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  • 1.
    Berger, Andrew J.
    et al.
    The Institute of Optics, University of Rochester, Rochester, NY, USA.
    Saager, Rolf B.
    The Institute of Optics, University of Rochester, Rochester, NY, USA.
    Characterization of scalp—and brain-layer heterogeneity for near infrared spectroscopy2006In: Biomedical Topical Meeting 2006 Fort Lauderdale, Florida, United States,19–22 March 2006, Poster Session II (ME), OSA Publishing , 2006Conference paper (Refereed)
    Abstract [en]

    Near-infrared monitoring of cerebral hemodynamics is hampered by biological noise. We propose noise reduction via a two-detector scheme and present measurements characterizing relevant heterogeneity scales for scalp and brain layers in human volunteers.

  • 2.
    Burns, Joshua M
    et al.
    Department of Bioengineering, University of California, Riverside, CA 92521, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA 92612, USA.
    Majaron, Boris
    Department of Complex Matter, Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia.
    Jia, Wangcun
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, CA 92612, USA.
    Anvari, Bahman
    Department of Bioengineering, University of California, Riverside, CA 92521, USA.
    Optical properties of biomimetic probes engineered from erythrocytes2016In: Nanotechnology, ISSN 0957-4484, E-ISSN 1361-6528, Vol. 28, no 3, article id 035101Article in journal (Refereed)
    Abstract [en]

    Light-activated theranostic materials offer a potential platform for optical imaging and phototherapeutic applications. We have engineered constructs derived from erythrocytes, which can be doped with the FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG). We refer to these constructs as NIR erythrocyte-mimicking transducers (NETs). Herein, we investigated the effects of changing the NETs mean diameter from micron- (≈4 μm) to nano- (≈90 nm) scale, and the ICG concentration utilized in the fabrication of NETs from 5 to 20 μM on the resulting absorption and scattering characteristics of the NETs. Our approach consisted of integrating sphere-based measurements of light transmittance and reflectance, and subsequent utilization of these measurements in an inverse adding-doubling algorithm to estimate the absorption (μ a) and reduced scattering (μ s') coefficients of these NETs. For a given NETs diameter, values of μ a increased over the approximate spectral band of 630–860 nm with increasing ICG concentration. Micron-sized NETs produced the highest peak value of μ a when using ICG concentrations of 10 and 20 μM, and showed increased values of μ s' as compared to nano-sized NETs. Spectral profiles of μ s' for these NETs showed a trend consistent with Mie scattering behavior for spherical objects. For all NETs investigated, changing the ICG concentration minimally affected the scattering characteristics. A Monte Carlo-based model of light distribution showed that the presence of these NETs enhanced the fluence levels within simulated blood vessels. These results provide important data towards determining the appropriate light dosimetry parameters for an intended light-based biomedical application of NETs.

  • 3.
    Grant, Alexander M.
    et al.
    University of California, Irvine, USA.
    Sry, Kelly
    University of California, Irvine, USA.
    Saager, Rolf B.
    University of California, Irvine, USA.
    Ayers, Frederick
    University of California, Irvine, USA.
    Pfefer, T. Joshua
    U.S. Food and Drug Administration, USA.
    Kelly, Kristen M.
    University of California, Irvine, USA.
    Tseng, Sheng-Hao
    University of California, Irvine, USA.
    Durkin, Anthony J.
    University of California, Irvine, USA.
    Diffuse optical spectroscopy of melanoma-simulating silicone phantoms2009In: PROCEEDINGS VOLUME 7187 SPIE BIOS, 24-29 JANUARY 2009 Biomedical Applications of Light Scattering III / [ed] Adam Wax and Vadim Backman, SPIE - International Society for Optical Engineering, 2009, Vol. 7187, p. 718702-1-718702-12Conference paper (Refereed)
    Abstract [en]

    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. These 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.

  • 4.
    Horan, Sean T
    et al.
    a University of California, Department of Mathematics, Irvine, California, United States; b University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States.
    Gardner, Adam R
    b University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States; c University of California, Department of Chemical Engineering and Materials Science, Irvine, California, United States.
    Saager, Rolf B.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States.
    Durkin, Anthony J
    University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States; University of California, Department of Biomedical Engineering, Irvine, California, United States.
    Venugopalan, Vasan
    University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, California, United States; University of California, Department of Chemical Engineering and Materials Science, Irvine, California, United States; University of California, Department of Biomedical Engineering, Irvine, California, United States.
    Recovery of layered tissue optical properties from spatial frequency-domain spectroscopy and a deterministic radiative transport solver2018In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 24, no 7, article id 071607Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Moy, Austin J.
    et al.
    University of California, Irvine, USA.
    Capulong, Bernard V.
    University of California, Irvine, USA.
    Saager, Rolf B.
    University of California, Irvine, USA.
    Wiersma, Matthew P.
    University of California, Irvine, USA.
    Lo, Patrick C.
    University of California, Irvine, USA.
    Durkin, Anthony J.
    University of California, Irvine, USA.
    Choi, Bernard
    University of California, Irvine, USA.
    Optical properties of mouse brain tissue after optical clearing with FocusClear™2015In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 9, article id 095010Article in journal (Refereed)
    Abstract [en]

    Fluorescence microscopy is commonly used to investigate disease progression in biological tissues. Biological tissues, however, are strongly scattering in the visible wavelengths, limiting the application of fluorescence microscopy to superficial (<200  μm) regions. Optical clearing, which involves incubation of the tissue in a chemical bath, reduces the optical scattering in tissue, resulting in increased tissue transparency and optical imaging depth. The goal of this study was to determine the time- and wavelength-resolved dynamics of the optical scattering properties of rodent brain after optical clearing with FocusClear™. Light transmittance and reflectance of 1-mm mouse brain sections were measured using an integrating sphere before and after optical clearing and the inverse adding doubling algorithm used to determine tissue optical scattering. The degree of optical clearing was quantified by calculating the optical clearing potential (OCP), and the effects of differing OCP were demonstrated using the optical histology method, which combines tissue optical clearing with optical imaging to visualize the microvasculature. We observed increased tissue transparency with longer optical clearing time and an analogous increase in OCP. Furthermore, OCP did not vary substantially between 400 and 1000 nm for increasing optical clearing durations, suggesting that optical histology can improve ex vivo visualization of several fluorescent probes.

  • 6.
    Nguyen, John Quan
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Cuccia, David J.
    Modulated Imaging, Inc., USA.
    Kelly, Kristen M.
    University of California, Irvine, USA.
    Hsiang, David
    University of California, Irvine, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Motion correction in spatial frequency domain imaging$\mathsemicolon$ optical property determination in pigmented lesions2011In: Proceedings Volume 7883 SPIE BIOS, 22-27 JANUARY 2011 Photonic Therapeutics and Diagnostics VII / [ed] Kenton W. Gregory, Guillermo J. Tearney, Laura Marcu, Nikiforos Kollias, Bernard Choi, Haishan Zeng, Andreas Mandelis, Henry Hirschberg, Steen J. Madsen, Hyun Wook Kang, Bodo E. Knudsen, Anita Mahadevan-Jansen, E. Duco Jansen, Brian Jet-Fei Wong, and Justus F. R. Ilgner, SPIE - International Society for Optical Engineering, 2011, Vol. 7883Conference paper (Refereed)
    Abstract [en]

    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.

  • 7.
    Nguyen, John Quan
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Cuccia, David J.
    Modulated Imaging, Inc., USA.
    Kelly, Kristen M.
    University of California, Irvine School of Medicine, USA.
    Jakowatz, James
    University of California, Irvine, USA.
    Hsiang, David
    University of California, Irvine, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Effects of motion on optical properties in the spatial frequency domain2011In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 16, no 12, p. 126009-1-126009-9, article id 126009Article in journal (Refereed)
    Abstract [en]

    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.

  • 8.
    Ponticorvo, A.
    et al.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Rowland, R.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Baldado, M.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Kennedy, G. T.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Saager, Rolf B.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Burmeister, D. M.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Christy, R. J.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Bernal, N.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    Durkin, A. J.
    Beckman Laser Institute, UC Irvine, Irvine, CA; US Army Institute of Surgical Research, San Antonio, TX; University of California Irvine, Irvine, CA, USA.
    529 Evaluating Clinical Observation, Spatial Frequency Domain Imaging (SFDI) and Laser Speckle Imaging (LSI) for the Assessment of Burns2018In: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 39, no Suppl_1, p. S238-S239Article in journal (Refereed)
    Abstract [en]

    Introduction

    The current standard for diagnosis of burn severity and subsequent wound healing is through clinical examination, which is highly subjective. Several new technologies focus on burn care in an attempt to help clinicians quantify burn severity earlier and more accurately. Laser Speckle Imaging (LSI) is a technique that quantifies perfusion to assess burn wounds while Spatial Frequency Domain Imaging (SFDI) can quantify the structural damage caused by burns. Here we test each system’s ability to categorize burn wounds and compare their performance.

