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bioRxiv · 10.1101/2025.11.18.689161

Association between white-matter lesion volume and heart-rate variability: A comparison of T1, T1-T2 and T1-FLAIR-based segmentations using FreeSurfer SAMSEG

Robinson, T. D.·Cerri, S.·Zhang, F. E.·van Leemput, K.·Chen, J. J.
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Abstract

BackgroundHeart disease is a crucial risk factor for brain degeneration, but the exact mechanisms are still under investigation. Notably, a growth in white-matter lesion (WML) volume, a hallmark of cerebral small-vessel disease (cSVD) with connections to progressive neurodegeneration and cognitive decline, has been linked to cardiovascular disease. As such, measures of cardiovascular function such as heart rate variability may represent early and accessible predictors of WML development. MethodsThis study used data from healthy adults drawn from the Leipzig Study for Mind-Body-Emotion Interactions (LEMON) dataset to examine heart function through measures of heart rate variability (HRV), as well as their relationship to cSVD as quantified through WML volumes, using FreeSurfer SAMSEG. WML volumes were segmented using 3T T1+FLAIR, T1+T2 or T1 images alone. ResultsResults indicate that both young and old adults exhibited WMLs, and that lower HRV was associated with higher WML volume. This was particularly strong for high-frequency HRV across both young and older adults, but it was low-frequency HRV that was related to WML volume in an age-specific manner. Moreover, we showed that the WML-HRV relationship that is apparent using T1+FLAIR or T1+T2 based WML volumes could be observed even with T1w-based WML estimation alone. ConclusionsThese results suggest HRV not only as an avenue through which cardiovascular risk translates into brain degeneration, but also as a potential early and readily measurable non-invasive predictor of later WML development and cognitive impairment. Research Perspective- Differences in heart rate variability show consistent associations with the volume of white-matter lesions in the brain, with low-frequency heart rate variability uniquely sensitive to age effects on lesion volume. - Associations between heart rate variability and white matter lesion volume are detectable using T1-weighted volume estimation in absence of more intensive T1-weighted + T2-weighted or T1-weighted + FLAIR lesion estimations. - The neuroanatomical basis for this relationship, particularly the difference in high- and low-frequency heart rate variability associations, will require incorporating lifestyle, hormonal, and genetic factors, as well as targeted examination of high-versus low-frequency heart rate variability bands.

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Robinson, T. D., Cerri, S., Zhang, F. E., van Leemput, K., Chen, J. J.. 2025-11-19. Association between white-matter lesion volume and heart-rate variability: A comparison of T1, T1-T2 and T1-FLAIR-based segmentations using FreeSurfer SAMSEG. https://doi.org/10.1101/2025.11.18.689161

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