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BACKGROUND: Although white matter hyperintensities (WMH) volumetric assessment is now customary in research studies, inconsistent WMH measures among homogenous populations may prevent the clinical usability of this biomarker. PURPOSE: To determine whether a point estimate and reference standard for WMH volume in the healthy aging population could be determined. STUDY TYPE: Systematic review and meta-analysis. POPULATION: In all, 9716 adult subjects from 38 studies reporting WMH volume were retrieved following a systematic search on EMBASE. FIELD STRENGTH/SEQUENCE: 1.0T, 1.5T, or 3.0T/fluid-attenuated inversion recovery (FLAIR) and/or proton density/T2 -weighted fast spin echo sequences or gradient echo T1 -weighted sequences. ASSESSMENT: After a literature search, sample size, demographics, magnetic field strength, MRI sequences, level of automation in WMH assessment, study population, and WMH volume were extracted. STATISTICAL TESTS: The pooled WMH volume with 95% confidence interval (CI) was calculated using the random-effect model. The I2 statistic was calculated as a measure of heterogeneity across studies. Meta-regression analysis of WMH volume on age was performed. RESULTS: Of the 38 studies analyzed, 17 reported WMH volume as the mean and standard deviation (SD) and were included in the meta-analysis. Mean and SD of age was 66.11 ± 10.92 years (percentage of men 50.45% ± 21.48%). Heterogeneity was very high (I2 = 99%). The pooled WMH volume was 4.70 cm3 (95% CI: 3.88-5.53 cm3 ). At meta-regression analysis, WMH volume was positively associated with subjects' age (β = 0.358 cm3 per year, P 

Original publication




Journal article


J Magn Reson Imaging

Publication Date



image processing, segmentation, small vessel disease, white matter hyperintensities