    Methods

    Clinical assessment of a Yorkshire pig (n=3) graded burn model was performed at 24 hours after burn injury. A commercial LSI (Periscan PIM 3, Perimed Inc.) and SFDI (OxImager RS, MI Inc.) device were used to measure hemodynamic (blood flow) and structural (reduced scattering coefficient) properties of the burn wounds. Burn severity was confirmed by histology. Additionally, both devices were used to collect preliminary data on clinical patients.

    Results

    Clinical assessments in the swine model were 83% percent accurate, while the LSI and SFDI systems were 81% and 85% percent accurate respectively. In addition to being more accurate than LSI in this study, SFDI data suggests that it can spatially resolve the heterogeneity of burn severity within a burn wound. This was not observed using the commercial LSI device. Preliminary results on clinical patients also showed both devices were capable of non-invasively predicting burn regions that would eventually require grafting.

    Conclusions

    The testing of these different imaging modalities in a controlled environment allows a direct comparison. Here we show that SFDI is capable of categorizing burn wounds in a swine model of histologically confirmed graded burn severity more accurately than clinical assessment or LSI. SFDI is also able to resolve spatial heterogeneity of burn severity within a wound. SFDI has the potential to improve clinical care with additional information related to tissue structure and function, thus aiding clinicians to make decisions on how to treat burn wounds accurately at earlier time points. Additionally, these noninvasive imaging technologies have the potential to enhance tracking of wound progression and treatment efficacy.

    Applicability of Research to Practice

    By improving diagnostic accuracy of which burn areas will require grafting, these devices may aid clinicians make appropriate treatment decisions sooner.

  • 9.
    Ponticorvo, Adrien
    et al.
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Burmeister, David M.
    United States Army Institute of Surgical Research, 36950 Chambers Pass, Fort Sam Houston, Texas 78234, USA.
    Rowland, Rebecca
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Baldado, Melissa
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Kennedy, Gordon T.
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Saager, Rolf B.
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Bernal, Nicole
    Department of Surgery, UC Irvine Regional Burn Center, 333 City Boulevard West, Suite 705, Orange, California 92868, USA.
    Choi, Bernard
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Durkin, Anthony J.
    Beckman Laser Institute Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92617, USA.
    Quantitative long-term measurements of burns in a rat model using Spatial Frequency Domain Imaging (SFDI) and Laser Speckle Imaging (LSI)2017In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 49, no 3, p. 293-304Article in journal (Refereed)
    Abstract [en]

    Background and Ojectives

    The current standard for diagnosis of burn severity and subsequent wound healing is through clinical examination, which is highly subjective. Several new technologies are shifting focus to burn care in an attempt to help quantify not only burn depth but also the progress of healing. While accurate early assessment of partial thickness burns is critical for dictating the course of treatment, the ability to quantitatively monitor wound status over time is critical for understanding treatment efficacy. SFDI and LSI are both non‐invasive imaging modalities that have been shown to have great diagnostic value for burn severity, but have yet to be tested over the course of wound healing.

    Methods

    In this study, a hairless rat model (n = 6, 300–450 g) was used with a four pronged comb to create four identical partial thickness burns (superficial n = 3 and deep n = 3) that were used to monitor wound healing over a 28 days period. Weekly biopsies were taken for histological analysis to verify wound progression. Both SFDI and LSI were performed weekly to track the evolution of hemodynamic (blood flow and oxygen saturation) and structural (reduced scattering coefficient) properties for the burns.

    Results

    LSI showed significant changes in blood flow from baseline to 220% in superficial and 165% in deep burns by day 7. In superficial burns, blood flow returned to baseline levels by day 28, but not for deep burns where blood flow remained elevated. Smaller increases in blood flow were also observed in the surrounding tissue over the same time period. Oxygen saturation values measured with SFDI showed a progressive increase from baseline values of 66–74% in superficial burns and 72% in deep burns by day 28. Additionally, SFDI showed significant decreases in the reduced scattering coefficient shortly after the burns were created. The scattering coefficient progressively decreased in the wound area, but returned towards baseline conditions at the end of the 28 days period. Scattering changes in the surrounding tissue remained constant despite the presence of hemodynamic changes.

    Conclusions Here, we show that LSI and SFDI are capable of monitoring changes in hemodynamic and scattering properties in burn wounds over a 28 days period. These results highlight the potential insights that can be gained by using non‐invasive imaging technologies to study wound healing. Further development of these technologies could be revolutionary for wound monitoring and studying the efficacy of different treatments.

  • 10.
    Ponticorvo, Adrien
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Rowland, Rebecca A.
    Beckman Laser Institute and Medical Clinic, USA.
    Baldado, Melissa L.
    Beckman Laser Institute and Medical Clinic, USA.
    Kennedy, Gordon T.
    Beckman Laser Institute and Medical Clinic, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Choi, Bernard
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Quantitative long term measurements of burns in a rat model using spatial frequency domain imaging and laser speckle imaging (Conference Presentation)2016In: Proceedings Volume 9711, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX; 971102 (2016) / [ed] Daniel L. Farkas, Dan V. Nicolau, and Robert C. Leif, SPIE - International Society for Optical Engineering, 2016, Vol. 9711, article id 971102Conference paper (Refereed)
    Abstract [en]

    The ability to accurately assess burn wound severity in a timely manner is a critical component of wound management as it dictates the course of treatment. While full thickness and superficial burns can be easily diagnosed through visual inspection, burns that fall in between these categories are difficult to classify. Additionally, the ability to better quantify different stages of wound healing from a burn of any severity would be important for evaluating the efficacy of different treatment options. Here we present a longitudinal (28 day) study that employs spatial frequency domain imaging (SFDI) and laser speckle imaging (LSI) as non-invasive technologies to characterize in-vivo burn wounds and healing in a murine model. Burn wounds were created using an established technique of a brass comb heated to a given temperature and applied for a set amount of time. They were imaged immediately after the initial injury and then at 2, 4, 7, 14, 21, and 28 days following the injury. Biopsies were taken on the day of the injury in order to verify the extent of the burn damage as well as at different time points after the injury in order to visualize different stages of inflammation and healing. The results of this study suggest that the reduced scattering coefficient measured using SFDI and blood flow as measured using LSI have the potential to provide useful metrics for quantifying the severity of burn injuries as well as track the different stages associated with wound healing progression.

  • 11.
    Rohrbach, Daniel J.
    et al.
    Department of Cell Stress Biology and PDT Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
    Muffoletto, Daniel
    Department of Electrical Engineering, University at Buffalo, Buffalo, NY, USA.
    Huihui, Jonathan
    Department of Cell Stress Biology and PDT Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
    Saager, Rolf B.
    Beckman Laser Institute, Irvine, CA, USA.
    Keymel, Kenneth
    Department of Cell Stress Biology and PDT Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
    Paquette, Anne
    Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Morgan, Janet
    Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Zeitouni, Nathalie
    Department of Dermatology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Sunar, Ulas
    Department of Cell Stress Biology and PDT Center, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA.
    Preoperative Mapping of Nonmelanoma Skin Cancer Using Spatial Frequency Domain and Ultrasound Imaging2014In: Academic Radiology, ISSN 1076-6332, E-ISSN 1878-4046, Vol. 21, no 2, p. 263-270Article in journal (Refereed)
    Abstract [en]

    Rationale and Objectives

    The treatment of nonmelanoma skin cancer (NMSC) is usually by surgical excision or Mohs micrographic surgery and alternatively may include photodynamic therapy (PDT). To guide surgery and to optimize PDT, information about the tumor structure, optical parameters, and vasculature is desired.

    Materials and Methods

    Spatial frequency domain imaging (SFDI) can map optical absorption, scattering, and fluorescence parameters that can enhance tumor contrast and quantify light and photosensitizer dose. High frequency ultrasound (HFUS) imaging can provide high-resolution tumor structure and depth, which is useful for both surgery and PDT planning.

    Results

    Here, we present preliminary results from our recently developed clinical instrument for patients with NMSC. We quantified optical absorption and scattering, blood oxygen saturation (StO2), and total hemoglobin concentration (THC) with SFDI and lesion thickness with ultrasound. These results were compared to histological thickness of excised tumor sections.

