Abstract
Background:
Imaging biomarkers of stroke recovery are critical for translational studies. Diffusion tensor imaging (DTI) to assess white matter microstructure in the brain using fractional anisotropy (FA) to dertermine the structural integrity of the corticospinal tract (CST). Our prior data suggest a possible correlation between neurological recovery and the improvement in FA. The purpose of this study was to compare DTI analysis of the CST at 30 days after an ipsilateral intra-arterial (IA) Mesenchymal Stem Cell (MSCs) versus control, in canines with a reversible Middle Cerebral Artery occlusion (rMCAo).
Methods:
Mongrel Hounds (n=7), aged 12-36 months, were included in this study. rMCAo was induced via endovascular approach using a detachable helical ultra-coil over 35-80 min. MSCs (1-20 millions) or saline (240 cc) were infused intra-arterially 48hrs post stroke in the ipsilesional cervical internal carotid. Brain MRIs were performed at 48h post rMCAo pre-IA cell delivery, 15 & 30 days. FA values of the right and left CST were determined. DTT was also generated for a visual analysis of the CST fibers. Weekly neuro evaluations were performed using blinded canine stroke-score.
Results:
We observed a higher average change in the FA values from at 30 days post stroke in the MSCs treated group versus control (0.085 ± 0.025, n=5 versus 0.068 ± 0.058, n=2: p=0.82). A visual increase in the caliber of CST ipsilateral to stroke from IA injection to day 30 post-stroke was observed on the DTT in two of the treated canines. Figure-1 from left to right, a. FA changes, b. DTT treated group, C. DTT control.
Conclusions:
Serial DTI-DTT imaging after IA MSCs therapy in large animal stroke model appears to have a trend towards higher change in FA. These findings could support further development of DTI-DTT biomarkers to measure neurologic recovery in experimental models as well as early clinical trials of novel stroke therapies.