Cerebrovascular manifestations of Hereditary Hemorrhagic Telangiectasia: a look beyond AVMs | A study of the prevalence of structural brain changes in HHT and an assessment of the MR cerebrovascular reactivity of HHT patients

The cerebrovascular manifestations of Hereditary Hemorrhagic Telangiectasia
(HHT) have not been studied beyond the arteriovenous malformations (AVM)
associated with this disease. From animal studies there are indications that in
addition to these macrovascular pathologies the function of normal appearing
vessels of HHT patients may also be affected. This may indicate that
pathological changes in the brain of HHT patients occur that may show
similarities to changes occurring in the brain of patients with small vessel
disease, in which stiffening and fragility of the vessel wall results in white
and grey matter abnormalities and reduced vascular reactivity. Furthermore, the
cerebrovascular manifestations of HHT are more severe in patients with
pulmonary AVMs (PAVMs) than those without PAVMs, and the source of this
discrepancy is currently not known. Finally, mapping the cerebral expressions
of HHT is of interest not only to extend our knowledge of the pathological
processes occurring in this particular disease but it may also offer the
opportunity to explore mechanisms potentially relevant to other - more common -
small vessel diseases.

The objectives of this study are:
1. to evaluate the occurrence and distribution of structural brain changes in
HHT patients with and without pulmonary AVMs as compared to healthy age matched
controls;
2. to evaluate the (autoregulatory) function of small brain vessels in HHT
patients using CO2 cerebrovascular reactivity measurements with MRI.

This is an observational cross-sectional study comparing the prevalence and
distribution of different small vessel disease markers in HHT patients with the
prevalence and distribution of these markers in healthy age matched controls.
This study consists of a single MRI scan session with a 3 Tesla clinical MRI
scanner consisting of different MR image types (e.g. Time-of-flight (TOF)
angiogram, T1-weighted, T2*-weighted and fluid-attenuated inversion recovery
(FLAIR) images) and CO2 cerebrovascular reactivity measurements. The acquired
images will be rated by trained radiologists for the aforementioned markers.

The study is observational and aims to elucidate the expression of different
small vessel disease markers in HHT patients with and without pulmonary AVMs.
As such, HHT patients are required to be included in this study. After careful
screening for contra indications for MRI and obtaining written informed
consent, MRI scans will be made, with a negligible risk to the participants
health. To further minimize the burden the total scan time is limited to 60
minutes.