Imaging of Intracranial Arterial Calcification

Abstract

Intracranial arterial calcification is a highly prevalent imaging finding that has been related to stroke and dementia. It is reported on CT examination of the brain in the majority of patients over 60 years of age and is most prevalent in the intracranial carotid artery and choroid plexus. The relevance of these calcifications is increasingly recognised but a lot of vital information such as prevalence the general, young population is still lacking. Comparison of CT images with underlying histology can also provide additional insight in these ectopic calcifications. In this thesis we examined calcifications in the intracranial carotid artery and hippocampus. Intracranial carotid artery calcification was found to be already present in 7.4% of patients younger than 10 years of age and prevalence increased with age similarly between women and men. By comparing intracranial carotid artery histology with the corresponding CT images, we were able to develop a visual CT-based score that can distinguish different calcification types (i.e. intimal and medial) in the intracranial carotid artery in vivo. By using this score, both types of intracranial carotid artery calcification were found to have a different cardiovascular risk profile. Hippocampal calcification was examined on CT and histopathology and was found to be related to multiple known vascular risk factors and appeared, in severe cases, to result in hippocampal atrophy. Because of this it was hypothesized that there could be a relation between hippocampal calcification, as seen on CT, and cognitive decline. Even though the results from our first pilot study suggested such a relation, they could not be repeated in a large cohort study of memory clinic patients. In this thesis we showed that intracranial calcification is multifaceted, occurring in multiple arterial layers, and is not synonymous with atherosclerosis. Our findings furthermore suggest that intracranial carotid artery calcification is the earliest manifestation of arterial calcification in humans, although its relevance in children and young adults remains to be determined. The new insights into hippocampal calcification can hopefully stimulate research to concentrate more on the vascular aspects of neurodegenerative disease and no longer ignore the tail of the hippocampus. Finally, the methods developed in this thesis, using CT and histology, can aid researchers with further investigating medial and intimal calcification in the intracranial carotid artery and hippocampal calcification.