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Recently, Eil et al. showed that tumors with necrotic cores had elevated K+ concentrations due to the release of K+ by necrosis, which acts to suppress T-cell function by high extracellular K+ concentration. These findings demonstrate the importance of developing a tool for imaging K+ distributions. Here, we demonstrate K+ nanosensor-enabled photoacoustic imaging for measuring K+ levels in vivo. The nanosensor is an in-house synthesized optical contrast agent that is sensitive to K+ levels within biological ranges. The use of this K+ nanosensor, combined with multi-spectral photoacoustic imaging, allowed measurement of K+ levels in vivo.

In vivo photoacoustic (PA) imaging with high spatial resolution and depth penetration has remained a challenge due to the high background signal from chromophores in biological tissue. In this study, we introduce a novel imaging technique called triplet differential (TD) imaging which allows for the substantial reduction of background signals from tissue. TD imaging uses the ability of molecules to enter a triplet state via intersystem crossing from an excited singlet state. Molecules in the triplet state exhibit a spectral shift in their optical absorption spectra, creating two separate absorption peaks for each molecule’s singlet and triplet states. Since the PA signal is proportional to optical absorption, a differential signal can be obtained by comparing the PA signal for molecules raised to the triplet state to those in the singlet state. We worked with methylene blue conjugated polyacrylamide nanoparticles with a polyethylene glycol dimethacrylate cross-linker (MBNP) which has a singlet peak absorption at 660nm and triplet peak absorption at 840nm. Since only certain molecules such as methylene blue can enter the triplet state efficiently, the difference in the PA signal before and after excitation of the MBNP to the triplet state is largely independent of the background noise and mainly contributed by the MBNP in the triplet state. Preliminary results have shown that up to an 8-fold increase in the PA signal of the MBNP in the triplet state can be achieved.

Ultrasound Computer Tomography (USCT) is a promising new imaging system for breast cancer diagnosis. An essential step before further processing is to remove the water background from the reconstructed images. In this paper we present a fully-automated image segmentation method based on three-dimensional active contours. The active contour method is extended by applying gradient vector flow and encoding the USCT aperture characteristics as additional weighting terms. A surface detection algorithm based on a ray model is developed to initialize the active contour, which is iteratively deformed to capture the breast outline in USCT reflection images. The evaluation with synthetic data showed that the method is able to cope with noisy images, and is not influenced by the position of the breast and the presence of scattering objects within the breast. The proposed method was applied to 14 in-vivo images resulting in an average surface deviation from a manual segmentation of 2.7 mm. We conclude that automated segmentation of USCT reflection images is feasible and produces results comparable to a manual segmentation. By applying the proposed method, reproducible segmentation results can be obtained without manual interaction by an expert.

This study examines the sensitivity and specificity of backscattered ultrasound (US) and backscattering photoacoustic (PA) signals for bone composition variation assessment. The conventional approach in the evaluation of bone health relies on measurement of bone mineral density (BMD). Although, a crucial and probably the most important parameter, BMD is not the only factor defining the bone health. New trends in osteoporosis research, also pursue the changes in collagen content and cross-links with bone diseases and aging. Therefore, any non-invasive method that can assess any of these parameters can improve the diagnostic tools and also can help with the biomedical studies on the diseases themselves. Our previous studies show that both US and PA are responsive to changes in the BMD, PA is, in addition, sensitive to changes in the collagen content of the bone. Measurements were performed on bone samples before and after mild demineralization and decollagenization at the exact same points. Results show that combining both modalities can enhance the sensitivity and specificity of diagnostic tool.