Longitudinal Multi-Tensor Analysis of Neocortical Microstructure in an Animal Model of Cortical Dysplasia

Abstract

The neocortex is a highly organized structure, with region-specific spatial patterns of cells and fibers constituting cyto- and myelo-architecture, respectively. These architectural features are modulated during neurodevelopment, aging, and disease. While invasive techniques have contributed significantly to our understanding of cortical patterning, the task remains challenging through non-invasive methods. Structural magnetic resonance imaging (MRI) has advanced to improve sensitivity in identifying cortical features, yet most methods focus on capturing macrostructural characteristics, often overlooking critical microscale components. Diffusion-weighted MRI (dMRI) offers an opportunity to extract quantitative information reflecting microstructural changes. Here we investigate whether advanced multi-tensor dMRI methods can detect microstructural characteristics related to the orientational organization of the myelo- and cyto-architecture in an animal model of cortical dysplasia, a malformation of cortical development. We scanned 32 animals (n=16 experimental; n=16 control) at four different time points (30, 60, 120, and 150 post-natal days) using both structural and multi-shell dMRI. Our dMRI metrics were sampled using a 2D curvilinear system of coordinates as a common anatomical descriptor across animals. Diffusion tensors were labeled according to their orientation with respect to the cortical surface, and derived metrics were analyzed separately. We identified abnormalities in the perpendicular and parallel diffusion components in deeper cortical areas, consistent with histological findings of neuronal and fiber disorganization in animals with dysplasia. Although our methodology is tailored for small species, our protocol shows promise for clinical applications.