Tracking labeled stem cells in TBI model by cellular MRI

实验模型创伤性脑损伤的病理表现包括急性炎症反应、血脑屏障破坏、出血、脱髓鞘、轴突横断和慢性轴突神经元丢失和神经胶质瘤。干细胞（SC）治疗是一种潜在的治疗方法，可以作为替代疗法，也可以通过释放生长因子和抗炎细胞因子的旁分泌作用治疗TBI损伤。我们报道了一项基于MRI的轻度TBI大鼠模型的纵向研究，并与组织学相关超过2个月。我们报道了扩散张量成像（DTI）轴向扩散率和分数各向异性（FA）对轴突完整性敏感，而径向扩散率与髓鞘致密度有显著相关性。我们还观察到FA与灰质中的星形胶质形成相关，而平均扩散率与细胞数量增加相关，磁化传递比（MTR）与轴突和髓鞘完整性密切相关。我们还能够证明，轻度脑室肥大（MVM）大鼠的FA变化不显著，表明与正常大鼠相比，轻度脑外伤后轴突损伤更小。轻度脑外伤后，MVM动物的MTR明显高于正常大鼠。组织学检查显示，与正常动物相比，MVM脑轴突损伤有限，小胶质细胞增生和星形胶质细胞增生明显增加。与正常大鼠相比，MVM大鼠在TBI后表现出更大的炎症。这些结果表明，在TBI研究中使用的实验动物中，使用MRI筛查脑异常的重要性，并且在TBI研究中观察到的变化可能是由于结构形态学对诱发创伤的反应的变异性

The pathology of traumatic brain injury in experimental models includes acute inflammatory reaction, blood brain barrier disruption, hemorrhage, demyelination, axonal transection and chronically with axonal neuronal loss and gliosis. Stem cell (SC) therapy is a potential treatment either as replacement therapy or via paracrine effect with release of growth factors and anti-inflammatory cytokines for TBI injury. We reported on a longitudinal study in a mild TBI rat model based on MRI and correlated to histology over 2 months. We reported that diffusion tensor imaging (DTI) axial diffusivity and fractional anisotropy (FA) were sensitive to axonal integrity, whereas radial diffusivity showed significant correlation to the myelin compactness. We also observed that FA was correlated with astrogliosis in the gray matter, whereas mean diffusivity was correlated with increased cellularity and magnetization transfer ratio (MTR) demonstrated a strong correlation with both axon and myelin integrity. We also were able to demonstrate that in rats with mild ventriculomegaly (MVM) demonstrated insignificant changes in FA, suggesting less axonal injury compared to normal rats following mild TBI. The MVM animals had significant increase in MTR compared to normal rats following mild TBI. On histological examination, limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brains compared with normal animals. MVM rats exhibited greater inflammation following TBI compared to normal rat brains. These results indicated the importance of using MRI to screen for brain abnormalities in experimental animals used in TBI studies and that the variation observed in TBI studies may be due to the variability in response to induced trauma as a result of structural morphology The relationship between changes in diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) and the underlying pathologies is still relatively unknown. We investigated the radiological-pathological correlation between these imaging techniques and immunohistochemistry using a closed head rat model of TBI. TBI was performed on female rats followed longitudinally by magnetic resonance imaging (MRI) out to 30 days postinjury, with a subset of animals selected for histopathological analyses. An MRI-based finite element analysis was generated to characterize the pattern of the mechanical insult and estimate the extent of brain injury to direct the pathological correlation with imaging findings. We observed that DTI axial diffusivity and fractional anisotropy (FA) were sensitive to axonal integrity, whereas radial diffusivity showed significant correlation to the myelin compactness. FA was correlated with astrogliosis in the gray matter, whereas mean diffusivity was correlated with increased cellularity. Secondary inflammatory responses also partly affected the changes of these DTI metrics. The magnetization transfer ratio (MTR) at 3.5ppm demonstrated a strong correlation with both axon and myelin integrity. Decrease in MTR at 20ppm correlated with the extent of astrogliosis in both gray and white matter. Conventional T2-weighted MRI did not detect abnormalities following TBI, DTI and MTI afforded complementary insight into the underlying pathologies reflecting varying injury states over time, and thus may substitute for histology to reveal diffusive axonal injury pathologies in vivo. Metabolic abnormalities are commonly observed in TBI patients associated with long-term neurological deficits. We investigated the feasibility and reproducibility using the chemical exchange saturation transfer (CEST) MRI to detect cerebral metabolic disorders in experimental TBI. Following the optimization of the CEST weighted imaging parameters we investigated the image contrast sensitivity and specificity in assessing glucose concentrations. The results demonstrated that saturation duration of 12 seconds at pulses powers 1.52T resulted in improved contrast-to-noise ratio between the gray and white matter that was comparable to 2DG autoradiographs. GlucoCEST weighted imaging was then performed in a closed head model of diffuse TBI in rats31 and the results were compared to postmortem 2-deoxy-D-14C-glucose (2DG) autoradiography to determine changes of glucose uptake and metabolism before and after TBI. In this study, we were able to show that the endogenous glucoCEST contrast was decreased following TBI, and correlated to finding on 2DG autoradiography.These results demonstrate that glucoCEST weighted imaging may be useful to detect metabolic abnormalities following TBI.