Photoacoustic computed tomography (PACT) has generated increasing interest for uses in preclinical research and clinical translation. However, the imaging depth, speed, and quality of existing PACT systems have previously limited the potential applications of this technology. To overcome these issues, we developed a three-dimensional photoacoustic computed tomography (3D-PACT) system that features large imaging depth, scalable field of view with isotropic spatial resolution, high imaging speed, and superior image quality. 3D-PACT allows for multipurpose imaging to reveal detailed angiographic information in biological tissues ranging from the rodent brain to the human breast. In the rat brain, we visualize whole brain vasculatures and hemodynamics. In the human breast, an in vivo imaging depth of 4 cm is achieved by scanning the breast within a single breath hold of 10 s. Here, we introduce the 3D-PACT system to provide a unique tool for preclinical research and an appealing prototype for clinical translation.

Neoadjuvant chemotherapy (NAC) has contributed to improving breast cancer outcomes, and it would ideally reduce the need for definitive breast surgery in patients who have no residual cancer after NAC treatment. However, there is no reliable noninvasive imaging modality accepted as the routine method to assess response to NAC. Because of the inability to detect complete response, post‐NAC surgery remains the standard of care. To overcome this limitation, a single‐breath‐hold photoacoustic computed tomography (SBH‐PACT) system is developed to provide contrast similar to that of contrast‐enhanced magnetic resonance imaging, but with much higher spatial and temporal resolution and without injection of contrast chemicals. SBH‐PACT images breast cancer patients at three time points: before, during, and after NAC. The analysis of tumor size, blood vascular density, and irregularity in the distribution and morphology of the blood vessels on SBH‐PACT accurately identifies response to NAC as confirmed by the histopathological diagnosis. SBH‐PACT shows its near‐term potential as a diagnostic tool for assessing breast cancer response to systemic treatment by noninvasively measuring the changes in cancer‐associated angiogenesis. Further development of SBH‐PACT may also enable serial imaging, rather than the use of current invasive biopsies, to diagnose and follow indeterminate breast lesions.

A major challenge of transcranial human brain photoacoustic computed tomography (PACT) is correcting for the acoustic aberration induced by the skull. Here, we present a modified universal back-projection (UBP) method, termed layered UBP (L-UBP), that can de-aberrate the transcranial PA signals by accommodating the skull heterogeneity into conventional UBP. In L-UBP, the acoustic medium is divided into multiple layers: the acoustic coupling fluid layer between the skull and detectors, the skull layer, and the brain tissue layer, which are assigned different acoustic properties. The transmission coefficients and wave conversion are considered at the fluid–skull and skull–tissue interfaces. Simulations of transcranial PACT using L-UBP were conducted to validate the method. Ex vivo experiments with a newly developed three-dimensional PACT system with 1-MHz center frequency demonstrated that L-UBP can substantially improve the image quality compared to conventional UBP.

Complementary to mainstream cardiac imaging modalities for preclinical research, photoacoustic computed tomography (PACT) can provide functional optical contrast with high imaging speed and resolution. However, PACT has not been demonstrated to reveal the dynamics of whole cardiac anatomy or vascular system without surgical procedure (thoracotomy) for tissue penetration. Here, we achieved non-invasive imaging of rat hearts using the recently developed three-dimensional PACT (3D-PACT) platform, demonstrating the regulated illumination and detection schemes to reduce the effects of optical attenuation and acoustic distortion through the chest wall; thereby, enabling unimpeded visualization of the cardiac anatomy and intracardiac hemodynamics following rapidly scanning the heart within 10 s. We further applied 3D-PACT to reveal distinct cardiac structural and functional changes among the healthy, hypertensive, and obese rats, with optical contrast to uncover differences in cardiac chamber size, wall thickness, and hemodynamics. Accordingly, 3D-PACT provides high imaging speed and nonionizing penetration to capture the whole heart for diagnosing the animal models, holding promises for clinical translation to cardiac imaging of human neonates.

We have developed a high-speed dual-modal imaging system (HDMI), designed to concurrently reveal anatomical and hematogenous details of the human breast within seconds. Through innovative system design and technical advancements, HDMI integrates large-view photoacoustic and ultrasonic computed tomography with standardized scanning and batch data processing for computer-aided diagnosis. It achieves dual-modal imaging at a 10-hertz frame rate and completes a whole-breast scan in 12 seconds, providing penetration up to 5 centimeters in vivo. In a clinical study involving 170 patients with 186 breast tumors, we developed a diagnostic model leveraging combined photoacoustic and ultrasound features. In a triple-blinded comparison using pathological diagnosis as the ground truth, HDMI significantly improved diagnostic specificity from 22.5 to 75.0% compared to clinical ultrasonography. This technology shows strong potential for early breast tumor diagnosis, offering enhanced accuracy without the need for ionizing radiation, exogenous contrast agents, pain, invasiveness, operator dependence, or extended examination times.