Diffusion-Derived Magnetic Resonance Imaging Measures of Longitudinal Microstructural Remodeling Induced by Marrow Stromal Cell Therapy after Traumatic Brain Injury.

Abstract

Using magnetic resonance imaging (MRI) and an animal model of traumatic brain injury (TBI), we investigated the capacity and sensitivity of diffusion-derived measures, fractional anisotropy (FA), and diffusion entropy, to longitudinally identify structural plasticity in the injured brain in response to the transplantation of human bone marrow stromal cells (hMSCs). Male Wistar rats (300-350g, n = 30) were subjected to controlled cortical impact TBI. At 6 h or 1 week post-injury, these rats were intravenously injected with 1 mL of saline (at 6 h or 1 week, n = 5/group) or with hMSCs in suspension (∼3 × 106 hMSCs, at 6 h or 1 week, n = 10/group). In vivo MRI measurements and sensorimotor function estimates were performed on all animals pre-injury, 1 day post-injury, and weekly for 3 weeks post-injury. Bielschowsky's silver and Luxol fast blue staining were used to reveal the axon and myelin status, respectively, with and without cell treatment after TBI. Based on image data and histological observation, regions of interest encompassing the structural alterations were made and the values of FA and entropy were monitored in these specific brain regions. Our data demonstrate that administration of hMSCs after TBI leads to enhanced white matter reorganization particularly along the boundary of contusional lesion, which can be identified by both FA and entropy. Compared with the therapy performed at 1 week post-TBI, cell intervention executed at 6 h expedites the brain remodeling process and results in an earlier functional recovery. Although FA and entropy present a similar capacity to dynamically detect the microstructural changes in the tissue regions with predominant orientation of fiber tracts, entropy exhibits a sensitivity superior to that of FA, in probing the structural alterations in the tissue areas with complex fiber patterns.