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  • 1.
    Jonasson, Hanna
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Model-based quantitative assessment of skin microcirculatory blood flow and oxygen saturation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The microcirculation, involving the smallest vessels in the body, is where the oxygen transport to all tissue occurs. Evaluating microcirculatory parameters is, therefore, important and involves the quantification of oxygen content of red blood cells (RBCs), the amount of RBCs and their speed.

    Diffuse reflectance spectroscopy (DRS) can be used to estimate blood oxygen saturation and fraction of RBCs in tissue since oxygenated and deoxygenated blood have different light absorption characteristics. By illuminating the skin with white light and detecting the spectrum of the backscattered light, tissue absorption and scattering can be assessed. Laser Doppler flowmetry (LDF) is a technique to measure blood flow in tissue. When laser light encounter moving objects in tissue, i.e. RBCs, the light is Doppler shifted, which can be detected and used to calculate tissue perfusion (the fraction of moving RBCs times their speed). With a small distance between light source and detector, both techniques measure superficially where most vessels are microcirculatory vessels. Photon transport in tissue can be simulated with Monte Carlo techniques and the simulations form the basis of modeled DRS and LDF spectra. The estimated microcirculatory parameters are given by the model that best describe measured DRS and LDF data.

    This thesis describes the development and the evaluation of an optical method to simultaneously measure oxygen saturation, RBC tissue fraction and speed resolved perfusion in absolute units by integrating DRS and LDF. By combining DRS and LDF into one system with a common tissue model, the two modalities can benefit from each other’s strengths. Different calibration methods and model assumptions for the system were evaluated in optical phantoms and in skin measurements. A simple calibration method with two detector distances for DRS was found adequate to accurately estimate absorption and scattering in optical phantoms. It was also necessary to model blood located in vessels, rather than homogeneously distributed in the skin, to obtain accurate parameter estimates. The system was evaluated in healthy subjects during standard provocations, where the parameters were in agreement with other studies and followed an expected pattern during the provocations. In patients with diabetes type 2, tissue fraction of RBCs and nutritive blood flow were reduced in baseline compared to healthy controls. These differences were not related to prevalence of microalbuminuria, a marker sign of microvascular complications in the kidneys.

    A combined system with DRS and LDF enables a more comprehensive assessment of the microcirculation by measuring oxygen saturation, RBC tissue fraction and speed resolved perfusion simultaneously and in absolute units. This system has clinical potential to assist in the evaluation of the microcirculation both in healthy and diseased individuals.

    List of papers
    1. Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?
    Open this publication in new window or tab >>Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?
    2011 (English)In: Optical Tomography and Spectroscopy of Tissue IX / [ed] Robert R. Alfano; Bruce J. Tromberg; Arjun G. Yodh; Mamoru Tamura; Eva M. Sevick-Muraca, SPIE - International Society for Optical Engineering, 2011, Vol. 7896, p. 78962Y-78962Y-9Conference paper, Published paper (Other academic)
    Abstract [en]

    Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

    Place, publisher, year, edition, pages
    SPIE - International Society for Optical Engineering, 2011
    Series
    Proceedings of SPIE - International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X ; 7896
    Keywords
    diffuse reflectance spectroscopy, light transport, Monte Carlso simulation, tissue moedeling, vessel packaging, skin
    National Category
    Medical Laboratory and Measurements Technologies
    Identifiers
    urn:nbn:se:liu:diva-81240 (URN)10.1117/12.873134 (DOI)
    Conference
    Optical Tomography and Spectroscopy of Tissue IX Conference, San Francisco, California, January 22, 2011
    Available from: 2012-09-14 Created: 2012-09-10 Last updated: 2017-02-10Bibliographically approved
    2. Inverse Monte Carlo for estimation of scattering and absorption in liquid optical phantoms
    Open this publication in new window or tab >>Inverse Monte Carlo for estimation of scattering and absorption in liquid optical phantoms
    2012 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 20, no 11, p. 12233-12246Article in journal (Refereed) Published
    Abstract [en]