    Conclusions

    SFDI quantified optical parameters with high precision, and multiwavelength analysis enabled 2D mappings of tissue StO2 and THC. HFUS quantified tumor thickness that correlated well with histology. The results demonstrate the feasibility of the instrument for noninvasive mapping of optical, physiological, and ultrasound contrasts in human skin tumors for surgery guidance and therapy planning.

  • 12.
    Rohrbach, Daniel J.
    et al.
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Zeitouni, Nathalie C.
    Department of Dermatology, University of Arizona Cancer Center, Tucson, AZ, USA.
    Muffoletto, Daniel
    Department of Electrical Engineering, University at Buffalo, Buffalo, NY, USA .
    Saager, Rolf B.
    Beckman Laser Institute, University of California Irvine, Irvine, CA, USA .
    Tromberg, Bruce J.
    Beckman Laser Institute, University of California Irvine, Irvine, CA, USA .
    Sunar, Ulas
    Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA / Department of Biomedical Engineering, University at Buffalo, Buffalo, NY, USA.
    Characterization of nonmelanoma skin cancer for light therapy using spatial frequency domain imaging2015In: Biomedical Optics Express, ISSN 2156-7085, E-ISSN 2156-7085, Vol. 6, no 5, p. 1761-1766Article in journal (Refereed)
    Abstract [en]

    The dosimetry of light-based therapies critically depends on both optical and vascular parameters. We utilized spatial frequency domain imaging to quantify optical and vascular parameters, as well as estimated light penetration depth from 17 nonmelanoma skin cancer patients. Our data indicates that there exist substantial spatial variations in these parameters. Characterization of these parameters may inform understanding and optimization of the clinical response of light-based therapies.

  • 13.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Rd., University of California – Irvine, CA 92617, USA.
    Au, Kendrew
    Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Rd., University of California – Irvine, CA 92617, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Rd., University of California – Irvine, CA 92617, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, 1002 Health Sciences Rd., University of California – Irvine, CA 92617, USA.
    Development of Spatial Frequency Domain Instrument for the Quantification of Layer Specific Optical Properties of Pigmented Lesions2012In: Biomedical Optics and 3-D Imaging, OSA Publishing , 2012, article id BW4B.2Conference paper (Refereed)
    Abstract [en]

    A clinical, spatially modulated quantitative spectroscopy (SMoQS) instrument has been designed and deployed to evaluate its ability to quantitatively isolate layer-specific optical properties of pigmented lesions in skin in vivo.

  • 14.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Baldado, Melissa L.
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Rowland, Rebecca A.
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Method using in vivo quantitative spectroscopy to guide design and optimization of low-cost, compact clinical imaging devices: emulation and evaluation of multispectral imaging systems2018In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 23, no 4, article id 046002Article in journal (Refereed)
    Abstract [en]

    With recent proliferation in compact and/or low-cost clinical multispectral imaging approaches and commercially available components, questions remain whether they adequately capture the requisite spectral content of their applications. We present a method to emulate the spectral range and resolution of a variety of multispectral imagers, based on in-vivo data acquired from spatial frequency domain spectroscopy (SFDS). This approach simulates spectral responses over 400 to 1100 nm. Comparing emulated data with full SFDS spectra of in-vivo tissue affords the opportunity to evaluate whether the sparse spectral content of these imagers can (1) account for all sources of optical contrast present (completeness) and (2) robustly separate and quantify sources of optical contrast (crosstalk). We validate the approach over a range of tissue-simulating phantoms, comparing the SFDS-based emulated spectra against measurements from an independently characterized multispectral imager. Emulated results match the imager across all phantoms (<3  %   absorption, <1  %   reduced scattering). In-vivo test cases (burn wounds and photoaging) illustrate how SFDS can be used to evaluate different multispectral imagers. This approach provides an in-vivo measurement method to evaluate the performance of multispectral imagers specific to their targeted clinical applications and can assist in the design and optimization of new spectral imaging devices.

  • 15.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Balu, Mihaela
    Beckman Laser Institute and Medical Clinic, USA.
    Crosignani, Viera
    Beckman Laser Institute and Medical Clinic, USA.
    Sharif, Ata
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Kelly, Kristen M.
    University of California, Irvine School of Medicine, USA.
    Tromberg, Bruce J.
    Beckman Laser Institute and Medical Clinic, USA.
    In vivo measurements of cutaneous melanin across spatial scales: using multiphoton microscopy and spatial frequency domain spectroscopy2015In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 6, article id 066005Article in journal (Refereed)
    Abstract [en]

    The combined use of nonlinear optical microscopy and broadband reflectance techniques to assess melanin concentration and distribution thickness in vivo over the full range of Fitzpatrick skin types is presented. Twelve patients were measured using multiphoton microscopy (MPM) and spatial frequency domain spectroscopy (SFDS) on both dorsal forearm and volar arm, which are generally sun-exposed and non-sun-exposed areas, respectively. Both MPM and SFDS measured melanin volume fractions between ∼5% (skin type I non-sun-exposed) and 20% (skin type VI sun exposed). MPM measured epidermal (anatomical) thickness values ∼30–65  μm, while SFDS measured melanin distribution thickness based on diffuse optical path length. There was a strong correlation between melanin concentration and melanin distribution (epidermal) thickness measurements obtained using the two techniques. While SFDS does not have the ability to match the spatial resolution of MPM, this study demonstrates that melanin content as quantified using SFDS is linearly correlated with epidermal melanin as measured using MPM (R2=0.8895). SFDS melanin distribution thickness is correlated to MPM values (R2=0.8131). These techniques can be used individually and/or in combination to advance our understanding and guide therapies for pigmentation-related conditions as well as light-based treatments across a full range of skin types.

  • 16.
    Saager, Rolf B.
    et al.
    University of Rochester, The Institute of Optics, USA.
    Berger, Andrew
    University of Rochester, The Institute of Optics, USA.
    Measurement of layer-like hemodynamic trends in scalp and cortex: implications for physiological baseline suppression in functional near-infrared spectroscopy2008In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 3, p. 034017-1-034017-10, article id 034017Article in journal (Refereed)
    Abstract [en]

    A multidetector, continuous wave, near-infrared spectroscopy (NIRS) system is developed to examine whether the hemodynamics of the scalp and brain in adults contain significant layer-like hemodynamic trends. NIRS measurements are made using contrasting geometries, one with four detectors equidistant from a source 33 mm away, and one with detectors collinear with the source (5 to 33 mm away). When NIRS time series are acquired over the prefrontal cortex from resting adults using both geometries, variations among the time series are consistent with a substantially homogeneous two-layer model (p<0.001) and inconsistent with one dominated by heterogeneities. Additionally, when time series measured 5 mm from the source are subtracted from corresponding 33-mm signals via a least-squares algorithm, 60% of the hemoglobin changes are on average removed. These results suggest that hemodynamic trends present in the scalp can contribute significantly to NIRS measurements, and that attempts to reduce this noise by subtracting a simultaneous near-channel measurement using a two-layer model are justified. Such subtractions are then performed on NIRS measurements from two stimulus protocols. For systemic stimulations (Valsalva maneuver), the subtraction cancels the hemodynamic response, as desired. For localized stimulation of the occipital lobe (viewing a flickering pattern), the subtraction isolated a stimulus-correlated hemodynamic feature from background noise.

  • 17.
    Saager, Rolf B.
    et al.
    The Institute of Optics, University of Rochester, Rochester, NY, USA.
    Berger, Andrew J.
    The Institute of Optics, University of Rochester, Rochester, NY, USA.
    Application of a Dual-Detector Scheme for Biological Noise Removal in NIRS Cerebral Hemodynamics Monitoring2006In: Frontiers in Optics, OSA Technical Digest (CD) (Optical Society of America, 2006), paper FWV4, OSA Publishing , 2006, article id FWV4Conference paper (Refereed)
    Abstract [en]

    We have proposed a method to isolate cerebral NIRS signatures using measurements at two source- detector separations. To examine the applicability of this method on human subjects, a series of different activation protocols are monitored via specialized NIRS probes.

