We review the history of photoacoustics from the discovery in 1880 that modulated light produces acoustic waves to the current time, when the pulsed variant of the discovery is fast developing into a powerful biomedical imaging modality. We trace the meandering and fascinating passage of the effect along several conceptual and methodological trajectories to several variants of the method, each with its set of proposed applications. The differences in mechanisms between the intensity modulated effect and the pulsed version are described in detail. We also learn the several names given to the effect, and trace the modern-day divide in nomenclature.

Near-infrared photoacoustic images of regions-of-interest in 4 of the 5 cases of patients with symptomatic breasts reveal higher intensity regions which we attribute to vascular distribution associated with cancer. Of the 2 cases presented here, one is especially significant where benign indicators dominate in conventional radiological images, while photoacoustic images reveal vascular features suggestive of malignancy, which is corroborated by histopathology. The results show that photoacoustic imaging may have potential in visualizing certain breast cancers based on intrinsic optical absorption contrast. A future role for the approach could be in supplementing conventional breast imaging to assist detection and/or diagnosis.

Non-invasive detection of breast cancer has been regarded as the holy grail of applications for photoacoustic (optoacoustic) imaging right from the early days of re-discovery of the method. Two-and-a-half decades later we report on the state-of-the-art in photoacoustic breast imaging technology and clinical studies. Even within the single application of breast imaging, we find imagers with various measurement geometries, ultrasound detection characteristics, illumination schemes, and image reconstruction strategies. We first analyze the implications on performance of a few of these design choices in a generic imaging system, before going into detailed descriptions of the imagers. Per imaging system we present highlights of patient studies, which barring a couple are mostly in the nature of technology demonstrations and proof-of-principle studies. We close this work with a discussion on several aspects that may turn out to be crucial for the future clinical translation of the method.

Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies and first insights were gained into the relationship with tumor vascularity.

Photoacoustic mammography is potentially an ideal technique, however, the amount of patient data is limited. To further our understanding of the in vivo performance of the method and to guide further research and development, we imaged 33 breast malignancies using the research system – the Twente Photoacoustic Mammoscope (PAM).