Editorial: Diffusive optics for medical imaging

Introduction

With continued advances in biomedical optics, diffusive optical techniques are becoming increasingly important for non-invasive medical imaging (Zhou et al., 2023; Wheelock et al., 2019; Re et al., 2025). These methods exploit near-infrared light propagation in highly scattering biological tissues (Jacques, 2013; Durduran et al., 2010; Durduran and Yodh, 2014). In such media, photons undergo multiple scattering events and propagate diffusively through tissue (Jacques, 2013; Arridge, 1999). This behavior enables quantitative measurements of tissue absorption and scattering related to physiological composition, structure and function (Fantini and Sassaroli, 2012; Boas and Franceschini, 2009).

Over the past decades, techniques including diffuse optical tomography, spatial frequency-domain imaging, time-resolved spectroscopy, and diffuse correlation spectroscopy (DCS) have advanced rapidly (Wang et al., 2024; Re et al., 2025; Guan et al., 2025). These approaches enable measurement of chromophore concentrations such as oxygenated hemoglobin, water, and lipids, as well as physiological parameters including blood flow dynamics (Re et al., 2025; Durduran et al., 2010; Fantini and Sassaroli, 2012; Carp et al., 2017; Blaney et al., 2022). Such measurements provide insight into tissue oxygenation, blood volume, blood flow, metabolism, and structural organization.

Diffusive optical imaging is attractive because it can provide functional and molecular information using safe and portable instrumentation (Wheelock et al., 2019; Wang et al., 2024; Pinti et al., 2020; Althobaiti and Al-Naib, 2020). These capabilities support biomedical applications including brain monitoring, breast imaging, wound assessment, and metabolic studies (Wheelock et al., 2019; Fantini and Sassaroli, 2012; Nouvong et al., 2009; van Beekvelt et al., 2001; Ayaz et al., 2022).

Despite these advances, important challenges remain. Light scattering complicates image reconstruction and leads to ill-posed inverse problems (Jacques, 2013; Arridge, 1999; Gibson et al., 2005). Spatial resolution and penetration depth also remain limited in highly scattering tissues (Durduran et al., 2010; Ntziachristos, 2010).

This Research Topic was organized to highlight recent advances addressing these challenges. The collection focuses on methodological developments that improve quantitative accuracy, depth sensitivity, and clinical applicability. Contributions include advances in structured illumination, time-resolved and frequency-domain techniques, and optical spectroscopy methods. These approaches enable improved measurement of physiological parameters such as tissue oxygenation, hydration, and metabolic activity. Together, the collected works illustrate the continued evolution of diffusive optics toward clinically relevant imaging solutions.

Summary of the papers

In their contribution, Livecchi et al. demonstrate the use of LED-based spatial frequency-domain imaging (SFDI) in the shortwave infrared (SWIR) spectral region for non-invasive assessment of tissue hydration. SFDI is a powerful yet sometimes underrepresented technique for directly quantifying tissue optical properties (Cuccia et al., 2009). By projecting sinusoidal illumination patterns at multiple spatial frequencies and phase shifts, the method separates absorption and reduced scattering coefficients that are otherwise convolved in conventional diffuse reflectance measurements. In this work, the authors employ SFDI in the SWIR spectral range, where absorption features of water and lipids are more pronounced and increasingly accessible due to recent advances in SWIR camera technology (Zhao et al., 2020). Through experiments using tissue phantoms, ex vivo porcine skin undergoing desiccation, and in vivo human measurements during exercise, the study demonstrates that reduced scattering is highly sensitive to hydration changes. Such measurements may enable non-invasive monitoring of physiological processes including wound healing, edema formation, and skin hydration dynamics associated with exercise or thermoregulation (Zhao et al., 2020; Sordillo et al., 2014). These results highlight the potential of SWIR-SFDI as a quantitative tool for monitoring physiological variations in tissue water content.

In another contribution, Maffeis et al. investigate non-invasive lung monitoring using time-domain diffuse optical spectroscopy (TD-DOS). TD-DOS launches ultrashort light pulses into tissue and records photon arrival times after propagation (Re et al., 2025). These time-of-flight measurements provide depth-sensitive information about tissue absorption and scattering properties. This depth sensitivity is a key strength of the technique. It enables probing of deeper structures than many other diffuse optical methods (Diop et al., 2013). Using Monte Carlo simulations and in vivo measurements, the authors study photon propagation through the chest wall to identify optimal probing conditions, an essential step for a future goal of determining lung composition in terms of tissues constituents. Their results show that wavelength selection and measurement geometry influence sensitivity to lung expansion during breathing. Current lung imaging methods often rely on ionizing radiation or invasive procedures (Gao et al., 2025). Optical approaches may provide safer and more accessible monitoring. The work highlights both the promise and the challenges of applying diffuse optics to deep organs. The approach may support future non-invasive monitoring of lung function and pulmonary physiology.

In another study, Parham et al. investigate diffuse reflectance spectroscopy for estimating retinal tissue oxygen saturation. Diffuse reflectance spectroscopy measures tissue absorption spectra related to hemoglobin oxygenation (Durduran et al., 2010). However, scattering variations, strong melanin absorption in the retinal pigment epithelium, and tissue geometry complicate interpretation of these spectra (Jacques, 2013; Hammer et al., 1995). To address this challenge, the authors apply principal component analysis (PCA) to extract relevant spectral features (Wold et al., 1987). PCA identifies patterns in complex datasets and isolates spectral components associated with oxygenation. The method is evaluated using simulated datasets and retinal tissue phantoms. Results show that the PCA-based approach can estimate oxygen saturation despite overlapping optical effects. Improved retinal oxygen measurements could support earlier detection and monitoring of diseases affecting ocular and systemic health (Re et al., 2025; Kashani et al., 2017). The study highlights how data-driven analysis can improve quantitative parameter extraction in diffuse optical measurements.

In another study, Herzog and Sick investigate fluorescence imaging of the anterior segment of the eye. The technique uses ultraviolet excitation to induce fluorescence from endogenous biomolecules in ocular tissues (Betz et al., 1999; Matsumoto et al., 2019). The authors implement a two-color imaging system to distinguish spectral signals from different molecular sources. This approach enables detection of biochemical changes that may not appear in conventional reflectance-based imaging methods. Such molecular sensitivity may improve early detection of infections and other ocular diseases affecting the cornea (Georgakoudi et al., 2002). Experiments using ex vivo porcine eyes demonstrate visualization of fluorescence signals from tissue structures and bacterial contamination. Although not strictly a diffuse optical technique, the work illustrates how optical spectroscopy and imaging can complement diffusive optical methods. These complementary approaches provide molecular contrast that may improve diagnostic capabilities in biomedical optics.

Conclusion

The contributions in this Research Topic highlight advances in instrumentation, modeling, and data analysis for diffusive optical measurements. The presented studies demonstrate applications including tissue hydration monitoring, lung assessment, retinal oxygenation measurement, and fluorescence-based ocular diagnostics. Together, these works illustrate how optical measurements can reveal functional and biochemical changes within biological tissues.

Future progress will depend on advances in optical instrumentation, computational modeling, and clinical translation. These developments may enable diffusive optical technologies to become routine tools for medical diagnostics and physiological monitoring. Ultimately, such technologies may help improve patient outcomes, accessibility, and contribute to broader improvements in human health and wellbeing.

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Footnotes

Edited and reviewed by: Stefan Carp, Harvard Medical School, United States