCE) technique. Multi-distance data were acquired to measure the tissue optical properties and to perform DCE experiments. Feasibility of the technique was assessed in piglets in which the optical properties were measured independently by time-resolved near-infrared spectroscopy. A strong linear correlation was observed between CBF values derived using the two sets of optical properties, demonstrating that this hybrid DCS approach can …