Abstract
Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development.
Highlights
Hydrocephalus is a common structural neurological disorder [1, 2]
This study aims to understand how tissue microstructure and mechanical properties change during ventricular enlargement in obstructive hydrocephalus using multimodal magnetic resonance (MR) imaging
No statistically significant differences were observed between control and hydrocephalic rats for brain deformation, mean diffusivity, fractional anisotropy or mechanical properties (t-test; shear modulus: cortical gray matter P = 0.94, caudate-putamen P = 0.46)
Summary
Hydrocephalus is a common structural neurological disorder [1, 2]. The disease is characterized by enlargement of cerebral ventricles, caused by the abnormal build-up of cerebrospinal fluid (CSF), which compresses the surrounding tissue and results in functional deficits and cognitive impairments [3,4,5]. It is widely assumed that brain mechanical properties play an important role during the development of the disease and that they change during ventricular enlargement [12]. How brain tissue mechanical properties change in obstructive hydrocephalus is unclear They have been estimated from measurements of the intracranial system's compensatory reserve [18] and indentation techniques [19] in animal models. Both techniques are far from ideal, as they either include the stiffness of other intracranial structures or are limited only to the superficial regions, both suggested that brain tissue stiffness is increased in the presence of enlarged ventricles
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