Imaging cerebral small vessel disease at 7 Tesla MRI

Abstract

Cerebral small vessel disease is a term often used to refer to lacunar infarcts, white matter lesions (WML) and microbleeds; lesions that are thought to be caused by changes in the small vessels of the brain. These lesions are commonly found in the general elderly population. However, it is hard to visualize these small vessels in vivo. As a result, lacunar infarcts, WML and microbleeds are adopted as marker of cerebral small vessel disease, and cerebral small vessel disease has become a synonym of brain parenchyma lesions. With the introduction of 7 Tesla MRI for clinical research, there are new opportunities to visualize the small, perforating arteries in the brain and to identify earlier stages of cerebral small vessel disease. The main aim of this thesis was to explore imaging biomarkers of early stages of cerebral small vessel disease with 7 Tesla MRI. Lacunar infarcts and WML are associated with stroke, cognitive decline and dementia in the general population. It is not known whether the presence of lacunar infarcts or WML imposes an additional risk of death or vascular events in patients with atherosclerosis, who already have a high risk of vascular events. We found that the presence of one or more lacunar infarcts on MRI increased the risk of death. WML increased the risk of vascular death and ischemic stroke. With time-of-flight MR angiography at 7T we were able to show the perforating arteries in the brain, without the use of contrast agents. The visualization of these small arteries in future studies may increase our understanding of infarcts in the deep brain structures supplied by these arteries. The presence of very small microbleeds could be one of the earliest manifestations of cerebral small vessel disease. We found that the use of a dual echo T2*-weighted sequence at 7T combines the advantages of a short and a long echo time for the visualization of microbleeds. The short echo time is beneficial to distinguish microbleeds from other structures with a high susceptibility, and with the long echo time a larger number of microbleeds can be detected. Comparing the dual echo T2*-weighted imaging at 7T with high resolution 3D T2*-weighted imaging at 1.5T, showed that the dual echo T2*-weighted imaging at 7T resulted in detection of microbleeds in more patients and also detection of a higher number of microbleeds. Furthermore, the detection of microbleeds was more reliable at 7T. As cerebral small vessel disease and iron deposition in the brain are both associated with endothelial dysfunction, we investigated iron deposition as a possible early marker of cerebral small vessel disease. Lacunar infarcts, but not WML or microbleeds, were associated with significantly more iron deposition. Besides increased permeability of the vessel wall, also the vascular reactivity may be altered due to changes in the vessel wall in patients with cerebral small vessel disease. With use of BOLD-fMRI at 7T a decreased vascular reactivity in the brain was found in patients with microbleeds, but not in patients with lacunar infarcts or WML. In conclusion, 7 Tesla MRI reveals several potential early biomarkers for cerebral small vessel disease and can be important for better understanding and early detection of cerebral small vessel disease.