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Sunnybrook Health Sciences Centre

6 ARTICLES PUBLISHED IN JoVE

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Medicine

An Investigation of the Effects of Sports-related Concussion in Youth Using Functional Magnetic Resonance Imaging and the Head Impact Telemetry System
Michelle Keightley 1,2,3,4,5, Stephanie Green 1, Nick Reed 1, Sabrina Agnihotri 1, Amy Wilkinson 3, Nancy Lobaugh 6,7
1Graduate Department of Rehabilitation Science, University of Toronto, 2Occupational Science and Occupational Therapy, University of Toronto, 3Department of Psychology, University of Toronto, 4Bloorview Kids Rehab, 5Toronto Rehab, 6Cognitive Neurology, Sunnybrook Health Sciences Centre, 7Faculty of Medicine, University of Toronto

This article provides an overview of a multi-modal approach to mild traumatic brain injury diagnosis and recovery in youth. This approach combines neuropsychological testing with functional magnetic resonance imaging and the Head Impact Telemetry System to monitor the relationship between head impacts and brain activity during cognitive testing.

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Medicine

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model
Meaghan A. O'Reilly 1, Adam C. Waspe 1,2, Rajiv Chopra 1,2, Kullervo Hynynen 1,3
1Imaging Research, Sunnybrook Research Institute, 2Department of Medical Biophysics, University of Toronto, 3Department of Medical Biophysics, and Institute of Biomaterials & Biomedical Engineering (IBBME), University of Toronto

Microbubble-mediated focused ultrasound disruption of the blood-brain barrier (BBB) is a promising technique for non-invasive targeted drug delivery in the brain1-3. This protocol outlines the experimental procedure for MRI-guided transcranial BBB disruption in a rat model.

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Medicine

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly
Joel Ramirez 1, Christopher J.M. Scott 1, Alicia A. McNeely 1, Courtney Berezuk 1, Fuqiang Gao 1, Gregory M. Szilagyi 1,2, Sandra E. Black 1,2
1LC Campbell Cognitive Neurology Research Unit, Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Brain Sciences Research Program, Sunnybrook Health Sciences Centre, 2Department of Medicine (Neurology), Institute of Medical Science, University of Toronto

Lesion Explorer (LE) is a semi-automatic, image-processing pipeline developed to obtain regional brain tissue and subcortical hyperintensity lesion volumetrics from structural MRI of Alzheimer's disease and normal elderly. To ensure a high level of accuracy and reliability, the following is a video-guided, standardized protocol for LE's manual procedures.

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Medicine

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor
Ying Meng 1, Yuexi Huang 2, Benjamin Solomon 2, Kullervo Hynynen 2, Nadia Scantlebury 1, Michael L. Schwartz 1, Nir Lipsman 1
1Division of Neurosurgery, Sunnybrook Health Sciences Centre, 2Sunnybrook Research Institute, Sunnybrook Health Sciences Centre

High-intensity MRI guided focused ultrasound is an emerging noninvasive technique to precisely ablate brain tissue. It has been shown to be safe and effective in treating medically-refractory essential tremor. This article describes the protocol for thalamotomy from patient selection to equipment setup to post-treatment follow-up.

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JoVE Journal

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Allison A. Dilliott 1,2, Sali M.K. Farhan 3, Mahdi Ghani 4, Christine Sato 4, Eric Liang 5, Ming Zhang 4, Adam D. McIntyre 1, Henian Cao 1, Lemuel Racacho 6,7, John F. Robinson 1, Michael J. Strong 1,8, Mario Masellis 9,10, Dennis E. Bulman 6,7, Ekaterina Rogaeva 4, Anthony Lang 10,11, Carmela Tartaglia 4,10, Elizabeth Finger 12,13, Lorne Zinman 9, John Turnbull 14, Morris Freedman 10,15, Rick Swartz 9, Sandra E. Black 9,16, Robert A. Hegele 1,2
1Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, 2Department of Biochemistry, Schulich School of Medicine and Dentistry, Western University, 3Analytic and Translational Genetics Unit, Center for Genomic Medicine, Harvard Medical School, Massachusetts General Hospital, Stanley Centre for Psychiatric Research, Broad Institute of MIT and Harvard, 4Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 5School of Medicine, Faculty of Health Sciences, Queen's University, 6Faculty of Medicine, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, 7CHEO Research Institute, Faculty of Medicine, University of Ottawa, 8Department of Clinical Neurological Sciences, Western University, 9Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, 10Division of Neurology, Department of Medicine, University of Toronto, 11Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, 12Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, 13Parkwood Institute, St. Joseph's Health Care, 14Department of Medicine, Division of Neurology, McMaster University, 15Division of Neurology, Department of Medicine, Baycrest Health Sciences, 16Canadian Partnership for Stroke Recovery Sunnybrook Site, Sunnybrook Health Science Centre, University of Toronto

Targeted next-generation sequencing is a time- and cost-efficient approach that is becoming increasingly popular in both disease research and clinical diagnostics. The protocol described here presents the complex workflow required for sequencing and the bioinformatics process used to identify genetic variants that contribute to disease.

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Bioengineering

Real-Time Intravital Multiphoton Microscopy to Visualize Focused Ultrasound and Microbubble Treatments to Increase Blood-Brain Barrier Permeability
Charissa Poon 1,2, Melina Mühlenpfordt *3, Marieke Olsman *3, Spiros Kotopoulis 4,5, Catharina de Lange Davies 3, Kullervo Hynynen 1,2,6
1Physical Sciences Platform, Sunnybrook Research Institute, 2Institute of Biomedical Engineering, University of Toronto, 3Department of Physics, Norwegian University of Science and Technology, 4Department of Clinical Medicine, University of Bergen, 5Exact Therapeutics AS, 6Department of Medical Biophysics, University of Toronto

This protocol describes the surgical and technical procedures that enable real-time in vivo multiphoton fluorescence imaging of the rodent brain during focused ultrasound and microbubble treatments to increase blood-brain barrier permeability.

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