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  • 1.
    Belcastro, Luigi
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Jonasson, Hanna
    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.
    Elserafy, Ahmed
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland.
    Saager, Rolf
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Beneath the skin: multi-frequency SFDI to detect thin layers of skin using light scattering2023In: PHOTONICS IN DERMATOLOGY AND PLASTIC SURGERY 2023, SPIE-INT SOC OPTICAL ENGINEERING , 2023, Vol. 12352, article id 1235209Conference paper (Refereed)
    Abstract [en]

    Wound healing assessment is usually performed visually by a trained physician. This type of evaluation is very subjective and returns limited information about the wound progression. In contrast, optical imaging techniques are non-invasive ways to quantitatively measure biological parameters. Spatial frequency domain imaging (SFDI) is an optical technique that exploits sinusoidal patterns of light with multiple spatial frequencies to measure the tissue frequency-specific response, from which the absorption and scattering coefficient of the material can be derived. While SFDI is based on models of light transport that assume the tissue is homogeneous, skin is composed by several layer with very different optical properties. An underutilized property of SFDI, however, is that the spatial frequency of the patterns determines the penetration depth of photons in the tissue. By using multiple ranges of spatial frequencies, we are developing a means to obtain morphological data from different volumes of tissue. This data is used to reconstruct the optical properties in depth, allowing us to differentiate between different thin layers of tissue. In this study we have developed a 2-layer optical phantom model with realistic optical properties and dimensions, that mimics the physiology of wound healing. We have used this physical model to validate the accuracy of this approach in obtaining layer specific optical properties.

  • 2.
    Belcastro, Luigi
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Jonasson, Hanna
    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.
    Saager, Rolf B.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Handheld multispectral imager for quantitative skin assessment in low resource settings2020In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 25, no 8, article id 082702Article in journal (Refereed)
    Abstract [en]

    Significance: Spatial frequency domain imaging (SFDI) is a quantitative imaging method to measure absorption and scattering of tissue, from which several chromophore concentrations (e.g., oxy-/deoxy-/meth-hemoglobin, melanin, and carotenoids) can be calculated. Employing a method to extract additional spectral bands from RGB components (that we named cross-channels), we designed a handheld SFDI device to account for these pigments, using low-cost, consumer-grade components for its implementation and characterization.

    Aim: With only three broad spectral bands (red, green, blue, or RGB), consumer-grade devices are often too limited. We present a methodology to increase the number of spectral bands in SFDI devices that use RGB components without hardware modification.

    Approach: We developed a compact low-cost RGB spectral imager using a color CMOS camera and LED-based mini projector. The components’ spectral properties were characterized and additional cross-channel bands were calculated. An alternative characterization procedure was also developed that makes use of low-cost equipment, and its results were compared. The device performance was evaluated by measurements on tissue-simulating optical phantoms and in-vivo tissue. The measurements were compared with another quantitative spectroscopy method: spatial frequency domain spectroscopy (SFDS).

    Results: Out of six possible cross-channel bands, two were evaluated to be suitable for our application and were fully characterized (520  ±  20  nm; 556  ±  18  nm). The other four cross-channels presented a too low signal-to-noise ratio for this implementation. In estimating the optical properties of optical phantoms, the SFDI data have a strong linear correlation with the SFDS data (R2  =  0.987, RMSE  =  0.006 for μa, R2  =  0.994, RMSE  =  0.078 for μs′).

    Conclusions: We extracted two additional spectral bands from a commercial RGB system at no cost. There was good agreement between our device and the research-grade SFDS system. The alternative characterization procedure we have presented allowed us to measure the spectral features of the system with an accuracy comparable to standard laboratory equipment.

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  • 3.
    Bergstrand, Sara
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Jonasson, Hanna
    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.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study)2024In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881Article in journal (Refereed)
    Abstract [en]

    Aims The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden. Methods and results The study enrolled 3809 individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 > 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76-8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals without subclinical atherosclerotic burdens (87.5 +/- 5.6% and 86.9 +/- 6.0%, vs. 88.6 +/- 5.8%, P < 0.01). Conclusion In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.

