TR&D2

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

TD Wang and G Xu will serve as Project Lead and co-Lead, respectively, for TRD2 to assemble fiber- coupled microendoscopes to achieve real-time in vivo imaging with sub-cellular resolution. Microendoscopes will be developed using different optical configurations to provide broad flexibility for use in pre-clinical and clinical imaging applications. 1st generation instruments will be prepared for use by CP/SPs at the beginning of funding. 2nd generation microendoscopes will be equipped with a scan mechanism installed in the distal end that performs static deflections and enables random access scanning. This location offers a very large image FOV limited only by the deflection angle of the scanner. Axial displacement of the scan mechanism enables images to be collected in vertical planes to follow the natural direction of disease progression. This view is preferred for evaluating pathology. Multiplexed detection methods will be developed to track the behaviors of different cell types and their interactions. Microendoscopes will be developed using different optical configurations to provide broad flexibility for in vivo imaging. The single axis confocal configuration will be scaled down to very small diameters to perform in vivo imaging of internal organs that are difficult to access otherwise, such as oral cavity and pancreas. Multiphoton microendoscopes will be implanted in pancreatic tumors of small animals to visualize the tumor microenvironment in vivo over time, and will be head-mounted to image neuronal activity in freely behaving mice. A confocal photoacoustic microendoscope will be developed for multi-modal imaging. Photoacoustic will be performed first with large FOV (low power) to grossly identify the depth of biological structures. Confocal will then be performed with high resolution (high power) to image below the tissue surface with sub-cellular resolution. 3D volumetric images will be generated using an acoustic sensor array to precisely localize diseased tissue regions for surgical resection. The microendoscopes will be equipped with thin-film PZT scan mechanisms for random access scanning. Unlike resonant scanners, this advance will enable arbitrary user-defined ROIs to be highlighted within the full image FOV to improve temporal resolution. This capability is critical for live imaging to mitigate motion artifact. In the multiphoton microendoscope, microsystems scan mechanisms will be installed to introduce equal but opposite aberrations in a polarized excitation beam to correct for optical aberrations over a large range of axial displacements. These compact devices reduce the size and weight of microendoscopes by comparison with other approaches that use bulky adaptive optics and spatial light modulators. A multi-modal dual axes confocal photoacoustic endoscope will be developed to visualize target specific agents that enhance molecular contrast in the surgical resection cavity. A sensor array consisting of fabricated on 2D layered materials will be used to collect acoustic signals. This compact design enables seamless integration with confocal.