  • 18.
    Saager, Rolf B.
    et al.
    The Institute of Optics, University of Rochester, Rochester, New York, USA .
    Berger, Andrew J.
    The Institute of Optics, University of Rochester, Rochester, New York, USA .
    Direct characterization and removal of interfering absorption trends in two-layer turbid media2005In: Journal of the Optical Society of America A, ISSN 0740-3232, Vol. 22, no 9, p. 1874-882Article in journal (Refereed)
    Abstract [en]

    We propose a method to isolate absorption trends confined to the lower layer of a two-layer turbid medium, as is desired in near-infrared spectroscopy (NIRS) of cerebral hemodynamics. Several two-layer Monte Carlo simulations of NIRS time series were generated using a physiologically relevant range of optical properties and varying the absorption coefficients due to bottom-layer, top-layer, and/or global fluctuations. Initial results showed that by measuring absorption trends at two source–detector separations and performing a least-squares fit of one to the other, processed signals strongly resemble the simulated bottom-layer absorption properties. Through this approach, it was demonstrated that fitting coefficients can be estimated within less than ±2% of the ideal value without any a priori knowledge of the optical properties present in the model. An analytical approximation for the least-squares coefficient provides physical insight into the nature of errors and suggests ways to reduce them.

  • 19.
    Saager, Rolf B.
    et al.
    The Institute of Optics, University of Rochester, Rochester, NY, USA.
    Berger, Andrew J
    The Institute of Optics, University of Rochester, Rochester, NY, USA.
    Explicit removal of surface layer signals in NIRS cerebral hemodynamics monitoring2004In: Frontiers in Optics 2004/Laser Science XXII/Diffractive Optics and Micro-Optics/Optical Fabrication and Testing, OSA Technical Digest Series (Optical Society of America, 2004), paper FTuG41, OSA Publishing , 2004, article id FTuG41Conference paper (Refereed)
    Abstract [en]

    We propose a method to isolate cerebral NIRS signatures from superficial fluctuations using measurements at two source-detector separations. Two-layer Monte-Carlo simulations were used as a model, varying the absorption of each layer. Initial results show processed signals strongly resemble the simulated bottom layer absorption properties.

  • 20.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute, UC Irvine, Irvine, California, USA.
    Cuccia, D. J.
    Modulated Imaging, Inc, Irvine, California, USA.
    Saggese, S.
    Modulated Imaging, Inc, Irvine, California, USA.
    Kelly, K. M.
    Beckman Laser Institute, UC Irvine, Irvine, California, USA.
    Durkin, A. J.
    Beckman Laser Institute, UC Irvine, Irvine, California, USA.
    A Light Emitting Diode (LED) Based Spatial Frequency Domain Imaging System for Optimization of Photodynamic Therapy of Nonmelanoma Skin Cancer: Quantitative Reflectance Imaging2013In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 45, no 4, p. 207-215Article in journal (Refereed)
    Abstract [en]

    Background

    Photodynamic therapy (PDT) offers the potential for enhanced treatment of nonmelanoma skin cancer (NMSC) with minimal scarring. Yet, PDT has not achieved consistent long term effectiveness to gain widespread clinical acceptance for treatment of skin cancer. Therapeutic response varies between practitioners, patients and lesions. One important contributing factor is the absence of quantitative tools to perform in vivo dosimetry. To this end, we have developed a new quantitative imaging device that can be used to investigate parameters related to optimizing dosimetry.

    Methods

    We present a spatial frequency domain imaging (SFDI) based device designed to: (1) determine the optical properties at the therapeutic wavelength, which can inform variations in light penetration depth and (2) measure the spatially resolved oxygen saturation of the skin cancer lesions and surrounding tissue. We have applied this system to a preliminary clinical study of nine skin cancer lesions.

    Results

    Optical properties vary greatly both spatially [101%, 48% for absorption and reduced scattering, respectively] and across patients [102%, 57%]. Blood volume maps determined using visible wavelengths (460, 525, and 630 nm) represent tissue volumes within ∼1 mm in tissue (1.17 ± 0.3 mm). Here the average total hemoglobin concentration is approximately three times greater in the lesion than that detected in normal tissue, reflecting increased vasculature typically associated with tumors. Data acquired at near infrared wavelengths (730 and 850 nm) reports tissue blood concentrations and oxygenations from the underlying dermal microvasculature (volumes reaching 4.36 ± 1.32 mm into tissue).

    Conclusions

    SFDI can be used to quantitatively characterize in vivo tissue optical properties that could be useful for better informing PDT treatment parameters. Specifically, this information provides spatially resolved insight into light delivery into tissue and local tissue oxygenation, thereby providing more quantitative and controlled dosimetry specific to the lesion. Ultimately, by optimizing the execution of PDT, this instrument has the potential to positively improve treatment outcomes. Lasers Surg. Med. 9999:XX–XX, 2013. © 2013 Wiley Periodicals, Inc.

  • 21.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Cuccia, David J.
    Modulated Imaging, Inc., USA.
    Saggese, Steve
    Modulated Imaging, Inc., USA.
    Kelly, Kristen M.
    University of California, Irvine School of Medicine, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Quantitative fluorescence imaging of protoporphyrin IX through determination of tissue optical properties in the spatial frequency domain2011In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 16, no 12, p. 126013-1-126013-5, article id 126013Article in journal (Refereed)
    Abstract [en]

    The ability to quantitatively determine tissue fluorescence is of interest for the purpose of better understanding the details of photodynamic therapy of skin cancer. In particular, we are interested in quantifying protoporphyrin IX (PpIX) in vivo. We present a method of correcting fluorescence for effects of native tissue absorption and scattering properties in a spatially resolved manner that preserves the resolution of the fluorescence imaging system, based off a homogeneous representation of tissue. Validation was performed using a series of liquid turbid phantoms having varying concentrations of absorber, scatterer, and fluorophore (PpIX). Through the quantification of tissue optical properties via spatial frequency domain imaging, an empirical model based on Monte Carlo simulations was deployed to successfully decouple the effects of absorption and scattering from fluorescence. From this we were able to deduce the concentration of the PpIX to within 0.2 μg/ml of the known concentration. This method was subsequently applied to the determination of PpIX concentration from in vivo normal skin where the model-based correction determined a concentration of 1.6 μg/ml, which is in agreement with literature.

  • 22.
    Saager, Rolf B.
    et al.
    The Beckman Laser Institute, University of California, Irvine, CA , USA.
    Cuccia, David J.
    Modulated Imaging, Inc., Irvine, CA, USA.
    Saggese, Steven
    Modulated Imaging, Inc., Irvine, CA, USA.
    Kelly, Kristen M.
    The Beckman Laser Institute, University of California, Irvine, CA , USA.
    Durkin, Anthony J.
    The Beckman Laser Institute, University of California, Irvine, CA , USA.
    A LED Based Spatial Frequency Domain Imaging System for Optimization of Photodynamic Therapy of Basal Cell Carcinoma (BCC)2010In: Frontiers in Optics 2010/Laser Science XXVI, Rochester, New York,  United States, 24–28 October 2010, OSA Publishing , 2010, article id FTuS2Conference paper (Refereed)
    Abstract [en]

    A LED based spatial frequency domain imaging (SFDI) system has been developed to provide personalized photodynamic therapy for BCC. We present the instrument design, validation of performance and initial characterization of wide-field properties of BCC.

  • 23.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Dang, An N.
    Beckman Laser Institute and Medical Clinic, USA.
    Huang, Samantha S.
    Beckman Laser Institute and Medical Clinic, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Handheld spatial frequency domain spectrographic imager for depth-sensitive, quantitative spectroscopy of skin tissue2017In: Proceedings Volume 10037, Photonics in Dermatology and Plastic Surgery; 1003703 (2017) / [ed] Bernard Choi, Haishan Zeng, and Nikiforos Kollias, SPIE - International Society for Optical Engineering, 2017, article id 1003703Conference paper (Refereed)
    Abstract [en]

    Here we present a handheld, implementation of Spatial Frequency Domain Spectroscopy (SFDS) that employs line imaging. The new instrument can measure 1088 spatial locations that span a 3 cm line as opposed to our benchtop system that only collects a single 1 mm diameter spot. This imager, however, retains the spectral resolution (~ 1 nm) and range (450 to 1000 nm) of our benchtop system. The device also has tremendously improved mobility and portability, allowing for greater ease of use in clinical setting. A smaller size also enables access to different tissue locations, which increases the flexibility of the device. The design of this portable system not only enables SFDS to be used in clinical settings, but also enables visualization of properties of layered tissues such as skin.

