Background Corticospinal tract (CST) integrity, assessed using diffusion weighted MR imaging, has frequently been associated with motor impairment following stroke. However, which specific biological features contribute to this relationship remains unknown. In the current paper we used quantitative multimodal imaging to shed light on the biophysical properties underlying this relationship in the CST and explore additional whole brain relationships with motor impairment.

Methods Twenty-seven chronic stroke survivors underwent MRI scanning, including multi-shell diffusion weighted imaging and quantitative Multi-Parameter Mapping, from which we derived ten metrics, sensitive to different microstructure properties. We tested the relationship between these MRI metrics and stroke survivors’ impairment scores on the Upper-Extremity Fugl Meyer (UE-FM), using multimodal and unimodal statistical inference, in both the CST and across the whole brain.

Results Using an ROI approach to replicate and extend on previous findings, a joint multimodal analysis revealed that greater CST microstructure asymmetry was associated with worse motor impairment. The strongest relationships were found between impairment and several modalities sensitive to free water and myelination. This result was further confirmed using a voxel-wise approach. Beyond the CST, modalities sensitive to free water, myelination and the Neurite Density Index, were also found to be related to motor impairment, particularly in the superior longitudinal fasciculus, corpus callosum and thalamic radiations, with magnetisation transfer saturation showing the strongest relationship in these areas.

Conclusion Modalities that are sensitive to myelin and free water exhibited the most significant correlation with motor impairment. This suggests that these specific biological features may account for the previously identified relationships between diffusion metrics and motor impairments. Myelin metrics in particular were also highly correlated with motor impairment in other brain regions. This study illustrates the advantages of using multimodal data to identify more specific biological factors that contribute to motor impairment in stroke patients.

Dr. Papp is an employee of Siemens Healthcare AB, Sweden, as of September 2023, but was a postdoc at the Wellcome Centre for Integrative Neuroimaging at the time of the study and the initial preparation of the manuscript.

NCT03775915

Z.B.S was supported by a Clarendon Scholarship and the Nuffield Department of Clinical Neurosciences. This work was supported by John Fell Award to C.S.B. E.M. was supported by a Wellcome Biomedical Vacation Scholarship. H.J-B was supported by Wellcome Trust grant 110027/Z/15/Z. The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust 203139/Z/16/Z. The funders had no role in the study design, data collection or analysis. The authors would like to thank the radiographers and IT support team at the Wellcome Centre for Integrative Neuroimaging.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The ethics committee of the University of Oxford and the National Research Ethics service (UK) gave ethical approval for this work (14/LO/0020).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Fully anonymized data from this study can be made available on request.