Quantitative Relationship Between White Matter Hyperintensity Volume and Fazekas Score on Brain MRI
BACKGROUND: The Fazekas score is widely used to grade white matter hyperintensities (WMHs) in cerebral small vessel disease, yet the equivalent volume of each grade is unclear. We quantified the correspondence between Fazekas scores and WMH volume, normalized ratios, and derived conversion equations across populations. METHODS: We analyzed 1220 participants from 4 mostly United Kingdom–based cohorts representing different cerebral small vessel disease severities: community-dwelling (LBC1936 [Lothian Birth Cohort 1936]), stroke (MSS2 [Mild Stroke Study 2] and MSS3 [Mild Stroke Study 3]), and a cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy-enriched cohort (INVESTIGATE [Imaging Neuro-Vascular, Endothelial and Structural Integrity in Preparation to Treat Small Vessel Diseases]). WMH burden was quantified as absolute WMH volume and as normalized ratios: WMH volume as a percentage of brain volume and WMH volume as a percentage of intracranial volume. Transition zones were defined as the overlap of WMH volume interquartile ranges between adjacent Fazekas scores. Linear, exponential (nonlinear least squares), and log-linear (ln WMH≈Fazekas score and zeros excluded) models were fitted; model fit was assessed using mean squared error, (pseudo-)R2, and Vuong tests. Periventricular-versus-deep WMH patterns within each total Fazekas score were compared using the Kruskal-Wallis test. RESULTS: The pooled cohort had a mean age of 69.4±8.9 years; 700 of 1227 records (57.1%) were male. WMH burden increased monotonically with a Fazekas score in all cohorts. Adjacent-grade separation was strongest in LBC1936 (all P≤0.002) but weaker at lower grades in MSS2, MSS3, and INVESTIGATE. The widest transition zones occurred between Fazekas grades of 3 to 4 and 4 to 5, whereas a clear WMH volume gap separated grades 5 and 6. Exponential models generally fit better than linear models, with lower mean squared error and supportive Vuong tests in most cohorts. Log-linear sensitivity analyses showed similar fitted trajectories after back-transformation. WMH burden did not differ consistently by periventricular-versus-deep distribution within Fazekas grades. CONCLUSIONS: WMH burden followed an exponential trajectory across Fazekas scores, with population-dependent progression. The resulting conversion equations enabled bidirectional translation between visual Fazekas score and quantitative WMH volume, facilitating cross-study comparison, large-scale epidemiology, and might facilitate clinical decision-making in cerebral small vessel disease.