Medicine and Health Sciences Commons^™

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

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 …

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 …

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 (

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 …

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 …

Piezo1: Proteins For Mechanotransduction And Integration Of Endothelial Shear Stress & Intravascular Pressure, Juan Garcia Robledo M.D.

Electronic Thesis and Dissertation Repository

Piezo proteins are transmembrane ion channels, specialized in detecting mechanosensitive stimuli and transduce mechanical forces into biochemical signals. Piezo proteins research has helped understand physiological mechanisms, but the integrative role that Piezo1 plays in the regulation of the microvasculature has remained unstudied. Our main objective was to characterize ex vivo microvascular responses to the blockade of Piezo1 mechanotransduction in male (n=29) and female (n=24) Sprague-Dawley (SD) rats. Gracilis arterioles (GA) and middle cerebral arterioles (MCA) were harvested for ex-vivo vessel preparations. After vessel viability confirmation, every vessel was submitted to myogenic and flow challenges under control conditions and after Grammostola …

Mri Investigations Of Metabolic And Structural Brain Changes In Alzheimer’S Disease And Vitamin D Deprivation, Dickson Wong

Electronic Thesis and Dissertation Repository

Alzheimer's disease (AD) is a neurodegenerative disorder of the brain that presents as progressive impairment across several cognitive domains. The biological mechanisms underlying the development of AD remain unclear, with amyloid-beta plaques, neurofibrillary tangles, calcium dysregulation, and oxidative stress all contributing to neurodegeneration in AD. Vitamin D (VitD) deficiency, a common condition in the elderly, may modulate these mechanisms and complicate the AD process. Due to this complicated pathogenesis, the diagnosis of AD requires subjective clinical judgement, staging of AD is challenging, and it remains difficult to predict when and who will progress to AD. The purpose of this thesis …

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 …

Evaluation Of Hyperspectral Nirs For Quantitative Measurements Of Tissue Oxygen Saturation By Comparison To Time-Resolved Nirs, Matthew Kewin, Ajay Rajaram, Daniel Milej, Androu Abdalmalak, Laura Morrison, Mamadou Diop, Keith St Lawrence

Medical Biophysics Publications

© 2019 Optical Society of America. Near-infrared spectroscopy (NIRS) is considered ideal for brain monitoring during preterm infancy because it is non-invasive and provides a continuous measure of tissue oxygen saturation (StO2). Hyperspectral NIRS (HS NIRS) is an inexpensive, quantitative modality that can measure tissue optical properties and oxygen saturation (StO2) by differential spectroscopy. In this study, experiments were conducted using newborn piglets to measure StO2 across a range of oxygenation levels from hyperoxia to hypoxia by HS and time-resolved (TR) NIRS for validation. A strong correlation between StO2 measurements from the two techniques was observed (R2 = 0.98, average …

Development Of A Computational Method For Assessing Static Field Induced Torque On Medical Implants, Xiao Fan Ding

Electronic Thesis and Dissertation Repository

The objective of this thesis is the development of a computational method for finding the torque induced on an object when placed in the static magnetic field of an MR scanner. As a preliminary step, the classic EM problems of a sphere and infinitely long cylinder of linear material was modeled in commercially available simulation software. Upon verification of the parameters implemented, the second step is the simulation of simple objects with realistic material properties, stainless-steel cylinders. Physical cylinders were machined to match those in the simulations and underwent the ASTM standard method for measuring induced torque. An adjacent study …

Functional Magnetic Resonance Spectroscopy In First-Episode Schizophrenia: Measuring Glutamate And Glutathione Dynamics At 7-Tesla, Peter Jeon

Electronic Thesis and Dissertation Repository

Schizophrenia is a neuropsychiatric illness without known etiology or cure. Current efforts for symptom treatment still seem to leave a large portion of affected individuals without proper symptom management, with those experiencing symptom relief still having to wrestle with potential side-effects from medication trials. There has been growing evidence suggesting that glutamate and glutathione abnormalities hold major roles in development and manifestation of schizophrenia symptoms.

Magnetic resonance spectroscopy (MRS) provides a non-invasive means to observe in-vivo brain chemistry, including glutamate and glutathione. By adding a functional component to an MRS paradigm (fMRS), such as the color-word Stroop task, it is …

Hyperpolarized Helium 3 Mri In Mild-To-Moderate Asthma: Prediction Of Postbronchodilator Reversibility, Rachel L Eddy, Sarah Svenningsen, Christopher Licskai, David G Mccormack, Grace Parraga

Medical Biophysics Publications

Background: Longitudinal progression to irreversible airflow limitation occurs in approximately 10% of patients with asthma, but it is difficult to identify patients who are at risk for this transition.

