Review of machine learning for optical imaging of burn wound severity assessment.

Significance: Over the past decade, machine learning (ML) algorithms have rapidly become much more widespread for numerous biomedical applications, including the diagnosis and categorization of disease and injury. Aim: Here, we seek to characterize the recent growth of ML techniques that use imaging data to classify burn wound severity and report on the accuracies of different approaches. Approach: To this end, we present a comprehensive literature review of preclinical and clinical studies using ML techniques to classify the severity of burn wounds. Results: The majority of these reports used digital color photographs as input data to the classification algorithms, but recently there has been an increasing prevalence of the use of ML approaches using input data from more advanced optical imaging modalities (e.g., multispectral and hyperspectral imaging, optical coherence tomography), in addition to multimodal techniques. The classification accuracy of the different methods is reported; it typically ranges from ∼70% to 90% relative to the current gold standard of clinical judgment. Conclusions: The field would benefit from systematic analysis of the effects of different input data modalities, training/testing sets, and ML classifiers on the reported accuracy. Despite this current limitation, ML-based algorithms show significant promise for assisting in objectively classifying burn wound severity.

Motion-resistant three-wavelength spatial frequency domain imaging system with ambient light suppression using an 8-tap CMOS image sensor.

Significance: We present a motion-resistant three-wavelength spatial frequency domain imaging (SFDI) system with ambient light suppression using an 8-tap complementary metal-oxide semiconductor (CMOS) image sensor (CIS) developed at Shizuoka University. The system addresses limitations in conventional SFDI systems, enabling reliable measurements in challenging imaging scenarios that are closer to real-world conditions. Aim: Our study demonstrates a three-wavelength SFDI system based on an 8-tap CIS. We demonstrate and evaluate the system's capability of mitigating motion artifacts and ambient light bias through tissue phantom reflectance experiments and in vivo volar forearm experiments. Approach: We incorporated the Hilbert transform to reduce the required number of projected patterns per wavelength from three to two per spatial frequency. The 8-tap image sensor has eight charge storage diodes per pixel; therefore, simultaneous image acquisition of eight images based on multi-exposure is possible. Taking advantage of this feature, the sensor simultaneously acquires images for planar illumination, sinusoidal pattern projection at three wavelengths, and ambient light. The ambient light bias is eliminated by subtracting the ambient light image from the others. Motion artifacts are suppressed by reducing the exposure and projection time for each pattern while maintaining sufficient signal levels by repeating the exposure. The system is compared to a conventional SFDI system in tissue phantom experiments and then in vivo measurements of human volar forearms. Results: The 8-tap image sensor-based SFDI system achieved an acquisition rate of 9.4 frame sets per second, with three repeated exposures during each accumulation period. The diffuse reflectance maps of three different tissue phantoms using the conventional SFDI system and the 8-tap image sensor-based SFDI system showed good agreement except for high scattering phantoms. For the in vivo volar forearm measurements, our system successfully measured total hemoglobin concentration, tissue oxygen saturation, and reduced scattering coefficient maps of the subject during motion (16.5 cm/s) and under ambient light (28.9 lx), exhibiting fewer motion artifacts compared with the conventional SFDI. Conclusions: We demonstrated the potential for motion-resistant three-wavelength SFDI system with ambient light suppression using an 8-tap CIS.

Quantitative hemodynamic imaging: a method to correct the effects of optical properties on laser speckle imaging.

