Detailed spatial and temporal mapping of anatomical changes in human brain is crucial in understanding the basis of age-related cognitive advancement and various neurological disorders. Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique that provides high resolution structural images of human brain. Tensor-based morphometry (TBM) is an image analysis technique that characterizes local shape differences from the gradients of the deformation field. TBM can be applied to cross-sectional MRI data for local shape comparisons between two or more groups of subjects, based on nonlinearly registering individual brain scans to a common anatomical template. Moreover, when TBM is applied to longitudinal MRI study, the derived Jacobian maps represent the percentage of tissue change over time. In my dissertation work, I explored the application of TBM in mapping anatomical changes of human brain during normal development, anomalous development in autism, age related memory condition known as mild cognitive impairment (MCI), and neurodegeneration in Alzheimer's disease (AD). In the normal development study, Jacobian maps tracking dynamic tissue growth were created for each of the 13 healthy developing children. Statistical analyses revealed significant tissue growth in cerebral white matter, contrasted with gray matter loss in parietal, temporal, and occipital lobe. A linear regression with age and gender suggested a slowing down of the growth rate in regions with the greatest white matter growth. Next, by comparing the regional tissue change rate from the longitudinal brain scans of 13 autistic and 7 normal developing boys, I revealed aberrant development in brain regions that have been implicated in autism's social impairment, communication deficits and repetitive behaviors. Finally, in one of the largest brain MRI studies to date, I compared the anatomical distribution of atrophy in 165 AD patients, 330 MCI subjects, and 181 controls and revealed 3D correlations between neuroimaging markers, genes, and future clinical changes. Baseline temporal lobe atrophy mapped by TBM correlated with current cognitive performance, future cognitive decline, and conversion from MCI to AD over the following year. Overall, I demonstrated that tensor-based Jacobian is a sensitive and reliable method to detect regional tissue changes during normal and pathological conditions.
Detailed spatial and temporal mapping of anatomical changes in human brain is crucial in understanding the basis of age-related cognitive advancement and various neurological disorders.