We present the creation of wearable devices that measure transcutaneous partial oxygen or carbon dioxide pressure (tcpO2 or tcpCO2) non-invasively. The devices are highly sensitive to the physiological pO2/pCO2, and detects changes in luminescence (lifetime or ratiometric brightness) of mellaporphyrins or HPTS dye molecules embedded within breathable, hydrophobic films. Our first in human measurements reveal the devices are able to detect quick and subtle changes in tcpO2 due to local and systemic changes in blood flow of skin or deeper muscle tissue. Models to extract tissue oxygenation and oxygen consumption rate are explored.
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 15 × 15 cm2 FOV from a working distance of 35 cm. At a 20-ms exposure time, 10 μM 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.
Extending the wavelength range of spatial frequency domain imaging (SFDI) into the short-wave infrared (SWIR) has the potential to provide enhanced sensitivity to chromophores such as water and lipids that have prominent absorption features in the SWIR region. Here, we present, for the first time, a method combining SFDI with unstructured (zero spatial frequency) illumination to extract tissue absorption and scattering properties over a wavelength range (850 to 1800 nm) largely unexplored by previous tissue optics techniques. To obtain images over this wavelength range, we employ a SWIR camera in conjunction with an SFDI system. We use SFDI to obtain in vivo tissue reduced scattering coefficients at the wavelengths from 850 to 1050 nm, and then use unstructured wide-field illumination and an extrapolated power-law fit to this scattering spectrum to extract the absorption spectrum from 850 to 1800 nm. Our proof-of-principle experiment in a rat burn model illustrates that the combination of multispectral SWIR imaging, SFDI, and unstructured illumination can characterize in vivo changes in skin optical properties over a greatly expanded wavelength range. In the rat burn experiment, these changes (relative to normal, unburned skin) included increased absorption and increased scattering amplitude and slope, consistent with changes that we previously reported in the near-infrared using SFDI.
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.
Background and Objective: Spatial Frequency Domain Imaging (SFDI) is a non-contact wide-field optical imaging technology currently being developed to investigate the feasibility of quantitative non-invasive evaluation of burn wound severity in a rat model. Our objective is to determine the potential of SFDI for mapping quantitative changes in spatially resolved tissue oxygen saturation and water concentration may be indicative of burn wound severity, healing, and further complications. In this portion of the investigation, we focus on the development of a rat burn model and the acute response of tissue to burn wounds. Study Design/Materials and Methods: A controlled burn protocol involving a heated brass comb was applied to 6 rats. Imaging was acquired at 17 evenly spaced wavelengths in the near-infrared from 650 to 970 nm. Over the course of the 3 hour post-burn period, we were able to map quantitative changes in spatially resolved chromophores. Burn severities were verified post-experiment using standard H and E histology and optical microscopy. Results/Conclusion: In total, we were able to induce 12 superficial-partial thickness burns, 8 deep-partial thickness burns, and 4 full thickness burns in our rat models. While several tissue chromophores were tracked, we found that changes in oxygen saturation and water concentration to be sensitive indicators of burn severity. Future work will include additional longitudinal studies over a period of days in order to investigate which parameters are correlated to tissue healing.
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.
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.
Background and Objective: Spatial Frequency Domain Imaging (SFDI) is a non-contact wide-field optical imaging
technology currently being used to study the optical properties and chromophore concentrations of in-vivo malignant
melanomas and benign pigmented lesions. Our objective is to develop a motion correction procedure in order to assess
the concerns of subject-motion related variables during clinical measurements.
Study Design/Materials and Methods: SFDI motion-correction is a two-part procedure which utilizes a fiduciary
marker and canny-edge detection in order to reposition and align the frame-to-frame regions-of-interest (ROI). Motioninduced
phase-shifts are subsequently sampled before the entire image-set is processed by a modified demodulation
formula. By comparing the results of the adjusted processing method with data gathered from the current non-corrected
method, we were able to systematically characterize the impact of motion variables on SFDI measurements.
Results: Motion-corrected SFDI data from moving phantom measurements and clinical patient measurements showed
up to 84.58% decrease in absorption (μa) variance and up to 92.63% decrease in reduced-scattering (μs') variance.
Stationary phantom test-measurements showed almost no difference between motion corrected and standard processing.
Conclusion: SFDI motion correction is necessary for obtaining high-fidelity in-vivo optical property measurements of
pigmented lesions in a clinical setting.
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