Runrun Wang1,2,3, Julien Poublanc1, Adrian P Crawley1, Olivia Sobczyk1, Sander Kneepkens1, Larissa Mcketton1, Charles Tator4, Renhua Wu3, David J Mikulis1. 1. Joint Department of Medical Imaging, University Health Network, The Toronto Western Hospital, The University of Toronto, Toronto, Ontario, Canada. 2. Department of Neurology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan, China. 3. Department of Medical Imaging, the Second Affiliated Hospital, Medical College of Shantou University, Shantou, China. 4. Department of Surgery, Division of Neurosurgery, University Health Network, The Toronto Western Hospital, The University of Toronto, Toronto, Ontario, Canada.
Abstract
BACKGROUND: Evidence suggests that cerebrovascular reactivity (CVR) increases within the first week after the incidence of concussion, indicating a disruption of normal autoregulation. We sought to extend these findings by investigating the effects of acute concussion on the speed of CVR response and by visualizing global and regional impairments in individual patients with acute concussion. METHODS: Twelve patients aged 18-40 years who experienced concussion less than a week before this prospective study were included. Twelve age and sex-matched healthy subjects constituted the control group. In all subjects, CVR was assessed using blood oxygenation level-dependent (BOLD) echo-planar imaging with a 3.0T MRI scanner, in combination with changes in end-tidal partial pressure of CO2 (PETCO2). In each subject, we calculated the CVR amplitude and CVR response time in the gray and white matter using a step and ramp PETCO2 challenge. In addition, a separate group of 39 healthy controls who underwent the same evaluation was used to create atlases with voxel-wise mean and standard deviation of CVR amplitude and CVR response time. This allowed us to convert each metric of the 12 patients with concussion and the 12 healthy controls into z-score maps. These maps were then used to generate and compare z-scores for each of the two groups. Group differences were calculated using an unpaired t-test. RESULTS: All studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study subjects. No differences in CO2 stimulus and O2 targeting were observed between the two participant groups during BOLD MRI. With regard to the gray matter, the CVR magnitude step (P=0.117) and ramp + 10 (P=0.085) were not significantly different between patients with concussion and healthy controls. However, the tau value was significantly lower in patients with concussion than in the healthy controls (P=0.04). With regard to the white matter, the CVR magnitude step (P=0.003) and ramp + 10 (P=0.031) were significantly higher and the tau value (P=0.024) was significantly shorter in patients with concussion than in healthy controls. After z-score transformation, the z tau value was significantly lower in patients with concussion than in healthy controls (Grey matter P=0.021, White matter P=0.003). Comparison of the three parameters, z ramp + 10, z step, and z tau, between the two groups showed that z step (Grey matter P=0.035, White matter P=0.005) was the most sensitive parameter and that z ramp + 10 (Grey matter P=0.073, White matter P=0.126) was the least sensitive parameter. CONCLUSIONS: Concussion is associated with patient-specific abnormalities in BOLD cerebrovascular responsiveness that occur in the setting of normal global CVR. This study demonstrates that the measurement of CVR using BOLD MRI and precise CO2 control is a safe, reliable, reproducible, and clinically useful method for evaluating the state of patients with concussion. It has the potential to be an important tool for assessing the severity and duration of symptoms after concussion. 2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.