  • 4.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Science & Engineering.
    Jonasson, Hanna
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Stridsman, Magnus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Region Östergötland.
    Carlsson, Lars
    Carlsson Consulting.
    Virtuell laboration för undervisning av elektrisk säkerhet inom medicinteknik2022Conference paper (Other academic)
  • 5.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Åby.
    Muller, David A.
    Univ Queensland, Australia.
    Togö, Totte
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Jonasson, Hanna
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Baker, Ben
    Vaxxas Pty Ltd, Australia.
    Anderson, Chris
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Henricson, Joakim
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Local Response and Barrier Recovery in Elderly Skin Following the Application of High-Density Microarray Patches2022In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 4, article id 583Article in journal (Refereed)
    Abstract [en]

    The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the >65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69-84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population.

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  • 6. Order onlineBuy this publication >>
    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: 2021-12-28Bibliographically 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, 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: 2022-09-15Bibliographically 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
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    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: 2021-12-28Bibliographically 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
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    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: 2021-12-28
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  • 7.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Anderson, Chris D
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Dermatology and Venerology.
    Saager, Rolf B.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Water and hemoglobin modulated gelatin-based phantoms to spectrally mimic inflamed tissue in the validation of biomedical techniques and the modeling of microdialysis data2022In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 27, no 7Article in journal (Refereed)
    Abstract [en]

    Significance: Tissue simulating phantoms are an important part of validating biomedical optical techniques. Tissue pathology in inflammation and oedema involves changes in both water and hemoglobin fractions.

    Aim: We present a method to create solid gelatin-based phantoms mimicking inflammation and oedema with adjustable water and hemoglobin fractions.

    Approach: One store-bought gelatin and one research grade gelatin were evaluated. Different water fractions were obtained by varying the water-to-gelatin ratio. Ferrous stabilized human hemoglobin or whole human blood was added as absorbers, and the stability and characteristics of each were compared. Intralipid® was used as the scatterer. All phantoms were characterized using spatial frequency domain spectroscopy.

    Results: The estimated water fraction varied linearly with expected values (R2  =  0.96 for the store-bought gelatin and R2  =  0.99 for the research grade gelatin). Phantoms including ferrous stabilized hemoglobin stayed stable up to one day but had methemoglobin present at day 0. The phantoms with whole blood remained stable up to 3 days using the store-bought gelatin.

    Conclusions: A range of physiological relevant water fractions was obtained for both gelatin types, with the stability of the phantoms including hemoglobin differing between the gelatin type and hemoglobin preparation. These low-cost phantoms can incorporate other water-based chromophores and be fabricated as thin sheets to form multilayered structures.

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  • 8.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Bergstrand, Sara
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. 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, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Normative data and the influence of age and sex on microcirculatory function in a middle-aged cohort: results from the SCAPIS study2020In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 318, no 4, p. H908-H915Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs), and speed-resolved perfusion. Furthermore, to examine the influence of age and sex on microcirculatory function. Measurements were performed using a noninvasive probe-based system, including diffuse reflectance spectroscopy and laser-Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1,765 men and women aged 50-65 yr from the Linkoping general population. Normative values are given at baseline, at the end of a 5-min occlusion of the brachial artery and during hyperemia after occlusion release. We found a consistent age distribution, in which the oldest individuals had the lowest peak oxygen saturation (P < 0.001) and the highest baseline low-speed perfusion (P < 0.001). Women had higher peak oxygen saturation (P < 0.001), lower RBC tissue fraction, in general (P < 0.001), lower baseline perfusion in all speed regions (P = 0.01). and lower peak high-speed perfusion at hyperemia (P < 0.001). The normative data can be used as reference values in future studies of disease-specific populations. The results show that age and sex are important aspects to consider in studies of microvascular function. Women and younger age were factors associated with higher peak oxygen saturation after ischemia. This is a novel parameter that reflects overall microcirculatory function associated with vascular dilation capacity. NEW & NOTEWORTHY This study expands experimental microcirculatory research to clinical use by providing normative values on microcirculatory function in a large population-based cohort. Women and younger age were factors associated with higher peak oxygen saturation after ischemia, which implies that age and sex are important aspects to consider in studies of micmvascular function. This study is the first step toward using microcirculatory assessment as a tool to improve diagnosis. prognosis. and treatment in disease-specific populations.

