Abstract.SignificanceWhen developing a new quantitative optoacoustic computed tomography (OAT) system for diagnostic imaging of breast cancer, objective assessments of various system designs through human trials are infeasible due to cost and ethical concerns. In prototype stages, however, different system designs can be cost-efficiently assessed via virtual imaging trials (VITs) employing ensembles of digital breast phantoms, i.e., numerical breast phantoms (NBPs), that convey clinically relevant variability in anatomy and optoacoustic tissue properties.AimThe aim is to develop a framework for generating ensembles of realistic three-dimensional (3D) anatomical, functional, optical, and acoustic NBPs and numerical lesion phantoms (NLPs) for use in VITs of OAT applications in the diagnostic imaging of breast cancer.ApproachThe generation of the anatomical NBPs was accomplished by extending existing NBPs developed by the U.S. Food and Drug Administration. As these were designed for use in mammography applications, substantial modifications were made to improve blood vasculature modeling for use in OAT. The NLPs were modeled to include viable tumor cells only or a combination of viable tumor cells, necrotic core, and peripheral angiogenesis region. Realistic optoacoustic tissue properties were stochastically assigned in the NBPs and NLPs.ResultsTo advance optoacoustic and optical imaging research, 84 datasets have been released; these consist of anatomical, functional, optical, and acoustic NBPs and the corresponding simulated multi-wavelength optical fluence, initial pressure, and OAT measurements. The generated NBPs were compared with clinical data with respect to the volume of breast blood vessels and spatially averaged effective optical attenuation. The usefulness of the proposed framework was demonstrated through a case study to investigate the impact of acoustic heterogeneity on OAT images of the breast.ConclusionsThe proposed framework will enhance the authenticity of virtual OAT studies and can be widely employed for the investigation and development of advanced image reconstruction and machine learning-based methods, as well as the objective evaluation and optimization of the OAT system designs.