    A spectroscopic probe with multiple detecting fibers was used for quantifying absorption and scattering in liquid optical phantoms. The phantoms were mixtures of Intralipid and red and blue food dyes. Intensity calibration for the detecting fibers was undertaken using either a microsphere suspension (absolute calibration) or a uniform detector illumination (relative calibration between detectors). Two different scattering phase functions were used in an inverse Monte Carlo algorithm. Data were evaluated for residual spectra (systematic deviations and magnitude) and accuracy in estimation of scattering and absorption. Spectral fitting was improved by allowing for a 10% intensity relaxation in the optimization algorithm. For a multi-detector setup, non-systematic residual spectrum was only found using the more complex Gegenbauer-kernel phase function. However, the choice of phase function did not influence the accuracy in the estimation of absorption and scattering. Similar estimation accuracy as in the multi-detector setup was also obtained using either two relative calibrated detectors or one absolute calibrated detector at a fiber separation of 0.46 mm.

    Place, publisher, year, edition, pages
    Optical Society of America, 2012
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-78815 (URN)10.1364/OE.20.012233 (DOI)000304403100070 ()
    Note

    Funding Agencies|VINNOVA||Perimed AB|2008-00149|ResearchGrow program|2011-03074|European Union||Linkoping University through the Center for Excellence NIMED-CBDP (Center for Biomedical Data Processing)||

    Available from: 2012-06-21 Created: 2012-06-21 Last updated: 2017-12-07Bibliographically approved
    3. Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry
    Open this publication in new window or tab >>Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry
    Show others...
    2014 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, no 5, p. 057002-Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    SPIE - International Society for Optical Engineering, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-107715 (URN)10.1117/1.JBO.19.5.057002 (DOI)000338334600033 ()24788373 (PubMedID)
    Available from: 2014-06-19 Created: 2014-06-19 Last updated: 2017-12-05Bibliographically approved
    4. Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment
    Open this publication in new window or tab >>Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment
    Show others...
    2015 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 102, p. 70-77Article in journal (Refereed) Published
    Abstract [en]

    We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0–1 mm/s, 1–10 mm/s and above 10 mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20–28 years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.

    Place, publisher, year, edition, pages
    Academic Press, 2015
    Keywords
    Diffuse reflectance spectroscopy; Hemoglobin oxygen saturation; Laser Doppler flowmetry; Microcirculation; Skin blood flow
    National Category
    Medical Laboratory and Measurements Technologies
    Identifiers
    urn:nbn:se:liu:diva-121774 (URN)10.1016/j.mvr.2015.08.006 (DOI)000362310700010 ()26279347 (PubMedID)
    Note

    Funding text:  VINNOVA (Swedens innovation agency); Perimed AB through the SamBIO research collaboration program [2008-00149]; Research&Grow program (VINNOVA) [2011-03074]; NovaMedTech - European Union Regional Development Fund [68737, 160382]

    Available from: 2015-10-05 Created: 2015-10-05 Last updated: 2017-12-01
  • 2.
    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.

  • 3.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Perimed AB, Järfälla-Stockholm, Sweden .
    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.
    Assessment of the microcirculation using combined model based diffuse reflectance spectroscopy and laser Doppler flowmetry2015In: 16th Nordic-Baltic Conference on Biomedical Engineering: 16. NBC & 10. MTD 2014 joint conferences. October 14-16, 2014, Gothenburg, Sweden, Springer, 2015, p. 52-54Conference paper (Refereed)
    Abstract [en]

    By using a combined inverse model for diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) the tissue fraction of red blood cells (RBCs), their oxygenation and speed-resolved perfusion are estimated in absolute units. DRS spectra (450 to 850 nm) are measured at two source-detector distances; 0.4 and 1.2 mm. LDF spectra are measured at 1.2 mm, integrated in the same fiber-optic probe. Inverse Monte Carlo technique and an adaptive tissue model is used to quantify the microcirculatory parameters. Measurements were done during venous occlusion of the tissue. The model fitting yields a good spectral fit for the two DRS spectra and the LDF spectrum. The physiological responses regarding for example which speed regions respond to provocations follows a priori expectations. The combined model gives quantitative measures of RBC tissue fraction, oxygenation and speed resolved perfusion from the same sampling volume which gives new opportunities to interpret data.

