Dr. Bacskai's laboratory uses sophisticated optical techniques to address fundamental questions in Alzheimer's disease research. Using the imaging technique multiphoton microscopy, the senile plaques of Alzheimer's disease can be detected in the brains of living transgenic mice, and characterized with chronic imaging. By multiplexing with other structural and functional fluorescent probes, we can examine specific cellular responses to disease progression in vivo as well. This detection platform was used to characterize a therapeutic approach to clearing the senile plaques based on immunotherapy, as well as to characterize novel amyloid-targeting ligands in preclinical development for PET imaging in humans. Current research is aimed at optimizing therapeutic approaches, and imaging the anatomy and physiology of specific cell types in the brain before and after treatment. Advances in viral delivery techniques allow targeting specific cell types and organelles in the living brain for both structural and functional imaging. We are currently exploring the roles of the vasculature, neurons, neural circuits, astrocytes, endothelium, smooth muscle cells, and the blood-brain barrier. Development of novel optical techniques is ongoing, and includes methods to measure protein-protein interactions using fluorescence lifetime imaging microscopy (FLIM), and non-invasive approaches to amyloid imaging in intact animals based on NIR fluorescence diffuse optical tomography.