Optical Property Estimation in Multi-layered Tissues using Structured Interrogation Frequency-Domain Near-Infrared Spectroscopy

Frequency-domain near-infrared spectroscopy (FD-NIRS) emerges as a noninvasive optical sensing and imaging modality, offering quantitative insights into tissue chromophores like hemoglobin, lipids, and water. This work introduces structured interrogation (SI) as an innovative interference-based approach within FD-NIRS, specifically designed to effectively estimate optical properties in multilayered tissues and enhance sensitivity to deeper regions. Through analysis of simulation and experimental results utilizing tissue models and mimicking phantoms, we showcase SI's capability to estimate optical properties accurately, which is comparable to the conventional Multi-Distance approach. Additionally, the phase-only component of SI's signal proves essential in improving sensitivity to dynamic changes in optical properties, thereby enhancing the detection of dynamic fluctuations in chromophore concentrations. As we transition to extracting optical properties from a multi-layered tissue, we utilize the Cramér–Rao Lower Bound (CRLB) to optimize the selection of SI measurements. Integrating MD with SI, particularly utilizing SI with the optimized phases, yields a lower variance than MD with five source-detector separations (SDS). Consequently, this integration results in a more accurate and precise estimation of the second layer's optical properties compared to MD measurements with the same SDS with less than 20% error.