Noninvasive Temperature Measurements in Tissue-Simulating Phantoms Using a Solid-State Near-Infrared Sensor.

The monitoring of body temperature is a recent addition to the plethora of parameters provided by wellness and fitness wearable devices. Current wearable temperature measurements are made at the skin surface, a measurement that is impacted by the ambient environment of the individual. The use of near-infrared spectroscopy provides the potential for a measurement below the epidermal layer of skin, thereby having the potential advantage of being more reflective of physiological conditions. The feasibility of noninvasive temperature measurements is demonstrated by using an in vitro model designed to mimic the near-infrared spectra of skin. A miniaturizable solid-state laser-diode-based near-infrared spectrometer was used to collect diffuse reflectance spectra for a set of seven tissue phantoms composed of different amounts of water, gelatin, and Intralipid. Temperatures were varied between 20-24 °C while collecting these spectra. Two types of partial least squares (PLS) calibration models were developed to evaluate the analytical utility of this approach. In both cases, the collected spectra were used without pre-processing and the number of latent variables was the only optimized parameter. The first approach involved splitting the whole dataset into separate calibration and prediction subsets for which a single optimized PLS model was developed. For this first case, the coefficient of determination (R2) is 0.95 and the standard error of prediction (SEP) is 0.22 °C for temperature predictions. The second strategy used a leave-one-phantom-out methodology that resulted in seven PLS models, each predicting the temperatures for all spectra in the held-out phantom. For this set of phantom-specific predicted temperatures, R2 and SEP values range from 0.67-0.99 and 0.19-0.65 °C, respectively. The stability and reproducibility of the sample-to-spectrometer interface are identified as major sources of spectral variance within and between phantoms. Overall, results from this in vitro study justify the development of future in vivo measurement technologies for applications as wearables for continuous, real-time monitoring of body temperature for both healthy and ill individuals.

Early visualization of skin burn severity using a topically applied dye-loaded liquid bandage.

Skin burns are a significant source of injury in both military and civilian sectors. They are especially problematic in low resource environments where non-fatal injuries can lead to high morbidity rates, prolonged hospitalization, and disability. These multifaceted wounds can be highly complex and must be quickly diagnosed and treated to achieve optimal outcomes. When the appropriate resources are available, the current gold standard for assessing skin burns is through tissue punch biopsies followed by histological analysis. Apart from being invasive, costly, and time-consuming, this method can suffer from heterogeneous sampling errors when interrogating large burn areas. Here we present a practical method for the early visualization of skin burn severity using a topically applied fluorescein-loaded liquid bandage and an unmodified commercial digital camera. Quantitative linear mixed effects models of color images from a four day porcine burn study demonstrate that colorimetric changes within the HSB colorspace can be used to estimate burn depth severity immediately after burning. The finding was verified using fluorescence imaging, tissue cross-sectioning, and histopathology. This low-cost, rapid, and non-invasive color analysis approach demonstrates the potential of dye-loaded liquid bandages as a method for skin burn assessment in settings such as emergency medicine triage and low resource environments.

Development of a modular fluorescence overlay tissue imaging system for wide-field intraoperative surgical guidance.

Fluorescence imaging is a well-established optical modality that has been used to localize and track fluorophores in vivo and has demonstrated great potential for surgical guidance. Despite the variety of fluorophores currently being researched, many existing intraoperative fluorescence imaging systems are specifically designed for a limited number of applications. We present a modular wide-field fluorescence overlay tissue imaging system for intraoperative surgical guidance that is comprised of commercially available standardized components. Its modular layout allows for the accommodation of a broad range of fluorophores, fields of view (FOV), and spatial resolutions while maintaining an integrated portable design for intraoperative use. Measurements are automatic and feature a real-time projection overlay technique that intuitively displays fluorescence maps directly onto a [Formula: see text] FOV from a working distance of 35 cm. At a 20-ms exposure time, [Formula: see text] samples of indocyanine green could be measured with high signal-to-noise ratio and was later tested in an in vivo mouse model before finally being demonstrated for intraoperative autofluorescence imaging of human soft tissue sarcoma margins. The system's modular design and ability to enable naked-eye visualization of wide-field fluorescence allow for the flexibility to adapt to numerous clinical applications and can potentially extend the adoption of fluorescence imaging for intraoperative use.

Near-infrared autofluorescence spectroscopy of in vivo soft tissue sarcomas.

