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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.

Abstract Background Accurate measurements of the optical properties of biological tissue in the ultraviolet A and short visible wavelengths are needed to achieve a quantitative understanding of novel optical diagnostic devices. Currently, there is minimal information on optical property measurement approaches that are appropriate for in vivo measurements in highly absorbing and scattering tissues. We describe a novel fiberoptic-based reflectance system for measurement of optical properties in highly attenuating turbid media and provide an extensive in vitro evaluation of its accuracy. The influence of collecting reflectance at the illumination fiber on estimation accuracy is also investigated. Methods A neural network algorithm and reflectance distributions from Monte Carlo simulations were used to generate predictive models based on the two geometries. Absolute measurements of diffuse reflectance were enabled through calibration of the reflectance system. Spatially-resolved reflectance distributions were measured in tissue phantoms at 405 nm for absorption coefficients (μa) from 1 to 25 cm-1 and reduced scattering coefficients (μ′s MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuaH8oqBgaqbamaaBaaaleaacqqGZbWCaeqaaaaa@3007@) from 5 to 25 cm-1. These data and predictive models were used to estimate the optical properties of tissue-simulating phantoms. Results By comparing predicted and known optical properties, the average errors for μa and μ′s MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuaH8oqBgaqbamaaBaaaleaacqqGZbWCaeqaaaaa@3007@ were found to be 3.0% and 4.6%, respectively, for a linear probe approach. When bifurcated probe data was included and samples with μa values less than 5 cm-1 were excluded, predictive errors for μa and μ′s MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuaH8oqBgaqbamaaBaaaleaacqqGZbWCaeqaaaaa@3007@ were further reduced to 1.8% and 3.5%. Conclusion Improvements in system design have led to significant reductions in optical property estimation error. While the incorporation of a bifurcated illumination fiber shows promise for improving the accuracy of μ′s MathType@MTEF@5@5@+=feaafiart1ev1aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacH8akY=wiFfYdH8Gipec8Eeeu0xXdbba9frFj0=OqFfea0dXdd9vqai=hGuQ8kuc9pgc9s8qqaq=dirpe0xb9q8qiLsFr0=vr0=vr0dc8meaabaqaciaacaGaaeqabaqabeGadaaakeaacuaH8oqBgaqbamaaBaaaleaacqqGZbWCaeqaaaaa@3007@ estimates, further study of this approach is needed to elucidate the source of discrepancies between measurements and simulation results at low μa values.

Various fluorescence imaging agents are currently under clinical studies. Despite significant benefits, phototoxicity is a barrier to the clinical translation of fluorophores. Current regulatory guidelines on medication‐based phototoxicity focus on skin effects during sun exposure. However, with systemic and local administration of fluorophores and targeted illumination, there is now possibility of photochemical damage to deeper tissues during intraoperative imaging procedures. Hence, independent knowledge regarding phototoxicity is required to facilitate the development of fluorescence imaging products. Previously, we studied a cell‐free assay for initial screening of reactive molecular species generation from fluorophores. The current work addresses a safety test method based on cell viability as an adjunct and a comparator with the cell‐free assay. Our goal is to modify and implement an approach based on the in vitro 3T3 neutral red uptake assay of the Organization for Economic Co‐Operation and Development Test Guideline 432 (OECD TG432) to evaluate the photocytotoxicity of clinically relevant fluorophores. These included indocyanine green (ICG), proflavine, methylene blue (MB), and IRDye800, as well as control photosensitizers, benzoporphyrin derivative (BPD) and rose bengal (RB). We performed measurements at agent concentrations and illumination parameters used for clinic imaging. Our results aligned with prior studies, indicating photocytotoxicity in RB and BPD and an absence of reactivity for ICG and IRDye800. DNA interactive agents, proflavine and MB, exhibited drug/light dose–response curves like photosensitizers. This study provides evidence and insights into practices useful for testing the photochemical safety of fluorescence imaging products. [ABSTRACT FROM AUTHOR]

Considerable advances in cancer-specific optical imaging have improved the precision of tumor resection. In comparison to traditional imaging modalities, this technology is unique in its ability to provide real-time feedback to the operating surgeon. Given the significant clinical implications of optical imaging, there is an urgent need to standardize surgical navigation tools and contrast agents to facilitate swift regulatory approval. Because fluorescence-enhanced surgery requires a combination of both device and drug, each may be developed in conjunction, or separately, which are important considerations in the approval process. This report is the result of a one-day meeting held on May 4, 2016 with officials from the National Cancer Institute, the FDA, members of the American Society of Image-Guided Surgery, and members of the World Molecular Imaging Society, which discussed consensus methods for FDA-directed human testing and approval of investigational optical imaging devices as well as contrast agents for surgical applications. The goal of this workshop was to discuss FDA approval requirements and the expectations for approval of these novel drugs and devices, packaged separately or in combination, within the context of optical surgical navigation. In addition, the workshop acted to provide clarity to the research community on data collection and trial design. Reported here are the specific discussion items and recommendations from this critical and timely meeting. Cancer Res; 77(9); 2197-206. ©2017 AACR.

