Project summary Chronic leg ulcers are affecting approximately 6.5 million Americans and the disease includes venous stasis ulcers, arterial ulcers, pressure ulcers, and diabetic (neuropathic) ulcers. They are associated with significant mortality (28% over two years), reduced quality of life (nonambulatory), and high treatment costs (>$25 billion/yr in the U.S.). Since many chronic ulcers have underlying vascular insufficiency, accurate assessment of blood perfusion to the wound is critical to treatment planning and monitoring. However, existing clinical tests fail to meet this need in practice. Without timely information on circulation, a patient may need to wait months after the revascularization surgery before any additional intervention can be planned. An accurate, noninvasive tool for circulation assessment would greatly improve post-surgical decision making and clinical outcomes of wound patients. This project aims to develop a three-dimensional (3D) wound assessment system using photoacoustic tomography (PAT), a hybrid modality that detects optical absorption in tissue through the photoacoustic effect. The conversion of optical absorption into acoustic waves breaks through the optical diffusion limit, allowing for high-resolution imaging in three dimensions. Since hemoglobin serves as the major endogenous contrast at near-infrared wavelengths, PAT provides label-free, three-dimensional imaging of hemoglobin distribution, which is closely related to circulation. While PAT has shown promising results in vascular imaging, various hurdles have prevented its application in wound evaluation. Capitalizing on the recent innovations in photoacoustic system development and image processing, the team will address these hurdles and develop a PAT-based wound imaging system with unique advantages in terms of spatial resolution, penetration depth, and portability. To ensure successful implementation of the project, the PI has gathered a multidisciplinary team with expertise in photoacoustic imaging, wound healing, vascular surgery, biostatistics, and computer science. The project has also secured support from the region’s busiest vascular clinic located at Buffalo Generation Hospital and Erie County Medical Center and their outpatient clinics. More importantly, the team has already worked together and acquired preliminary data through support from the University at Buffalo’s NIH Clinical and Translational Science Awards (CTSA) Program. Through the four-year project, the team will achieve the following aims: Aim 1: Develop a versatile, high-resolution 3D photoacoustic imaging system that can be easily rotated and positioned to image any regions on the foot; Aim 2: Validate the system at vascular clinics and identify photoacoustic features of tissue perfusion; and Aim 3: Test the feasibility of using PAT to monitor tissue perfusion and guide post-surgical assessment and treatment planning.