Significance: Studying cerebral hemodynamics may provide diagnostic information on neurological conditions. Wide-field imaging techniques, such as laser speckle imaging (LSI) and optical intrinsic signal imaging, are commonly used to study cerebral hemodynamics. However, they often do not account appropriately for the optical properties of the brain that can vary among subjects and even during a single measurement. Here, we describe the combination of LSI and spatial-frequency domain imaging (SFDI) into a wide-field quantitative hemodynamic imaging (QHI) system that can correct the effects of optical properties on LSI measurements to achieve a quantitative measurement of cerebral blood flow (CBF). Aim: We describe the design, fabrication, and testing of QHI. Approach: The QHI hardware combines LSI and SFDI with spatial and temporal synchronization. We characterized system sensitivity, accuracy, and precision with tissue-mimicking phantoms. With SFDI optical property measurements, we describe a method derived from dynamic light scattering to obtain absolute CBF values from LSI and SFDI measurements. We illustrate the potential benefits of absolute CBF measurements in resting-state and dynamic experiments. Results: QHI achieved a 50-Hz raw acquisition frame rate with a 10×10 mm field of view and flow sensitivity up to ∼4 mm/s. The extracted SFDI optical properties agreed well with a commercial system (R2≥0.98). The system showed high stability with low coefficients of variations over multiple sessions within the same day (<1%) and over multiple days (<4%). When optical properties were considered, the in-vivo hypercapnia gas challenge showed a slight difference in CBF (-1.5% to 0.5% difference). The in-vivo resting-state experiment showed a change in CBF ranking for nine out of 13 animals when the correction method was applied to LSI CBF measurements. Conclusions: We developed a wide-field QHI system to account for the confounding effects of optical properties on CBF LSI measurements using the information obtained from SFDI.

Current and Emerging Imaging Techniques for Neurofibromatosis Type 1-Associated Cutaneous Neurofibromas.

A consistent set of measurement techniques must be applied to reliably and reproducibly evaluate the efficacy of treatments for cutaneous neurofibromas (cNFs) in people with neurofibromatosis type 1 (NF1). cNFs are neurocutaneous tumors that are the most common tumor in people with NF1 and represent an area of unmet clinical need. This review presents the available data regarding approaches in use or development to identify, measure, and track cNFs, including calipers, digital imaging, and high-frequency ultrasound sonography. We also describe emerging technologies such as spatial frequency domain imaging and the application of imaging modalities such as optical coherence tomography that may enable the detection of early cNFs and prevention of tumor-associated morbidity.

Evaluation of the robustness of cerebral oximetry to variations in skin pigmentation using a tissue-simulating phantom.

Clinical studies have demonstrated that epidermal pigmentation level can affect cerebral oximetry measurements. To evaluate the robustness of these devices, we have developed a phantom-based test method that includes an epidermis-simulating layer with several melanin concentrations and a 3D-printed cerebrovascular module. Measurements were performed with neonatal, pediatric and adult sensors from two commercial oximeters, where neonatal probes had shorter source-detector separation distances. Referenced blood oxygenation levels ranged from 30 to 90%. Cerebral oximeter outputs exhibited a consistent decrease in saturation level with simulated melanin content; this effect was greatest at low saturation levels, producing a change of up to 15%. Dependence on pigmentation was strongest in a neonatal sensor, possibly due to its high reflectivity. Overall, our findings indicate that a modular channel-array phantom approach can provide a practical tool for assessing the impact of skin pigmentation on cerebral oximeter performance and that modifications to algorithms and/or instrumentation may be needed to mitigate pigmentation bias.

Quantitative measurement of optical properties and Hb concentration in a rodent model of inflammatory Meibomian gland dysfunction using spatial frequency domain imaging.

Herein, to investigate a new diagnostic method for Meibomian gland dysfunction (MGD) induced by eyelid inflammation, optical properties and deoxy-hemoglobin (Hb) concentrations in rodent eyelid tissues, including Meibomian glands(MGs), were measured using spatial frequency domain imaging (SFDI). Complete Freund's adjuvant solutions were injected into the eyelid margins of Sprague-Dawley rats to induce MGD. After three weeks, the optical properties and Hb of the MG and non-MG regions of the eyelids were measured ex-vivo using an SFDI system. The comparison of Hb showed that the MGD group exhibited significantly higher values than those of the control group in both regions. The optical properties at 730 and 850 nm for the MG regions in the MGD group were significantly different from those in the control group. In addition, the 630 nm absorption coefficients of both regions were significantly higher in the MGD group than in the control group. Thus, the SFDI technique can detect the increased Hb concentration and changes in the optical properties of the eyelids due to inflammatory MGD in a noncontact manner and has the potential to be used as a novel quantitative diagnostic method for the occurrence of MGD.

