Abstract
Down Syndrome is a chromosomal disorder that affects the development of cerebellar cortical lobules. Impaired neurogenesis in the cerebellum varies among different types of neuronal cells and neuronal layers. In this study, we developed an imaging analysis framework that utilizes gadolinium-enhanced ex vivo mouse brain MRI. We extracted the middle Purkinje layer of the mouse cerebellar cortex, enabling the estimation of the volume, thickness, and surface area of the entire cerebellar cortex, the internal granular layer, and the molecular layer in the Tc1 mouse model of Down Syndrome. The morphometric analysis of our method revealed that a larger proportion of the cerebellar thinning in this model of Down Syndrome resided in the inner granule cell layer, while a larger proportion of the surface area shrinkage was in the molecular layer.
Highlights
The cerebellum is an important structure in the hindbrain located between the cerebrum and the brain stem
The overall pipeline of the image processing framework is presented in Fig. 1, which includes the extraction of the cerebellum, the white matter (WM) and gray matter (GM) tissue segmentation, the laminar layer separation, the parcellation of the cerebellar cortex based on the functional characteristics, and the measurement of layer-wise morphologies such as volume, thickness, and surface area
To evaluate whether the cortical laminar layer segmentation can provide better insights when comparing the group of Tc1 Down Syndrome (DS) mice with their wild type control littermates, we evaluated and compared the cortical morphologies for the full cerebellar cortex, the internal granular layer, and the molecular layer
Summary
The cerebellum is an important structure in the hindbrain located between the cerebrum and the brain stem. Due to the limited resolution of clinical MRI and the highly convoluted nature of the human cerebellar cortex compared to cerebral cortex, studies on cortical layer morphology in neurological disorders tend to focus more on the cerebral cortex (Eickhoff et al, 2007; Wagstyl et al, 2018). Using high-resolution ex vivo MRI, it is possible to reveal the different cell layers in the mouse cerebellum. We developed an analysis framework to estimate the volume, thickness, and surface area of the cortical laminar layers of the cerebellum in a mouse model of DS (Tc1 (O’Doherty et al, 2005)) using high resolution ex vivo MRI data with a gadolinium-induced active staining contrast enhancement technique to achieve high tissue contrast among cortical layers. NeuroImage 223 (2020) 117271 ness, and surface area - of the two other layers (i.e. the granular, and the molecular layer)
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