Abstract Our central goal is to create a volumetric real-time system combining ultrasound (US) and photoacoustic (PA) tomography (USPAT) for high resolution structural and functional imaging. The recent development of high channel count ultrafast US systems creates the opportunity to capture volumes at a high frame rate. Tomography, defined as a technique for displaying a representation of a cross section through a human body, facilitates high resolution (lamba/2) imaging by effectively rotating the US point spread function to reduce the effect of diffraction. We have developed an ultrafast US capability mated to a tomographic ring of transducers and scanned in depth by motorized acquisition. Leveraging the ultrafast capability provides the opportunity for acquisition of volumetric, functional breast images within 1 minute. The acquisition is controlled by 1024 coherent channels of Verasonics imaging systems (to be increased to 2048) and includes embedded GPUs for real-time imaging and analysis. When operated at 5 MHz, the resulting spatial resolution is nearly isotropic in plane with resolution of ~ half a wavelength (in this case ~150 microns). Compared to US images acquired with conventional imaging, the image quality is far improved. Ultrasound methods are attractive for integration into breast management due to their utility in guiding biopsy and the very high sensitivity (97.3%) that can be achieve by combining ultrasound with conventional screening. Both transmission and reflection tomography modes will be evaluated in order to facilitate both high resolution reflective modes and highly quantitative transmission imaging. PA imaging (PAI) is particularly well suited to complement US and improve diagnostic imaging of the breast. Our immediate goal is to reduce the number of biopsies required in women undergoing breast screening. Photoacoustic tomography (PAT) enhances the signal to noise ratio and visualization of morphology over conventional PAI. Healthy breast tissue has low optical absorption and US scattering, allowing for highly efficient PAT. Since abnormally increased vasculature and hemoglobin at tumor sites produces strong intrinsic photoacoustic contrast, PAT is ideally suited for visualizing angiogenesis. Further, PAT can assess the relative oxygenation of a region. With our combined strategy, we will evaluate characterization algorithms based on each feature – blood flow, oxygenation and structural changes, assessing the sensitivity of individual and combined imaging features. With a first study of this technique in a mouse model of premalignant to malignant transformation and a human study of lesion characterization, we will determine whether USPAT can add to the sensitivity and specificity of lesion characterization by MRI. Our resulting specific aims are to: 1) implement and integrate blood mapping, US tomography, and PAT for breast imaging, 2) assess the sensitivity and specificity of the resulting system in a rodent model of...