  • 24.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA.
    Dang, An N.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA.
    Huang, Samantha S.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA / Department of Dermatology, University of California, Irvine, 118 Medical Surge 1, Irvine, California 92697, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, California 92612, USA.
    Portable (handheld) clinical device for quantitative spectroscopy of skin, utilizing spatial frequency domain reflectance techniques2017In: Review of Scientific Instruments, ISSN 0034-6748, E-ISSN 1089-7623, Vol. 88, no 9Article in journal (Refereed)
    Abstract [en]

    Spatial Frequency Domain Spectroscopy (SFDS) is a technique for quantifying in-vivo tissue optical properties. SFDS employs structured light patterns that are projected onto tissues using a spatial light modulator, such as a digital micromirror device. In combination with appropriate models of light propagation, this technique can be used to quantify tissue optical properties (absorption, μa, and scattering, μs′, coefficients) and chromophore concentrations. Here we present a handheld implementation of an SFDS device that employs line (one dimensional) imaging. This instrument can measure 1088 spatial locations that span a 3 cm line as opposed to our original benchtop SFDS system that only collects a single 1 mm diameter spot. This imager, however, retains the spectral resolution (∼1 nm) and range (450–1000 nm) of our original benchtop SFDS device. In the context of homogeneous turbid media, we demonstrate that this new system matches the spectral response of our original system to within 1% across a typical range of spatial frequencies (0-0.35 mm−1). With the new form factor, the device has tremendously improved mobility and portability, allowing for greater ease of use in a clinical setting. A smaller size also enables access to different tissue locations, which increases the flexibility of the device. The design of this portable system not only enables SFDS to be used in clinical settings but also enables visualization of properties of layered tissues such as skin.

  • 25.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, University of California‐Irvine, Irvine, California 92617, USA.
    Hassan, Khaled M.
    Department of Dermatology, University of California‐Irvine, Irvine, California 92697, USA.
    Kondru, Clement
    Beckman Laser Institute and Medical Clinic, University of California‐Irvine, Irvine, California 92617, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, University of California‐Irvine, Irvine, California 92617, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, University of California‐Irvine, Irvine, California 92617, USA / Department of Dermatology, University of California‐Irvine, Irvine, California 92697, USA.
    Quantitative near infrared spectroscopic analysis of Q-Switched Nd:YAG treatment of generalized argyria2013In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 45, no 1, p. 15-21Article in journal (Refereed)
    Abstract [en]

    Background and Objective

    Generalized argyria is a blue‐gray hyperpigmentation of the skin resulting from ingestion or application of silver compounds, such as silver colloid. Case reports have noted improvement after Q‐Switched Neodymium–Yttrium Aluminum Garnet laser (1,064 nm QS Nd:YAG) laser treatment to small surface areas. No reports have objectively monitored laser treatment of generalized argyria over large areas of skin, nor have long‐term outcomes been evaluated.

    Study Design/Materials and Methods

    An incremental treatment plan was developed for a subject suffering from argyria. A quantitative near infrared spectroscopic measurement technique was employed to non‐invasively analyze tissue‐pigment characteristics pre‐ and post‐laser treatment. Post‐treatment measurements were collected at weeks 1, 2, 3, and 4, and again at 1 year.

    Results

    Immediate apparent removal of pigment was observed with 1 Q‐switched 1,064 nm Nd:YAG laser treatment (3–6 mm spot; 0.8–2 J/cm2) per area. Entire face, neck, upper chest, and arms were treated over multiple sessions. Treatments were very painful and general anesthesia was utilized in order to treat large areas. Near‐infrared spectroscopy was used to characterize and quantify the concentration of silver particles in the dermis based on the absorption features of the silver particles as well as the optical scattering effects they impart. We were able to estimate that there was, on average, 0.042 mg/ml concentration of silver prior to treatment and that these levels went below the minimum detectable limit of the instrument post‐treatment. There was no recurrence of discoloration over the 1‐year study period.

    Conclusion

    QS 1,064 nm laser treatment of argyria is a viable method to restore normal skin pigmentation with no evidence of recurrence over study period. Quantitative spectroscopic measurements: (1) confirmed dyspigmentation was due to silver, (2) validated our clinical assessment of no recurrence up to 1‐year post‐treatment, and (3) indicated no collateral tissue damage with treatments. Lasers Surg. Med. 45: 15–21, 2013. © 2013 Wiley Periodicals, Inc.

  • 26.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute, University of California, Irvine, USA.
    Kondru, Clement
    Beckman Laser Institute, University of California, Irvine, USA.
    Au, Kendrew
    Beckman Laser Institute, University of California, Irvine, USA.
    Sry, Kelly
    Beckman Laser Institute, University of California, Irvine, USA.
    Ayers, Frederick
    Beckman Laser Institute, University of California, Irvine, USA.
    Durkin, Anthony J.
    Beckman Laser Institute, University of California, Irvine, USA.
    Multilayer silicone phantoms for the evaluation of quantitative optical techniques in skin imaging2010In: Proceedings Volume 7567, Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurement of Tissue II; 756706 (2010) / [ed] Robert J. Nordström, SPIE - International Society for Optical Engineering, 2010, Vol. 7567, p. 756706-1-756706-8, article id 756706Conference paper (Refereed)
    Abstract [en]

    With the development of multilayer models for the analysis of quantitative spectroscopic techniques, there is a need to generate controlled and stable phantoms capable of validating these new models specific to the particular instrument performance and/or probe geometry. Direct applications for these multilayer phantoms include characterization or validation of depth penetration for specific probe geometries or describing layer specific sensitivity of optical instrumentation. We will present a method of producing interchangeable silicone phantoms that vary in thickness from 90 microns up to several millimeters which can be combined to produce multilayered structures to mimic optical properties of physiologic tissues such as skin. The optical properties of these phantoms are verified through inverse addingdoubling methods and the homogeneous distribution of optical properties will be discussed

  • 27.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Quach, Alan
    Beckman Laser Institute and Medical Clinic, USA.
    Kennedy, Gordon T.
    Beckman Laser Institute and Medical Clinic, USA.
    Tromberg, Bruce J.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    From theory to practice: the broadening role of polydimethylsiloxane phantoms as an intermediary between model validation and instrument performance testing (Conference Presentation)2016In: Proceedings Volume 9700, Design and Quality for Biomedical Technologies IX; 97000G (2016) / [ed] Ramesh Raghavachari, Rongguang Liang, SPIE - International Society for Optical Engineering, 2016, Vol. 9700, article id 97000GConference paper (Refereed)
    Abstract [en]

    Polydimethylsiloxane (PDMS) has been a popular medium to fabricate tissue simulating optical phantoms. Recently, its use has significantly expanded in instrument calibration and performance testing, validation of advanced models of light transport of complex tissue geometries and evaluation of novel measurement modalities. To meet these demands, fabrication methods of these optical phantoms have become more refined and its structure and constituent components (i.e. dyes and scattering agents) have evolved to better mimic optical properties of tissue spanning both visible and near infrared regimes. We present efforts at the Beckman Laser Institute that address these challenges through PDMS phantoms.

  • 28.
    Saager, Rolf B.
    et al.
    University of California, Irvine, USA.
    Quach, Alan
    University of California, Irvine, USA.
    Rowland, Rebecca A.
    University of California, Irvine, USA.
    Baldado, Melissa L.
    University of California, Irvine, USA.
    Durkin, Anthony J.
    University of California, Irvine, USA.
    Low-cost tissue simulating phantoms with adjustable wavelength-dependent scattering properties in the visible and infrared ranges2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 6, article id 067001Article in journal (Refereed)
    Abstract [en]

    We present a method for low-cost fabrication of polydimethylsiloxane (PDMS) tissue simulating phantoms with tunable scattering spectra, spanning visible, and near-infrared regimes. These phantoms use optical polishing agents (aluminum oxide powders) at various grit sizes to approximate in vivo tissue scattering particles across multiple size distributions (range: 17 to 3  μm). This class of tunable scattering phantoms is used to mimic distinct changes in wavelength-dependent scattering properties observed in tissue pathologies such as partial thickness burns. Described by a power-law dependence on wavelength, the scattering magnitude of these phantoms scale linearly with particle concentration over a physiologic range [μ's=(0.5 to 2.0  mm−1)] whereas the scattering spectra, specific to each particle size distribution, correlate to distinct exponential coefficients (range: 0.007 to 0.32). Aluminum oxide powders used in this investigation did not detectably contribute to the absorption properties of these phantoms. The optical properties of these phantoms are verified through inverse adding-doubling methods and the tolerances of this fabrication method are discussed.