BACKGROUND: Evidence suggests that cerebrovascular reactivity (CVR) increases within the first week after the incidence of concussion, indicating a disruption of normal autoregulation. We sought to extend these findings by investigating the effects of acute concussion on the speed of CVR response and by visualizing global and regional impairments in individual patients with acute concussion. METHODS: Twelve patients aged 18-40 years who experienced concussion less than a week before this prospective study were included. Twelve age and sex-matched healthy subjects constituted the control group. In all subjects, CVR was assessed using blood oxygenation level-dependent (BOLD) echo-planar imaging with a 3.0T MRI scanner, in combination with changes in end-tidal partial pressure of CO2 (PETCO2). In each subject, we calculated the CVR amplitude and CVR response time in the gray and white matter using a step and ramp PETCO2 challenge. In addition, a separate group of 39 healthy controls who underwent the same evaluation was used to create atlases with voxel-wise mean and standard deviation of CVR amplitude and CVR response time. This allowed us to convert each metric of the 12 patients with concussion and the 12 healthy controls into z-score maps. These maps were then used to generate and compare z-scores for each of the two groups. Group differences were calculated using an unpaired t-test. RESULTS: All studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study subjects. No differences in CO2 stimulus and O2 targeting were observed between the two participant groups during BOLD MRI. With regard to the gray matter, the CVR magnitude step (P=0.117) and ramp + 10 (P=0.085) were not significantly different between patients with concussion and healthy controls. However, the tau value was significantly lower in patients with concussion than in the healthy controls (P=0.04). With regard to the white matter, the CVR magnitude step (P=0.003) and ramp + 10 (P=0.031) were significantly higher and the tau value (P=0.024) was significantly shorter in patients with concussion than in healthy controls. After z-score transformation, the z tau value was significantly lower in patients with concussion than in healthy controls (Grey matter P=0.021, White matter P=0.003). Comparison of the three parameters, z ramp + 10, z step, and z tau, between the two groups showed that z step (Grey matter P=0.035, White matter P=0.005) was the most sensitive parameter and that z ramp + 10 (Grey matter P=0.073, White matter P=0.126) was the least sensitive parameter. CONCLUSIONS: Concussion is associated with patient-specific abnormalities in BOLD cerebrovascular responsiveness that occur in the setting of normal global CVR. This study demonstrates that the measurement of CVR using BOLD MRI and precise CO2 control is a safe, reliable, reproducible, and clinically useful method for evaluating the state of patients with concussion. It has the potential to be an important tool for assessing the severity and duration of symptoms after concussion. 2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.
Authors: Yang Wang; Andrew S Nencka; Timothy B Meier; Kevin Guskiewicz; Jason P Mihalik; M Alison Brooks; Andrew J Saykin; Kevin M Koch; Yu-Chien Wu; Lindsay D Nelson; Thomas W McAllister; Steven P Broglio; Michael A McCrea Journal: Brain Imaging Behav Date: 2019-10 Impact factor: 3.978
Authors: Chad A Tagge; Andrew M Fisher; Olga V Minaeva; Amanda Gaudreau-Balderrama; Juliet A Moncaster; Xiao-Lei Zhang; Mark W Wojnarowicz; Noel Casey; Haiyan Lu; Olga N Kokiko-Cochran; Sudad Saman; Maria Ericsson; Kristen D Onos; Ronel Veksler; Vladimir V Senatorov; Asami Kondo; Xiao Z Zhou; Omid Miry; Linnea R Vose; Katisha R Gopaul; Chirag Upreti; Christopher J Nowinski; Robert C Cantu; Victor E Alvarez; Audrey M Hildebrandt; Erich S Franz; Janusz Konrad; James A Hamilton; Ning Hua; Yorghos Tripodis; Andrew T Anderson; Gareth R Howell; Daniela Kaufer; Garth F Hall; Kun P Lu; Richard M Ransohoff; Robin O Cleveland; Neil W Kowall; Thor D Stein; Bruce T Lamb; Bertrand R Huber; William C Moss; Alon Friedman; Patric K Stanton; Ann C McKee; Lee E Goldstein Journal: Brain Date: 2018-02-01 Impact factor: 13.501
Authors: Olivia Sobczyk; Anne Battisti-Charbonney; Julien Poublanc; Adrian P Crawley; Kevin Sam; Jorn Fierstra; Daniel M Mandell; David J Mikulis; James Duffin; Joseph A Fisher Journal: J Cereb Blood Flow Metab Date: 2014-11-12 Impact factor: 6.200
Authors: Julien Poublanc; Adrian P Crawley; Olivia Sobczyk; Gaspard Montandon; Kevin Sam; Daniel M Mandell; Paul Dufort; Lashmikumar Venkatraghavan; James Duffin; David J Mikulis; Joseph A Fisher Journal: J Cereb Blood Flow Metab Date: 2015-07-01 Impact factor: 6.200
Authors: David Attwell; Alastair M Buchan; Serge Charpak; Martin Lauritzen; Brian A Macvicar; Eric A Newman Journal: Nature Date: 2010-11-11 Impact factor: 49.962