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

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

  • 2.
    Hultman, Martin
    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, Järfälla-Stockholm, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Alvandpour, Atila
    Linköping University, Department of Electrical Engineering, Integrated Circuits and Systems. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    A 15.6 frames per second 1 megapixel Multiple Exposure Laser Speckle Contrast Imaging setup2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 2, article id e201700069Article in journal (Refereed)
    Abstract [en]

    A multiple exposure laser speckle contrast imaging (MELSCI) setup for visualizing blood perfusion was developed using a field programmable gate array (FPGA), connected to a 1000 frames per second (fps) 1-megapixel camera sensor. Multiple exposure time images at 1, 2, 4, 8, 16, 32 and 64 milliseconds were calculated by cumulative summation of 64 consecutive snapshot images. The local contrast was calculated for all exposure times using regions of 4 × 4 pixels. Averaging of multiple contrast images from the 64-millisecond acquisition was done to improve the signal-to-noise ratio. The results show that with an effective implementation of the algorithm on an FPGA, contrast images at all exposure times can be calculated in only 28 milliseconds. The algorithm was applied to data recorded during a 5 minutes finger occlusion. Expected contrast changes were found during occlusion and the following hyperemia in the occluded finger, while unprovoked fingers showed constant contrast during the experiment. The developed setup is capable of massive data processing on an FPGA that enables processing of MELSCI data in 15.6 fps (1000/64 milliseconds). It also leads to improved frame rates, enhanced image quality and enables the calculation of improved microcirculatory perfusion estimates compared to single exposure time systems.

  • 3.
    Hultman, Martin
    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, Järfälla-Stockholm, Sweden.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Evaluation of a high framerate multi-exposure laser speckle contrast imaging setup2018In: High-Speed Biomedical Imaging and Spectroscopy III: Toward Big Data Instrumentation and Management / [ed] Kevin K. Tsia, Keisuke Goda, SPIE - International Society for Optical Engineering, 2018Conference paper (Refereed)
    Abstract [en]

    We present a first evaluation of a new multi-exposure laser speckle contrast imaging (MELSCI) system for assessing spatial variations in the microcirculatory perfusion. The MELSCI system is based on a 1000 frames per second 1-megapixel camera connected to a field programmable gate arrays (FPGA) capable of producing MELSCI data in realtime. The imaging system is evaluated against a single point laser Doppler flowmetry (LDF) system during occlusionrelease provocations of the arm in five subjects. Perfusion is calculated from MELSCI data using current state-of-the-art inverse models. The analysis displayed a good agreement between measured and modeled data, with an average error below 6%. This strongly indicates that the applied model is capable of accurately describing the MELSCI data and that the acquired data is of high quality. Comparing readings from the occlusion-release provocation showed that the MELSCI perfusion was significantly correlated (R=0.83) to the single point LDF perfusion, clearly outperforming perfusion estimations based on a single exposure time. We conclude that the MELSCI system provides blood flow images of enhanced quality, taking us one step closer to a system that accurately can monitor dynamic changes in skin perfusion over a large area in real-time

  • 4.
    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.

  • 5.
    Strömberg, Tomas
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Saager, Rolf B.
    Beckman Laser Institute and Medical Clinic, USA.
    Kennedy, Gordon T.
    Beckman Laser Institute and Medical Clinic, USA.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Durkin, Anthony J.
    Beckman Laser Institute and Medical Clinic, USA.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Spatial frequency domain imaging using a snap-shot filter mosaic camera with multi-wavelength sensitive pixels2018In: Proceedings Volume 10467, Photonics in Dermatology and Plastic Surgery 2018; 104670D (2018) / [ed] Bernard Choi, and Haishan Zeng, SPIE - International Society for Optical Engineering, 2018, Vol. 10467, article id 104670DConference paper (Refereed)
    Abstract [en]

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

  • 6.
    Bergstrand, Sara
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Morales, Maria-Aurora
    CNR Inst Clin Physiol, Italy.
    Coppini, Giuseppe
    CNR Inst Clin Physiol, Italy.
    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.
    The relationship between forearm skin speed-resolved perfusion and oxygen saturation, and finger arterial pulsation amplitudes, as indirect measures of endothelial function2018In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 25, no 2, article id e12422Article in journal (Refereed)
    Abstract [en]

