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

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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow> <mml:mfenced><mml:mrow><mml:mi>a</mml:mi> <mml:mo>,</mml:mo> <mml:mi>b</mml:mi></mml:mrow> </mml:mfenced> </mml:mrow> <mml:annotation>$$ \left(a,b\right) $$</mml:annotation></mml:semantics> </mml:math> to relate phantom fabrication to clinically relevant optical targets. Nonlinear regression of continuous <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow><mml:msubsup><mml:mi>μ</mml:mi> <mml:mi>s</mml:mi> <mml:mo>'</mml:mo></mml:msubsup> <mml:mfenced><mml:mi>λ</mml:mi></mml:mfenced> </mml:mrow> <mml:annotation>$$ {\mu}_s^{\prime}\left(\lambda \right) $$</mml:annotation></mml:semantics> </mml:math> spectra shows that selected PVC plastisol formulations reproduce dermal-like scattering slopes and that the power-law model provides consistent spectral descriptions ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow> <mml:msup><mml:mover><mml:mi>R</mml:mi> <mml:mo>¯</mml:mo></mml:mover> <mml:mn>2</mml:mn></mml:msup> <mml:mo>=</mml:mo> <mml:mn>0.98</mml:mn></mml:mrow> <mml:annotation>$$ {\overline{R}}^2=0.98 $$</mml:annotation></mml:semantics> </mml:math> ). By linking measurement methodology, spectral fitting, and mapping in <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:semantics> <mml:mrow> <mml:mfenced><mml:mrow><mml:mi>a</mml:mi> <mml:mo>,</mml:mo> <mml:mi>b</mml:mi></mml:mrow> </mml:mfenced> </mml:mrow> <mml:annotation>$$ \left(a,b\right) $$</mml:annotation></mml:semantics> </mml:math> space, this work provides a practical framework to interpret variability and guide development of tissue-equivalent phantoms for reliable calibration of biophotonic devices.