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Cerebral hemodynamics in CADASIL before and after acetazolamide challenge assessed with MRI bolus tracking
H Chabriat1, S Pappata, L Ostergaard
1Department of Neurology, CHU Lariboisière, Université Paris VII, France. chabriat@ccr.jussieu.fr
Insights
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients show reduced white matter blood flow and reserve, especially in lesions. This hypoperfusion correlates with disease severity and may improve with vasodilation therapy.
Area of Science:
- Neuroimaging
- Cerebrovascular Diseases
- White Matter Lesions
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by white matter lesions due to arteriolar wall changes.
- Chronic ischemia is suspected, but white matter perfusion and hemodynamic reserve patterns in CADASIL are not well understood.
Purpose of the Study:
- To investigate white matter perfusion abnormalities and hemodynamic reserve in CADASIL patients.
- To assess the impact of acetazolamide (ACZ) on cerebral blood flow (CBF) and blood volume (CBV) in CADASIL.
Main Methods:
- MRI bolus tracking was used in 15 CADASIL patients and 10 controls.
- Cerebral blood flow (CBF), blood volume (CBV), and mean transit time (MTT) were calculated before and after acetazolamide (ACZ) administration.
- Perfusion parameters were analyzed in white matter hyperintensities and normal-appearing white matter.
Main Results:
- CADASIL patients exhibited reduced white matter CBF and CBV in T2 hyperintensities, more pronounced in those with dementia.
- Cortical CBF and CBV showed no significant change, though relative values decreased in the occipital cortex.
- Acetazolamide (ACZ) increased CBF and CBV in both groups, but the response was blunted in white matter lesions of CADASIL patients.
Conclusions:
- Areas of white matter hyperintensities in CADASIL demonstrate reduced basal perfusion and hemodynamic reserve.
- This hypoperfusion is linked to clinical severity.
- Pharmacological vasodilation with ACZ shows potential for improving cerebral perfusion in CADASIL.
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.