Tissue Mimicking Phantoms for Biomedical Optics: A Systematic Review of Inverse Adding–Doubling Characterization and Clinical Relevance

Abstract

Tissue mimicking phantoms are essential for calibration and clinical translation of biophotonic techniques. Although the inverse adding–doubling (IAD) method is widely regarded as a reference standard for determining absorption and reduced scattering coefficients, significant inter-laboratory variability persists due to differences in integrating-sphere configurations, loss-compensation strategies, and model assumptions. This PRISMA-guided review (2015–2025) analyzes 10 experimental studies and proposes a unified comparison framework based on scattering power-law parameters $\left(a,b\right)$ to relate phantom fabrication to clinically relevant optical targets. Nonlinear regression of continuous ${\mu }_s^{\prime }\left(\lambda \right)$ spectra shows that selected PVC plastisol formulations reproduce dermal-like scattering slopes and that the power-law model provides consistent spectral descriptions (${\overline{R}}^2=0.98$). By linking measurement methodology, spectral fitting, and mapping in $\left(a,b\right)$ space, this work provides a practical framework to interpret variability and guide development of tissue-equivalent phantoms for reliable calibration of biophotonic devices.