Clinical Trial: MRI Study of Blood-brain Barrier Function in CADASIL

Study Status: RECRUITING
Recruit Status: RECRUITING
Study Type: OBSERVATIONAL

Official Title: MRI Study of Blood-brain Barrier Function in CADASIL

Brief Summary: Diffusion prepared pseudo-continuous ASL (DP-pCASL) is a newly proposed MRI method to noninvasively measure the function of blood-brain barrier (BBB).
The investigators aim to investigate whether the water exchange rate across the BBB, estimated with DP-pCASL, is changed in patients with CADASIL, and to analyze the association between BBB water exchange rate and MRI/clinical features in these patients.

Detailed Summary: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by NOTCH3 gene mutations, is the most frequent monogenic type of hereditary cerebral small vessel disease (CSVD).
The unique pathophysiological mechanisms that small vessel disorders in CADASIL are caused by genetic mutations and that the majority of patients do not combine cerebrovascular disease risk factors make CADASIL an ideal model for studying CSVD, and the imaging findings on CADASIL can be used to diagnose and investigate the etiology of CSVD.
While abnormalities in the cerebrovascular structure and hemodynamics have been well demonstrated in CADASIL, the abnormality of the BBB remains controversial.
One DCE-MRI study suggested an increase in BBB permeability to gadolinium contrast in CADASIL, whereas no abnormality of BBB was found in subsequent studies in mouse models and patients.
The aim of this study was to assess whether BBB function is abnormal in patients with CADASIL using DP-pCASL, which is more sensitive to subtle changes in the BBB compared to DCE-MRI.
The investigators hypothesized that the BBB water exchange rate (kw) is reduced in patients with CADASIL compared to controls as assessed by DP-pCASL and that the degree of reduction in BBB water exchange rate correlates with the severity of disease in patients with CADASIL.
Sponsor: Peking University First Hospital

Current Primary Outcome: Post-processing of DP-pCASL data was performed offline using LOFT BBB Toolbox.
Head motion was corrected using SPM12 and the temporal fluctuations were minimized by using principal component analysis.
DP-pCASL data with the b value of 50 s/mm2 were used to obtain the ASL signal from the tissue and capillary compartments respectively, and kw was quantified by using a single-pass approximation model with total generalized variation regularization.

Original Primary Outcome: Post-processing of DP-pCASL data was performed offline using LOFT BBB Toolbox.
Head motion was corrected using SPM12 and the temporal fluctuations were minimized by using principal component analysis.
DP-pCASL data with the b value of 50 s/mm2 were used to obtain the ASL signal from the tissue and capillary compartments respectively, and kw was quantified by using a single-pass approximation model with total generalized variation regularization.

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Peking University First Hospital

Dates:
Date Received: April 21, 2023
Date Started: 2021-04-01
Date Completion: {'date': '2021-04-01', 'type': 'ACTUAL'}
Last Updated: 2023-06-04
Last Verified: 2023-06