Whole-Body Functional and Molecular Imaging by Integrated Photoacoustic and Ultrasound Imaging

The complexity of biomedical research, particularly studies of brain activity, the tumor microenvironment, and aging, demands imaging technologies capable of concurrently revealing multiple aspects of tissue pathology and physiology. Traditional single-modality imaging approaches, such as photoacoustic imaging or ultrasound imaging alone, often fall short by lacking either molecular specificity, functional detail, or sufficient resolution. To address these limitations, we present a ring array-based integrated photoacoustic and ultrasound imaging (iPAUS) system that enables full-view, whole-body imaging of small animals. iPAUS combines multispectral photoacoustic computed tomography for deep-tissue functional and molecular imaging with ultrasound pulse-echo imaging, and further incorporates transmission-mode ultrasound tomography to obtain cross-sectional speed-of-sound distributions. These speed-of-sound maps are used to improve the reconstruction accuracy of both photoacoustic and ultrasound images. In addition, we implement microbubble-enhanced power Doppler and super-resolution ultrasound localization microscopy to achieve high-resolution mapping of vascular structure and blood flow dynamics. We demonstrate the capabilities of iPAUS through three representative applications. First, we perform neck-to-tail scanning of a live mouse to map blood perfusion and oxygenation across major organs. Second, we image a tumor-bearing mouse expressing photoswitchable bacterial phytochromes, enabling the combined assessment of hemodynamics and specific molecular details. iPAUS further reveals key tumor microenvironment features such as hypoxic cores and reduced blood perfusion. Finally, we perform longitudinal imaging of a mouse kidney ischemia-reperfusion injury model to monitor pre- and post-operative renal blood flow. With co-registered anatomical, functional, and molecular imaging at high spatial resolution, iPAUS holds strong potential for biomedical research in cancer, metabolism, transplantation, and beyond.

Duke Scholars

Author Irma Husain Medicine, Nephrology

Author Junjie Yao Biomedical Engineering