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bioRxiv · 10.1101/590497

Brain connectivity measures improve modeling of functional outcome after acute ischemic stroke

Ktena, S. I.·Schirmer, M.·Etherton, M. R.·Giese, A.-K.·Tuozzo, C.·Mills, B. B.·Rueckert, D.·Wu, O.·Rost, N. S.
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Abstract

BackgroundThe ability to model long-term functional outcomes after acute ischemic stroke (AIS) represents a major clinical challenge. One approach to potentially improve prediction modeling involves the analysis of connectomics. The field of connectomics represents the brains connectivity as a graph, whose topological properties have helped uncover underlying mechanisms of brain function in health and disease. Specifically, we assessed the impact of stroke lesions on rich club (RC) organization, a high capacity backbone system of brain function.\n\nMethodsIn a hospital-based cohort of 41 AIS patients, we investigated the effect of acute infarcts on the brains pre-stroke RC backbone and post-stroke functional connectomes with respect to post-stroke outcome. Functional connectomes were created utilizing three anatomical atlases and characteristic path-length (L) was calculated for each connectome. The number of RC regions (NRC) affected were manually determined using each patients diffusion weighted image (DWI). We investigated differences in L with respect to outcome (modified Rankin Scale score (mRS); 90-days; poor: mRS>2) and the National Institutes of Health Stroke Scale (NIHSS; early: 2-5 days; late: 90-day follow-up). Furthermore, we assessed the effect of including NRC and L in outcome models, using linear regression and assessing the explained variance (R2).\n\nResultsOf 41 patients (mean age (range): 70 (45-89) years), 61% were male. There were differences in L between patients with good and poor outcome (mRS). Including NRC in the backward selection models of outcome, R2 increased between 1.3- and 2.6-fold beyond that of traditional markers (age and acute lesion volume) for NIHSS and mRS.\n\nConclusionIn this proof-of-concept study, we showed that information on network topology can be leveraged to improve modeling of post-stroke functional outcome. Future studies are warranted to validate this approach in larger prospective studies of outcome prediction in stroke.

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Ktena, S. I., Schirmer, M., Etherton, M. R., Giese, A.-K., Tuozzo, C., Mills, B. B., Rueckert, D., Wu, O., Rost, N. S.. 2019-03-28. Brain connectivity measures improve modeling of functional outcome after acute ischemic stroke. https://doi.org/10.1101/590497

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