The focus of the proposal is in the area of breast cancer imaging and tumor characterization using oxygen sensitive phosphorescent labels and hybrid imaging modality. We propose to use simultaneous diffuse optical tomography (DOT) and magnetic resonance imaging (MRI) to obtain high spatial-resolution and quantitative functional images of breast tumors. Imaging in pre-clinical models with injected contrast agents and imaging the oxygen concentration within tissue are important for a number of clinical and scientific reasons. Low oxygen content in tumors is a marker of radiation-resistant tumor regions, and is also correlated with a poor treatment outcome. For basic research applications, it is also very important to understand how hypoxia develops in tumors and how it is correlated with exogenous and endogenous markers of low oxygen. During Phase I, in conjunction with standard diffuse optical tomography (DOT), we obtained high contrast images of hypoxic regions in breast tissue simulating phantoms using long-lived oxygen sensitive contrast agents and a simple lifetime imaging system with cooled avalanche photodiodes. In Phase II, a prototype of the CW and time domain lifetime imaging module will be developed which will have parallel acquisition across a cooled 16-element avalanche photodiode (APD) array for high resolution and high throughput imaging. The low-cost, compact lifetime imager module will be designed to be compatible with high magnetic and RF fields associated with MR units in hybrid imaging systems. Using this APD module in a dual-modality imaging setup at our collaborator's facility at Dartmouth College, NH (Prof. Brian Pogue, Thayer School of Engineering), phantom and animal model imaging will be performed to obtain functional optical images with high resolution and high contrast. The optical image reconstruction will be aided by the spatial and anatomical information obtained from simultaneously obtained high-resolution MR images in order to improve the accuracy of these images. The compact APD based detector prototype will have a small footprint and will be mounted inside the magnet of the MRI unit, dramatically decreasing the complexity of the current PMT based detection systems.
Hybrid imaging with simultaneous diffuse luminescence imaging and magnetic resonance imaging can be used to obtain high resolution functional maps of tumors based on their oxygen concentration. Hypoxic breast cancer detection is the primary target application, with the goal of improving diagnostic accuracy and treatment prognosis using exogenous contrast agents. Other applications could include brain imaging to monitor cerebral function or cerebral hemorrhage, and monitoring tissue and muscle oxygenation, histotoxicity, etc.
