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

BACKGROUND: 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. METHODS: 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. RESULTS: 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]; P <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]; P <0.0001]. Better preservation of the ipsilateral corticospinal tract measured with fractional anisotropy was significantly correlated with clinical outcomes (ie, modified Rankin Scale score [ r =−0.478], National Institutes of Health Stroke Scale score [ r =−0.594], Barthel index [ r =0.466] at 6 months [all P <0.01]). CONCLUSIONS: 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. REGISTRATION: https://www.clinicaltrials.gov ; Unique identifier: NCT02178657.