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 wail, Although chronic ischemia is presumed to cause the tissue lesions, the pattern of perfusion abnormalities and hemodynamic reserve in CADASIL, particularly within the w hite matter, remains unknown. Methods-We used the MRI bolus tracking method in 15 symptomatic patients wi th 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 (MT T) were calculated both in the cortex and in the white matter according to the singular value decomposition technique. Perfusion parameters were obtai ned in regions of hyperintensities and within the normal-appearing white ma tter as observed on T2-weighted images. Analysis was performed with both ab solute and relative (region/whole brain) values. Results-A significant reduction in absolute and relative CBF and CBV was fo und within areas of T2 hyperintensities in white matter in the absence of s ignificant variations of MTT, This reduction was more severe in demented th an in nondemented patients. No significant change in absolute CBF and CBV v alues was observed in the cortex of patients with CADASIL, A decrease in re lative CBF and CBV values was detected in the occipital cortex. After ACZ a dministration, CBF and CBV increased significantly in both the cortex and w hite matter of affected subjects, but the increase in absolute CBF was lowe r within areas of increased signal on T2-weighted images in patients than i n 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 hypoper fusion appears to be related to the clinical severity. The significant effe ct of ACZ on CBF and CBV suggests that cerebral perfusion might be increase d using pharmacological vasodilation in CADASIL.