Purpose: To investigate 6-year longitudinal changes in hyperpolarized helium 3 (3He) MRI ventilation defects in study participants with mild-to-moderate asthma and identify predictors of longitudinal changes in postbronchodilator forced expiratory volume in 1 second (FEV1) reversibility

Materials and Methods: Spirometry and hyperpolarized 3He MRI were evaluated in participants with mild-to-moderate asthma in two prospectively planned visits approximately 6 years apart. Participants underwent methacholine challenge at baseline (January 2010 to April 2011) …

Methodological Consensus On Clinical Proton Mrs Of The Brain: Review And Recommendations, Martin Wilson, Ovidiu Andronesi, Peter B. Barker, Robert Bartha, Alberto Bizzi, Patrick J. Bolan, Kevin M. Brindle, In Young Choi, Cristina Cudalbu, Ulrike Dydak, Uzay E. Emir, Ramon G. Gonzalez, Stephan Gruber, Rolf Gruetter, Rakesh K. Gupta, Arend Heerschap, Anke Henning, Hoby P. Hetherington, Petra S. Huppi, Ralph E. Hurd, Kejal Kantarci, Risto A. Kauppinen, Dennis W.J. Klomp, Roland Kreis, Marijn J. Kruiskamp, Martin O. Leach, Alexander P. Lin, Peter R. Luijten, Małgorzata Marjańska, Andrew A. Maudsley, Dieter J. Meyerhoff, Carolyn E. Mountford

Medical Biophysics Publications

© 2019 International Society for Magnetic Resonance in Medicine Proton MRS (1H MRS) provides noninvasive, quantitative metabolite profiles of tissue and has been shown to aid the clinical management of several brain diseases. Although most modern clinical MR scanners support MRS capabilities, routine use is largely restricted to specialized centers with good access to MR research support. Widespread adoption has been slow for several reasons, and technical challenges toward obtaining reliable good-quality results have been identified as a contributing factor. Considerable progress has been made by the research community to address many of these challenges, and in this paper a …

Microvascular Stenosis In Critical Limb Ischemia: Role Of Partial Endothelial To Mesenchymal Transition, Jacqueline M. Chevalier

Electronic Thesis and Dissertation Repository

Critical limb ischemia (CLI) is a widespread and debilitating manifestation of atherosclerosis. Unfortunately, revascularization strategies are often precluded or unsuccessful, resulting in amputation. A major reason for treatment failure is likely co-existing abnormalities in ­­the microvasculature. However, the specific microvascular defects present in end-stage PAD in humans remain unknown.

The purpose of this study was to delineate abnormalities in the microvascular wall in the critically ischemic skeletal muscle of patients with CLI.

To elucidate the microvascular landscape in CLI, we studied human tibialis anterior and gastrocnemius muscles harvested from below-knee amputations of 10 individuals with CLI. Control muscles are from …

An Apodized-Aperture X-Ray Detector Design For Improved Image Quality In Mammography, Tomi F. Nano

Electronic Thesis and Dissertation Repository

X-ray imaging for early cancer detection, such as screening mammography, requires images with high signal-to-noise ratio (SNR) using low levels of radiation exposure. Conventional detectors consist of a matrix of sensor elements, producing images where each pixel corresponds to a single sensor element. This imposes a fundamental limitation on image contrast and SNR for imaging fine detail for a given exposure. The work presented here reconsiders x-ray image formation using a new x-ray detector design that synthesizes image pixels from a large number of very small sensor elements with the goal of optimizing contrast and SNR.

Our new detector design, …

Functional Network Resilience To Pathology In Presymptomatic Genetic Frontotemporal Dementia, Timothy Rittman, Robin Borchert, Simon Jones, John Van Swieten, Barbara Borroni, Daniela Galimberti, Mario Masellis, Maria Carmela Tartaglia, Caroline Graff, Fabrizio Tagliavini, Giovanni B. Frisoni, Robert Laforce, Elizabeth Finger, Alexandre Mendonça, Sandro Sorbi, Jonathan D. Rohrer, James B. Rowe, Sónia Afonso, Maria Rosario Almeida, Sarah Anderl-Straub, Christin Andersson, Anna Antonell, Silvana Archetti, Andrea Arighi, Mircea Balasa, Myriam Barandiaran, Nuria Bargalló, Robart Bartha, Benjamin Bender, Luisa Benussi, Valentina Bessi, Giuliano Binetti

Medical Biophysics Publications

© 2019 The Authors The presymptomatic phase of neurodegenerative diseases are characterized by structural brain changes without significant clinical features. We set out to investigate the contribution of functional network resilience to preserved cognition in presymptomatic genetic frontotemporal dementia. We studied 172 people from families carrying genetic abnormalities in C9orf72, MAPT, or PGRN. Networks were extracted from functional MRI data and assessed using graph theoretical analysis. We found that despite loss of both brain volume and functional connections, there is maintenance of an efficient topological organization of the brain's functional network in the years leading up to the estimated age …

Towards On-Line Plan Adaptation Of Unified Intensity-Modulated Arc Therapy Using A Fast-Direct Aperture Optimization Algorithm, Michael Macfarlane

Electronic Thesis and Dissertation Repository

External beam radiotherapy (EBRT) plays a vital role in the treatment of cancer, with close to half of all cancer patients receiving EBRT at some point over their course of treatment. Although EBRT is a well-established form of treatment, there are a number of ways in which EBRT could still be improved in terms of quality and efficiency for treatment planning and radiation dose delivery. This thesis reports a series of improvements made to EBRT.

First, we developed and evaluated a new treatment planning technique called unified intensity-modulated arc therapy (UIMAT) which combines the optimization and delivery of rotational volumetric …

Texture Analysis And Machine Learning To Predict Pulmonary Ventilation From Thoracic Computed Tomography, Andrew Westcott

Electronic Thesis and Dissertation Repository

Chronic obstructive pulmonary disease (COPD) leads to persistent airflow limitation, causing a large burden to patients and the health care system. Thoracic CT provides an opportunity to observe the structural pathophysiology of COPD, whereas hyperpolarized gas MRI provides images of the consequential ventilation heterogeneity. However, hyperpolarized gas MRI is currently limited to research centres, due to the high cost of gas and polarization equipment. Therefore, I developed a pipeline using texture analysis and machine learning methods to create predicted ventilation maps based on non-contrast enhanced, single-volume thoracic CT. In a COPD cohort, predicted ventilation maps were qualitatively and quantitatively related …

Reproducibility Of Neurite Orientation Dispersion And Density Imaging (Noddi) In Rats At 9.4 Tesla, Patrick Mccunn, Kyle M. Gilbert, Peter Zeman, Alex X. Li, Michael J. Strong, Ali R. Khan, Robert Bartha

Medical Biophysics Publications

© 2019 McCunn et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose Neurite Orientation Dispersion and Density Imaging (NODDI) is a diffusion MRI (dMRI) technique used to characterize tissue microstructure by compartmental modelling of neural water fractions. Intra-neurite, extra-neurite, and cerebral spinal fluid volume fractions are measured. The purpose of this study was to determine the reproducibility of NODDI in the rat brain at 9.4 Tesla. Methods Eight data sets were successfully …

The Effect Of Sepsis On Cerebral Microvascular Blood Flow, Laura Mawdsley, Mamadou Diop, Chris G. Ellis

Western Research Forum

Background: Sepsis is a dysregulated host response to infection that affects 18 000 000 people worldwide, and over 325 000 000 dollars are spent treating sepsis in Canada every year. One of the symptoms of severe sepsis is an altered mental state, which is accompanied with a measured decrease in oxygen levels in the skeletal muscle microvasculature. It is hypothesized that his altered mental state is due to a lack of oxygenated blood reaching the brain.

Hypothesis: After the onset of sepsis, microvascular cerebral blood flow and oxygen levels in the blood will decrease. Onset of decreased blood flow in …

Ambroxol As A Novel Disease-Modifying Treatment For Parkinson's Disease Dementia: Protocol For A Single-Centre, Randomized, Double-Blind, Placebo-Controlled Trial, C. R.A. Silveira, J. Mackinley, K. Coleman, Z. Li, E. Finger, R. Bartha, S. A. Morrow, J. Wells, M. Borrie, R. G. Tirona, C. A. Rupar, G. Zou, R. A. Hegele, D. Mahuran, Penny A. Macdonald, M. E. Jenkins, M. Jog, S. H. Pasternak

Medical Biophysics Publications

© 2019 The Author(s). Background: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for β-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The …