Cerebral White Matter Hypoperfusion Increases with Small-Vessel Disease Burden. Data From the Third International Stroke Trial.
BACKGROUND
Leukoaraiosis is associated with impaired cerebral perfusion, but the effect of individual and combined small-vessel disease (SVD) features on white matter perfusion is unclear.


METHODS
We studied patients recruited with perfusion imaging in the Third International Stroke Trial. We rated individual SVD features (leukoaraiosis, lacunes) and brain atrophy on baseline plain computed tomography or magnetic resonance imaging. Separately, we assessed white matter at the level of the lateral ventricles in the cerebral hemisphere contralateral to the stroke for visible areas of hypoperfusion (present or absent) on 4 time-based perfusion imaging parameters. We examined associations between SVD features (individually and summed) and presence of hypoperfusion using logistic regression adjusted for age, sex, baseline National Institutes of Health Stroke Scale, hypertension, and diabetes.


RESULTS
A total of 115 patients with median (interquartile range) age of 81 (72-86) years, 78 (52%) of which were male, had complete perfusion data. Hypoperfusion was most frequent on mean transit time (MTT; 63 patients, 55%) and least frequent on time to maximum flow (19 patients, 17%). The SVD score showed stronger independent associations with hypoperfusion (e.g., MTT, odds ratio [OR] = 2.80; 95% confidence interval [CI] = 1.56-5.03) than individual SVD markers (e.g., white matter hypoattenuation score, MTT, OR = 1.49, 95% CI = 1.09-2.04). Baseline blood pressure did not differ by presence or absence of hypoperfusion or across strata of SVD score. Presence of white matter hypoperfusion increased with SVD summed score.


CONCLUSIONS
The SVD summed score was associated with hypoperfusion more consistently than individual SVD features, providing validity to the SVD score concept. Increasing SVD burden indicates worse perfusion in the white matter.
NEUROFARBA Department, University of Florence, Florence, Italy; Division of Neuroimaging Sciences, Brain Research Imaging Centre, University of Edinburgh, UK; Brain Research Imaging Centre, SINAPSE Collaboration, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Francesco
F
Arba
Division of Neuroimaging Sciences, Brain Research Imaging Centre, University of Edinburgh, UK; Brain Research Imaging Centre, SINAPSE Collaboration, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Grant
G
Mair
Division of Neuroimaging Sciences, Brain Research Imaging Centre, University of Edinburgh, UK; Brain Research Imaging Centre, SINAPSE Collaboration, UK.
Trevor
T
Carpenter
Division of Neuroimaging Sciences, Brain Research Imaging Centre, University of Edinburgh, UK; Brain Research Imaging Centre, SINAPSE Collaboration, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Eleni
E
Sakka
Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.
Peter A G
PAG
Sandercock
Westmead Hospital Clinical School and the George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia.
Richard I
RI
Lindley
NEUROFARBA Department, University of Florence, Florence, Italy.
Domenico
D
Inzitari
Division of Neuroimaging Sciences, Brain Research Imaging Centre, University of Edinburgh, UK; Brain Research Imaging Centre, SINAPSE Collaboration, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Western General Hospital, Edinburgh, UK. Electronic address: joanna.wardlaw@ed.ac.uk.
Joanna M
JM
Wardlaw
D000368:Aged; D000369:Aged, 80 and over; D001284:Atrophy; D001783:Blood Flow Velocity; D059345:Cerebral Small Vessel Diseases / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D049292:Leukoaraiosis; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D016017:Odds Ratio; D055420:Perfusion Imaging / Q000379:methods; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D066127:White Matter / Q000098:blood supply*
CT perfusion; Cerebral small-vessel disease; cerebral blood flow; stroke; white matter