  • 9.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Bergstrand, Sara
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. 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, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Post-ischemic skin peak oxygen saturation is associated with cardiovascular risk factors: a Swedish cohort study2022In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 140, article id 104284Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to explore the associations between skin microcirculatory function and established cardiovascular risk factors in a large Swedish cohort. As part of the Swedish CArdioPulmonary bioImage Study (SCAPIS), microcirculatory data were acquired at Linko center dot ping University hospital, Linko center dot ping, Sweden during 2016-2017. The subjects, aged 50-64 years, were randomly selected from the national population register. Microcirculatory reactivity was assessed using a 5-min arterial occlusion-release protocol. Comprehensive skin microcirculatory data were continuously acquired by using a fiberoptic probe placed on the lower right arm. After exclusion of missing data (208), 1557 subjects were remaining. Among the parameters, skin microcirculatory peak oxygen saturation after occlusion release, had the strongest relationship to the cardiovascular risk factors. The linear associations between peak oxygen saturation and cardiovascular risk factors were analyzed adjusted for age and sex. We found a negative association with peak oxygen saturation (standardized regression coefficient) for blood pressure (systolic-0.05 (95% CI:-0.10;-0.003) and diastolic-0.05 (-0.10;-0.003)), BMI-0.18 (-0.23;-0.13), waist circumference (males-0.20 (-0.32;-0.16), females-0.18 (-0.25;-0.11)), prevalent diabetes-0.31 (-0.49;-0.12), hypertension-0.30 (-0.42;-0.18), dyslipidemia-0.24 (-0.40;-0.09), fasting glucose level-0.06 (-0.12;-0.01), HbA1c-0.07 (-0.12;-0.02), triglyceride level-0.09 (-0.14;-0.04), hsCRP-0.12 (-0.17;-0.07), and current smoker versus never smoked-0.50 (-0.67;-0.34). A positive association with peak oxygen saturation was found for cholesterol level 0.05 (0.005; 0.11) and HDL 0.11 (0.06; 0.17). This is the first study showing that post-ischemic skin microvascular peak oxygen saturation is associated with virtually all established cardiovascular risk factors in a population-based middle-aged cohort.

  • 10.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Bergstrand, Sara
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    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.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. 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, 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.
    Skin microvascular endothelial dysfunction is associated with type 2 diabetes independently of microalbuminuria and arterial stiffness2017In: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 14, no 4, p. 363-371, article id UNSP 1479164117707706Article in journal (Refereed)
    Abstract [en]

    Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells x mm/s) divided into three speed regions: 0-1, 1-10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0-1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

  • 11.
    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.
    Bergstrand, Sara
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Nursing Sciences and Reproductive Health. Linköping University, Faculty of Medicine and Health Sciences.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.
    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.
    Absorption and reduced scattering coefficients in epidermis and dermis from a Swedish cohort study2023In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 28, no 11Article in journal (Refereed)
    Abstract [en]

    Significance Knowledge of optical properties is important to accurately model light propagation in tissue, but in vivo reference data are sparse.Aim The aim of our study was to present in vivo skin optical properties from a large Swedish cohort including 3809 subjects using a three-layered skin model and spatially resolved diffuse reflectance spectroscopy (Periflux PF6000 EPOS).Approach Diffuse reflectance spectra (475 to 850 nm) at 0.4 and 1.2 mm source-detector separations were analyzed using an inverse Monte Carlo method. The model had one epidermis layer with variable thicknesses and melanin-related absorptions and two dermis layers with varying hemoglobin concentrations and equal oxygen saturations. The reduced scattering coefficient was equal across all layers.Results Median absorption coefficients (mm (- 1)) in the upper dermis ranged from 0.094 at 475 nm to 0.0048 at 850 nm and similarly in the lower dermis from 0.059 to 0.0035. The reduced scattering coefficient (mm( - 1)) ranged from 3.22 to 1.20, and the sampling depth (mm) ranged from 0.23 to 0.38 (0.4 mm separation) and from 0.49 to 0.68 (1.2 mm separation). There were differences in optical properties across sex, age groups, and BMI categories.Conclusions Reference material for skin optical properties is presented.

  • 12.
    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.

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  • 13.
    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.

  • 14.
    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.

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  • 15.
    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.

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  • 16.
    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, 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.

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  • 17.
    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)
  • 18.
    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)
  • 19.
    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.