Currently the only method for positively identifying malignant melanoma involves invasive and often undesirable biopsy procedures. Available ex-vivo data indicates increased vascularization in the lower regions of excised melanoma, as compared to dysplastic nevi. The ability to interrogate this region of tissue in-vivo could lead to useful diagnostic information. Using a newly developed fiber based superficial probe in conjunction with a steady-state frequency-domain photon migration (SSFDPM) system, we can probe the upper 1-2 mm of tissue, extracting functional information in the near infrared (650-1000 nm) range. To test the resolution and detection range of the superficial probe in this context,deformable silicone phantoms have been fabricated that simulate normal skin with melanocytic lesions. These phantoms consist of a two-layered matrix with the optical properties of normal light skin, containing several cylindrical inclusions that simulate highly absorbing pigmented lesions such as melanoma. The e inclusions are varied in depth, diameter, and optical properties in order to fully test the probe's detection capabilities. It was found that, depending on absorption, we can typically probe to a depth of 1.0-1.5 mm in an inclusion, likely reaching the site of angiogenesis in an early-stage melanoma. Additionally, we can successfully interrogate normal tissue below lesions 1.5mm deep when absorption is about 0.4/mm or less. This data indicates that the superficial probe shows great promise for non-invasive diagnosis of pigmented lesions.© 2009 SPIE.

The last decade has seen a large growth in fluorescence‐guided surgery (FGS) imaging and interventions. With the increasing number of clinical specialties implementing FGS, the range of systems with radically different physical designs, image processing approaches, and performance requirements is expanding. This variety of systems makes it nearly impossible to specify uniform performance goals, yet at the same time, utilization of different devices in new clinical procedures and trials indicates some need for common knowledge bases and a quality assessment paradigm to ensure that effective translation and use occurs. It is feasible to identify key fundamental image quality characteristics and corresponding objective test methods that should be determined such that there are consistent conventions across a variety of FGS devices. This report outlines test methods, tissue simulating phantoms and suggested guidelines, as well as personnel needs and professional knowledge bases that can be established. This report frames the issues with guidance and feedback from related societies and agencies having vested interest in the outcome, coming from an independent scientific group formed from academics and international federal agencies for the establishment of these professional guidelines. [ABSTRACT FROM AUTHOR]

Accurate in vivo optical property data in the ultraviolet to visible range are scarce for many endoscope-accessible organs, yet such information is essential for understanding light propagation and identifying dosimetry standards for biomedical optical spectroscopy. We have performed a preliminary study towards the development of a reflectance-based system for endoscopic measurement of tissue optical properties relevant to fluorescence spectroscopy. To address the constraint of instrument channel diameter and strong attenuation of light in the spectral region of interest, maximum fiber separation distance was limited to 2.5 mm. Measurements were performed on tissue phantoms for a range of optical properties relevant to gastrointestinal mucosal tissues in the ultraviolet to visible range: absorption coefficients from 1 to 256 cm-1 and reduced scattering coefficients from 5 to 25 cm-1. Neural network and partial least squares algorithms were trained on radial reflectance profiles generated by a Monte Carlo model as well as by experimental data. These routines were then used to estimate absorption and reduced scattering coefficients from reflectance data. Results are discussed in terms of the optimization of models for optical property determination.

Infrared laser ablation of urinary calculi was investigated as a function of wavelength to determine the relation of ablation threshold fluences, ablation depths, and optical absorption. A simple photothermal ablation model was employed to examine this relationship. Human urinary calculi composed of > 95% uric acid, > 95% cystine, > 95% calcium oxalate monohydrate (COM), and > 90% magnesium ammonium phosphate hexahydrate (MAPH) were used. Various wavelengths between 2.1 and 6.5 μm were selected to perform threshold fluence and ablation depth measurements. The laser source for this study was the tunable pulsed infrared free electron laser (FEL) at Vanderbilt University. Experimental results indicated a correlation of threshold fluence and ablation depth to the optical absorption properties of the calculi. When calculus optical absorption increased, the threshold fluences decreased. Although the ablation depths increased with calculus optical absorption, results indicated that in certain calculi the ablation depth was affected by optical attenuation through the ablation plume. These observations were in agreement with the photothermal ablation model, but fractures in striated calculi at higher optical absorptions, indicated the contribution of a photomechanical mechanism. Threshold fluences and ablation depths are a function of the wavelength dependent absorption properties of the calculi. These observations suggest that the 3-μm and 6-μm absorption bands are optimal for ablation or fragmentation of urinary calculus.