  • 4.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Perimed AB, Datavägen 9A, 175 43 Järfälla, Stockholm, Sweden.
    Pettersson, Anders
    Perimed AB, Datavägen 9a, 175 26 Järfälla-Stockholm.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 102, p. 70-77Article in journal (Refereed)
    Abstract [en]

    We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0–1 mm/s, 1–10 mm/s and above 10 mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20–28 years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.

  • 5.
    Karlsson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fredriksson, Ingemar
    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 for estimation of scattering and absorption in liquid optical phantoms2012In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 20, no 11, p. 12233-12246Article in journal (Refereed)
    Abstract [en]

    A spectroscopic probe with multiple detecting fibers was used for quantifying absorption and scattering in liquid optical phantoms. The phantoms were mixtures of Intralipid and red and blue food dyes. Intensity calibration for the detecting fibers was undertaken using either a microsphere suspension (absolute calibration) or a uniform detector illumination (relative calibration between detectors). Two different scattering phase functions were used in an inverse Monte Carlo algorithm. Data were evaluated for residual spectra (systematic deviations and magnitude) and accuracy in estimation of scattering and absorption. Spectral fitting was improved by allowing for a 10% intensity relaxation in the optimization algorithm. For a multi-detector setup, non-systematic residual spectrum was only found using the more complex Gegenbauer-kernel phase function. However, the choice of phase function did not influence the accuracy in the estimation of absorption and scattering. Similar estimation accuracy as in the multi-detector setup was also obtained using either two relative calibrated detectors or one absolute calibrated detector at a fiber separation of 0.46 mm.

  • 6.
    Karlsson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Kvantitativa mätningar av mikrocirkulatoriska parametrar med optiska tekniker och en realistisk hudmodell2011Conference paper (Other academic)
  • 7.
    Karlsson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Perimed AB, Järfälla, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Speed resolved assessment of the microcirculation using combined model based diffuse reflectance spectroscopy and laser Doppler flowmetry2014Conference paper (Other academic)
  • 8.
    Karlsson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Pettersson, Anders
    Perimed AB, Järfälla-Stockholm.
    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.
    Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?2011In: Optical Tomography and Spectroscopy of Tissue IX / [ed] Robert R. Alfano; Bruce J. Tromberg; Arjun G. Yodh; Mamoru Tamura; Eva M. Sevick-Muraca, SPIE - International Society for Optical Engineering, 2011, Vol. 7896, p. 78962Y-78962Y-9Conference paper (Other academic)
    Abstract [en]

    Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

  • 9.
    Strömberg, Tomas
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Karlsson, Hanna
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fredriksson, Ingemar
    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.
    Experimental results using a three-layer skin model for diffuse reflectance spectroscopy2013In: Optical Tomography and Spectroscopy of Tissue X / [ed] Bruce J. Tromberg, Arjun G. Yodh, Eva M. Sevick-Muraca, SPIE - International Society for Optical Engineering, 2013, p. 857834-1-857834-8Conference paper (Other academic)
    Abstract [en]

    We have previously presented an inverse Monte Carlo algorithm based on a three-layer semi-infinite skin model for analyzing diffuse reflectance spectroscopy (DRS) data. The algorithm includes pre-simulated Monte Carlo data for a range of physiologically relevant epidermal thicknesses and tissue scattering levels. The simulated photon pathlength distributions in each layer are stored and the absorption effect from tissue chromophores added in the post-processing. Recorded DRS spectra at source-detector distances of 0.4 and 1.2 mm were calibrated for the relative intensity between the two distances and matched to simulated spectra in a non-linear optimization algorithm. This study evaluates the DRS spectral fitting accuracy and presents data on the main output parameters; the tissue fraction of red blood cells and local oxygenation (SO2). As a reference, the microcirculatory perfusion (Perf) was measured simultaneously in the same probe using laser Doppler Flowmetry. Data were recorded on the volar forearm of three healthy subjects in a protocol involving a 5 min systolic occlusion. The DRS spectra were modeled with an rms-error < 2%. In two subjects, SO2 decreased during occlusion to <10%, and increased to above baseline after hyperemia, while Perf increased >7 times compared to baseline. In the third subject the SO2 decreased less during occlusion and increased to baseline values at hyperemia with only a 2-fold increase in Perf. The observed difference could be due to different microvascular beds being probed. It is concluded that integrating DRS and LDF enables new possibilities to deduce microcirculation status.

  • 10.
    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.

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