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  • 20.
    Persson, Anna
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Vaderstad AB, Sweden.
    Jonasson, Hanna
    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.
    Wiklund, Urban
    Umea Univ, Sweden.
    Ahlstrom, Christer
    Swedish Natl Rd & Transport Res Inst, S-58195 Linkoping, Sweden.
    Heart Rate Variability for Classification of Alert Versus Sleep Deprived Drivers in Real Road Driving Conditions2021In: IEEE transactions on intelligent transportation systems (Print), ISSN 1524-9050, E-ISSN 1558-0016, Vol. 22, no 6, p. 3316-3325Article in journal (Refereed)
    Abstract [en]

    Driver sleepiness is a contributing factor in many road fatalities. A long-standing goal in driver state research has therefore been to develop a robust sleepiness detection system. It has been suggested that various heart rate variability (HRV) metrics can be used for driver sleepiness classification. However, since heart rate is modulated not only by sleepiness but also by several other time-varying intra-individual factors such as posture, distress, boredom and relaxation, it is relevant to highlight not only the possibilities but also the difficulties involved in HRV-based driver sleepiness classification. This paper investigates the reliability of HRV as a standalone feature for driver sleepiness detection in a realistic setting. Data from three real-road driving studies were used, including 86 drivers in both alert and sleep-deprived conditions. Subjective ratings based on the Karolinska sleepiness scale (KSS) were used as ground truth when training four binary classifiers (k-nearest neighbours, support vector machine, AdaBoost, and random forest). The best performance was achieved with the random forest classifier with an accuracy of 85%. However, the accuracy dropped to 64% for three-class classification and to 44% for subject-independent, leave-one-participant-out classification. The worst results were obtained in the severely sleepy class. The results show that in realistic driving conditions, subject-independent sleepiness classification based on HRV is poor. The conclusion is that more work is needed to control for the many confounding factors that also influence HRV before it can be used as input to a driver sleepiness detection system.

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  • 21.
    Persson, Anna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry. Linköping University, Faculty of Medicine and Health Sciences. Etteplan Sweden AB, S-58330 Linkoping, Sweden.
    Jonasson, Hanna
    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.
    Wiklund, Urban
    Umea Univ, Sweden.
    Ahlström, Christer
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Swedish Natl Rd & Transport Res Inst VTI, S-58195 Linkoping, Sweden.
    Heart Rate Variability for Driver Sleepiness Classification in Real Road Driving Conditions2019In: 2019 41ST ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY (EMBC), IEEE , 2019, p. 6537-6540Conference paper (Refereed)
    Abstract [en]

    Approximately 20-30% of all road fatalities are related to driver sleepiness. A long-lasting goal in driver state research has therefore been to develop a robust sleepiness detection system. Since the alertness level is reflected in autonomous nervous system activity, it has been suggested that various heart rate variability (HRV) metrics can be used as features for driver sleepiness classification. Since the heart rate is modulated by many different factors, and not just by sleepiness, it is relevant to question the high driver sleepiness classification accuracies that have occasionally been presented in the literature. The main objective of this paper is thus to test how well a sleepiness classification system based on HRV features really is. A unique data set with 86 drivers, obtained while driving on real roads in real traffic, both in alert and sleep deprived conditions, was used to train and test a support vector machine (SVM) classifier. Subjective ratings based on the Karolinska sleepiness scale (KSS) was used as ground truth to divide the data into three classes (alert, somewhat sleepy and severely sleepy). Even though nearly all the 24 investigated HRV metrics showed significant differences between sleepiness levels, the SVM results only reached a mean accuracy of 61 %, with the worst results originating from the severely sleepy cases. In summary, the high classification performance that may arise in studies with high experimental control could not be replicated under realistic driving conditions. Future works should focus on how various confounding factors should be accounted for when using HRV based metrics as input to a driver sleepiness detection system.

  • 22.
    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.

  • 23.
    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.

