The non-invasive quantification of total haemoglobin concentrations [tHb] is highly desired for the assessment of haematologic disorders in vulnerable patient groups, but invasive blood sampling is still the gold standard in current clinical practice. This work demonstrates the potential of visible-light spectroscopic optical coherence tomography (sOCT) for quantifying the [tHb] in human whole blood. To accurately quantify the [tHb] from the substantial optical attenuation by blood in the visible wavelength range, we used a combination of zero-delay acquisition and focus tracking that ensures optimal system sensitivity at any depth inside the sample. Subsequently, we developed an analysis model to adequately correct for the high scattering contribution by red blood cells to the sOCT signal. We validate our method and compare it to conventional sOCT (without focus tracking and zero-delay acquisition) through ex-vivo measurements on flowing human whole blood, with [tHb] values in the clinical range of 7–23 g/dL. For our method with optimized sensitivity, the measured and expected values correlate well (Pearson correlation coefficient = 0.89, p < 0.01), with a precision of 3.8 g/dL. This is a considerable improvement compared to conventional sOCT (Pearson correlation coefficient = 0.59, p = 0.16; precision of 9.1 g/dL).

. 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.

Significance: During the development and early testing phases of new photoacoustic (PA) breast imaging systems, several choices need to be made in aspects of system design and measurement sequences. Decision-making can be complex for state-of-the-art systems such as 3D hybrid photoacoustic-ultrasound (PA-US) breast imagers intended for multispectral quantitative imaging. These systems have a large set of design choices and system settings that affect imaging performance in different ways and often require trade-offs. Decisions have to be made carefully as they can strongly influence the imaging performance.Aim: A systematic approach to assess the influence of various choices on the imaging performance in carefully controlled laboratory situations is crucial before starting with human studies. Test objects and phantoms are used for first imaging studies, but most reported structures have a 2D geometry and are not suitable to assess all the image quality characteristics (IQCs) of 3D hybrid PA-US systems.Approach: Our work introduces a suite of five test objects designed for hybrid PA-US systems with a 3D detection aperture. We present the test object designs and production protocols and explain how they can be used to study various performance measures. To demonstrate the utility of the developed objects, measurements are made with an existing tomographic PA system.Results: Two test objects were developed for measurements of the US detectors' impulse responses and light distribution on the breast surface. Three others were developed to assess image quality and quantitative accuracy of the PA and US modes. Three of the five objects were imaged to demonstrate their use. Conclusions:The developed test objects allow one to study influences of various choices in design and system settings. With this, IQCs can be assessed as a function of measurement sequence settings for the PA and US modes in a controlled way. Systematic studies and measurements using these objects will help to optimize various system settings and measurement protocols in laboratory situations before embarking on human studies.

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