Transit time homogenization in ischemic stroke - A novel biomarker of penumbral microvascular failure?

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 H

AU - Serena, Joaquín

AU - Siemonsen, Susanne

AU - Thomalla, Götz

AU - Nighoghossian, Norbert

AU - Fiehler, Jens

AU - Mouridsen, Kim

AU - Østergaard, Leif

PY - 2017/1/1

Y1 - 2017/1/1

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

U2 - 10.1177/0271678X17721666

DO - 10.1177/0271678X17721666

M3 - SCORING: Journal article

C2 - 28758524

SP - 271678X17721666

JO - J CEREBR BLOOD F MET

JF - J CEREBR BLOOD F MET

SN - 0271-678X

ER -