Sunnybrook Health Sciences Centre

6 ARTICLES PUBLISHED IN JoVE

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 Green¹, Nick Reed¹, Sabrina Agnihotri¹, Amy Wilkinson³, 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.

Medicine

MRI-guided Disruption of the Blood-brain Barrier using Transcranial Focused Ultrasound in a Rat Model

Meaghan A. O'Reilly¹, 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 brain^1-3. This protocol outlines the experimental procedure for MRI-guided transcranial BBB disruption in a rat model.

Medicine

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Joel Ramirez¹, Christopher J.M. Scott¹, Alicia A. McNeely¹, Courtney Berezuk¹, Fuqiang Gao¹, 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.

Medicine

MRI-guided Focused Ultrasound Thalamotomy for Patients with Medically-refractory Essential Tremor

Ying Meng¹, Yuexi Huang², Benjamin Solomon², Kullervo Hynynen², Nadia Scantlebury¹, Michael L. Schwartz¹, Nir Lipsman¹

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.

JoVE Journal

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Allison A. Dilliott^1,2, Sali M.K. Farhan³, Mahdi Ghani⁴, Christine Sato⁴, Eric Liang⁵, Ming Zhang⁴, Adam D. McIntyre¹, Henian Cao¹, Lemuel Racacho^6,7, John F. Robinson¹, Michael J. Strong^1,8, Mario Masellis^9,10, Dennis E. Bulman^6,7, Ekaterina Rogaeva⁴, Anthony Lang^10,11, Carmela Tartaglia^4,10, Elizabeth Finger^12,13, Lorne Zinman⁹, John Turnbull¹⁴, Morris Freedman^10,15, Rick Swartz⁹, 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.

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 Davies³, 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.