Quantifying the confounding effect of pigmentation on measured skin tissue optical properties: a comparison of colorimetry with spatial frequency domain imaging.

SIGNIFICANCE: Spatial frequency domain imaging (SFDI) is a wide-field diffuse optical imaging technique for separately quantifying tissue reduced scattering (µs ' ) and absorption (µa) coefficients at multiple wavelengths, providing wide potential utility for clinical applications such as burn wound characterization and cancer detection. However, measured µs ' and µa can be confounded by absorption from melanin in patients with highly pigmented skin. This issue arises because epidermal melanin is highly absorbing for visible wavelengths and standard homogeneous light-tissue interaction models do not properly account for this complexity. Tristimulus colorimetry (which quantifies pigmentation using the L * "lightness" parameter) can provide a point of comparison between µa, µs ' , and skin pigmentation. AIM: We systematically compare SFDI and colorimetry parameters to quantify confounding effects of pigmentation on measured skin µs ' and µa. We assess the correlation between SFDI and colorimetry parameters as a function of wavelength. APPROACH: µs ' and µa from the palm and ventral forearm were measured for 15 healthy subjects with a wide range of skin pigmentation levels (Fitzpatrick types I to VI) using a Reflect RS® (Modulim, Inc., Irvine, California) SFDI instrument (eight wavelengths, 471 to 851 nm). L * was measured using a Chroma Meter CR-400 (Konica Minolta Sensing, Inc., Tokyo). Linear correlation coefficients were calculated between L * and µs ' and between L * and µa at all wavelengths. RESULTS: For the ventral forearm, strong linear correlations between measured L * and µs ' values were observed at shorter wavelengths (R > 0.92 at ≤659 nm), where absorption from melanin confounded the measured µs ' . These correlations were weaker for the palm (R < 0.59 at ≤659 nm), which has less melanin than the forearm. Similar relationships were observed between L * and µa. CONCLUSIONS: We quantified the effects of epidermal melanin on skin µs ' and µa measured with SFDI. This information may help characterize and correct pigmentation-related inaccuracies in SFDI skin measurements.

Assessing multimodal optical imaging of perfusion in burn wounds.

A critical need exists for early, accurate diagnosis of burn wound severity to help identify the course of treatment and outcome of the wound. Laser speckle imaging (LSI) is a promising blood perfusion imaging approach, but it does not account for changes in tissue optical properties that can occur with burn wounds, which are highly dynamic environments. Here, we studied optical property dynamics following burn injury and debridement and the associated impact on interpretation of LSI measurements of skin perfusion. We used spatial frequency domain imaging (SFDI) measurements of tissue optical properties to study the impact of burn-induced changes in these properties on LSI measurements. An established preclinical porcine model of burn injury was used (n = 8). SFDI and LSI data were collected from burn wounds of varying severity. SFDI measurements demonstrate that optical properties change in response to burn injury in a porcine model. We then apply theoretical modeling to demonstrate that the measured range of optical property changes can affect the interpretation of LSI measurements of blood flow, but this effect is minimal for most of the measured data. Collectively, our results indicate that, even with a dynamic burn wound environment, blood-flow measurements with LSI can serve as an appropriate strategy for accurate assessment of burn severity.

A Quantitative Assessment of Wound Healing With Oxygenated Micro/Nanobubbles in a Preclinical Burn Model.

