A Tract-Specific Framework for White Matter Morphometry Combining Macroscopic and Microscopic Tract Features

Diffusion tensor imaging plays a key role in our understanding of white matter (WM) both in normal populations and in populations with brain disorders. Existing techniques focus primarily on using diffusivity-based quantities derived from diffusion tensor as surrogate measures of microstructural tissue properties of WM. In this paper, we describe a novel tract-specific framework that enables the examination of WM morphometry at both the macroscopic and microscopic scales. The framework leverages the skeleton-based modeling of sheet-like WM fasciculi using the continuous medial representation, which gives a natural definition of thickness and supports its comparison across subjects. The thickness measure provides a macroscopic characterization of WM fasciculi that complements existing analysis of microstructural features. The utility of the framework is demonstrated in quantifying WM atrophy in Amyotrophic Lateral Sclerosis, a severe neurodegenerative disease of motor neurons. We show that, compared to using microscopic features alone, combining the macroscopic and microscopic features gives a more holistic characterization of the disease.