The Penn FTD Center uses a variety of neuroimaging methods to advance our understanding of neurodegenerative diseases, and to address basic questions in the cognitive neuroscience of language, memory, and social cognition.
The Penn FTD Center routinely collects high-resolution structural MRI measurements of grey matter density and cortical thickness. We use these measurements to assess normal brain structure in healthy adults and to perform comparative structural studies of different neurodegenerative disease groups, such as FTD, Alzheimer’s disease (AD) and progressive supranuclear palsy (PSP). These studies help to improve diagnosis. We also perform longitudinal analyses to evaluate prognosis and characterize disease progression. Other structural MRI studies involve the comparison of different clinical syndrome groups, such as primary progressive aphasia (PPA) and behavioral variant FTD (bvFTD). In these studies, we often employ regression analyses to relate cognitive performance directly to the regional neuroanatomic changes brought about by conditions such as FTD. More recently, we have begun to evaluate how individual differences in the brain structure of healthy adults relate to individual differences in cognitive performance.
Functional MRI (fMRI) provides a measure of blood flow in the brain that can be used to determine what regions of the brain are recruited to perform a cognitive task, like sentence comprehension or semantic memory judgments. Most fMRI studies in the Penn FTD Center are performed with healthy young adult volunteers. Investigators combine fMRI activation studies with structural imaging studies. For example, we can identify the white matter tracts that help integrate functioning between two activated regions in an fMRI study. We also obtain converging evidence for cognitive neuroscience models by performing parallel fMRI studies in healthy adults and structural imaging studies with behavioral regressions in patients. Here we look for regression results implicating a specific brain region in structural MRI and DTI studies of patients, and identify the same regions activated by the same materials in fMRI studies of healthy adults. Investigators at the Penn FTD Center also perform fMRI studies in healthy seniors and patients to evaluate the brain’s ability to compensate for the neural changes brought about by aging and neurodegenerative disease.
Arterial Spin labeling (ASL) provides a quantitative measure of cerebral blood flow in the brain. This technique takes alternating measures of tagged water molecules and untagged molecules, and then calculates the perfusion of blood. ASL provides a complementary functional neuroimaging technique that is better suited to measuring slower fluctuations in activity than standard fMRI, such as emotional states and paragraph-length comprehension. This technique also allows us to measure focal perfusion changes at rest in the brains of patients. We have observed reduced perfusion in brain areas that are not functioning optimally. We have also found increased perfusion in brain areas that are attempting to compensate prior to neuronal cell death in neurodegenerative disease.
Diffusion Tensor Imaging (DTI) provides a measure of water diffusion in the brain, which can be used to identify the paths of white matter fibers. As with structural MRI, DTI is used to improve our understanding of normal brain structure and help in the differential diagnosis of neurodegenerative diseases. Investigators at the Penn FTD Center also use DTI to evaluate white matter changes in clinical syndromes like primary progressive aphasia, and relate these changes directly to cognitive performance. Another DTI method involves using deterministic or probabilistic tractography to identify white matter tracts that support the large-scale neural networks involved in language, memory, and social cognition.
Many of the analysis methods used in the Penn FTD Center are developed by our scientists in collaboration with the Penn Image & Computing Science Laboratory (PICSL) in the Department of Radiology at the University of Pennsylvania. We provide these resources to the public using open-source licensing in an effort to encourage multi-center collaboration and the replication of experimental results.