Spatial patterns of white matter hyperintensities: a systematic review

Abstract

Background: White matter hyperintensities are an important marker of cerebral small vessel disease. This disease burden is commonly described as hyperintense areas in the cerebral white matter, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging data. Studies have demonstrated associations with various cognitive impairments, neurological diseases, and neuropathologies, as well as clinical and risk factors, such as age, sex, and hypertension. Due to their heterogeneous appearance in location and size, studies have started to investigate spatial distributions and patterns, beyond summarizing this cerebrovascular disease burden in a single metric-its volume. Here, we review the evidence of association of white matter hyperintensity spatial patterns with its risk factors and clinical diagnoses.

Design/methods: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We used the standards for reporting vascular changes on neuroimaging criteria to construct a search string for literature search on PubMed. Studies written in English from the earliest records available until January 31st, 2023, were eligible for inclusion if they reported on spatial patterns of white matter hyperintensities of presumed vascular origin.

Results: A total of 380 studies were identified by the initial literature search, of which 41 studies satisfied the inclusion criteria. These studies included cohorts based on mild cognitive impairment (15/41), Alzheimer's disease (14/41), Dementia (5/41), Parkinson's disease (3/41), and subjective cognitive decline (2/41). Additionally, 6 of 41 studies investigated cognitively normal, older cohorts, two of which were population-based, or other clinical findings such as acute ischemic stroke or reduced cardiac output. Cohorts ranged from 32 to 882 patients/participants [median cohort size 191.5 and 51.6% female (range: 17.9-81.3%)]. The studies included in this review have identified spatial heterogeneity of WMHs with various impairments, diseases, and pathologies as well as with sex and (cerebro)vascular risk factors.

Conclusion: The results show that studying white matter hyperintensities on a more granular level might give a deeper understanding of the underlying neuropathology and their effects. This motivates further studies examining the spatial patterns of white matter hyperintensities.

Keywords: MRI; magnetic resonance; pattern; spatial; systematic review; topography; topology; white matter hyperintensity (WMH).

FIGURE 1

Flow-chart of study selection based on the PRISMA statement (Page et al., 2021). Studies were identified through an advanced search on PubMed. First, abstracts were screened, followed by reading the retrieved publications and excluding non-relevant studies. Exclusion criteria–Reason 1: cohort included less than 20 subjects. Reason 2: study was not performed in adult populations (>18 years). Reason 3: study did not investigate spatial patterns of WMHs (e.g., studies investigated spatial patterns of other markers, such as activation patterns of functional MRI, only included total WMH burden as a covariate, or fully descriptive studies). Reason 4: study did not assess the whole brain for analysis. Reason 5: study investigating multiple sclerosis (Kamson et al., 2012) or tuberous sclerosis (Chou et al., 2008) which do not meet the STRIVE (Wardlaw et al., 2013) definition of WMH. The reference list of each retrieved report was additionally examined for eligible studies.