Ammad Mahmood, MBChB
Small vessel disease is a common finding on brain imaging which is increasingly identified with the widespread use of MRI. The clinical significance of this finding remains an area requiring further research. This review begins by defining the components and patterns of abnormalities that are encompassed by the term “small vessel disease,” which is widely used but ambiguous in its meaning. Techniques which identify earlier structural and functional changes in the brain in response to vascular risk factors are then discussed. Finally, the clinical implications of these findings and further opportunities for research in this area are highlighted.
The lesions which constitute small vessel disease, and their relation to risk of cognitive impairment, include:
- Acute subcortical infarcts, seen on diffusion weighted imaging as hyperintense lesions.
- White matter hyperintensities (WMH) and lacunes best imaged on FLAIR imaging. These are more common with age and in those with vascular risk factors. There is a correlation with the burden of WMH and incidence of cognitive impairment, stroke, and dementia.
- Microbleeds, areas of leakage of blood from a damaged blood vessel, are seen on T2* gradient recalled echo (GRE) or susceptibility weighted imaging (SWI) as areas of hemosiderin deposition. Subcortical microbleeds are associated with vascular risk factors, whereas lobar microbleeds are associated with cerebral amyloid angiopathy (CAA). Presence of microbleeds correlates with cognitive dysfunction, though whether this is independent of other brain lesion presence is unclear. Cortical superficial siderosis is also seen in these sequences and is commonly found in CAA; it is a strong predictor for future intracerebral hemorrhage and poor functional outcome.
- Cortical microinfarcts, seen at 7 tesla ultrahigh field MRI as tiny microinfarcts in the cortex on T1 and T2. Can be seen transiently on DWI but often with no trace on follow-up imaging, suggesting these are too small to be seen on routine MRI. Cortical microinfarcts have an effect on cognitive impairment and dementia risk independent of other vascular risk factors and imaging markers of small vessel disease.
Microstructural and functional changes in the brain seen in cerebrovascular disease have been studied by a number of techniques:
- Diffusion MRI assesses brain microstructure by studying water mobility in tissues with various techniques, such as diffusion tensor imaging. Diffusion MRI-based metrics have shown stronger correlation with clinical outcomes, such as cognitive and gait impairment, than lesion-based assessments. Tracking of small vessel disease has also shown high accuracy. Emerging techniques can study the white matter tracts, and correlation with clinical outcomes is an area of interest.
- Arterial spin labelling (ASL) relies on using water in arterial blood as an endogenous tracer with labelled spins travelling from a labelling plane to the imaged voxel. It can provide a measure of cerebral blood flow but suffers from several drawbacks such as low signal to noise ratio, prolonged transit causing artefacts, and reduced perfusion due to non-cerebrovascular causes of neurodegeneration.
- Assessment of enlarged perivascular spaces on T2 images is of interest as they may be useful imaging markers in age-related disorders and cognitive impairment. However, the literature is not yet conclusive in this area.
- Volumetric assessments by MRI have been postulated as a marker of cerebrovascular disease; however, the non-specific nature of volumetric assessment has made this unpopular.
The authors discuss the impact of cerebrovascular disease on Alzheimer’s disease incidence and the extent to which the two disease processes co-exist and combine to cause dementia. Cerebrovascular disease is a risk factor for Alzheimer’s disease and has an additive effect on cognitive decline. Synergistic effects of the two pathologies have been proposed with hypoperfusion caused by cerebrovascular disease contributing to production of amyloid plaques involved in Alzheimer’s disease, thereby promoting atherosclerotic lesions leading to a spiral of damage.
Finally, the authors highlight areas of potential further study:
- MRI markers which are repeatable and reproducible – ideally, MRI markers should be reliably reproduced when the same patient is scanned at different times or on different scanners. Validation studies in this area are lacking, and collaborative efforts to validate imaging methods are underway.
- Quantitative methods of measuring lesion load rather than only recording the presence or absence of lesions will help better understand the changes in lesions over time and any correlation with clinical outcomes.
- Advances in diffusion MRI techniques which may allow better characterization of brain microstructure.
- Correlation of imaging markers with pathological studies.
- Study of small vessels using techniques such as blood oxygenation level dependent (BOLD) MRI or using ultra high field 7T MRI, which is able to image single perforating arteries, measuring flow characteristics and vessel stiffness.
- Automated methods for lesion detection which are robust.
MRI imaging techniques continue to expand, and as more information on brain lesions is gathered, the relevance to clinical outcomes is crucial. Reliable early markers of dementia risk will enable further research into treatment of underlying pathological processes and reducing the risk of cognitive decline in patients with cerebrovascular disease.