    Objective: Endothelial function is important for regulating peripheral blood flow to meet varying metabolic demands and can be measured indirectly during vascular provocations. In this study, we compared the PAT finger response (EndoPAT) after a 5-minutes arterial occlusion to that from forearm skin comprehensive microcirculation analysis (EPOS). Methods: Measurements in 16 subjects with varying cardiovascular risk factors were carried out concurrently with both methods during arterial occlusion, while forearm skin was also evaluated during local heating. Results: Peak values for EPOS skin Perf(conv) and speed-resolved total perfusion after the release of the occlusion were significantly correlated to the EndoPAT RHI (rho =.68, P = .007 and rho =.60, P = .025, respectively), mainly due to high-speed blood flow. During local heating, EPOS skin oxygen saturation, SO2, was significantly correlated to RHI (rho = .62, P =.043). This indicates that SO2 may have diagnostic value regarding endothelial function. Conclusions: We have demonstrated for the first time a significant relationship between forearm skin microcirculatory perfusion and oxygen saturation and finger PAT. Both local heating and reactive hyperemia are useful skin provocations. Further studies are needed to understand the precise regulation mechanisms of blood flow and oxygenation during these tests.

  • 7.
    Larsson, Marcus
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Favilla, Riccardo
    Institute of Clinical Physiology, Council of National Research, Pisa, Italy.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Assessment of advanced glycated end product accumulation in skin using auto fluorescence multispectral imaging2017In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 85, p. 106-111Article in journal (Refereed)
    Abstract [en]

    Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF).A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, while displaying promising results, it is limited to single-point measurements performed in contact to skin tissue. Furthermore, in vivo imaging of AGE accumulation is virtually unexplored.We proposed a non-invasive, contact-less novel technique for quantifying fluorescent AGE deposits in skin tissue using a multispectral imaging camera setup (MSI) during ultraviolet (UV) exposure. Imaging involved applying a region-of-interest mask, avoiding specular reflections and a simple calibration. Results of a study conducted on 16 subjects with skin types ranging from fair to deeply pigmented skin, showed that AGE measured with MSI in forearm skin was significantly correlated with the AGE reference method (AGE Reader on forearm skin, R=0.68, p=0.005). AGE measured in facial skin was borderline significantly related to AGE Reader on forearm skin (R=0.47, p=0.078). These results support the use of the technique in devices for non-touch measurement of AGE content in either facial or forearm skin tissue over time.

  • 8.
    Danielis, Alessandro
    et al.
    CNR, Italy.
    Giorgi, Daniela
    CNR, Italy.
    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.
    Colantonio, Sara
    CNR, Italy.
    Salvetti, Ovidio
    CNR, Italy.
    Lip segmentation based on Lambertian shadings and morphological operators for hyper-spectral images2017In: Pattern Recognition, ISSN 0031-3203, E-ISSN 1873-5142, Vol. 63, p. 355-370Article in journal (Refereed)
    Abstract [en]

    Lip segmentation is a non-trivial task because the colour difference between the lip and the skin regions maybe not so noticeable sometimes. We propose an automatic lip segmentation technique for hyper-spectral images from an imaging prototype with medical applications. Contrarily to many other existing lip segmentation methods, we do not use colour space transformations to localise the lip area. As input image, we use for the first time a parametric blood concentration map computed by using narrow spectral bands. Our method mainly consists of three phases: (i) for each subject generate a subset of face images enhanced by different simulated Lambertian illuminations, then (ii) perform lip segmentation on each enhanced image by using constrained morphological operations, and finally (iii) extract features from Fourier-based modeled lip boundaries for selecting the lip candidate. Experiments for testing our approach are performed under controlled conditions on volunteers and on a public hyper-spectral dataset. Results show the effectiveness of the algorithm against low spectral range, moustache, and noise.

