TY - JOUR
T1 - Transit time homogenization in ischemic stroke - A novel biomarker of penumbral microvascular failure?
AU - Engedal, Thorbjørn S
AU - Hjort, Niels
AU - Hougaard, Kristina D
AU - Simonsen, Claus Z
AU - Andersen, Grethe
AU - Mikkelsen, Irene Klærke
AU - Boldsen, Jens K
AU - Eskildsen, Simon F
AU - Hansen, Mikkel B
AU - Angleys, Hugo
AU - Jespersen, Sune N
AU - Pedraza, Salvador
AU - Cho, Tae-Hee
AU - Serena, Joaquín
AU - Siemonsen, Susanne
AU - Thomalla, Götz
AU - Nighoghossian, Norbert
AU - Fiehler, Jens
AU - Mouridsen, Kim
AU - Østergaard, Leif
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Cerebral ischemia causes widespread capillary no-flow in animal studies. The extent of microvascular impairment in human stroke, however, is unclear. We examined how acute intra-voxel transit time characteristics and subsequent recanalization affect tissue outcome on follow-up MRI in a historic cohort of 126 acute ischemic stroke patients. Based on perfusion-weighted MRI data, we characterized voxel-wise transit times in terms of their mean transit time (MTT), standard deviation (capillary transit time heterogeneity - CTH), and the CTH:MTT ratio (relative transit time heterogeneity), which is expected to remain constant during changes in perfusion pressure in a microvasculature consisting of passive, compliant vessels. To aid data interpretation, we also developed a computational model that relates graded microvascular failure to changes in these parameters. In perfusion-diffusion mismatch tissue, prolonged mean transit time (>5 seconds) and very low cerebral blood flow (≤6 mL/100 mL/min) was associated with high risk of infarction, largely independent of recanalization status. In the remaining mismatch region, low relative transit time heterogeneity predicted subsequent infarction if recanalization was not achieved. Our model suggested that transit time homogenization represents capillary no-flow. Consistent with this notion, low relative transit time heterogeneity values were associated with lower cerebral blood volume. We speculate that low RTH may represent a novel biomarker of penumbral microvascular failure.
AB - Cerebral ischemia causes widespread capillary no-flow in animal studies. The extent of microvascular impairment in human stroke, however, is unclear. We examined how acute intra-voxel transit time characteristics and subsequent recanalization affect tissue outcome on follow-up MRI in a historic cohort of 126 acute ischemic stroke patients. Based on perfusion-weighted MRI data, we characterized voxel-wise transit times in terms of their mean transit time (MTT), standard deviation (capillary transit time heterogeneity - CTH), and the CTH:MTT ratio (relative transit time heterogeneity), which is expected to remain constant during changes in perfusion pressure in a microvasculature consisting of passive, compliant vessels. To aid data interpretation, we also developed a computational model that relates graded microvascular failure to changes in these parameters. In perfusion-diffusion mismatch tissue, prolonged mean transit time (>5 seconds) and very low cerebral blood flow (≤6 mL/100 mL/min) was associated with high risk of infarction, largely independent of recanalization status. In the remaining mismatch region, low relative transit time heterogeneity predicted subsequent infarction if recanalization was not achieved. Our model suggested that transit time homogenization represents capillary no-flow. Consistent with this notion, low relative transit time heterogeneity values were associated with lower cerebral blood volume. We speculate that low RTH may represent a novel biomarker of penumbral microvascular failure.
KW - Journal Article
UR - http://www.scopus.com/inward/record.url?scp=85044378781&partnerID=8YFLogxK
U2 - 10.1177/0271678X17721666
DO - 10.1177/0271678X17721666
M3 - Journal article
C2 - 28758524
SN - 0271-678X
VL - 38
SP - 2006
EP - 2020
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 11
ER -