Areas of research

CADA7: High resolution Magnetic Resonance Imaging in a monogenic model of cerebral small vessel disease.

CADA7 is a prospective 7 Tesla MRI study. In this study, we aim to assess microstructural and morphological modifications of cerebral cortex in CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), a monogenic model of cerebral small vessel disease.

PHRC 2009

Onset: October 2009

End: December 2015

Main investigator: Pr Hugues CHABRIAT, Neurology department, Lariboisière Hospital, Paris.

Background: CADASIL is a hereditary microvascular cerebral disease. Subcortical lesions observed in CADASIL occur frequently in aging populations with vascular risk factors. Thus, this genetic disease offers a unique opportunity to assess the impact of such  lesions on the structure, morphology and function of cerebral cortex.

Both high field (7 Tesla) and high resolution (200 microns) MRI are used to study this model of “pure” vascular dementia and  allow better understanding of the underlying mechanisms that rely subcortical ischemic lesions and secondary cortical degenerative phenomenon observed in CADASIL.

Purpose: The endpoints of our search would be to determine and assess:

  • The effect of age, sex and subcortical lesions on the micro and macrostructure as well as the morphology of the cerebral cortex in CADASIL
  • The presence and the localization of microinfarcts or microbleedings within cerebral cortex and their eventual relationships with subcortical lesions during the course of CADASIL
  • The modifications of  the vascular cortical architecture and  white matter in CADASIL
  • The correlations between clinical and cognitive status of the subjects and  the cortical modifications observed  globally and regionally

Selection of subjects: 30 CADASIL patients and 30 healthy age and sex matched controls were included in this study.

  • The patients were aged more than 18 years old and presented with  genetically proven  characteristic mutation of  Notch 3 gene
  • The healthy controls were aged more than 18 years old and were free of  past neurologic or vascular medical history

Design of the study: 3 consecutive visits were planned.

  • Visit 1: assessment of past medical history, blood samples, blood pressure measurement, clinical and neurologic examination, neuropsychological battery tests, brain MRI (3 and 7 Tesla).
  • Visit 2: second visit, similar to the first one, planned 42 months later.
  • Visit 3: Ongoing visit. Performed 60 months after the onset of  the study. Includes brain MRI (3 and 7 T).

Expected results: Our aim is to assess the extend, the severity and the distribution of microstructural and  morphological modifications of cerebral cortex in the course of CADASIL through the use of high resolution and high field MRI. This research program would therefore help understanding the physio pathological mechanisms of cortical atrophy. It may also establish a correlation between clinical status and  cortical alterations observed in high field and high resolution MRI.

Thanks to high resolution MRI, we can now describe the histology and the cyto-myeloarchitecture of cerebral cortex in vivo. Thus, the application of such techniques on a model of pure vascular cerebral disease as CADASIL would allow assessing the long term consequences of microvascular lesions in aging populations with vascular risk factors or in different neurodegenerative diseases.