In vivo optimization of the experimental conditions for the non-invasive optical assessment of breast density.

In this study, time domain diffuse optical spectroscopy is performed in the range 600-1100 nm on 11 healthy volunteers with a portable system for the quantitative characterization of breast tissue in terms of optical properties and optically-derived blood parameters, tissue constituent concentrations, and scattering parameters. A measurement protocol involving different geometries (reflectance and transmittance), subject's positions (sitting and lying down), probing locations (outer, lower, and inner breast quadrants), and source-detector distances (2 and 3 cm) allowed us to investigate the effect of tissue heterogeneity and different measurement configurations on the results with the aim of identifying the best experimental conditions for the estimate of breast density (i.e., amount of fibro-glandular tissue in the breast) as a strong independent risk factor for breast cancer. Transmittance results, that in previous studies correlated strongly with mammographic density, are used as a reference for the initial test of the simpler and more comfortable reflectance measurement configuration. The higher source-detector distance, which probes deeper tissue, retrieves optical outcomes in agreement with higher average density tissue. Similarly, results on the outer quadrants indicate higher density than internal quadrants. These findings are coherent with breast anatomy since the concentration of dense fibro-glandular stroma is higher in deep tissue and towards the external portion of the breast, where the mammary gland is located. The dataset generated with this laboratory campaign is used to device an optimal measurement protocol for a future clinical trial, where optical results will be correlated with conventional mammographic density, allowing us to identify a subset of wavelengths and measurement configurations for an effective estimate of breast density. The final objective is the design of a simplified, compact and cost-effective optical device for a non-invasive, routine assessment of density-associated breast cancer risk.