  • 29.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Quach, Alan
    Beckman Laser Institute and Medical Clinic, USA.
    Rowland, Rebecca A.
    Beckman Laser Institute and Medical Clinic, USA.
    Baldado, Melissa L.
    Beckman Laser Institute and Medical Clinic, USA.
    Ponticorvo, Adrien
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Low-cost tissue simulating phantoms with tunable, wavelength-dependent scattering properties (Conference Presentation)2016In: Proceedings Volume 9700, Design and Quality for Biomedical Technologies IX; 970005 (2016), SPIE - International Society for Optical Engineering, 2016, Vol. 9700Conference paper (Refereed)
    Abstract [en]

    Tissue-simulating phantoms provide the opportunity to evaluate the performance of optical and spectroscopic instruments under controlled experimental conditions. Recent efforts have advanced phantom fabrication methods to provide more tissue realistic phantoms, both in terms of a) incorporating absorbing agents that more faithfully mimic in vivo tissue chromophores spanning visible and near infrared regimes and b) accounting for multi-layer tissue structures with distinct optical properties. The spectral scattering properties in these phantoms, however, are typically based only on a single scattering agent, thereby locking the spectral scattering properties to a single particle size distribution. However, in both healthy tissue as well as pathologic tissue, regions of distinct and differentiated scattering may be present. With differing mean size and distribution of scattering objects in these tissue regions, the relative wavelength-dependent scattering spectra may vary. For example, partial thickness burns exhibit significant cellular damage and collagen denaturation that will significantly alter the wavelength-dependent scattering properties resembling large Mie-like scatterer distributions in both visible and near infrared regimes. We present a low-cost method to fabricate silicone tissue-simulating phantoms with tunable scattering spectra properties that span visible and near infrared wavelengths. We use optical polishing agents (white aluminum oxides powders) at various grit sizes to approximate Mie scattering across multiple mean particle sizes. Mean particle sizes used in this study range from 17-3 micron. The optical properties of these phantoms are verified using an integrating sphere in combination with inverse adding-doubling methods. The tolerances of this fabrication method will be discussed.

  • 30.
    Saager, Rolf B.
    et al.
    University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States.
    Rowland, Rebecca A
    University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States.
    Baldado, Melissa L
    University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States.
    Kennedy, Gordon T
    University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States.
    Bernal, Nicole P
    UC Irvine Regional Burn Center, Department of Surgery, Orange, California, United States.
    Ponticorvo, Adrien
    University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States.
    Christy, Robert J
    United States Army Institute of Surgical Research, Burn and Soft Tissue Injury, San Antonio, Texas, United States.
    Durkin, Anthony J
    University of California Irvine, Beckman Laser Institute and Medical Clinic, Irvine, California, United States; University of California Irvine, Department of Biomedical Engineering, Irvine, California, United States.
    Impact of hemoglobin breakdown products in the spectral analysis of burn wounds using spatial frequency domain spectroscopy2019In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 24, no 2, article id 020501Article in journal (Refereed)
    Abstract [en]

    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.

  • 31.
    Saager, Rolf B.
    et al.
    University of California, Irvine, USA.
    Sharif, Ata
    University of California, Irvine, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    University of California, Irvine, USA.
    In vivo isolation of the effects of melanin from underlying hemodynamics across skin types using spatial frequency domain spectroscopy2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 5, article id 057001Article in journal (Refereed)
    Abstract [en]

    Skin is a highly structured tissue, raising concerns as to whether skin pigmentation due to epidermal melanin may confound accurate measurements of underlying hemodynamics. Using both venous and arterial cuff occlusions as a means of inducing differential hemodynamic perturbations, we present analyses of spectra limited to the visible or near-infrared regime, in addition to a layered model approach. The influence of melanin, spanning Fitzpatrick skin types I to V, on underlying estimations of hemodynamics in skin as interpreted by these spectral regions are assessed. The layered model provides minimal cross-talk between melanin and hemodynamics and enables removal of problematic correlations between measured tissue oxygenation estimates and skin phototype.

  • 32.
    Saager, Rolf B.
    et al.
    The Institute of Optics, University of Rochester, Rochester, NY 14627, USA.
    Telleri, Nicole L.
    Department of Biomedical Engineering, University of Rochester, Rochester, NY 14627, USA.
    Berger, Andrew J.
    The Institute of Optics, University of Rochester, Rochester, NY 14627, USA.
    Two-detector Corrected Near Infrared Spectroscopy (C-NIRS) detects hemodynamic activation responses more robustly than single-detector NIRS2011In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 55, no 4, p. 1679-1685Article in journal (Refereed)
    Abstract [en]

    In near-infrared spectroscopy (NIRS) of human cerebral hemodynamics, detection of stimulus-related responses is confounded by the presence of unrelated trends in both the brain and the overlying scalp. A proposed strategy for reducing hemodynamic noise has been to record “scalp only” trends simultaneously via a second shorter-separation detector (~5 mm rather than ~30 mm) and perform a subtraction (C-NIRS, for “corrected near-infrared spectroscopy”). To compare the single- and dual-detector strategies, a 21-volunteer study of visual stimulation responses (6 stimulation blocks and 8 recording channels per measurement run) has been conducted. Activation-flagged channels were defined based upon (a) the significance (p-value) of the average rise in oxyhemoglobin concentration and (b) the average signal-to-noise over 6 stimulation epochs. At reasonable thresholds (p < 0.025, SNR> 1), the C-NIRS method increased the number of activation-flagged channels from 47 to 66, an increase of 40%, adding 24 channels and eliminating only 5. Of the 71 channels that were activation-flagged by at least one modality, the C-NIRS time series exhibited more significant oxyhemoglobin rise in 80% of such channels, and better signal-to-noise in 73%. In addition, single-subject C-NIRS stimulus responses were more consistent than NIRS over the six stimulation epochs, with significantly lower coefficients of variation in both amplitude and latency (i.e.  time between stimulus onset and maximum hemoglobin rise). These results demonstrate that two-detector C-NIRS provides a straightforward way of (a) removing hemodynamic interference from NIRS data, (b) increasing the detection rate of cerebrally-unique responses, and (c) improving the quality of those recorded responses. Parallel insights regarding deoxyhemoglobin trends could not be drawn from this data set but should be attainable in future studies with higher signal to noise ratios.

  • 33.
    Saager, Rolf B.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Truong, Alex
    Beckman Laser Institute and Medical Clinic, USA.
    Cuccia, David J.
    Modulated Imaging, Inc. USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Method for depth-resolved quantitation of optical properties in layered media using spatially modulated quantitative spectroscopy2011In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 16, no 7, article id 077002Article in journal (Refereed)
    Abstract [en]

    We have demonstrated that spatially modulated quantitative spectroscopy (SMoQS) is capable of extracting absolute optical properties from homogeneous tissue simulating phantoms that span both the visible and near-infrared wavelength regimes. However, biological tissue, such as skin, is highly structured, presenting challenges to quantitative spectroscopic techniques based on homogeneous models. In order to more accurately address the challenges associated with skin, we present a method for depth-resolved optical property quantitation based on a two layer model. Layered Monte Carlo simulations and layered tissue simulating phantoms are used to determine the efficacy and accuracy of SMoQS to quantify layer specific optical properties of layered media. Initial results from both the simulation and experiment show that this empirical method is capable of determining top layer thickness within tens of microns across a physiological range for skin. Layer specific chromophore concentration can be determined to <±10% the actual values, on average, whereas bulk quantitation in either visible or near infrared spectroscopic regimes significantly underestimates the layer specific chromophore concentration and can be confounded by top layer thickness.

  • 34.
    Skeldon, Mark D.
    et al.
    Laboratory for Laser Energetics, University of Rochester, Rochester, NY, USA.
    Saager, Rolf B.
    Laboratory for Laser Energetics, University of Rochester, Rochester, NY, USA.
    Seka, Wolf
    Laboratory for Laser Energetics, University of Rochester, Rochester, NY, USA.
    Quantitative pump-induced wavefront distortions in laser-diode- and flashlamp-pumped Nd:YLF laser rods1999In: IEEE Journal of Quantum Electronics, ISSN 0018-9197, E-ISSN 1558-1713, Vol. 35, no 3, p. 381-386Article in journal (Refereed)
    Abstract [en]

    Detailed interferometric measurements of the induced thermal distortions due to laser-diode and xenon flashlamp pumping of Nd:LiYF/sub 4/ are presented. The thermal distortions are quantified in terms of the primary aberrations of defocus, astigmatism, coma, and spherical. Defocus and astigmatism are shown to dominate the thermal aberrations. The measured defocus and astigmatism are converted to the conventional thermal-focal lengths in two perpendicular directions with respect to the Nd:YLF crystalline c axis for each of the two polarization states /spl sigma/ and /spl pi/. A comparison of the thermal-focal lengths measured with our xenon flashlamp and laser-diode-pumped rods is given when the rods are pumped to the same small signal gain. We calculate effective dioptric-power coefficients from our data for comparison to those reported in the literature for krypton-flashlamp pumping. A thermal time constant of 1.5 s is measured for our laser-diode-pumped Nd:YLF laser rod.

