Automated quantification of white matter hyperintensity confluence: A measure of spatial organisation beyond volume and visual rating scales

Schmidt, T. V.; Salzmann, R.; Montagnese, M.; Chan, D.; Bernal, J.; Pfister, M.; Arndt, P.; Peters, O.; Hellmann-Regen, J.; Preis, L.; Gref, D.; Priller, J.; Spruth, E.; Gemenetzi, M.; Altenstein, S.; Schneider, A.; Fliessbach, K.; Kimmich, O.; Wiltfang, J.; Bartels, C.; Schott, B.; Rostamzadeh, A.; Glanz, W.; Incesoy, E.; Butryn, M.; Buerger, K.; Janowitz, D.; Stoecklein, S.; Perneczky, R.; Rauchmann, B.-S.; Teipel, S.; Mladinov, M.; Grazia, A.; Laske, C.; Sodenkamp, S.; Spottke, A.; Petzold, G.; Wagner, M.; Lusebrink, F.; Kleineidam, L.; Hetzer, S.; Dechent, P.; Schreiber, S.; Duezel, E.; Je

doi:10.64898/2026.07.24.740551

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bioRxiv · 10.64898/2026.07.24.740551

Automated quantification of white matter hyperintensity confluence: A measure of spatial organisation beyond volume and visual rating scales

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Abstract

White matter hyperintensities (WMH) are a highly prevalent finding on FLAIR MRI scans and a prominent feature of white matter pathology across cerebrovascular and neurodegenerative diseases. Currently, WMH are assessed with visual rating scales such as the Fazekas scale or with their volume, as calculated from automatic or manual segmentations. Both methods have limitations: Visual rating scales are rater-dependent and coarse, while WMH volume does not take the confluence of lesions into account and thus disregards their spatial organisation. As an alternative, here we propose a novel automated method for quantifying the confluence of white matter hyperintensities on a continuous standardised scale between 0 and 1. The metric is based on WMH segmentations from routine MRI and quantifies the extent to which individual WMH merge into coherent lesions, independently of total lesion volume. We apply the method to QMIN-MC, a large UK memory clinic cohort, and show associations of the confluence metric with age, cognitive performance across domains, and Fazekas ratings. Participants with vascular and mixed dementia showed higher confluence than other diagnostic groups, whereas cognitively unimpaired participants showed lower confluence. However, confluence did not explain additional cognitive variance after accounting for log-transformed WMH volume. Findings were validated in DELCODE, an independent cohort of individuals with neurodegenerative disorders, replicating our original results. In this validation cohort, periventricular WMH confluence remained associated with cognition after adjustment for WMH volume. These findings introduce WMH confluence as a reproducible, automated, and fine-grained measure of lesion spatial organisation. It provides complementary information about morphological WMH severity beyond volume and is an alternative to visual rating scales. Although related to WMH volume in memory-clinic populations, confluence captures clinically interpretable information and may complement existing WMH measures for improved lesion characterisation in studies of white matter disease, ageing, and cognitive impairment.

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Schmidt, T. V., Salzmann, R., Montagnese, M., Chan, D., Bernal, J., Pfister, M., Arndt, P., Peters, O., Hellmann-Regen, J., Preis, L., Gref, D., Priller, J., Spruth, E., Gemenetzi, M., Altenstein, S., Schneider, A., Fliessbach, K., Kimmich, O., Wiltfang, J., Bartels, C., Schott, B., Rostamzadeh, A., Glanz, W., Incesoy, E., Butryn, M., Buerger, K., Janowitz, D., Stoecklein, S., Perneczky, R., Rauchmann, B.-S., Teipel, S., Mladinov, M., Grazia, A., Laske, C., Sodenkamp, S., Spottke, A., Petzold, G., Wagner, M., Lusebrink, F., Kleineidam, L., Hetzer, S., Dechent, P., Schreiber, S., Duezel, E., Je. 2026-07-28. Automated quantification of white matter hyperintensity confluence: A measure of spatial organisation beyond volume and visual rating scales. https://doi.org/10.64898/2026.07.24.740551

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