LAUSR

Editorial for “Myelin Water Imaging of Nerve Recovery in Rehabilitating Stroke Patients” The most common debilitating consequence of stroke is motor impairment. Recently, there has been growing interest in developing and implementing biomarkers that can act as a surrogate of motor recovery and outcomes after stroke, which is crucial for evaluating rehabilitation methods. Several neuroimaging biomarkers including structural magnetic resonance imaging and functional transcranial magnetic stimulation have been widely used in clinical practice, particularly to predict long-term outcomes that would allow planning of rehabilitation strategies and clinical trials. Changes in white matter integrity in corticospinal tracts (CST) have been found to be important in the process of motor recovery after stroke. Diffusion tensor imaging (DTI) derived metrics are widely used to evaluate rehabilitation interventions, but crossing fibers, trauma, and axonal remodelling prevent them from being completely specific measures of myelin content. Advances such as multicomponent T2 and T2* relaxation imaging provide the feasibility of measuring the amount of myelin water relative to total water (coined as myelin water fraction, MWF) as an in vivo marker for myelin content in the brain. In the present study, authors performed myelin water imaging and DTI in 24 stroke patients and 10 healthy volunteers to determine the change in myelin during the rehabilitation of stroke patients. They performed imaging right after the occurrence of stroke and after the extensive rehabilitation training in 4–5 weeks. As part of the rehabilitation procedure, the authors divided the patients into two subgroups and conducted two kinds of protocols such as conventional upper limb physical rehabilitation in the first group and conventional plus robot-assisted upper limb rehabilitation in the second group. This study showed a significant difference in MWF in the CST between post and pre-rehabilitation, but not for fractional anisotropy (FA). The authors also identified a more significant rate of change in the MWF (6.69%) in comparison with FA (0.439%) in stroke patients during the rehabilitation process. These outcomes provide evidence that MWF is a feasible biomarker to monitor myelin changes during rehabilitation and can be used for studying brain plasticity. The study also shows clear evidence that robot-assisted rehabilitation training facilitates the reorganization of the brain that can be captured by MWF. Despite the small sample size, the methodological perspective is interesting and needs further validation in future studies. It is important to note that the CST region used for both the MWF and DTI measures was defined using tractography based on the DTI data, so the possibility of using an MWF scan without a diffusion one was not investigated. Additionally, it may be imposing a selection effect on the FA measure, since the envelope of a bundle of recovered tracks in tractography is typically set by where FA drops below a certain threshold. It would be otherwise difficult to explain why the apparent CST FA is so much higher in their elderly stroke patients (both before and after rehabilitation) than their young healthy volunteers. The study brings forth the interesting paradigm of measuring myelin plasticity and its role in stroke recovery. It also opens new opportunities for future research. While the CST is the major pathway involved in motor recovery, it is relatively simple compared to the association, sensorimotor, and language pathways that are also of interest after a stroke. Studying the possible changes to alternate pathways that may be compensatory after a hemispheric stroke is an important goal and would involve more crossing fiber regions where FA would be expected to be a less specific measure than MWF. Further, does consideration of additional quantitative measures along with the proposed measures provide a more proximal prediction of response to neurorehabilitative interventions? Overall, measuring myelin plasticity has important implications for motor recovery after stroke and can aid in the cost-effective management of treatment plans after acute stroke. The current findings also shed light on the heterogeneity of the patient response to therapies that can be incorporated into clinical trials for better patient gains.