White matter hyperintensities (WMH) observed on FLAIR MRI are highly prevalent in Alzheimer’s disease. Although often associated with cognitive decline, such associations are highly variable, likely due to the underlying pathological heterogeneity within these lesions. Here, we explore this potential heterogeneity in vivo in an Alzheimer’s disease cohort, by investigating relative tissue fractions obtained using single-shell 3-tissue constrained spherical deconvolution (SS3T-CSD). We show distinguishable tissue profiles of lesions based on classification as periventricular or deep, and additionally show heterogeneity within lesions, thus highlighting the pitfalls of binary classification of WMH, and the value of investigating their underlying diffusional properties.
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