Assessment of vasculatures and lymphatics is critical to surgery. Fluorescence angiography is an excellent method for identifying anastomotic failure. Intraoperative detection of anastomotic failures and hypoperfusion can reduce surgical re-exploration and follow-up surgery. For lymphatic surgery such as lymphovenous bypass, fluorescence lymphography is important for diagnosis, staging, and surgical planning. Unfortunately, commercially available fluorescence imaging systems are bulky, expensive, and not user-friendly. There is an unmet clinical need for an affordable and intuitive multiscale fluorescence imaging system suitable for diverse vascular and lymphatic assessment use cases. The long-term goal is to improve outcomes of microvascular, lymphatic, transplant, and trauma surgery by enhancing intraoperative imaging and tissue assessment. The overall objective in this application is to develop a wearable multiscale fluorescence imaging and 3D display device with edge computing capability. The project will be guided by the following specific aims: Aim 1. Develop a wearable multiscale fluorescence imaging and display device for vascular and lymphatic assessment. A compact prototype will be developed that offers real-time stereoscopic fluorescence imaging and 3D augmented reality display for vascular and lymphatic assessment. Multiscale fluorescence imaging with 2X-10X dynamic magnification will be implemented to accommodate diverse surgical applications, including lymphatic mapping, perfusion angiography, and anastomosis patency testing. Heterogeneous computing will be implemented to support machine learning tasks using deep convolutional neural networks. Voice control and autofocus will be implemented on the edge. Medical information including duplex ultrasound images will be overlaid in augmented reality. Aim 2. Characterize the device and demonstrate wearable multiscale fluorescence imaging in vivo. Comprehensively characterization of the system performance will be performed. Wearable multiscale fluorescence imaging will be demonstrated in a rat model. Lymphatic mapping (wide-field fluorescence imaging) and an anastomotic patency check (magnified fluorescence imaging) will be demonstrated in vivo. The proposed research is innovative, in applicant’s opinion, because it represents a substantive departure from the status quo by offering real-time multiscale fluorescence imaging capability and edge computing capability in a wearable 3D system. The proposed project is significant because it is expected to provide strong evidence-based proof of principle for further development and future clinical trials of the wearable multiscale fluorescence imaging device for vascular and lymphatic assessment. If the proposed device is successfully commercialized, surgeons will have access to an innovative product that can improve surgical outcomes of multiple surgical subspecialities.