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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 SO2 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.

Significance: Two-dimensional (2-D) fully convolutional neural networks have been shown capable of producing maps of sO2 from 2-D simulated images of simple tissue models. However, their potential to produce accurate estimates in vivo is uncertain as they are limited by the 2-D nature of the training data when the problem is inherently three-dimensional (3-D), and they have not been tested with realistic images. Aim: To demonstrate the capability of deep neural networks to process whole 3-D images and output 3-D maps of vascular sO2 from realistic tissue models/images. Approach: Two separate fully convolutional neural networks were trained to produce 3-D maps of vascular blood oxygen saturation and vessel positions from multiwavelength simulated images of tissue models. Results: The mean of the absolute difference between the true mean vessel sO2 and the network output for 40 examples was 4.4% and the standard deviation was 4.5%. Conclusions: 3-D fully convolutional networks were shown capable of producing accurate sO2 maps using the full extent of spatial information contained within 3-D images generated under conditions mimicking real imaging scenarios. We demonstrate that networks can cope with some of the confounding effects present in real images such as limited-view artifacts and have the potential to produce accurate estimates in vivo.

Quantitative photoacoustic imaging in biomedicine relies on accurate measurements of relevant material properties of target absorbers. Here, we present a method for simultaneous measurements of the absorption coefficient and Grüneisen parameter of small volume of liquid scattering and absorbing media using a coupled-integrating sphere system which we refer to as quantitative photoacoustic integrating sphere (QPAIS) platform. The derived equations do not require absolute magnitudes of optical energy and pressure values, only calibration of the setup using aqueous ink dilutions is necessary. As a demonstration, measurements with blood samples from various human donors are done at room and body temperatures using an incubator. Measured absorption coefficient values are consistent with known oxygen saturation dependence of blood absorption at 750 nm, whereas measured Grüneisen parameter values indicate variability among five different donors. An increasing Grüneisen parameter value with both hematocrit and temperature is observed. These observations are consistent with those reported in literature.

A method for simultaneously measuring the absorption coefficient μa and Gruneisen parameter Γ of biological absorbers in photoacoustics is designed and implemented using a coupled-integrating sphere system. A soft transparent tube with inner diameter of 0.58mm is used to mount the liquid absorbing sample horizontally through the cavity of two similar and adjacent integrating spheres. One sphere is used for measuring the sample’s μa using a continuous halogen light source and a spectrometer fiber coupled to the input and output ports, respectively. The other sphere is used for simultaneous photoacoustic measurement of the sample’s Γ using an incident pulsed light with wavelength of 750nm and a flat transducer with central frequency of 5MHz. Absolute optical energy and pressure measurements are not necessary. However, the derived equations for determining the sample’s μa and Γ require calibration of the setup using aqueous ink dilutions. Initial measurements are done with biological samples relevant to biomedical imaging such as human whole blood, joint and cyst fluids. Absorption of joint and cyst fluids is enhanced using a contrast agent like aqueous indocyanine green dye solution. For blood sample, measured values of μa = 0.580 ± 0.016 mm-1 and Γ = 0.166 ± 0.006 are within the range of values reported in literature. Measurements with the absorbing joint and cyst fluid samples give Γ values close to 0.12, which is similar to that of water and plasma.

Photoacoustic imaging is an upcoming technique with potential in breast cancer screening and diagnosis. It is able to visualize the breast's vasculature. Its quantitative counterpart, called quantitative photoacoustics, potentially enables the derivation of local blood oxygen saturations when two or more optical wavelengths are used. Tumors can potentially be detected by looking at abnormal vessel shapes, high vascular densities or regions with a low oxygenation. In order to obtain accurate oxygen saturation estimations with quantitative photoacoustics, realistic light propagation models are required. Several models are available, but it is difficult to check their validity on real breasts due to the unknown ground truths, while simple objects having known ground truths are known to overestimate the performance of the algorithms. Therefore, measurements on an object that mimics the breast both optically as well as acoustically, and which has a complex but known morphology, are therefore required. We have previously reported on the first semi-anthropomorphic photoacoustic-ultrasound breast phantom. In this work, we build further upon this to make it suitable for use in quantitative photoacoustics. We demonstrate a method to embed blood vessels and tumors into the phantom where blood with a controlled oxygenation level can be flushed through.