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.

Imaging parameters of photoacoustic breast imaging systems such as the spatial resolution and imaging depth are often characterized with phantoms. These objects usually contain simple structures in homogeneous media such as absorbing wires or spherical objects in scattering gels. While these kinds of basic phantoms are uncluttered and useful, they do not challenge the system as much as a breast does, and can thereby overestimate the system's performance. The female breast is a complex collection of tissue types, and the acoustic and optical attenuation of these tissues limit the imaging depth, the resolution and the ability to extract quantitative information. For testing and challenging photoacoustic breast imaging systems to the full extent before moving to in vivo studies, a complex breast phantom which simulates the breast's most prevalent tissues is required. In this work we present the first three dimensional multi-layered semi-anthropomorphic photoacoustic breast phantom. The phantom aims to simulate skin, fat, fibroglandular tissue and blood vessels. The latter three are made from custom polyvinyl chloride plastisol (PVCP) formulations and are appropriately doped with additives to obtain tissue realistic acoustic and optical properties. Two tumors are embedded, which are modeled as clusters of small blood vessels. The PVCP materials are surrounded by a silicon layer mimicking the skin. The tissue mimicking materials were cast into the shapes and sizes expected in the breast using 3D-printed moulds developed from a magnetic resonance imaging segmented numerical breast model. The various structures and layers were assembled to obtain a realistic breast morphology. We demonstrate the phantom's appearance in both ultrasound imaging as photoacoustic tomography and make a comparison with a photoacoustic image of a real breast. A good correspondence is observed, which confirms the phantom's usefulness.

Pulsed lasers in photoacoustic tomography systems are expensive, which limit their use to a few clinics and small animal labs. We present a method to realize tomographic ultrasound and photoacoustic imaging using a commercial LED-based photoacoustic and ultrasound system. We present two illumination configurations using LED array units and an optimal number of angular views for tomographic reconstruction. The proposed method can be a cost-effective solution for applications demanding tomographic imaging and can be easily integrated into conventional linear array-based ultrasound systems. We present a potential application for finger joint imaging in vivo, which can be used for point-of-care rheumatoid arthritis diagnosis and monitoring.

. Significance : Recovering accurate oxygenation estimations in the breast with quantitative photoacoustic tomography (QPAT) is not straightforward. Accurate light fluence models are required, but the unknown ground truth of the breast makes it difficult to validate them. Phantoms are often used for the validation, but most reported phantoms have a simple architecture. Fluence models developed in these simplistic objects are not accurate for application on the complex tissues of the breast. Aim : We present a sophisticated breast phantom platform for photoacoustic (PA) and ultrasound (US) imaging in general, and specifically for QPAT. The breast phantom is semi-anthropomorphic in distribution of optical and acoustic properties and contains wall-less channels with blood. Approach : 3D printing approaches are used to develop the solid 3D breast phantom from custom polyvinyl chloride plastisol formulations and additives for replicating the tissue optical and acoustic properties. A flow circuit was developed to flush the channels with bovine blood with a controlled oxygen saturation level. To showcase the phantom’s functionality, PA measurements were performed on the phantom with two oxygenation levels. Image reconstructions with and without fluence compensation from Monte Carlo simulations were analyzed for the accuracy of oxygen saturation estimations. Results : We present design aspects of the phantom, demonstrate how it is developed, and present its breast-like appearance in PA and US imaging. The oxygen saturations were estimated in two regions of interest with and without using the fluence models. The fluence compensation positively influenced the estimations in all cases and confirmed that highly accurate fluence models are required to minimize estimation errors. Conclusions : This phantom allows studies to be performed in PA in carefully controlled laboratory settings to validate approaches to recover both qualitative and quantitative features sought after in in-vivo studies. We believe that testing with phantoms of this complexity can streamline the transition of new PA technologies from the laboratory to studies in the clinic.

A HYBRID MULTISPECTRAL PHOTOACOUSTIC-ULTRASOUND BREAST IMAGER from the lab towards the clinic PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit Twente, op gezag van de rector magnificus, prof. dr. A. Veldkamp, volgens besluit van het College voor Promoties, in het openbaar te verdedigen op vrijdag