An investigation of the effects of laser irradiation with a wavelength of 532 nm and pulse duration of 10 ms on whole blood was performed in vitro. Threshold radiant exposures for coagulation were quantified and transient radiometric temperatures were measured. The progression of effects with increasing radiant exposure--from evaporation to coagulation-induced light scattering to aggregated coagulum formation to ablation--is described. Results indicate that coagulation and ablation occur at temperatures significantly in excess of those assumed in previous theoretical studies. An Arrhenius rate process analysis based on hemoglobin data indicates good agreement with experimental results.

Quantitative data regarding photothermal and damage processes during pulsed laser irradiation of blood are necessary to achieve a better understanding of laser treatment of cutaneous vascular lesions and improve numerical models. In this study, multiple experimental techniques were employed to quantify the effects of single-pulse KTP laser (λ = 532 nm, τp = 10 ms) irradiation of whole blood in vitro: high-speed temperature measurement with a thermal camera in line-scan mode (8 kHz); optical coherence tomography (for determination of coagulum morphology); and transmission measurement with a co-aligned laser beam (λ = 635 nm). Threshold radiant exposures for coagulation (4.4-5.0 J/cm2) and ablation (approximately J/cm2) were identified. Thermal camera measurements indicated threshold coagulation temperatures of 90-100 °C, and peak temperatures of up to 145 °C for sub-ablation radiant exposures. Significant changes in coagulum thickness and consistency, and a corresponding decrease in transmission, were observed with increasing radiant exposure. The Arrhenius equation was shown to produce accurate predictions of coagulation onset (using appropriate rate process coefficients). The significance of dynamic effects such as evaporative loss and dynamic changes in optical properties was indicated. Implications for numerical modeling are discussed. Most importantly, the threshold temperatures typically quoted in the literature for pulsed laser coagulation (60-70 °C) and ablation (100 °C) of blood do not match the results of this study.

Optical low-coherence reflectometry and confocal microscopy images were taken of the rat dorsal skin flap window model. Blood vessel depths and diameters measured with the two techniques, and preparation thickness determined from reflectometry images, are in reasonable agreement with measurements from histologic sections. Blood vessels appear as areas of low signal when constant-depth reflectometry images are taken at a depth near the center of a vessel, whereas they appear bright when taken close to the blood-dermis boundary. Doppler shift plus increased light absorption in blood, and the blood-dermis index of refraction mismatch, are discussed as possible causes of the dark- and bright-appearing vessels, respectively. One reflectometry image was used to generate an input grid for a novel Monte Carlo analysis program that is capable of determining the light distribution and heat generation [J/m3] within complex blood vessel geometries. The feasibility of imaging skin blood vessel accurately with optical low-coherence tomography, and using the acquired knowledge of blood vessels structure to create more realistic Monte Carlo analyses is demonstrated by the results of the study. © 1997 Society of Photo-Optical Instrumentation Engineers.

Improvements in measurement of epithelial tissue optical properties (OPs) in the ultraviolet and visible (UV-Vis) may lead to enhanced understanding of optical techniques for neoplasia detection. In this study, we investigated an approach based on fiber-optic measurement of reflectance to determine absorption and reduced scattering coefficients ([[mu].sub.a] and [mu]'.sub.a]) in two-layer turbid media. Neural network inverse models were trained on simulation data for a wide variety of OP combinations ([[mu].sub.a] - 1-22.5, [[mu]'.sub.s] = 5-42.5 [cm.sup.-1]). Experimental measurements of phantoms with top-layer thicknesses (D) ranging from 0.22 to 0.66 mm were performed at three UV-Vis wavelengths. OP estimation accuracy was calculated and compared to theoretical results. Mean prediction errors were strongly correlated with D and ranged widely, from 1.5 to 12.1[cm.sup.-1]. Theoretical analyses indicated the potential for improving accuracy with alternate probe geometries. Although numerous challenges remain, this initial experimental study of an unconstrained approach for fiber-optic-based OP determination in two-layer epithelial tissue indicates the potential to provide useful measurements. OCIS codes: 170.3890, 170.6510, 120.3890, 120.4630, 300.6540, 300.1030.

The fiber-optic probe is an essential component of many quantitative fluorescence spectroscopy systems, enabling delivery of excitation light and collection of remitted fluorescence in a wide variety of clinical and laboratory situations. However, there is little information available on the role of illumination-collection geometry to guide the design of these components. Therefore we used a Monte Carlo model to investigate the effect of multifiber probe design parameters--numerical aperture, fiber diameter, source-collection fiber separation distance, and fiber-tissue spacer thickness--on light propagation and the origin of detected fluorescence. An excitation wavelength of 400 nm and an emission wavelength of 630 nm were simulated. Noteworthy effects included an increase in axial selectivity with decreasing fiber size and a transition with increasing fiber-tissue spacer size from a subsurface peak in fluorophore sensitivity to a nearly monotonic decrease typical of single-fiber probes. We provide theoretical evidence that probe design strongly affects tissue interrogation. Therefore application-specific customization of probe design may lead to improvements in the efficacy of fluorescence-based diagnostic devices.