  • 24.
    Svensson, Christina
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Bjarnegård, Niclas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Eriksson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Jonasson, Hanna
    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.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Zachrisson, Helene
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Affected Microcirculation and Vascular Hemodynamics in Takayasu Arteritis2022In: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 13, article id 926940Article in journal (Refereed)
    Abstract [en]

    Introduction: Takayasu arteritis (TAK) is a rare inflammatory disease affecting aorta and its major branches. Ultrasound (US) can detect inflammatory features in the arterial wall, but less is known regarding skin microcirculation and vascular hemodynamics. The aim was to study if assessment of these variables could add valuable information regarding vascular affection in TAK.Methods: 17 patients diagnosed with TAK and 17 age- and sex-matched healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) in the skin after induced ischemia was evaluated with laser Doppler flowmetry/diffuse reflectance spectroscopy. Cerebrovascular reserve capacity (CVR) in the brain was assessed with transcranial Doppler (TCD). Pulse waves were recorded in the radial artery by the aid of applanation tonometry, for calculation of central augmentation index (AIx75). Intima-media thickness (IMT) and stenosis/occlusions were evaluated using US in carotid and central arteries.Results: Reduced OxyP (79 +/- 8% vs. 87 +/- 4%, p &lt; 0.001) was seen in patients with TAK regardless of significant arterial stenosis/occlusion or not. Increased AIx75 (22.3 +/- 13.6 vs. 9.2 +/- 16.3, p = 0.01) was seen in TAK patients without significant stenosis/occlusions. No differences were found in CVR, regardless of proximal stenosis. However, signs of a more high-resistance flow profile were seen in arteria cerebri media.Conclusion: Regardless of arterial stenosis or not, impaired microcirculation of the skin and preserved CVR in the brain were found in subjects with TAK. Signs of increased arterial stiffness in the brain and central arteries were observed. The value of these findings for prediction of future cardiovascular events needs to be clarified in further studies.

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  • 25.
    Svensson, Christina
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Eriksson, Per
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Bjarnegård, Niclas
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Jonasson, Hanna
    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.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Medicine Center, Department of Rheumatology.
    Zachrisson, Helene
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Impaired Microcirculation and Vascular Hemodynamics in Relation to Macrocirculation in Patients With Systemic Lupus Erythematosus2021In: Frontiers in Medicine, E-ISSN 2296-858X, Vol. 8, article id 722758Article in journal (Refereed)
    Abstract [en]

    Introduction: Systemic lupus erythematosus (SLE) is associated with premature cardiovascular disease (CVD) and mortality, unexplained by traditional risk factors. Impairment of microcirculation and vascular hemodynamics may represent early signs of vascular affection. We hypothesized that studies of microcirculation and pulse waves may provide additional information, compared to ultrasound (US) alone, for the detection of early vascular disease in SLE.Methods: Sixty well-characterized SLE-patients (52 women, eight men; mean age 43.21 +/- 1.3 years) characterized by lupus nephritis (LN; n = 20), antiphospholipid syndrome (APS; n = 20) or skin and joint involvement (n = 20) and 60 healthy controls were included. Microcirculatory peak oxygen saturation (OxyP) was evaluated using a novel combined laser Doppler flowmetry/diffuse reflectance spectroscopy method. Pulse waves were recorded in the radial artery by the aid of applanation tonometry in order to calculate central augmentation index (AIx75). Intima-media thickness (IMT) and plaque occurrence were evaluated using high frequency US, in carotid and central arteries.Results: Lower OxyP (84 +/- 8 vs. 87 +/- 5 %, p = 0.01) and higher AIx75 (17.3 +/- 13.9 vs. 10.0 +/- 14.2 %, p = 0.005) were seen in the SLE cohort. OxyP was inversely correlated with IMT in internal carotid artery (ICA), (R = -0.32, p = 0.01). AIx75 correlated with IMT in common carotid artery (CCA), (R = 0.36, p = 0.005), common femoral artery (CFA), (R = 0.43, p = 0.001), and ICA (R = 0.27, p = 0.04). AIx75 correlated negatively with OxyP (R = -0.29, p = 0.02). SLE-patients with plaque had lower OxyP values (80 +/- 8 vs. 85 +/- 7 %, p &lt; 0.001) and higher AIx75 (23.0 +/- 11.6 vs. 15.5 +/- 14.2 %, p &lt; 0.001) compared to those without plaque.Conclusion: Impaired microcirculation and vessel hemodynamics were observed in SLE. These methods correlated with IMT and plaque occurrence. The importance of early macro- and micro-circulatory vascular affection for increased risk of CVD in SLE will be followed-up in future studies.

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