BACKGROUND: Burns are devastating injuries, carry significant morbidity, and require long-term treatment or multiple reconstructive procedures. Wound healing and secondary insults caused by burn wound conversion are amendable to therapeutic intervention, where ischemia has been cited as one of the major factors (Dermatol Surg. 2008;34:1159-1169). Halting injury progression in the zone of stasis is crucial as conversion creates increased burn surface area and depth, leading to local and systemic consequences (J Burns Wounds. 2006;5:e2). Oxygen-carrying micro/nanobubbles, MNB(O2), offer a novel technology that can be used to effectively deliver oxygen to burn wounds and potentially counteract burn wound ischemia. METHODS: Topical irrigation with MNB(O2) of full-thickness burn wounds on a rodent model (n = 3) was compared against saline-treated controls (n = 3). Tissue structure (reduced scattering coefficient, µs'), oxyhemoglobin concentration (cHbO2), and tissue perfusion were quantified over the course of 28 days through spatial frequency domain imaging and laser speckle imaging. Histological samples taken at the end of the experiment were examined for evidence of wound healing. RESULTS: Findings in this preliminary study showed hastened healing with significant differences in spatial frequency domain imaging-measured µs' during wound healing (days 11-28) in MNB(O2) group. The healing "tipping point" seemed to occur at days 9 to 11 with increased collagen organization and increased cHbO2 occurring around that period confirming the gross healing improvements observed. In addition, histological evidence indicated that only the MNB(O2) burns had reached the remodeling phase by the end of 28-day study period. CONCLUSIONS: These preliminary findings propose the potential of MNB(O2) as a topical method for improving burn wound healing.

Spatial frequency domain imager based on a compact multiaperture camera: testing and feasibility for noninvasive burn severity assessment.

SIGNIFICANCE: Spatial frequency domain imaging (SFDI) is a wide-field imaging technique that provides quantitative maps of tissue optical properties. We describe a compact SFDI imager that employs a multispectral compound-eye camera. This design enables simultaneous image acquisition at multiple wavelengths. Such a device has potential for application for quantitative evaluation of superficial tissues by nonspecialists in low-resource settings. AIM: The aim of this work was to develop a compact SFDI imager for widefield imaging of in-vivo tissue optical properties and verify its ability to measure optical properties of tissue-simulating phantoms and in a preclinical model of burn wounds. APPROACH: This compound-eye imager was constructed using a CMOS sensor subdivided into multiple regions, each having a bandpass filter and objective lens. The ability of the instrument to image optical properties was compared with (1) a commercial SFDI imager and (2) a laboratory-based system. Initial validation of ability to accurately characterize optical properties was performed using a tissue-simulating optical phantom. It was then applied to an established murine model of thermal contact burn severity. In-vivo measurements of the optical properties of rat skin were performed before and after the application of burns. Histology was used to verify burn severity. RESULTS: Measurements of the tissue-simulating phantom optical properties made using the compound-eye imager agree with measurements made using the two comparison SFDI devices. For the murine burn model, the burns showed a decrease in the reduced scattering coefficient at all measurement wavelengths compared with preburn measurements at the same locations. This is consistent with previously reported changes in scattering that occur in full-thickness burns. CONCLUSION: We demonstrate the potential for SFDI to be translated into compact form factor using a compound-eye camera that is capable of obtaining multiple wavelengths channels simultaneously.

Characterizing reduced scattering coefficient of normal human skin across different anatomic locations and Fitzpatrick skin types using spatial frequency domain imaging.