  • 35.
    Strömberg, Tomas
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Kennedy, Gordon T.
    Beckman Laser Institute and Medical Clinic, USA.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Spatial frequency domain imaging using a snap-shot filter mosaic camera with multi-wavelength sensitive pixels2018In: Proceedings Volume 10467, Photonics in Dermatology and Plastic Surgery 2018; 104670D (2018) / [ed] Bernard Choi, and Haishan Zeng, SPIE - International Society for Optical Engineering, 2018, Vol. 10467, article id 104670DConference paper (Refereed)
    Abstract [en]

    Spatial frequency domain imaging (SFDI) utilizes a digital light processing (DLP) projector for illuminating turbid media with sinusoidal patterns. The tissue absorption (μa) and reduced scattering coefficient (μ,s) are calculated by analyzing the modulation transfer function for at least two spatial frequencies. We evaluated different illumination strategies with a red, green and blue light emitting diodes (LED) in the DLP, while imaging with a filter mosaic camera, XiSpec, with 16 different multi-wavelength sensitive pixels in the 470-630 nm wavelength range. Data were compared to SFDI by a multispectral camera setup (MSI) consisting of four cameras with bandpass filters centered at 475, 560, 580 and 650 nm. A pointwise system for comprehensive microcirculation analysis was used (EPOS) for comparison. A 5-min arterial occlusion and release protocol on the forearm of a Caucasian male with fair skin was analyzed by fitting the absorption spectra of the chromophores HbO2, Hb and melanin to the estimatedμa. The tissue fractions of red blood cells (fRBC), melanin (/mel) and the Hb oxygenation (S02 ) were calculated at baseline, end of occlusion, early after release and late after release. EPOS results showed a decrease in S02 during the occlusion and hyperemia during release (S02 = 40%, 5%, 80% and 51%). The fRBC showed an increase during occlusion and release phases. The best MSI resemblance to the EPOS was for green LED illumination (S02 = 53%, 9%, 82%, 65%). Several illumination and analysis strategies using the XiSpec gave un-physiological results (e.g. negative S02 ). XiSpec with green LED illumination gave the expected change in /RBC , while the dynamics in S02 were less than those for EPOS. These results may be explained by the calculation of modulation using an illumination and detector setup with a broad spectral transmission bandwidth, with considerable variation in μa of included chromophores. Approaches for either reducing the effective bandwidth of the XiSpec filters or by including their characteristic in a light transport model for SFDI modulation, are proposed.

  • 36.
    Sunar, Ulas
    et al.
    Dept of Cell Stress Biology & Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA / Dept of Biomedical Engineering, University at Buffalo, Buffalo, NY, USA.
    Rohrbach, Dan
    Dept of Cell Stress Biology & Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Muffoletto, Dan
    Dept of Biomedical Engineering, University at Buffalo, Buffalo, NY, USA.
    Saager, Rolf B.
    Dept Dermatology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Mo, Weirong
    Dept of Cell Stress Biology & Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Kowalczewski, Andrew
    Dept of Cell Stress Biology & Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Morgan, Janet
    Beckman Laser Institute, University of California Irvine, Irvine, CA, USA.
    Paquette, Anne
    Dept of Biomedical Engineering, University at Buffalo, Buffalo, NY, USA.
    Tromberg, Bruce J.
    Dept Dermatology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Zeitouni, Nathalie
    Dept of Cell Stress Biology & Oncology, Roswell Park Cancer Institute, Buffalo, NY, USA.
    Characterization of nonmelanoma skin cancer with multimodal imaging2014In: Biomedical Optics 2014, OSA Publishing , 2014, article id BS5A.5Conference paper (Refereed)
    Abstract [en]

    To guide intervention planning of nonmelanoma skin cancer (NMSC), information about the tumor depth and thickness as well as functional contrast is desired. The results indicate that ultrasound and spatial frequency domain imaging can provide accurate structural and enhanced contrasts in NMSC.

  • 37.
    Torabzadeh, Mohammad
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Stockton, Patrick A.
    Colorado State University, USA.
    Tromberg, Bruce J.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Kennedy, Gordon T.
    Beckman Laser Institute and Medical Clinic, USA.
    Bartels, Randy A.
    Colorado State University, USA.
    hyperspectral characterization of tissue simulating phantoms using a supercontinuum laser in a spatial frequency domain imaging instrument2018In: Proceedings Volume 10486, Design and Quality for Biomedical Technologies XI; 104860G (2018) / [ed] Ramesh Raghavachari and Rongguang Liang, SPIE - International Society for Optical Engineering, 2018, Vol. 10486, article id 104860GConference paper (Refereed)
    Abstract [en]

    Hyperspectral Imaging (HSI) is a growing field in tissue optics due to its ability to collect continuous spectral features of a sample without a contact probe. Spatial Frequency Domain Imaging (SFDI) is a non-contact wide-field spectral imaging technique that is used to quantitatively characterize tissue structure and chromophore concentration. In this study, we designed a Hyperspectral SFDI (H-SFDI) instrument which integrated a supercontinuum laser source to a wavelength tuning optical configuration and a sCMOS camera to extract spatial (Field of View: 2cm×2cm) and broadband spectral features (580nm-950nm). A preliminary experiment was also performed to integrate the hyperspectral projection unit to a compressed single pixel camera and Light Labeling (LiLa) technique.

  • 38.
    Vasefi, Fartash
    et al.
    Spectral Molecular Imaging Inc., USA.
    MacKinnon, Nicholas
    Spectral Molecular Imaging Inc., USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Chave, Robert
    Spectral Molecular Imaging Inc., USA.
    Farkas, Daniel L.
    Spectral Molecular Imaging Inc., USA.
    Quantifying the optical properties of turbid media using polarization sensitive hyperspectral imaging (SkinSpect): two-layer optical phantom studies2015In: Proceedings SPIE 9328, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XIII, 93280A (25 March 2015) / [ed] Daniel L. Farkas, Dan V. Nicolau, and Robert C. Leif, SPIE - International Society for Optical Engineering, 2015, Vol. 9328,, article id 93280AConference paper (Refereed)
    Abstract [en]

    A polarization-sensitive hyperspectral imaging system (SkinSpect) has been built and evaluated using two-layer tissue phantoms, fabricated to mimic the optical properties of melanin in different epidermal thickness and hemoglobin in dermal layers. Multiple tissue-mimicking phantoms with varying top layer thicknesses were measured for optical system calibration and performance testing. Phantom properties were characterized and validated using SkinSpect. The resulting analysis shows that the proposed system is capable of distinguishing and differentiating the layer-dependent absorption spectra and the depths at which this absorption occurs.

  • 39.
    Vasefi, Fartash
    et al.
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    MacKinnon, Nicholas
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA, USA.
    Chave, Robert
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    Lindsley, Erik H.
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA.
    Farkas, Daniel L.
    Spectral Molecular Imaging Inc., 250 N. Robertson Blvd., Beverly Hills CA, USA / Department of Biomedical Engineering, University of Southern California, Los Angeles CA, USA.
    Polarization-Sensitive Hyperspectral Imaging in vivo: A Multimode Dermoscope for Skin Analysis2014In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 4, no 1, article id 4924Article in journal (Refereed)
    Abstract [en]

    Attempts to understand the changes in the structure and physiology of human skin abnormalities by non-invasive optical imaging are aided by spectroscopic methods that quantify, at the molecular level, variations in tissue oxygenation and melanin distribution. However, current commercial and research systems to map hemoglobin and melanin do not correlate well with pathology for pigmented lesions or darker skin. We developed a multimode dermoscope that combines polarization and hyperspectral imaging with an efficient analytical model to map the distribution of specific skin bio-molecules. This corrects for the melanin-hemoglobin misestimation common to other systems, without resorting to complex and computationally intensive tissue optical models. For this system's proof of concept, human skin measurements on melanocytic nevus, vitiligo, and venous occlusion conditions were performed in volunteers. The resulting molecular distribution maps matched physiological and anatomical expectations, confirming a technologic approach that can be applied to next generation dermoscopes and having biological plausibility that is likely to appeal to dermatologists.

