SignificancePhotoacoustic imaging (PAI) promises to measure spatially resolved blood oxygen saturation but suffers from a lack of accurate and robust spectral unmixing methods to deliver on this promise. Accurate blood oxygenation estimation could have important clinical applications from cancer detection to quantifying inflammation.AimWe address the inflexibility of existing data-driven methods for estimating blood oxygenation in PAI by introducing a recurrent neural network architecture.ApproachWe created 25 simulated training dataset variations to assess neural network performance. We used a long short-term memory network to implement a wavelength-flexible network architecture and proposed the Jensen–Shannon divergence to predict the most suitable training dataset.ResultsThe network architecture can flexibly handle the input wavelengths and outperforms linear unmixing and the previously proposed learned spectral decoloring method. Small changes in the training data significantly affect the accuracy of our method, but we find that the Jensen–Shannon divergence correlates with the estimation error and is thus suitable for predicting the most appropriate training datasets for any given application.ConclusionsA flexible data-driven network architecture combined with the Jensen–Shannon divergence to predict the best training data set provides a promising direction that might enable robust data-driven photoacoustic oximetry for clinical use cases.
Longitudinal characterisation of the tumour vascular response to radiotherapy is essential for understanding the role of oxygenation and microvascular disruption in response to therapy. Using multi-scale in vivo photoacoustic imaging (PAI), we assessed early response to two hypofractionated radiotherapy schemes in two human breast cancer models. Mesoscopic and multispectral tomographic photoacoustic imaging was performed 24h pre-, post-radiotherapy, and at endpoint. PAI biomarkers were validated ex vivo with multiplex immunofluorescence using a 20-plex panel developed specifically for vascular response assessment at sub-cellular resolution. PAI captured radiotherapy response, revealing the differential effect between radiotherapy schemes and models with different hypoxia phenotypes.
SignificancePhotoacoustic imaging (PAI) provides contrast based on the concentration of optical absorbers in tissue, enabling the assessment of functional physiological parameters such as blood oxygen saturation (sO2). Recent evidence suggests that variation in melanin levels in the epidermis leads to measurement biases in optical technologies, which could potentially limit the application of these biomarkers in diverse populations.AimTo examine the effects of skin melanin pigmentation on PAI and oximetry.ApproachWe evaluated the effects of skin tone in PAI using a computational skin model, two-layer melanin-containing tissue-mimicking phantoms, and mice of a consistent genetic background with varying pigmentations. The computational skin model was validated by simulating the diffuse reflectance spectrum using the adding-doubling method, allowing us to assign our simulation parameters to approximate Fitzpatrick skin types. Monte Carlo simulations and acoustic simulations were run to obtain idealized photoacoustic images of our skin model. Photoacoustic images of the phantoms and mice were acquired using a commercial instrument. Reconstructed images were processed with linear spectral unmixing to estimate blood oxygenation. Linear unmixing results were compared with a learned unmixing approach based on gradient-boosted regression.ResultsOur computational skin model was consistent with representative literature for in vivo skin reflectance measurements. We observed consistent spectral coloring effects across all model systems, with an overestimation of sO2 and more image artifacts observed with increasing melanin concentration. The learned unmixing approach reduced the measurement bias, but predictions made at lower blood sO2 still suffered from a skin tone-dependent effect.ConclusionPAI demonstrates measurement bias, including an overestimation of blood sO2, in higher Fitzpatrick skin types. Future research should aim to characterize this effect in humans to ensure equitable application of the technology.
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