Diffusion Abnormity In Several Relared Brain Regions Of Visual Or Olfactory System Of Diabtic Rats

Diabetes mellitus is caused by the immune dysfunction, genetic factors, free radical toxins and other virulence factors playing roles in islet dysfunction or insulin resistance and triggering a series of metabolic disorder syndrome. High blood sugar is as the main clinical characteristic. Accounting for5-10%of all types of diabetes, type1diabetes mellitus (T1DM), throughout many countries and regions, is mainly seen in children under the age of15-18. Clinical and animal model studies have shown that T1DM can cause brain atrophy and white matter lesions. Brain atrophy and white matter lesions are generally considered to be the pathological basis of cognitive dysfunction in patients with diabetes. The neuropathological manifestation is loss of neurons/reduced synapsis, white matter axonal injury and demyelination. Early white matter lesions on conventional magnetic resonance imaging (MRI) may be difficult to detect. The main work of this paper is using diffusion MRI, including diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI), to study1) whether or not visual pathway and olfactory bulb of diabetic rats occur white matter microstructure change visible on diffusion MRI;2) the effect of these microscopic structural change on its diffusion properties; and combining with3) histological results to discuss the possibility of using anisotropic FA to characterize the white matter microstructure integrity, and three fundamental diffusion parameters (the average diffusion coefficient ADC, the parallel diffusion coefficient ADC||and the vertical diffusion coefficient ADCi) to reflect more comprehensive microstructure changes.The first two chapters of the paper is the background section. In first chapter, the MRI technique, diffusion MRI principles and applications were introduced. In second chapter, the diabetic complications of the central nervous system and related applications of conventional MRI and diffusion MRI in the study of white matter lesions in diabetes were described.In third chapter, we examined the relationship between the changes in MRI and the pathological alterations of the optic nerve of streptozotocin (STZ)-induced T1DM rat. This paper exploited diffuse abnormity in TIDM rat optic nerve using the directional diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) measurements, in order to get in vivo MRI data to reflect integrity of axon and myelin, and found no significant FA change, significantly reduced parallel direction diffusivities (ADC||), vertical direction diffusivities (ADC|) and average diffusivities (ADC) in the diabetic rat optic nerve. We explored the mechanism beyond the diffusion property changes caused by the white matter injury via histological methods, and found optic nerve atrophy, axonal degeneration but without severe demyelination in this model. The positive correlation between the degree of axonal injury and ADC||are significant, as well as ADC(?). In addition, we found damaged fast axonal transport in T1DM rat optic nerve by manganese enhanced MRI after intravitreal Mn2+injections.In fourth chapter, we examined the relationship between the histopathological alterations of the optic tract and the visual cortex of the TIDM animal model, and its corresponding changes in the MRI measurements. The pathology of the TIDM rat optic tract was identified as a mixture of axonal injury and demyelination. The pathology of the T1DM rat visual cortex was identified as a mixture of the pyramidal cell body atrophy, lightly stained axons, myelin lamellar loose and mitochondrial abnormalities. The DTI results showed significantly decreased FA, significantly decreased ADC||and significantly increased ADd in the optic tract; and significantly decreased FA accompanied with a slight reduction in ADC||and a slight increase in ADC(?) in the visual cortex. No significant changes in ADC of the optic tract and visual cortex.In fifth chapter, we explored the mechanism beyond diffusion abnormity and voxel based morphology (VBM)-based atrophy of the T1DM rat olfactory bulb. The histopathological results verified the DTI abnormity found in diabetic rat olfactory bulb. The DTI results found significantly declined FA, accompanied with significantly rised ADC, ADC||and ADC(?) in olfactory nerve layer/glomerular layer/external plexiform layer (ONL/GL/EPL) of T1DM rat olfactory bulb. Initially ADC and ADC(?) significantly rised, and afterwards FA significantly decreased in the granule cell layer (GCL). No diffusion abnormality occurred in subventricular zone (SEZ). The histological results showed demyelination/loss of axolemma and axoplasm vacuolization in the ONL. VBM analyse revealed GCL and SEZ were involved in the atrophy initially, and with the illness ongoing, all layers were pronounced affected on rostral side, and EPL, GCL and SEZ were involved on caudual side of olfactory bulb. Nissl staining confirmed the olfactory bulb atrophy. Immunohistochemical staining showed increased apoptosis in the olfactory bulb, immature neurons reduced in the lateral ventricles. The results showed evidence of olfactory bulb microstructural damage after diabetes onset, and the spatial and temporal patterns were not coincided with that of the olfactory bulb atrophy.In the third, fourth and fifth chapters, we found that the diffusion MRI (mainly DTI) was sensitive to white matter injury in T1DM rat. Diffusion parameters changes varied in several kinds of white matter (optic nerve, optic tract and olfactory nerve). It prompts to investigate a variety of diffusion parameters as far as possible. There are multiple factors contributing to the diffusion changes which need to be further explored.This work enriched our knowledge of white matter injury and pathological features in T1DM animal model, and facilitated the application of diffusion MRI to the pathological research and preclinical therapeutic assessments of T1DM brain complication.