  • 40.
    Vasefi, Fartash
    et al.
    Spectral Molecular Imaging, Inc., USA.
    MacKinnon, Nicholas
    Spectral Molecular Imaging, Inc., USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, USA.
    Maly, Tyler
    Beckman Laser Institute and Medical Clinic, USA.
    Booth, Nicholas
    Spectral Molecular Imaging, Inc., USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Farkas, Daniel L.
    Spectral Molecular Imaging, Inc., USA.
    Separating melanin from hemodynamics in nevi using multimode hyperspectral dermoscopy and spatial frequency domain spectroscopy2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 11, article id 114001Article in journal (Refereed)
    Abstract [en]

    Changes in the pattern and distribution of both melanocytes (pigment producing) and vasculature (hemoglobin containing) are important in distinguishing melanocytic proliferations. The ability to accurately measure melanin distribution at different depths and to distinguish it from hemoglobin is clearly important when assessing pigmented lesions (benign versus malignant). We have developed a multimode hyperspectral dermoscope (SkinSpect™) able to more accurately image both melanin and hemoglobin distribution in skin. SkinSpect uses both hyperspectral and polarization-sensitive measurements. SkinSpect’s higher accuracy has been obtained by correcting for the effect of melanin absorption on hemoglobin absorption in measurements of melanocytic nevi. In vivo human skin pigmented nevi (N=20) were evaluated with the SkinSpect, and measured melanin and hemoglobin concentrations were compared with spatial frequency domain spectroscopy (SFDS) measurements. We confirm that both systems show low correlation of hemoglobin concentrations with regions containing different melanin concentrations (R=0.13 for SFDS, R=0.07 for SkinSpect).

  • 41.
    Vasefi, Fartash
    et al.
    Spectral Molecular Imaging, Inc., USA.
    MacKinnon, Nicholas
    Spectral Molecular Imaging, Inc., USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Kelly, Kristen M.
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Maly, Tyler
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Chave, Robert
    Spectral Molecular Imaging, Inc., USA.
    Booth, Nicholas
    Spectral Molecular Imaging, Inc., USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, Univ. of California, Irvine, USA.
    Farkas, Daniel L.
    Spectral Molecular Imaging, Inc., USA.
    Multimode optical dermoscopy (SkinSpect) analysis for skin with melanocytic nevus2016In: Proceedings Volume 9711, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues IX; 971110 (2016) / [ed] Daniel L. Farkas, Dan V. Nicolau, and Robert C. Leif, SPIE - International Society for Optical Engineering, 2016, Vol. 8711, article id 971110Conference paper (Refereed)
    Abstract [en]

    We have developed a multimode dermoscope (SkinSpect™) capable of illuminating human skin samples in-vivo with spectrally-programmable linearly-polarized light at 33 wavelengths between 468nm and 857 nm. Diffusely reflected photons are separated into collinear and cross-polarized image paths and images captured for each illumination wavelength. In vivo human skin nevi (N = 20) were evaluated with the multimode dermoscope and melanin and hemoglobin concentrations were compared with Spatially Modulated Quantitative Spectroscopy (SMoQS) measurements. Both systems show low correlation between their melanin and hemoglobin concentrations, demonstrating the ability of the SkinSpect™ to separate these molecular signatures and thus act as a biologically plausible device capable of early onset melanoma detection.

  • 42.
    Vasefi, Fartash
    et al.
    Spectral Molecular Imaging Inc., USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    MacKinnon, Nicholas
    Spectral Molecular Imaging Inc., USA.
    Gussakovsky, Eugene
    Spectral Molecular Imaging Inc., USA.
    Chave, Robert
    Spectral Molecular Imaging Inc., USA.
    Farkas, Daniel L.
    Spectral Molecular Imaging Inc., USA.
    Quantifying the optical properties and chromophore concentrations of turbid media using polarization sensitive hyperspectral imaging: optical phantom studies2013In: Proceedings Volume 8587, Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XI; 85870Z (2013) SPIE BiOS, 2013, San Francisco, California, United States / [ed] aniel L. Farkas, Dan V. Nicolau, and Robert C. Leif, SPIE - International Society for Optical Engineering, 2013, Vol. 8587, article id 85870ZConference paper (Refereed)
    Abstract [en]

    We present a polarization-sensitive hyperspectral imaging system (SkinSpect) that employs a spectrally-programmable light source in the visible and NIR domains. Multiple tissue-mimicking phantoms were fabricated to mimic the optical properties of normal skin as well as pigmented light and dark moles. The phantoms consist of titanium dioxide and a mixture of coffee, red food dye, and naphthol green as the scattering and the three absorptive agents in a polydimethylsiloxane (PDMS) base. Phantoms were produced with both smooth and rough textured surfaces and tested using Spatial Frequency Domain Imaging (SFDI) and Spatially Modulated Quantitative Spectroscopy (SMoQS) for homogeneity as well as determining absorption and scattering variance, respectively. The reflectance spectral images were also recorded using the SkinSpect research prototype; the spectral signatures of the phantoms were calculated using a two-flux single-layer Kubelka-Munk model and non-negative least square fitting routine was applied to extract the relative concentrations of the individual phantom components.

  • 43.
    Wilson, Robert H.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Nadeau, Kyle P.
    Beckman Laser Institute and Medical Clinic, USA.
    Jaworski, Frank B.
    Raytheon Vision Systems, USA.
    Rowland, Rebecca
    Beckman Laser Institute and Medical Clinic, USA.
    Nguyen, John Q.
    Beckman Laser Institute and Medical Clinic, USA.
    Crouzet, Christian
    Beckman Laser Institute and Medical Clinic, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Choi, Bernard
    Beckman Laser Institute and Medical Clinic, USA.
    Tromberg, Bruce J.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Quantitative short-wave infrared multispectral imaging of in vivo tissue optical properties2014In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, no 8, article id 086011Article in journal (Refereed)
    Abstract [en]

    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

  • 44.
    Yafi, Amr
    et al.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA 92617, USA.
    Vetter, Thomas S.
    Aesthetic and Plastic Surgery Institute, University of California, Irvine 200 S. Manchester Ave., Suite 650, Orange, CA 92868, USA.
    Scholz, Thomas
    Aesthetic and Plastic Surgery Institute, University of California, Irvine 200 S. Manchester Ave., Suite 650, Orange, CA 92868, USA.
    Patel, Sarin
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA 92617, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA 92617, USA.
    Cuccia, David J.
    Modulated Imaging Inc., Beckman Laser Institute Photonic Incubator 1002 Health Sciences Rd. East, Irvine, CA 92617, USA.
    Evans, Gregory R.
    Aesthetic and Plastic Surgery Institute, University of California, Irvine 200 S. Manchester Ave., Suite 650, Orange, CA 92868, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Rd. East, Irvine, CA 92617, USA.
    Postoperative Quantitative Assessment of Reconstructive Tissue Status in a Cutaneous Flap Model Using Spatial Frequency Domain Imaging2011In: Plastic and reconstructive surgery (1963), ISSN 0032-1052, E-ISSN 1529-4242, Vol. 127, no 1, p. 117-130Article in journal (Refereed)
    Abstract [en]

    Background:

    The purpose of this study was to investigate the capabilities of a novel optical wide-field imaging technology known as spatial frequency domain imaging to quantitatively assess reconstructive tissue status.

    Methods:

    Twenty-two cutaneous pedicle flaps were created on 11 rats based on the inferior epigastric vessels. After baseline measurement, all flaps underwent vascular ischemia, induced by clamping the supporting vessels for 2 hours (either arteriovenous or selective venous occlusions); normal saline was injected into the control flap and hypertonic-hyperoncotic saline solution was injected into the experimental flap. Flaps were monitored for 2 hours after reperfusion. The spatial frequency domain imaging system was used for quantitative assessment of flap status over the duration of the experiment.

    Results:

    All flaps demonstrated a significant decline in oxyhemoglobin and tissue oxygen saturation in response to occlusion. Total hemoglobin and deoxyhemoglobin were increased markedly in the selective venous occlusion group. After reperfusion and the administration of solutions, oxyhemoglobin and tissue oxygen saturation in those flaps that survived gradually returned to baseline levels. However, flaps for which oxyhemoglobin and tissue oxygen saturation did not show any signs of recovery appeared to be compromised and eventually became necrotic within 24 to 48 hours in both occlusion groups.

    Conclusions:

    Spatial frequency domain imaging technology provides a quantitative, objective method of assessing tissue status. This study demonstrates the potential of this optical technology to assess tissue perfusion in a very precise and quantitative way, enabling wide-field visualization of physiologic parameters. The results of this study suggest that spatial frequency domain imaging may provide a means for prospectively identifying dysfunctional flaps well in advance of failure.

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