Soft tissue sarcomas (STS) are a rare and heterogeneous group of malignant tumors that are often treated via surgical resection. Inadequate resection can lead to local recurrence and decreased survival rates. In this study, we investigate the hypothesis that near-infrared (NIR) autofluorescence can be utilized for tumor margin analysis by differentiating STS from the surrounding normal tissue. Intraoperative in vivo measurements were acquired from 30 patients undergoing STS resection and were characterized to differentiate between normal tissue and STS. Overall, normal muscle and fat were observed to have the highest and lowest autofluorescence intensities, respectively, with STS falling in between. With the exclusion of well-differentiated liposarcomas, the algorithm's accuracy for classifying muscle, fat, and STS was 93%, 92%, and 88%, respectively. These findings suggest that NIR autofluorescence spectroscopy has potential as a rapid and nondestructive surgical guidance tool that can inform surgeons of suspicious margins in need of immediate re-excision.

Acute discrimination between superficial-partial and deep-partial thickness burns in a preclinical model with laser speckle imaging.

A critical need exists for a robust method that enables early discrimination between superficial-partial and deep-partial thickness burn wounds. In this study, we report on the use of laser speckle imaging (LSI), a simple, non-invasive, optical imaging modality, to measure acute blood flow dynamics in a preclinical burn model. We used a heated brass comb to induce burns of varying severity to nine rats and collected raw speckle reflectance images over the course of three hours after burn. We induced a total of 12 superficial-partial and 18 deep-partial thickness burn wounds. At 3h after burn we observed a 28% and 44% decrease in measured blood flow for superficial-partial and deep-partial thickness burns, respectively, and that these reductions were significantly different (p=0.00007). This preliminary data suggests the potential role of LSI in the clinical management of burn wounds.

Spatial frequency domain imaging of burn wounds in a preclinical model of graded burn severity.

Frequent monitoring of early-stage burns is necessary for deciding optimal treatment and management. Both superficial and full thickness burns are relatively easy to diagnose based on clinical observation. In between these two extremes are superficial-partial thickness and deep-partial thickness burns. These burns, while visually similar, differ dramatically in terms of clinical treatment and are known to progress in severity over time. The objective of this study was to determine the potential of spatial frequency domain imaging (SFDI) for noninvasively mapping quantitative changes in chromophore and optical properties that may be an indicative of burn wound severity. A controlled protocol of graded burn severity was developed and applied to 17 rats. SFDI data was acquired at multiple near-infrared wavelengths over a course of 3 h. Burn severity was verified using hematoxylin and eosin histology. From this study, we found that changes in water concentration (edema), deoxygenated hemoglobin concentration, and optical scattering (tissue denaturation) to be statistically significant at differentiating superficial partial-thickness burns from deep-partial thickness burns.

In vivo spatial frequency domain spectroscopy of two layer media.

Monitoring of tissue blood volume and local oxygen saturation can inform the assessment of tissue health, healing, and dysfunction. These quantities can be estimated from the contribution of oxyhemoglobin and deoxyhemoglobin to the absorption spectrum of the dermis. However, estimation of blood related absorption in skin can be confounded by the strong absorption of melanin in the epidermis and epidermal thickness and pigmentation varies with anatomic location, race, gender, and degree of disease progression. Therefore, a method is desired that decouples the effect of melanin absorption in the epidermis from blood absorption in the dermis for a large range of skin types and thicknesses. A previously developed inverse method based on a neural network forward model was applied to simulated spatial frequency domain reflectance of skin for multiple wavelengths in the near infrared. It is demonstrated that the optical thickness of the epidermis and absorption and reduced scattering coefficients of the dermis can be determined independently and with minimal coupling. Then, the same inverse method was applied to reflectance measurements from a tissue simulating phantom and in vivo human skin. Oxygen saturation and total hemoglobin concentrations were estimated from the volar forearms of weakly and strongly pigmented subjects using a standard homogeneous model and the present two layer model.

Effects of motion on optical properties in the spatial frequency domain.

Spatial frequency domain imaging (SFDI) is a noncontact and wide-field optical imaging technology currently being used to study the optical properties and chromophore concentrations of in vivo skin including skin lesions of various types. Part of the challenge of developing a clinically deployable SFDI system is related to the development of effective motion compensation strategies, which in turn, is critical for recording high fidelity optical properties. Here we present a two-part strategy for SFDI motion correction. After verifying the effectiveness of the motion correction algorithm on tissue-simulating phantoms, a set of skin-imaging data was collected in order to test the performance of the correction technique under real clinical conditions. Optical properties were obtained with and without the use of the motion correction technique. The results indicate that the algorithm presented here can be used to render optical properties in moving skin surfaces with fidelities within 1.5% of an ideal stationary case and with up to 92.63% less variance. Systematic characterization of the impact of motion variables on clinical SFDI measurements reveals that until SFDI instrumentation is developed to the point of instantaneous imaging, motion compensation is necessary for the accurate localization and quantification of heterogeneities in a clinical setting.