Diffusion Tensor Imaging Study After Intraarterial Cell Therapy in Acute Ischemic Stroke: A Substudy of the IBIS Randomized Clinical Trial.

Abstract

Bone marrow mononuclear cell (BM-MNC) intraarterial transplantation has emerged as a potential stroke therapy. We aimed to determine whether BM-MNC therapy induces changes in diffusion tensor imaging metrics of major white matter tracts. The IBIS trial was an investigator-initiated multicenter, phase IIb, randomized, controlled, assessor-blinded, clinical trial. Seventy-seven patients (aged 18-80 years) with a nonlacunar middle cerebral artery ischemic stroke within 1 to 7 days from stroke onset and a National Institutes of Health Stroke Scale score of 6 to 20 were included. The primary outcome was the modified Rankin Scale score at 6 months. Among these participants, 38 patients (20 BM-MNCs-treated and 18 controls) had diffusion tensor imaging data available at both baseline and 6-month follow-up. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity for white matter tracts were obtained. We determined the average changes in diffusion tensor imaging-metric values over the follow-up period and correlated corticospinal tract integrity with clinical outcomes using Spearman´s correlation coefficient. The mean (SD) age was 60.7 (14.01) years; 22 (57.9%) were men, and 31 (81.6%) underwent thrombectomy. The median (interquartile range) National Institutes of Health Stroke Scale score before randomization was 12 (9-15). Baseline diffusion tensor imaging metrics were comparable between groups. Fractional anisotropy values of patients treated with BM-MNC decreased significantly less throughout corticospinal tract ipsilateral to stroke lesion (-0.05 [95% CI, -0.07 to -0.03] versus -0.06 [95% CI, -0.09 to -0.04]; <i>P</i><0.0001) and the body of corpus callosum (-0.03 [95% CI, -0.01 to -0.07] versus -0.04 [95% CI, -0.02 to 0.08]; <i>P</i><0.0001]. Better preservation of the ipsilateral corticospinal tract measured with fractional anisotropy was significantly correlated with clinical outcomes (ie, modified Rankin Scale score [<i>r</i>=-0.478], National Institutes of Health Stroke Scale score [<i>r</i>=-0.594], Barthel index [<i>r</i>=0.466] at 6 months [all <i>P</i><0.01]). Intraarterial autologous BM-MNC transplantation within 7 days after stroke onset seems to modify long-term white matter tract microstructure, suggesting that this cell therapy may mitigate acute stroke damage, through main projection fibers. Greater corticospinal tract preservation was associated with improved clinical outcomes. https://www.clinicaltrials.gov; Unique identifier: NCT02178657.