Neuroimaging of cerebral small vessel disease
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Date
05/07/2011Author
Potter, Gillian Margaret
Metadata
Abstract
Lacunar stroke accounts for one quarter of all ischaemic stroke and in the long term
carries a greater risk of death and disability than was previously realised. Much of
our current knowledge originated from neuropathological studies in the 1950s and
1960s. In the last thirty years, brain computed tomography (CT) and magnetic
resonance imaging (MRI) have revolutionised our understanding of lacunar stroke
and associated features of cerebral small vessel disease (SVD), namely white matter
lesions (WML), enlarged perivascular spaces (EPVS) and brain microbleeds (BMB).
The purpose of the projects which led to the writing of this thesis was to improve
understanding of imaging characteristics of cerebral SVD. We aimed to assess (i)
clinical and imaging features which might explain misclassification of lacunar
infarcts as cortical infarcts and vice versa, (ii) the proportion of symptomatic lacunar
infarcts progressing to lacunar cavities and associations of cavitation, (iii)
completeness of reporting of lacunar lesions in the lacunar stroke literature, (iv)
definitions and detection of lacunar lesions amongst SVD researchers, (v) the
relationship between WML and carotid stenosis, (vi) clinical and imaging
associations of EPVS and, (vii) observer variability in the assessment of EPVS and
BMB, in order to develop visual rating scales.
Section one describes neuroimaging of lacunar stroke. To investigate features which
might explain clinical stroke subtype misclassification (‘clinical-imaging
dissociation’), I used data from a stroke study. The main factor associated with
clinical-imaging dissociation was diabetes, and in patients with acute lacunar
infarction, proximity of the lacunar infarct to the cortex, age, diabetes and left hemisphere location. To investigate the proportion of symptomatic lacunar infarcts
progressing to cavities, I used data from two stroke studies. A fifth of patients with
acute lacunar ischaemic stroke showed definite cavitation on follow-up imaging at a
median of 227 days; cavitation was associated with increasing time to follow-up. To
assess completeness of reporting of lacunar lesions in the lacunar stroke literature, I
reviewed 50 articles from three journals with a stroke focus. There was marked
variation in terminology and descriptions of imaging definitions of lacunar lesions.
To assess lacunar lesion definitions and detection amongst SVD researchers, I used
an online survey consisting of case-based and non-case-based questions. There was
marked variation in definitions and descriptions. Cavitated lesions were detected
with the highest degree of confidence.
Section two describes neuroimaging of associated features of cerebral SVD. Using
data from two stroke studies, I examined the relationship between WML and
ipsilateral carotid artery stenosis. There was no association between carotid stenosis
and WML. I tested the association of EPVS with WML and lacunar stroke subtype
using data from a stroke study. Total EPVS were associated with age and deep
WML; basal ganglia (BG) EPVS were associated with age, centrum semiovale (CS)
EPVS, cerebral atrophy and lacunar stroke subtype. Quantification of observer
variability in EPVS rating was assessed on 60 MRI scans selected from a stroke
study and an ageing cohort. Intrarater agreement was good and interrater agreement
was moderate. Main reasons for interrater disagreement included the visualisation of
very small EPVS and the presence of concomitant WML and lacunar lesions.
Observer variability in BMB rating was quantified using MRI scans from a stroke
study. Interrater agreement was moderate but improved following modification of the pilot rating scale (BOMBS; Brain Observer MicroBleed Scale), which had its main
effect by differentiating ‘certain’ BMB from ‘uncertain’ BMB and BMB ‘mimics’.
In conclusion, neuroimaging, particularly MRI, is a valuable tool for the
investigation of lacunar stroke and associated features of cerebral SVD. With recent
technological advances in both CT and MRI, neuroimaging will remain central to
future SVD studies, hopefully leading to a much improved understanding of this
important disease.