SIGNIFICANCE: Spatial frequency domain imaging (SFDI), a noncontact wide-field imaging technique using patterned illumination with multiple wavelengths, has been used to quantitatively measure structural and functional parameters of in vivo tissue. Using SFDI in a porcine model, we previously found that scattering changes in skin could potentially be used to noninvasively assess burn severity and monitor wound healing. Translating these findings to human subjects necessitates a better understanding of the variation in "baseline" human skin scattering properties across skin types and anatomical locations. AIM: Using SFDI, we aim to characterize the variation in the reduced scattering coefficient (µs') for skin across a range of pigmentation and anatomic sites (including common burn locations) for normal human subjects. These measurements are expected to characterize baseline human skin properties to inform our use of SFDI for clinical burn severity and wound healing assessments. APPROACH: SFDI was used to measure µs' in the visible- and near-infrared regime (471 to 851 nm) in 15 subjects at 10 anatomical locations. Subjects varied in age, gender, and Fitzpatrick skin type. RESULTS: For all anatomical locations, the coefficient of variation in measured µs' decreased with increasing wavelength. High intersubject variation in µs' at visible wavelengths coincided with large values of the melanin extinction coefficient at those wavelengths. At 851 nm, where intersubject variation in µs' was smallest for all anatomical locations and absorption from melanin is minimal, significant intrasubject differences in µs' were observed at the different anatomical locations. CONCLUSIONS: Our study is the first report of wide-field mapping of human skin scattering properties across multiple skin types and anatomical locations using SFDI. Measured µs' values varied notably between skin types at wavelengths where absorption from melanin was prominent. Additionally, µs' varied considerably across different anatomical locations at 851 nm, where the confounding effects from melanin absorption are minimized.

Spatial Frequency Domain Imaging (SFDI) of clinical burns: A case report.

While visual assessment by a clinician is the standard of care for burn severity evaluations, new technologies at various stages of development are attempting to add objectivity to this practice by quantifying burn severity. Assessment accuracy generally improves after the burn injury has progressed, but early assessments that correctly identify superficial partial and deep partial burns have the potential to lead to more prompt treatments and shorter recovery times. To date, Spatial Frequency Domain Imaging (SFDI) has only been used in animal models of burns, but has shown the potential to categorize burns accurately at earlier time points. Here we examine the potential for SFDI to assess burn severity in clinical patients. We also utilize Laser Speckle Imaging (LSI), an FDA cleared non-invasive imaging technology that typically measures blood perfusion in order to evaluate burns in clinical patients. We present a case series of two patients, both with partial thickness burns of varying severity. Partial thickness burns are often difficult for clinicians to categorize based on visual appearance alone. SFDI and LSI were both performed on each patient at approximately 24 and 72 h after their respective burn incidents. Each technique was able to render spatially resolved information that enabled improved assessment accuracy for each burn. This represents the first publication of SFDI applied to clinical burn patients after being successfully utilized in animal models, and highlights the potential for SFDI as a feasible tool for the timely categorization of burn severity.

Spatial frequency domain imaging: a quantitative, noninvasive tool for in vivo monitoring of burn wound and skin graft healing.

There is a need for noninvasive, quantitative methods to characterize wound healing in the context of longitudinal investigations related to regenerative medicine. Such tools have the potential to inform the assessment of wound status and healing progression and aid the development of new treatments. We employed spatial frequency domain imaging (SFDI) to characterize the changes in optical properties of tissue during wound healing progression in a porcine model of split-thickness skin grafts and also in a model of burn wound healing with no graft intervention. Changes in the reduced scattering coefficient measured using SFDI correlated with structural changes reported by histology of biopsies taken concurrently. SFDI was able to measure spatial inhomogeneity in the wounds and predicted heterogeneous healing. In addition, we were able to visualize differences in healing rate, depending on whether a wound was debrided and grafted, versus not debrided and left to heal without intervention apart from topical burn wound care. Changes in the concentration of oxy- and deoxyhemoglobin were also quantified, giving insight into hemodynamic changes during healing.

Special Section Guest Editorial: Special Section on Spatial Frequency Domain Imaging.

This guest editorial introduces the Special Section on Spatial Frequency Domain Imaging.

Hyperspectral imaging in the spatial frequency domain with a supercontinuum source.

