Abstract

White matter hyperintensities (WMH) or white matter lesions exhibit high variability in their characteristics both at population- and subject-level, making their detection a challenging task. Population-level factors such as age, vascular risk factors and neurodegenerative diseases affect lesion load and spatial distribution. At the individual level, WMH vary in contrast, amount and distribution in different white matter regions.In this work, we aimed to improve BIANCA, the FSL tool for WMH segmentation, in order to better deal with these sources of variability. We worked on two stages of BIANCA by improving the lesion probability map estimation (classification stage) and making the lesion probability map thresholding stage automated and adaptive to local lesion probabilities. Firstly, in order to take into account the effect of population-level factors, we included population-level lesion probabilities, modelled with respect to a parametric factor (e.g. age), in the classification stage. Secondly, we tested BIANCA performance when using four alternative classifiers commonly used in the literature with respect to K-nearest neighbour algorithm (currently used for lesion probability map estimation in BIANCA). Finally, we propose LOCally Adaptive Threshold Estimation (LOCATE), a supervised method for determining optimal local thresholds to apply to the estimated lesion probability map, as an alternative option to global thresholding (i.e. applying the same threshold to the entire lesion probability map). For these experiments we used data from a neurodegenerative cohort, a vascular cohort and the cohorts available publicly as a part of a segmentation challenge.We observed that including population-level parametric lesion probabilities with respect to age and using alternative machine learning techniques provided negligible improvement. However, LOCATE provided a substantial improvement in the lesion segmentation performance, when compared to the global thresholding. It allowed to detect more deep lesions and provided better segmentation of periventricular lesion boundaries, despite the differences in the lesion spatial distribution and load across datasets. We further validated LOCATE on a cohort of CADASIL (Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) patients, a genetic form of cerebral small vessel disease, and healthy controls, showing that LOCATE adapts well to wide variations in lesion load and spatial distribution.

Highlights

  • White matter hyperintensities of presumed vascular origin (WMH, known as white matter lesions Wardlaw et al, 2013) are common radiological abnormalities often associated with cognitive impairment and one of the main signs of cerebral small vessel disease (SVD) (Pantoni, 2010)

  • We studied the effect of single-subject and populationlevel heterogeneity in amount, location and characteristics of WMH on the performance of BIANCA, with the aim of improving both the classification and the thresholding steps

  • We analysed the effect on the subject-level lesion probability maps of using population-level lesion probability map (PPLPM, with age as factor of interest) and of using alternative classifiers, which have been previously used for this task in the literature

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Summary

Introduction

White matter hyperintensities of presumed vascular origin (WMH, known as white matter lesions Wardlaw et al, 2013) are common radiological abnormalities often associated with cognitive impairment and one of the main signs of cerebral small vessel disease (SVD) (Pantoni, 2010). Despite their assumed clinical importance based on their spatial location (Duchesnay et al, 2018; De Guio et al, 2018; Kim et al, 2008), accurate automated detection of WMH is very challenging due to the high variability of their characteristics both between- and within-subjects. Periventricular WMH are brighter on T2-weighted, FLAIR or proton density images and bigger compared to deep ones (Kim et al, 2008), and can be detected more

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