A novel approach of detecting corticospinal tract recovery using DTI/DTT analysis, after intra-arterial mesenchymal stem cell infusion in a canine stroke model

Abstract

Developing valid imaging biomarkers of stroke recovery are critical for translational-stroke research. Diffusion-Tensor-Imaging (DTI) assesses white matter microstructure in the brain and Diffusion-Tensor-tractography (DTT) for visual mapping of CST. Our data suggests a possible correlation between neurological recovery and the improvement in DTI/DTT. The purpose of this pilot-study was to implement/compare MRI stroke vol and DTI/DTT biomarkers of neurological-recovery in a canine stroke model over one month after ipsilateral intra-arterial (IA) Mesenchymal Stem Cell (MSC) infusion vs control. five Female Mongrel-Hound(n:3 MSCs, n:2 control saline only, aged 12-36-months). Reversible MCA-stroke was induced using a detachable-coil(2x8mm) over 60 min, permanent ACA occlusion(2 × 4 mm-coil). MSC (40-80 million/240 cc) or saline/240 cc were infused IA, 48 h post-stroke. Brain-MRIs were performed prior to IA infusion/post stroke, and 15th-30th-days post-stroke. DTT of the CST was generated. Weekly neurological score-evaluations were performed. We observed a significant decreased of stroke vol and qualitative increase in CST-caliber on the treated group, not seen in controls. Also, a faster neuro-recovery was seen in the treated group at the 1st week not seen in the control group. It is important to mentioned that all dogs achieved recovery by 30 days close to baseline, but the difference was noticed at the speed of recovery seen on the treated-group. DTT imaging post IA-MSC therapy showed an increase of CST-caliber correlating with motor-recovery. These findings could support further development of DTI-DTT biomarkers to measure neurological-recovery in experimental models as well as in clinical-trials of stroke-therapies.