We introduce a method for quantitative hyperspectral optical imaging in the spatial frequency domain (hs-SFDI) to image tissue absorption (µa) and reduced scattering (µs') parameters over a broad spectral range. The hs-SFDI utilizes principles of spatial scanning of the spectrally dispersed output of a supercontinuum laser that is sinusoidally projected onto the tissue using a digital micromirror device. A scientific complementary metal-oxide-semiconductor camera is used for capturing images that are demodulated and analyzed using SFDI computational models. The hs-SFDI performance is validated using tissue-simulating phantoms over a range of µa and µs' values. Quantitative hs-SFDI images are obtained from an ex-vivo beef sample to spatially resolve concentrations of oxy-, deoxy-, and met-hemoglobin, as well as water and fat fractions. Our results demonstrate that the hs-SFDI can quantitatively image tissue optical properties with 1000 spectral bins in the 580- to 950-nm range over a wide, scalable field of view. With an average accuracy of 6.7% and 12.3% in µa and µs', respectively, compared to conventional methods, hs-SFDI offers a promising approach for quantitative hyperspectral tissue optical imaging.

Burn wound classification model using spatial frequency-domain imaging and machine learning.

Accurate assessment of burn severity is critical for wound care and the course of treatment. Delays in classification translate to delays in burn management, increasing the risk of scarring and infection. To this end, numerous imaging techniques have been used to examine tissue properties to infer burn severity. Spatial frequency-domain imaging (SFDI) has also been used to characterize burns based on the relationships between histologic observations and changes in tissue properties. Recently, machine learning has been used to classify burns by combining optical features from multispectral or hyperspectral imaging. Rather than employ models of light propagation to deduce tissue optical properties, we investigated the feasibility of using SFDI reflectance data at multiple spatial frequencies, with a support vector machine (SVM) classifier, to predict severity in a porcine model of graded burns. Calibrated reflectance images were collected using SFDI at eight wavelengths (471 to 851 nm) and five spatial frequencies (0 to 0.2 mm - 1). Three models were built from subsets of this initial dataset. The first subset included data taken at all wavelengths with the planar (0 mm - 1) spatial frequency, the second comprised data at all wavelengths and spatial frequencies, and the third used all collected data at values relative to unburned tissue. These data subsets were used to train and test cubic SVM models, and compared against burn status 28 days after injury. Model accuracy was established through leave-one-out cross-validation testing. The model based on images obtained at all wavelengths and spatial frequencies predicted burn severity at 24 h with 92.5% accuracy. The model composed of all values relative to unburned skin was 94.4% accurate. By comparison, the model that employed only planar illumination was 88.8% accurate. This investigation suggests that the combination of SFDI with machine learning has potential for accurately predicting burn severity.

Impact of hemoglobin breakdown products in the spectral analysis of burn wounds using spatial frequency domain spectroscopy.

Burn wounds and wound healing invoke several biological processes that may complicate the interpretation of spectral imaging data. Through analysis of spatial frequency domain spectroscopy data (450 to 1000 nm) obtained from longitudinal investigations using a graded porcine burn wound healing model, we have identified features in the absorption spectrum that appear to suggest the presence of hemoglobin breakdown products, e.g., methemoglobin. Our results show that the calculated concentrations of methemoglobin directly correlate with burn severity, 24 h after the injury. In addition, tissue parameters such as oxygenation (StO2) and water fraction may be underestimated by 20% and 78%, respectively, if methemoglobin is not included in the spectral analysis.

Evaluating clinical observation versus Spatial Frequency Domain Imaging (SFDI), Laser Speckle Imaging (LSI) and thermal imaging for the assessment of burn depth.

