Research in animal models has shown promise for the development of treatments designed to promote axonal rescue and regeneration. While behavioral studies are useful in evaluating the effect of treatment on function, histology has, up to now, been the only method to detect and follow axonal regeneration. Obviously, this method of evaluation will not be feasible in clinical trials. Early studies with diffusion-based MR imaging have shown that this modality has the potential to evaluate the integrity of axons. Our central hypothesis is that diffusion-based MR measurements will detect and quantify axonal survival, neuronal cell rescue and axonal regeneration following spinal cord injury and treatment in the adult rat, and that these measurements will correlate with histologic findings and predict functional outcome. The basis for this hypothesis is that structural changes following injury and regeneration affect the Apparent Diffusion Coefficients (ADC) within the spinal cord white matter tracts. The proposed project will initially evaluate ex vivo specimens to determine, by diffusion-based MR measurements, the changes in ADC within white matter tracts following spinal cord injury and treatment. The second part of this study will evaluate spinal cord injury and response to treatment in vivo with serial diffusion-based MR measurements. In both parts of the study, ADC values will be correlated with histologic and behavioral findings behavioral findings. In the future, diffusion-based MR imaging will be critical in the clinical setting where direct tissue evaluation is not possible. The data obtained in this study will translate to the clinical setting, both in determining axon disruption following injury and in evaluating the effect of treatments for spinal cord injury. As part of the mentored clinical scientist development award, the principal investigator will take a series of didactic courses in neuroscience, MR imaging physics, bioethics, and statistics. Hands-on experience will be obtained in a neuroscience lab led by a mentor with thirty years experience of researching spinal cord injury. Imaging experience will include using high resolution MR scanners and creating MR radiofrequency coils under the tutelage of a mentor with over ten years experience researching MR and spinal cord injury.
| Gullapalli, Jayaroop; Krejza, Jaroslaw; Schwartz, Eric D (2006) In vivo DTI evaluation of white matter tracts in rat spinal cord. J Magn Reson Imaging 24:231-4 |
| Schwartz, Eric D; Chin, Chih-Liang; Shumsky, Jed S et al. (2005) Apparent diffusion coefficients in spinal cord transplants and surrounding white matter correlate with degree of axonal dieback after injury in rats. AJNR Am J Neuroradiol 26:7-18 |
| Schwartz, Eric D; Cooper, Emily T; Chin, Chih-Liang et al. (2005) Ex vivo evaluation of ADC values within spinal cord white matter tracts. AJNR Am J Neuroradiol 26:390-7 |
| Chin, Chih-Liang; Wehrli, Felix W; Fan, Yingli et al. (2004) Assessment of axonal fiber tract architecture in excised rat spinal cord by localized NMR q-space imaging: simulations and experimental studies. Magn Reson Med 52:733-40 |
