Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking.
BACKGROUND
White matter lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are underlaid by severe ultrastructural changes of the arteriolar wall. Although chronic ischemia is presumed to cause the tissue lesions, the pattern of perfusion abnormalities and hemodynamic reserve in CADASIL, particularly within the white matter, remains unknown.


METHODS
We used the MRI bolus tracking method in 15 symptomatic patients with CADASIL (5 with dementia) and 10 age-matched control subjects before and 20 minutes after the intravenous injection of acetazolamide (ACZ, 17 mg/kg). Cerebral blood flow (CBF), blood volume (CBV), and mean transit time (MTT) were calculated both in the cortex and in the white matter according to the singular value decomposition technique. Perfusion parameters were obtained in regions of hyperintensities and within the normal-appearing white matter as observed on T2-weighted images. Analysis was performed with both absolute and relative (region/whole brain) values.


RESULTS
A significant reduction in absolute and relative CBF and CBV was found within areas of T2 hyperintensities in white matter in the absence of significant variations of MTT. This reduction was more severe in demented than in nondemented patients. No significant change in absolute CBF and CBV values was observed in the cortex of patients with CADASIL. A decrease in relative CBF and CBV values was detected in the occipital cortex. After ACZ administration, CBF and CBV increased significantly in both the cortex and white matter of affected subjects, but the increase in absolute CBF was lower within areas of increased signal on T2-weighted images in patients than in the white matter of control subjects.


CONCLUSIONS
In CADASIL, both basal perfusion and hemodynamic reserve are decreased in areas of T2 hyperintensities in the white matter. This hypoperfusion appears to be related to the clinical severity. The significant effect of ACZ on CBF and CBV suggests that cerebral perfusion might be increased using pharmacological vasodilation in CADASIL.
Department of Neurology, CHU Lariboisière, Université Paris VII, France. chabriat@ccr.jussieu.fr
H
H
Chabriat
S
S
Pappata
L
L
Ostergaard
C A
CA
Clark
M
M
Pachot-Clouard
K
K
Vahedi
A
A
Jobert
D
D
Le Bihan
M G
MG
Bousser
D000086:Acetazolamide / Q000008:administration & dosage*; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001921:Brain / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D015161:Dementia, Multi-Infarct / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D017352:Echo-Planar Imaging; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015588:Observer Variation
D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide