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  • 1.
    Antonsson, Johan
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Eriksson, Ola
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Radio frequency electrode system for optical lesion size estimation in functional neurosurgery2005In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 10, no 3, p. 1-6Article in journal (Refereed)
    Abstract [en]

    Radiofrequency(RF) lesioning in the human brain is one possible surgicaltherapy for severe pain as well as movement disorders. Oneobstacle for a safer lesioning procedure is the lack ofsize monitoring. The aim of this study was to investigateif changes in laser Doppler or intensity signals could beused as markers for size estimation during experimental RF lesioning.A 2 mm in diameter monopolar RF electrode was equippedwith optical fibers and connected to a digital laser Dopplersystem. The optical RF electrode's performance was equal to astandard RF electrode with the same dimensions. An albumin solutionwith scatterers was used to evaluate the intensity and laserDoppler signal changes during lesioning at 70, 80, and 90 °C.Significant signal changes were found for these three different clotsizes, represented by the temperatures (p<0.05,  n=10). The volume, width, andlength of the created coagulations were correlated to the intensitysignal changes (r=0.88, n=30, p<0.0001) and to the perfusion signalchanges (r=0.81, n=30, p<0.0001). Both static and Doppler-shifted light canbe used to follow the lesioning procedure as well asbeing used for lesion size estimation during experimental RF lesioning.

  • 2.
    Arildsson, Mikael
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Higher order moment processing of laser Doppler perfusion signals1997In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 2, no 4, p. 358-363Article in journal (Refereed)
    Abstract [en]

    The laser Doppler technique is used to assess tissue perfusion. Traditionally an integrated, ω-weighted (first-order filter) power spectrum is used to estimate perfusion. In order to be able to obtain selective information about the flow in vessels with different blood cell velocities, higher order filters have been implemented, investigated, and evaluated. Theoretical considerations show that the output of the signal processor will depend on the flow speed, for a given concentration of blood cells, according to Soutνn where v is the average blood cell speed and n is the spectral filter order. An implementation of filters using zero-, first-, second-, and third-order spectral moments was utilized to experimentally verify the theory by using a laser Doppler perfusion imager. Two different flow models were utilized: A Plexiglas model was used to demonstrate the various signatures of the power spectrum for different flow speeds and filter orders, whereas a Delrin model was used to study the relationship between the flow velocity and the output of the signal processor for the different filters. The results show good agreement with theory and also good reproducibility. Recordings made on the skin of the wrist area demonstrated that the flow in small veins can be visualized by the use of higher spectral orders.

  • 3.
    Blockhuys, Stephanie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Chalmers University of Technology, Sweden.
    Rani Agarwal, Nisha
    Chalmers University of Technology, Sweden; McMaster University, Canada; McMaster University, Canada.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Jarlsfelt, Ingvar
    Ryhov Hospital, Sweden.
    Wittung-Stafshede, Pernilla
    Chalmers University of Technology, Sweden.
    Sun, Xiao-Feng
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
    Second harmonic generation for collagen I characterization in rectal cancer patients with and without preoperative radiotherapy2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 10, article id 106006Article in journal (Refereed)
    Abstract [en]

    Rectal cancer is treated with preoperative radiotherapy (RT) to downstage the tumor, reduce local recurrence, and improve patient survival. Still, the treatment outcome varies significantly and new biomarkers are desired. Collagen I (Col-I) is a potential biomarker, which can be visualized label-free by second harmonic generation (SHG). Here, we used SHG to identify Col-I changes induced by RT in surgical tissue, with the aim to evaluate the clinical significance of RT-induced Col-I changes. First, we established a procedure for quantitative evaluation of Col-I by SHG in CDX2-stained tissue sections. Next, we evaluated Col-I properties in material from 31 non-RT and 29 RT rectal cancer patients. We discovered that the Col-I intensity and anisotropy were higher in the tumor invasive margin than in the inner tumor and normal mucosa, and RT increased and decreased the intensity in inner tumor and normal mucosa, respectively. Furthermore, higher Col-I intensity in the inner tumor was related to increased distant recurrence in the non-RT group but to longer survival in the RT group. In conclusion, we present a new application of SHG for quantitative analysis of Col-I in surgical material, and the first data suggest Col-I intensity as a putative prognostic biomarker in rectal cancer. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 4.
    Briers, David
    et al.
    University of Kingston, England .
    Duncan, Donald D.
    Portland State University, OR USA .
    Hirst, Evan
    Callaghan Innovat, New Zealand .
    Kirkpatrick, Sean J.
    Michigan Technology University, MI USA .
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Steenbergen, Wiendelt
    University of Twente, Netherlands .
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Thompson, Oliver B.
    Callaghan Innovat, New Zealand .
    Laser speckle contrast imaging: theoretical and practical limitations2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 6Article in journal (Refereed)
    Abstract [en]

    When laser light illuminates a diffuse object, it produces a random interference effect known as a speckle pattern. If there is movement in the object, the speckles fluctuate in intensity. These fluctuations can provide information about the movement. A simple way of accessing this information is to image the speckle pattern with an exposure time longer than the shortest speckle fluctuation time scale-the fluctuations cause a blurring of the speckle, leading to a reduction in the local speckle contrast. Thus, velocity distributions are coded as speckle contrast variations. The same information can be obtained by using the Doppler effect, but producing a two-dimensional Doppler map requires either scanning of the laser beam or imaging with a high-speed camera: laser speckle contrast imaging (LSCI) avoids the need to scan and can be performed with a normal CCD- or CMOS-camera. LSCI is used primarily to map flow systems, especially blood flow. The development of LSCI is reviewed and its limitations and problems are investigated. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

  • 5.
    Ellingsen, Pal Gunnar
    et al.
    Norwegian University of Science and Technology, Norway .
    Nyström, Sofie
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
    Reitan, Nina Kristine
    Norwegian University of Science and Technology, Norway .
    Lindgren, Mikael
    Norwegian University of Science and Technology, Norway .
    Spectral correlation analysis of Amyloid beta plaque inhomogeneity from double staining experiments2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 10Article in journal (Refereed)
    Abstract [en]

    A spectral correlation algorithm for the analysis of hyperspectral fluorescence images is proposed by Ellingsen et al. [J. Biomed. Opt. 18, 020501 (2013)]. Here, it is applied to the analysis of double-stained A beta amyloid plaques being related to the Alzheimers disease (AD). Sections of APP/PS1 AD mice model brains are double stained with luminescent-conjugated oligothiophenes, known to bind to amyloid protein deposits. Hyperspectral fluorescence images of the brain sections are recorded and by applying the correlation algorithm the spectral inhomogeneity of the double-stained samples is mapped in terms of radial distribution and spectral content. To further investigate the progression of A beta amyloid plaque formation, 19 AD mice of different ages up to 23 months are characterized, enabling a statistical analysis of the plaque heterogeneity. In accordance with recent findings by Nystrom et al. [ACS Chem. Biol. 8, 1128-1133 (2013)], the spectral distribution within A beta plaques is found to vary with age throughout the lifespan of the mouse. With the new correlation algorithm, it is possible to quantify the spectral abundance of the two stains depending on the relative distance from the plaque center and mouse age. Thus, we demonstrate the use of the correlation analysis approach in double-staining experiments and how it is possible to relate these to structural/spectral changes in biological samples. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

  • 6.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Perimed AB, Järfälla, Sweden.
    Burdakov, Oleg
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 12, p. 127004-1-127004-14Article in journal (Refereed)
    Abstract [en]

    The tissue fraction of red blood cells (RBCs) and their oxygenation and speed-resolved perfusion areestimated in absolute units by combining diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry(LDF). The DRS spectra (450 to 850 nm) are assessed at two source–detector separations (0.4 and 1.2 mm), allowingfor a relative calibration routine, whereas LDF spectra are assessed at 1.2mmin the same fiber-optic probe. Data areanalyzed using nonlinear optimization in an inverse Monte Carlo technique by applying an adaptive multilayeredtissue model based on geometrical, scattering, and absorbing properties, as well as RBC flow-speed information.Simulations of 250 tissue-like models including up to 2000 individual blood vessels were used to evaluatethe method. The absolute root mean square (RMS) deviation between estimated and true oxygenation was 4.1percentage units, whereas the relative RMS deviations for the RBC tissue fraction and perfusion were 19% and23%, respectively. Examples of in vivo measurements on forearm and foot during common provocations arepresented. The method offers several advantages such as simultaneous quantification of RBC tissue fractionand oxygenation and perfusion from the same, predictable, sampling volume. The perfusion estimate is speedresolved, absolute (% RBC × mm∕s), and more accurate due to the combination with DRS.

  • 7.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Hultman, Martin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Machine learning in multiexposure laser speckle contrast imaging can replace conventional laser Doppler flowmetry2019In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 24, no 1, article id 016001Article in journal (Refereed)
    Abstract [en]

    Laser speckle contrast imaging (LSCI) enables video rate imaging of blood flow. However, its relation to tissue blood perfusion is nonlinear and depends strongly on exposure time. By contrast, the perfusion estimate from the slower laser Doppler flowmetry (LDF) technique has a relationship to blood perfusion that is better understood. Multiexposure LSCI (MELSCI) enables a perfusion estimate closer to the actual perfusion than that using a single exposure time. We present and evaluate a method that utilizes contrasts from seven exposure times between 1 and 64 ms to calculate a perfusion estimate that resembles the perfusion estimate from LDF. The method is based on artificial neural networks (ANN) for fast and accurate processing of MELSCI contrasts to perfusion. The networks are trained using modeling of Doppler histograms and speckle contrasts from tissue models. The importance of accounting for noise is demonstrated. Results show that by using ANN, MELSCI data can be processed to LDF perfusion with high accuracy, with a correlation coefficient R = 1.000 for noise-free data, R = 0.993 when a moderate degree of noise is present, and R = 0.995 for in vivo data from an occlusion-release experiment. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

  • 8.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    On the equivalence and differencesbetween laser Doppler flowmetry andlaser speckle contrast analysis2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 12, article id 126018Article in journal (Refereed)
    Abstract [en]

    Laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LASCA) both utilize the spatiotemporalproperties of laser speckle patterns to assess microcirculatory blood flow in tissue. Although the techniquesanalyze the speckle pattern differently, there is a close relationship between them. We present atheoretical overview describing how the LDF power spectrum and the LASCA contrast can be calculatedfrom each other, and how both these can be calculated from an optical Doppler spectrum containing variousdegrees of Doppler shifted light. The theoretical relationships are further demonstrated using time-resolvedspeckle simulations. A wide range of Monte Carlo simulated tissue models is then used to show how perfusionestimates for LDF and LASCA are affected by changes in blood concentration and speed distribution, as well asby geometrical and optical properties. We conclude that perfusion estimates from conventional single exposuretime LASCA are in general more sensitive to changes in optical and geometrical properties and are less accuratein the prediction of real perfusion changes, especially speed changes. Since there is a theoretical one-to-onerelationship between Doppler power spectrum and contrast, one can conclude that those drawbacks with theLASCA technique can be overcome using a multiple exposure time setup.

  • 9.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Vessel packaging effect in laser speckle contrast imaging and laser Doppler imaging2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 10, article id 106005Article in journal (Refereed)
    Abstract [en]

    Laser speckle-based techniques are frequently used to assess microcirculatory blood flow. Perfusion estimates are calculated either by analyzing the speckle fluctuations over time as in laser Doppler flowmetry (LDF), or by analyzing the speckle contrast as in laser speckle contrast imaging (LSCI). The perfusion estimates depend on the amount of blood and its speed distribution. However, the perfusion estimates are commonly given in arbitrary units as they are nonlinear and depend on the magnitude and the spatial distribution of the optical properties in the tissue under investigation. We describe how the spatial confinement of blood to vessels, called the vessel packaging effect, can be modeled in LDF and LSCI, which affect the Doppler power spectra and speckle contrast, and the underlying bio-optical mechanisms for these effects. As an example, the perfusion estimate is reduced by 25% for LDF and often more than 50% for LSCI when blood is located in vessels with an average diameter of 40 aem, instead of being homogeneously distributed within the tissue. This significant effect can be compensated for only with knowledge of the average diameter of the vessels in the tissue. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 10.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo method in a multilayered tissue model for diffuse reflectance spectroscopy2012In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 17, no 4, p. 047004-Article in journal (Refereed)
    Abstract [en]

    Model based data analysis of diffuse reflectance spectroscopy data enables the estimation of optical and structural tissue parameters. The aim of this study was to present an inverse Monte Carlo method based on spectra from two source-detector distances (0.4 and 1.2 mm), using a multilayered tissue model. The tissue model variables include geometrical properties, light scattering properties, tissue chromophores such as melanin and hemoglobin, oxygen saturation and average vessel diameter. The method utilizes a small set of presimulated Monte Carlo data for combinations of different levels of epidermal thickness and tissue scattering. The path length distributions in the different layers are stored and the effect of the other parameters is added in the post-processing. The accuracy of the method was evaluated using Monte Carlo simulations of tissue-like models containing discrete blood vessels, evaluating blood tissue fraction and oxygenation. It was also compared to a homogeneous model. The multilayer model performed better than the homogeneous model and all tissue parameters significantly improved spectral fitting. Recorded in vivo spectra were fitted well at both distances, which we previously found was not possible with a homogeneous model. No absolute intensity calibration is needed and the algorithm is fast enough for real-time processing.

  • 11.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Model-based quantitative laser Doppler flowmetry in skin2010In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 5Article in journal (Refereed)
    Abstract [en]

    Laser Doppler Flowmetry (LDF) can be used for assessing the microcirculatory perfusion. However, conventional LDF (cLDF) gives only a relative perfusion estimate in an unknown measurement volume. To overcome these limitations a model-based analysis method for quantitative LDF (qLDF) is proposed. The method uses an inverse Monte Carlo technique with an adaptive three layer skin model. By analyzing the optimal model where measured and simulated LDF spectra using two different source-detector separations match, the absolute microcirculatory perfusion for a specified velocity region in a predefined volume is determined. The robustness of the qLDF method and how much it is affected by physiologically relevant variations in optical properties were evaluated using additional Monte Carlo simulations. When comparing qLDF to cLDF, a much smaller deviation from the true perfusion was attained. For physiologically relevant variations in the optical properties of static tissue and blood absorption, qLDF displayed errors <12%. Variations in the scattering properties of blood displayed larger errors (<58%). Evaluations on inhomogeneous models containing small blood vessels, hair and sweat glands displayed errors <5%. For extremely inhomogeneous models containing larger blood vessels, the error increased substantially, but this was detected by analyzing the qLDF model residual. The qLDF algorithm was applied to an in vivo local heat provocation. The perfusion increase was higher with qLDF than cLDF, due to non-linear effects in the latter. The qLDF showed that the perfusion increase was due to an increased amount of blood cells with a velocity > 1 mm/s.

  • 12.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry2008In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 1, p. 14015-Article in journal (Refereed)
    Abstract [en]

    An optical microvascular skin model, valid at 780 nm, was developed. The model consisted of six layers with individual optical properties, and variable thicknesses and blood concentrations at three different blood flow velocities. Monte Carlo simulations were used to evaluate the impact of various model parameters on the traditional Laser Doppler flowmetry (LDF) measures. A set of reference Doppler power spectra was generated by simulating 7,000 configurations, varying the thickness and blood concentrations. Simulated spectra, at two different source detector separations, were compared with in vivo recorded spectra, using a non-linear search algorithm for minimizing the deviation between simulated and measured spectra. The model was validated by inspecting the thickness and blood concentrations which generated the best fit. These four parameters followed a priori expectations for the measurement situations, and the simulated spectra agreed well with the measured spectra for both detector separations. Average estimated dermal blood concentration was 0.08% at rest and 0.63% during heat provocation (44°C) on the volar side of the forearm, and 1.2% at rest on the finger pulp. The model is crucial for developing a technique for velocity-resolved absolute LDF measurements with known sampling volume, and can also be useful for other bio-optical modalities.

  • 13.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Saager, Rolf B.
    University of Calif Irvine, CA 92715 USA.
    Durkin, Anthony J.
    University of Calif Irvine, CA USA.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. University of Calif Irvine, CA 92715 USA.
    Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 11, article id 115004Article in journal (Refereed)
    Abstract [en]

    A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (f(RBC)), oxygen saturation (S-O2), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source-detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The rootmean-square (RMS) deviations for f(RBC) for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for SO2 was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (mus), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter (D) was 1 mu m. In conclusion, the skin microcirculation parameters fRBC and SO2, as well as, mu(s) and D are estimated with reasonable accuracy. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 14.
    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.

  • 15.
    Horan, Sean T
    et al.
    University of California, Department of Mathematics, Irvine, California, United States; University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, Cali, United States.
    Gardner, Adam R
    University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, Cali, United States; University of California, Department of Chemical Engineering and Materials Science, Irvine, Californ, United States.
    Saager, Rolf
    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, Cali, United States.
    Durkin, Anthony J
    University of California, Beckman Laser Institute, Laser Microbeam and Medical Program, Irvine, Cali, 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, Cali, United States; University of California, Department of Chemical Engineering and Materials Science, Irvine, Californ, 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  −  0.8<i>l</i><sup>  *  </sup>  )  . We utilize an analytic forward solver, based upon the <i>N</i>’th-order spherical harmonic expansion with Fourier decomposition   (  SHEF<sub>N</sub>  )   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.

  • 16.
    Häggblad, Erik
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Lindbergh, Tobias
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Karlsson, M. G. Daniel
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Medical Informatics.
    Casimir-Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Myocardial tissue oxygenation estimated with calibrated diffuse reflectance spectroscopy during coronary artery bypass grafting2008In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 5, p. 054030-Article in journal (Refereed)
    Abstract [en]

    We present a study using a method able to assess tissue oxygenation, taking into account the absorption and the level of scattering in myocardial tissue using a calibrated fiber optic probe. With this method, interindividual comparisons of oxygenation can be made despite varying tissue optical properties during coronary artery bypass grafting (CABG). During CABG, there are needs for methods allowing continuous monitoring and prediction of the metabolism in the myocardial tissue. 14 patients undergoing CABG are investigated for tissue oxygenation during different surgical phases using a handheld fiber optic spectroscopic probe with a source-detector distance of less than 1 mm. The probe is calibrated using a light transport model, relating the absorption and reduced scattering coefficients (mu(a) and mu()(s)) to the measured spectra. By solving the inverse problem, absolute measures of tissue oxygenation are evaluated by the sum of oxygenized hemoglobin and myoglobin. Agreement between the model and measurements is obtained with an average correlation coefficient R-2 of 0.96. Oxygenation is found to be significantly elevated after aorta cross-clamping and cardioplegic infusion, as well as after reperfusion, compared to a baseline (p < 0.05). Tissue oxygenation decreases during cardiac arrest and increases after reperfusion.

  • 17.
    Jacob, Stefan
    et al.
    Karolinska Institutet / Karolinska University Hospital, Stockholm, Sweden.
    Tomo, Igor
    Karolinska Institutet / Karolinska University Hospital, Stockholm, Sweden.
    Fridberger, Anders
    Karolinska Institutet / Karolinska University Hospital, Stockholm, Sweden.
    Boutet de Monvel, Jacques
    Karolinska Institutet / Karolinska University Hospital, Stockholm, Sweden.
    Ulfendahl, Mats
    Karolinska Institutet / Karolinska University Hospital, Stockholm, Sweden.
    Rapid confocal imaging for measuring sound-induced motion of the hearing organ in the apical region2007In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 12, no 2, p. 021005-1-021005-6Article in journal (Refereed)
    Abstract [en]

    We describe a novel confocal image acquisition system capable of measuring the sound-evoked motion of the organ of Corti. The hearing organ is imaged with a standard laser scanning confocal microscope during sound stimulation. The exact temporal relation between each image pixel and the sound stimulus is quantified. The motion of the structures under study is obtained by fitting a Fourier series to the time dimension of a continuous sequence of acquired images. Previous versions of this acquisition system used a simple search to find pixels with similar phase values. The Fourier series approach permits substantially faster image acquisition with reduced noise levels and improved motion estimation. The system is validated by imaging various vibrating samples attached to a feedback-controlled piezoelectric translator. When using a rigid sample attached to the translator, the system is capable of measuring motion with peak-to-peak amplitudes smaller than 50 nm with an error below 20% at frequencies between 50 and 600 Hz. Examples of image sequences from the inner ear are given, along with detailed performance characteristics of the method.

  • 18.
    Johansson, Johannes
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Spectroscopic method for determination of the absorption coefficient in brain tissue2010In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 5, p. 057005-1-057005-9Article in journal (Refereed)
    Abstract [en]

    I use MonteCarlo simulations and phantom measurements to characterize a probe withadjacent optical fibres for diffuse reflectance spectroscopy during stereotactic surgeryin the brain. Simulations and measurements have been fitted toa modified Beer–Lambert model for light transport in order tobe able to quantify chromophore content based on clinically measuredspectra in brain tissue. It was found that it isimportant to take the impact of the light absorption intoaccount when calculating the apparent optical path length, lp, forthe photons in order to get good estimates of theabsorption coefficient, µa. The optical path length was found tobe well fitted to the equation lp=a+b ln(Is)+c ln(µa)+d ln(Is)ln(µa), where Is isthe reflected light intensity for scattering alone (i.e., zero absorption).Although coefficients ad calculated in this study are specific tothe probe used here, the general form of the equationshould be applicable to similar probes.

  • 19.
    Johansson, Johannes D.
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Eriksson, Ola
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Simulation of reflected light intensity changes during navigation and radio frequency lesioning in the brain2009In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 14, no 044040Article in journal (Refereed)
    Abstract [en]

    An electrode with adjacent optical fibers for measurements during navigation and radio frequency lesioning in the brain was modeled for Monte Carlo simulations of light transport in brain tissue. Relative reflected light intensity at 780 nm, I780, from this electrode and probes with identical fiber configuration were simulated using the intensity from native white matter as reference. Models were made of homogeneousnative and coagulated gray, thalamus, and white matter as well as blood. Dual layermodels, including models with a layer of cerebrospinal fluid between the fibers andthe brain tissue, were also made. Simulated I780 was 0.16 for gray matter, 0.67 forcoagulate gray matter, 0.36 for thalamus, 0.39 for coagulated thalamus, unity forwhite matter, 0.70 for coagulated white matter and 0.24 for blood. Thalamic matterhas also been found to reflect more light than gray matter and less than white matterin clinical studies. In conclusion the reflected light intensity can be used todifferentiate between gray and white matter during navigation. Furthermore,coagulation of light gray tissue, such as the thalamus, might be difficult to detectusing I780, but coagulation in darker gray tissue should result in a rapid increase of I780.

  • 20.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Järfälla, Stockholm, Sweden.
    Bergstrand, Sara
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    In vivo characterization of light scattering properties of human skin in the 475- to 850-nm wavelength range in a Swedish cohort2018In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 23, no 12, article id 121608Article in journal (Refereed)
    Abstract [en]

    We have determined in vivo optical scattering properties of normal human skin in 1734 subjects, mostly with fair skin type, within the Swedish CArdioPulmonary bioImage Study. The measurements were performed with a noninvasive system, integrating spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical, and absorbing properties of the tissue. The reduced scattering coefficient was found to decrease from 3.16 ± 0.72 to 1.13 ± 0.27 mm-1 (mean ± SD) in the 475- to 850-nm wavelength range. There was a negative correlation between the reduced scattering coefficient and age, and a significant difference between men and women in the reduced scattering coefficient as well as in the fraction of small scattering particles. This large study on tissue scattering with mean values and normal variation can serve as a reference when designing diagnostic techniques or when evaluating the effect of therapeutic optical systems.

  • 21.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Validation of speed-resolved laser Doppler perfusion in a multimodal optical system using a blood-flow phantom2019In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 24, no 9, article id 095002Article in journal (Refereed)
    Abstract [en]

    The PeriFlux 6000 EPOS system combines diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) for the assessment of oxygen saturation (expressed in percentage), red blood cell (RBC) tissue fraction (expressed as volume fraction, %RBC), and perfusion (%RBC x mm/s) in the microcirculation. It also allows the possibility of separating the perfusion into three speed regions (0 to 1, 1 to 10, and amp;gt;10 mm/s). We evaluate the speed-resolved perfusion components, i.e., the relative amount of perfusion within each speed region, using a blood-flow phantom. Human blood was pumped through microtubes with an inner diameter of 0.15 mm. Measured DRS and LDF spectra were compared to Monte Carlo-simulated spectra in an optimization routine, giving the best-fit parameters describing the measured spectra. The root-mean-square error for each of the three speed components (0 to 1, 1 to 10, and amp;gt;10 mm/s, respectively) when describing the blood-flow speed in the microtubes was 2.9%, 8.1%, and 7.7%. The presented results show that the system can accurately discriminate blood perfusion originating from different blood-flow speeds, which may enable improved measurement of healthy and dysfunctional microcirculatory flow. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

  • 22.
    Karlsson, Daniel M G
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Polarized laser Doppler perfusion imaging—reduction of movement-induced artifacts2005In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 10, no 6Article in journal (Refereed)
    Abstract [en]

    Laser Doppler perfusion imaging (LDPI) enables superficial tissue perfusion assessment, but is sensitive to tissue motion not related to blood cells. The aim was to investigate if a polarization technique could reduce movement-induced artifacts. A linearly polarized laser and a cross-polarized filter, placed in front of the detectors, were used to block specular reflection. Measurements were performed with, and without, the polarization filter, at a single site during horizontal and vertical movement of skin tissue (index finger, twelve subjects, n=112) and of a flow model (n=432), with varying surface structures. Measurements were repeated during different flow conditions and at increased skin specular reflection. Statistical analysis was performed using ANOVA models. The perfusion signal was lower (p<0.001, skin and p<0.05, flow model) using the polarization filter, due to movement artifact reduction. No significant influence from surface structure was found when using the polarization filter. Movement artifacts were lower (p<0.05) in the vertical movement direction, however, depending on flow conditions for skin measurements. Increased skin specular reflection gave rise to large movement artifacts without the polarization filter. In conclusion, the polarized LDPI technique reduces movement artifacts and is particularly appropriate when assessing, e.g., ulcers and burns, where specular reflection is high.

  • 23.
    Kennedy, Gordon T.
    et al.
    Beckman Laser Institute and Medical Clinic, USA.
    Lentsch, Griffin R.
    Beckman Laser Institute and Medical Clinic, USA.
    Trieu, Brandon
    Beckman Laser Institute and Medical Clinic, USA.
    Ponticorvo, Adrien
    Beckman Laser Institute and Medical Clinic, USA.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Solid tissue simulating phantoms having absorption at 970 nm for diffuse optics2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 7, article id 076013Article in journal (Refereed)
    Abstract [en]

    Tissue simulating phantoms can provide a valuable platform for quantitative evaluation of the performance of diffuse optical devices. While solid phantoms have been developed for applications related to characterizing exogenous fluorescence and intrinsic chromophores such as hemoglobin and melanin, we report the development of a poly(dimethylsiloxane) (PDMS) tissue phantom that mimics the spectral characteristics of tissue water. We have developed these phantoms to mimic different water fractions in tissue, with the purpose of testing new devices within the context of clinical applications such as burn wound triage. Compared to liquid phantoms, cured PDMS phantoms are easier to transport and use and have a longer usable life than gelatin-based phantoms. As silicone is hydrophobic, 9606 dye was used to mimic the optical absorption feature of water in the vicinity of 970 nm. Scattering properties are determined by adding titanium dioxide, which yields a wavelength-dependent scattering coefficient similar to that observed in tissue in the near-infrared. Phantom properties were characterized and validated using the techniques of inverse adding-doubling and spatial frequency domain imaging. Results presented here demonstrate that we can fabricate solid phantoms that can be used to simulate different water fractions.

  • 24.
    Larsson, Marcus
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Steenbergen, Wiendelt
    University of Twente, Faculty of Applied Physics, Enschede, The Netherlands.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Influence Of Optical Properties and Fiber separation on Laser Doppler Flowmetry2002In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 7, no 2, p. 236-243Article in journal (Refereed)
    Abstract [en]

    Microcirculatory blood flow can be measured using a laser Doppler flowmetry (LDF) probe. However, the readings are affected by tissue optical properties (absorption and scattering coefficient; µa and µs) and probe geometry. In this study the influence of optical properties (µa∈[0.053, 0.23] mm-1; µs∈[14.7, 45.7] mm-1) on LDF perfusion and sampling depth were evaluated for different fiber separations. In-vitro measurements were made on a sophisticated tissue phantom with known optical properties, mimicking blood flow at different depths. Monte Carlo simulations were carried out to extend the geometry of the tissue phantom.

    A good correlation between measured and simulated data was found. The

    simulations showed that, for a fixed flow at a discrete depth, the influence of µs or µa on the LDF perfusion increased with increasing flow depth and decreased with increasing fiber separation. For a homogeneous flow distribution, however, the perfusion varied 40% due to the variations in optical properties, almost independent of fiber separation (0.23-1.61 mm). Therefore, the effect in real tissue is likely to vary due to the unknown heterogeneous blood flow distribution. Further, LDF sampling depth increased with decreasing µs or µa and increasing fiber separation. For a fiber separation of 0.46 mm, the e-1 sampling depth ranged from 0.21-0.39 mm.

  • 25.
    Larsson, Marcus
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Towards a velocity-resolved microvascular blood flow measure by decomposition of the laser Doppler spectrum2006In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 11, no 1Article in journal (Refereed)
    Abstract [en]

    The tissue microcirculation, as measured by laser Doppler flowmetry (LDF), comprises both capillary, arterial and venous blood flow. With the classical LDF approach, it has been impossible to differentiate between different vascular compartments. We suggest an alternative LDF algorithm that estimates at least three concentration measures of flowing red blood cells (RBCs), each associated with a predefined, physiologically relevant, absolute velocity in mm/s. As the RBC flow velocity depends on the dimension of the blood vessel, this approach might enable a microcirculatory flow differentiation. The LDF concentration estimates are derived by fitting predefined Monte Carlo simulated, single velocity, spectra to a measured, multiple velocity LDF spectrum. Validation measurements, using both single and double-tube flow phantoms perfused with a microsphere solution, showed that it is possible to estimate velocity and concentration changes, and to differentiate between flows with different velocities. The presented theory was also applied to RBC flow measurements. A Gegenbauer kernel phase function (αgk = 1:05; ggk = 0:93), with an anisotropy factor of 0.987 at 786 nm, was found suitable for modelling Doppler scattering by red blood cells diluted in physiological saline. The method was developed for low concentrations of RBCs, but can in theory be extended to cover multiple Doppler scattering.

  • 26.
    Lilledahl, Magnus B.
    et al.
    Norwegian University of Science and Technoogy, Norway.
    Gustafsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Diagnostics, Department of Biomedical Engineering.
    Gunnar Ellingsen, Pal
    Norwegian University of Science and Technoogy, Norway.
    Zachrisson, Helene
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Stenhjem Hagen, Vegard
    Norwegian University of Science and Technoogy, Norway.
    Kildemo, Morten
    Norwegian University of Science and Technoogy, Norway.
    Lindgren, Mikael
    Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology. Norwegian University of Science and Technoogy, Norway.
    Combined imaging of oxidative stress and microscopic structure reveals new features in human atherosclerotic plaques2015In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 20, no 2, p. 020503-Article in journal (Refereed)
    Abstract [en]

    Human atherosclerotic samples collected by carotid endarterectomy were investigated using electronic paramagnetic resonance imaging (EPRI) for visualization of reactive oxygen species, and nonlinear optical microscopy (NLOM) to study structural features. Regions of strong EPRI signal, indicating a higher concentration of reactive oxygen species and increased inflammation, were found to colocalize with regions dense in cholesterol crystals as revealed by NLOM.

  • 27.
    Lindbergh, Tobias
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Casimir-Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Intramyocardial oxygen transport by quantitative diffuse reflectance spectroscopy in calves2010In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 2Article in journal (Refereed)
    Abstract [en]

    Intramyocardial oxygen transport was assessed during open-chest surgery in calves by diffuse reflectance spectroscopy using a small intramuscular fiber-optic probe. The sum of hemo- and myoglobin tissue fraction and oxygen saturation, the tissue fraction and oxidation of cytochrome aa3, and the tissue fraction of methemoglobin, were estimated using a calibrated empirical light transport model. Increasing the oxygen content in the inhaled gas; 21%-50%-100%, in five calves (group A) gave an oxygen saturation of 19+/-4%, 24+/-5% and 28+/-8%, and mean tissue fractions of 1.6% (cytochrome aa3), and 1.1% (hemo- and myoglobin). Cardiac arrest in two calves gave an oxygen saturation lower than 5%. In two calves (group B) a left ventricular assistive device (LVAD pump) was implanted. Group B animals displayed similar trends in hemo- and myoglobin oxygen saturation as in group A, but at higher levels (maxima of 38% (B1) and 44% (B2)). The cytochrome aa3 oxidation level was above 96% in both group A and B calves, including the two cases involving cardiac arrest.

    In conclusion, the estimated tissue fractions and oxygenation/oxidation levels of the myocardial chromophores during respiratory and hemodynamic provocations where in agreement with previously presented results, demonstrating the potential of the method.

  • 28.
    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.

  • 29.
    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.

  • 30.
    Nilsson, Henrik
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Photon pathlength determination based on spatially resolved diffuse reflectance2002In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 7, no 3, p. 478-485Article in journal (Refereed)
    Abstract [en]

    A method for the prediction of the average photon pathlength in turbid media has been developed. The method is based on spatially resolved diffuse reflectance with discrete source detector distances up to 2 mm. Light reflectance was simulated using a Monte Carlo technique with a one-layer model utilizing a wide range of optical properties, relevant to human skin. At a source detector separation of 2 mm, the pathlength can vary sixfold due to differences in optical properties. By applying various preprocessing and prediction techniques, the pathlength can be predicted with a root-mean-square error of approximately 5%. Estimation of the photon pathlength can be used, e.g., to remove the influence of optical properties on laser Doppler flowmetry perfusion readings, which are almost linearly related to the average photon pathlength.

  • 31.
    Ramamoorthy, Sripriya
    et al.
    Oregon Health and Science University, OR 97239 USA.
    Zhang, Yuan
    Oregon Health and Science University, OR 97239 USA.
    Petrie, Tracy
    Oregon Health and Science University, OR 97239 USA.
    Fridberger, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ren, Tianying
    Oregon Health and Science University, OR 97239 USA.
    Wang, Ruikang
    University of Washington, WA 98195 USA.
    Jacques, Steven L.
    Oregon Health and Science University, OR 97239 USA; Oregon Health and Science University, OR 97239 USA.
    Nuttall, Alfred L.
    Oregon Health and Science University, OR 97239 USA; University of Michigan, MI 48105 USA.
    Minimally invasive surgical method to detect sound processing in the cochlear apex by optical coherence tomography2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 2, p. 025003-Article in journal (Refereed)
    Abstract [en]

    Sound processing in the inner ear involves separation of the constituent frequencies along the length of the cochlea. Frequencies relevant to human speech (100 to 500 Hz) are processed in the apex region. Among mammals, the guinea pig cochlear apex processes similar frequencies and is thus relevant for the study of speech processing in the cochlea. However, the requirement for extensive surgery has challenged the optical accessibility of this area to investigate cochlear processing of signals without significant intrusion. A simple method is developed to provide optical access to the guinea pig cochlear apex in two directions with minimal surgery. Furthermore, all prior vibration measurements in the guinea pig apex involved opening an observation hole in the otic capsule, which has been questioned on the basis of the resulting changes to cochlear hydrodynamics. Here, this limitation is overcome by measuring the vibrations through the unopened otic capsule using phase-sensitive Fourier domain optical coherence tomography. The optically and surgically advanced method described here lays the foundation to perform minimally invasive investigation of speech-related signal processing in the cochlea. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 32.
    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.

  • 33.
    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.

  • 34.
    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.

  • 35.
    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.

  • 36.
    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.

  • 37.
    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.

  • 38.
    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.

  • 39.
    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.

  • 40.
    Strömberg, Tomas
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Karlsson, Hanna
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. Perimed AB, Järfälla, Sweden.
    Nyström, Fredrik H.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry2014In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, no 5, p. 057002-Article in journal (Refereed)
    Abstract [en]

    Microvascular assessment would benefit from co-registration of blood flow and hemoglobin oxygenation dynamics during stimulus response tests. We used a fiber-optic probe for simultaneous recording of white light diffuse reflectance (DRS; 475-850 nm) and laser Doppler flowmetry (LDF; 780 nm) spectra at two source-detector distances (0.4 and 1.2 mm). An inverse Monte Carlo algorithm, based on a multiparameter three-layer adaptive skin model, was used for analyzing DRS data. LDF spectra were conventionally processed for perfusion. The system was evaluated on volar forearm recordings of 33 healthy subjects during a 5-min systolic occlusion protocol. The calibration scheme and the optimal adaptive skin model fitted DRS spectra at both distances within 10%. During occlusion, perfusion decreased within 5 s while oxygenation decreased slowly (mean time constant 61 s; dissociation of oxygen from hemoglobin). After occlusion release, perfusion and oxygenation increased within 3 s (inflow of oxygenized blood). The increased perfusion was due to increased blood tissue fraction and speed. The supranormal hemoglobin oxygenation indicates a blood flow in excess of metabolic demands. In conclusion, by integrating DRS and LDF in a fiber-optic probe, a powerful tool for assessment of blood flow and oxygenation in the same microvascular bed has been presented.

  • 41.
    Sundberg, Mikael
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Peebo, Markus
    Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of ENT - Head and Neck Surgery UHL.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    In vitro tympanic membrane position identification with a co-axial fiber optic otoscope2011In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 16, no 9, p. 097002-Article in journal (Refereed)
    Abstract [en]

    Otitis media diagnosis can be assisted by measuring the shape of the tympanic membrane. We have developed an ear speculum for an otoscope, including spatially distributed source and detector optical fibers, to generate source-detector intensity matrices (SDIMs), representing the curvature of surfaces. The surfaces measured were a model ear with a latex membrane and harvested temporal bones including intact tympanic membranes. The position of the tympanic membrane was shifted from retracted to bulging by air pressure and that of the latex membrane by water displacement. The SDIM was normalized utilizing both external (a sheared flat plastic cylinder) and internal references (neutral position of the membrane). Data was fitted to a two-dimensional Gaussian surface representing the shape by its amplitude and offset. Retracted and bulging surfaces were discriminated for the model ear by the sign of the Gaussian amplitude for both internal and external reference normalization. Tympanic membranes were separated after a two-step normalization: first to an external reference, adjusted for the distance between speculum and the surfaces, and second by comparison with an average normally positioned SDIM from tympanic membranes. In conclusion, we have shown that the modified otoscope can discriminate between bulging and retracted tympanic membranes in a single measurement, given a two-step normalization. (C) 2011 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3622486]

  • 42.
    Torabzadeh, M
    et al.
    Beckman Laser Institute and Medical Clinic, United States.; Univ. of California, Irvine, United States..
    Stockton, P
    Colorado State Univ., United States..
    Kennedy, G
    Beckman Laser Institute and Medical Clinic, United States..
    Saager, Rolf
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Durkin, AJ
    Beckman Laser Institute and Medical Clinic, United States.; Univ. of California, Irvine, United States..
    Bartels, R
    Colorado State Univ., United States..
    Tromberg, B
    Beckman Laser Institute and Medical Clinic, United States.; Univ. of California, Irvine, United States..
    Hyperspectral imaging in the spatial frequency domain with a supercontinuum source.2019In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 24, no 7, p. StartPage-EndPageArticle in journal (Refereed)
    Abstract [en]

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

  • 43.
    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).

  • 44.
    Vikinge, Trine P.
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Hansson, Kenny
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Benesch, Johan
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Johansen, Knut
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Rånby, Mats
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Lindahl, Tomas
    Linköping University, Department of Biomedicine and Surgery, Clinical Chemistry. Linköping University, Faculty of Health Sciences.
    Liedberg, Bo
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Lundström, Ingemar
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Tengvall, Pentti
    Linköping University, Department of Physics, Chemistry and Biology, Applied Physics. Linköping University, The Institute of Technology.
    Blood plasma coagulation studied by surface plasmon resonance2000In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 5, no 1, p. 51-55Article in journal (Refereed)
    Abstract [en]

    A surface plasmon resonance (SPR) apparatus was used to investigate blood plasma coagulation in real time as a function of thromboplastin and heparin concentrations. The response curves were analyzed by curve fitting to a sigmoid curve equation, followed by extraction of the time constant. Clotting activation by thromboplastin resulted in increased time constant, as compared to spontaneously clotted plasma, in a dose dependent way. Addition of heparin to the thromboplastin-activated plasma counteracted this effect. Atomic force microscopy (AFM) pictures of sensor surfaces dried after completed clotting, revealed differences in fibrin network structures as a function of thromboplastin concentration, and the fiber thickness increased with decreased thromboplastin concentration. The physical reason for the SPR signal observed is ambiguous and is therefore discussed. However, the results summarized in the plots and the fibrin network properties observed by AFM correlate well with present common methods used to analyze blood coagulation.

  • 45.
    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

  • 46.
    Yazdi, Hossein S.
    et al.
    University of Calif Irvine, CA 92715 USA.
    OSullivan, Thomas D.
    University of Calif Irvine, CA 92715 USA.
    Leproux, Anais
    University of Calif Irvine, CA 92715 USA.
    Hill, Brian
    University of Calif Irvine, CA 92715 USA.
    Durkin, Amanda
    University of Calif Irvine, CA 92715 USA.
    Telep, Seraphim
    University of Calif Irvine, CA 92715 USA.
    Lam, Jesse
    University of Calif Irvine, CA 92715 USA.
    Yazdi, Siavash S.
    University of Calif Irvine, CA 92715 USA.
    Police, Alice M.
    University of Calif Irvine, CA 92668 USA.
    Carroll, Robert M.
    University of Calif Irvine, CA 92668 USA.
    Combs, Freddie J.
    University of Calif Irvine, CA 92668 USA.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. University of Calif Irvine, CA 92715 USA.
    Yodh, Arjun G.
    University of Penn, PA 19104 USA.
    Tromberg, Bruce J.
    University of Calif Irvine, CA 92715 USA.
    Mapping breast cancer blood flow index, composition, and metabolism in a human subject using combined diffuse optical spectroscopic imaging and diffuse correlation spectroscopy2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 4, article id 045003Article in journal (Refereed)
    Abstract [en]

    Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are modelbased near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, mu(a), and reduced scattering, mu(s)) and blood flow (blood flow index, BFI), respectively. DOSI-derived mu(a) values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin(HbO2,HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/ DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 mm(-1) (37%) in mu(s) and 0.003 mm(-1) (33%) in mu(a) lead to similar to 53% and 9% errors in BFI, respectively. DOSI/ DCS imaging of a solid tissue-simulating flow phantom and a breast cancer patient reveals well-defined spatial distributions of BFI and composition that clearly delineates both the flow channel and the tumor. BFI reconstructed with DOSI-corrected mu(a) and mu(s) values had a tumor/ normal contrast of 2.7, 50% higher than the contrast using commonly assumed fixed optical properties. In conclusion, spatially coregistered imaging of DOSI and DCS enhances intrinsic tumor contrast and information content. This is particularly important for imaging diseased tissues where there are significant spatial variations in mu(a) and mu(s) as well as potential uncoupling between flow and metabolism. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication,

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