ABSTRACT Prostate cancer is the most common cancer among men in the United States, and early detection is crucial for effective treatment or management. Following an initial screening for prostate cancer based on elevated prostate-specific antigen (PSA) levels or suspicious digital rectal exam, the current clinical standard of care for diagnosis is a transrectal ultrasound (TRUS)-guided biopsy, in which 10 to 12 systematically sampled cores are taken and examined. Because the TRUS procedure is guided by conventional B-mode ultrasound imaging, in which prostate cancer does not typically have a unique appearance, the biopsy cores are sampled from a predetermined grid of locations throughout the gland, and are not specifically targeted to cancer-suspicious regions. As a result, there is often a need for repeat biopsies when the first biopsy fails to detect cancer. Recent studies have demonstrated the ability of alternative imaging modalities, such as multiparametric MRI (mpMRI) or contrast-enhanced ultrasound (CEUS), to provide imaging guidance for a targeted prostate biopsy. These techniques have drawbacks, however, including challenges with registering the mpMRI volume with the real- time B-mode ultrasound image during the biopsy, or the need to inject microbubble contrast agents into the patient’s vasculature for CEUS imaging. The goal of this proposal is to develop a low-cost, clinic-ready 3D ultrasound elasticity imaging system to guide a targeted biopsy that is specific for clinically significant disease in the prostate. Previous work has demonstrated that prostate cancer is stiffer than the surrounding healthy tissue and can thus be imaged using ultrasonic acoustic radiation force-based techniques. The proposed system will simultaneously acquire two elasticity imaging modes: acoustic radiation force impulse (ARFI) imaging and shear wave elasticity imaging (SWEI), in order to create high-resolution, quantitative stiffness maps of the prostate. I hypothesize that using combined 3D ARFI/SWEI prostate volumes to guide a targeted biopsy for prostate cancer will result in improved diagnostic sensitivity and staging accuracy compared to current transrectal ultrasound standard-of-care biopsy. In this proposed work, I will develop advanced ARFI/SWEI reconstruction methods in order to examine the tradeoff between the number and intensity of acoustic radiation force excitations, transducer heating, and reconstructed image quality. In particular, I will use specialized finite-element simulation tools to compare different ultrasonic imaging sequences and implement these sequences on a state-of-the-art commercial ultrasound scanner. In order to evaluate these sequences in an in vitro setting, I will acquire combined ARFI/SWEI data in custom tissue-mimicking prostate anatomy phantoms. From here, I will assess the performance of the 3D ARFI/SWEI imaging system in a clinical setting, by using the system to obtain targeted biopsy cores in patients with suspect...