While clinical examination is needed for burn severity diagnosis, several emerging technologies aim to quantify this process for added objectivity. Accurate assessments become easier after burn progression, but earlier assessments of partial thickness burn depth could lead to earlier excision and grafting and subsequent improved healing times, reduced rates of scarring/infection, and shorter hospital stays. Spatial Frequency Domain Imaging (SFDI), Laser Speckle Imaging (LSI) and thermal imaging are three non-invasive imaging modalities that have some diagnostic ability for noninvasive assessment of burn severity, but have not been compared in a controlled experiment. Here we tested the ability of these imaging techniques to assess the severity of histologically confirmed graded burns in a swine model. Controlled, graded burn wounds, 3cm in diameter were created on the dorsum of Yorkshire pigs (n=3, 45-55kg) using a custom-made burn tool that ensures consistent pressure has been employed by various burn research groups. For each pig, a total of 16 burn wounds were created on the dorsal side. Biopsies were taken for histological analysis to verify the severity of the burn. Clinical analysis, SFDI, LSI and thermal imaging were performed at 24 and 72h after burn to assess the accuracy of each imaging technique. In terms of diagnostic accuracy, using histology as a reference, SFDI (85%) and clinical analysis (83%) performed significantly better that LSI (75%) and thermography (73%) 24h after the burn. There was no statistically significant improvement from 24 to 72h across the different imaging modalities. These data indicate that these imaging modalities, and specifically SFDI, can be added to the burn clinicians' toolbox to aid in early assessment of burn severity.

Characterisation of impaired wound healing in a preclinical model of induced diabetes using wide-field imaging and conventional immunohistochemistry assays.

Major complications of diabetes lead to inflammation and oxidative stress, delayed wound healing, and persistent ulcers. The high morbidity, mortality rate, and associated costs of management suggest a need for non-invasive methods that will enable the early detection of at-risk tissue. We have compared the wound-healing process that occurs in streptozotocin (STZ)-treated diabetic rats with non-diabetic controls using contrast changes in colour photography (ie, Weber Contrast) and the non-invasive optical method Spatial Frequency Domain Imaging (SFDI). This technology can be used to quantify the structural and metabolic properties of in-vivo tissue by measuring oxyhaemoglobin concentration (HbO2 ), deoxyhaemoglobin concentration (Hb), and oxygen saturation (StO2 ) within the visible boundaries of each wound. We also evaluated the changes in inducible nitric oxide synthase (iNOS) in the dermis using immunohistochemistry. Contrast changes in colour photographs showed that diabetic rats healed at a slower rate in comparison with non-diabetic control, with the most significant change occurring at 7 days after the punch biopsy. We observed lower HbO2 , StO2 , and elevated Hb concentrations in the diabetic wounds. The iNOS level was higher in the dermis of the diabetic rats compared with the non-diabetic rats. Our results showed that, in diabetes, there is higher level of iNOS that can lead to an observed reduction in HbO2 levels. iNOS is linked to increased inflammation, leading to prolonged wound healing. Our results suggest that SFDI has potential as a non-invasive assessment of markers of wound-healing impairment.

Recovery of layered tissue optical properties from spatial frequency-domain spectroscopy and a deterministic radiative transport solver.

We present a method to recover absorption and reduced scattering spectra for each layer of a two-layer turbid media from spatial frequency-domain spectroscopy data. We focus on systems in which the thickness of the top layer is less than the transport mean free path ( 0.1 - 0.8l * ) . We utilize an analytic forward solver, based upon the N'th-order spherical harmonic expansion with Fourier decomposition ( SHEFN ) method in conjunction with a multistage inverse solver. We test our method with data obtained using spatial frequency-domain spectroscopy with 32 evenly spaced wavelengths within λ = 450 to 1000 nm on six-layered tissue phantoms with distinct optical properties. We demonstrate that this approach can recover absorption and reduced scattering coefficient spectra for both layers with accuracy comparable with current Monte Carlo methods but with lower computational cost and potential flexibility to easily handle variations in parameters such as the scattering phase function or material refractive index. To our knowledge, this approach utilizes the most accurate deterministic forward solver used in such problems and can successfully recover properties from a two-layer media with superficial layer thicknesses.