  • 9.
    Henriquez, Pedro
    et al.
    University of Central Lancashire, England.
    Matuszewski, Bogdan J.
    University of Central Lancashire, England.
    Andreu-Cabedo, Yasmina
    University of Central Lancashire, England.
    Bastiani, Luca
    CNR, Italy.
    Colantonio, Sara
    CNR, Italy.
    Coppini, Giuseppe
    CNR, Italy.
    DAcunto, Mario
    CNR, Italy.
    Favilla, Riccardo
    CNR, Italy.
    Germanese, Danila
    CNR, Italy.
    Giorgi, Daniela
    CNR, Italy.
    Marraccini, Paolo
    CNR, Italy.
    Martinelli, Massimo
    CNR, Italy.
    Morales, Maria-Aurora
    CNR, Italy.
    Antonietta Pascali, Maria
    CNR, Italy.
    Righi, Marco
    CNR, Italy.
    Salvetti, Ovidio
    CNR, Italy.
    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.
    Randeberg, Lise
    Norwegian University of Science and Technology, Norway.
    Bjorgan, Asgeir
    Norwegian University of Science and Technology, Norway.
    Giannakakis, Giorgos
    Fdn Research and Technology Hellas, Greece.
    Pediaditis, Matthew
    Fdn Research and Technology Hellas, Greece.
    Chiarugi, Franco
    Fdn Research and Technology Hellas, Greece.
    Christinaki, Eirini
    Fdn Research and Technology Hellas, Greece.
    Marias, Kostas
    Fdn Research and Technology Hellas, Greece.
    Tsiknakis, Manolis
    Fdn Research and Technology Hellas, Greece; Technology Educ Institute Crete, Greece.
    Mirror Mirror on the Wall ... An Unobtrusive Intelligent Multisensory Mirror for Well-Being Status Self-Assessment and Visualization2017In: IEEE transactions on multimedia, ISSN 1520-9210, E-ISSN 1941-0077, Vol. 19, no 7, p. 1467-1481Article in journal (Refereed)
    Abstract [en]

    A persons well-being status is reflected by their face through a combination of facial expressions and physical signs. The SEMEOTICONS project translates the semeiotic code of the human face into measurements and computational descriptors that are automatically extracted from images, videos, and three-dimensional scans of the face. SEMEOTICONS developed a multisensory platform in the form of a smart mirror to identify signs related to cardio-metabolic risk. The aim was to enable users to self-monitor their well-being status over time and guide them to improve their lifestyle. Significant scientific and technological challenges have been addressed to build the multisensory mirror, from touchless data acquisition, to real-time processing and integration of multimodal data.

  • 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.
    Ewerlöf, Maria
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Spatial and temporal skin blood volume and saturation estimation using a multispectral snapshot imaging camera2017In: IMAGING, MANIPULATION, AND ANALYSIS OF BIOMOLECULES, CELLS, AND TISSUES XV, SPIE-INT SOC OPTICAL ENGINEERING , 2017, Vol. 10068, article id UNSP 1006814Conference paper (Refereed)
    Abstract [en]

    Hyperspectral imaging (HSI) can estimate the spatial distribution of skin blood oxygenation, using visible to near-infrared light. HSI oximeters often use a liquid-crystal tunable filter, an acousto-optic tunable filter or mechanically adjustable filter wheels, which has too long response/switching times to monitor tissue hemodynamics. This work aims to evaluate a multispectral snapshot imaging system to estimate skin blood volume and oxygen saturation with high temporal and spatial resolution. We use a snapshot imager, the xiSpec camera (MQ022HG-IM-SM4X4-VIS, XIMEA (R)), having 16 wavelength-specific Fabry-Perot filters overlaid on the custom CMOS-chip. The spectral distribution of the bands is however substantially overlapping, which needs to be taken into account for an accurate analysis. An inverse Monte Carlo analysis is performed using a two-layered skin tissue model, defined by epidermal thickness, haemoglobin concentration and oxygen saturation, melanin concentration and spectrally dependent reduced-scattering coefficient, all parameters relevant for human skin. The analysis takes into account the spectral detector response of the xiSpec camera. At each spatial location in the field-of-view, we compare the simulated output to the detected diffusively backscattered spectra to find the best fit. The imager is evaluated for spatial and temporal variations during arterial and venous occlusion protocols applied to the forearm. Estimated blood volume changes and oxygenation maps at 512x272 pixels show values that are comparable to reference measurements performed in contact with the skin tissue. We conclude that the snapshot xiSpec camera, paired with an inverse Monte Carlo algorithm, permits us to use this sensor for spatial and temporal measurement of varying physiological parameters, such as skin tissue blood volume and oxygenation.

  • 12.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Vessel packaging effect in laser speckle contrast imaging and laser Doppler imaging2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 10, article id 106005Article in journal (Refereed)
    Abstract [en]

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

  • 13.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    On the equivalence and differencesbetween laser Doppler flowmetry andlaser speckle contrast analysis2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 12, article id 126018Article in journal (Refereed)
    Abstract [en]

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

  • 14.
    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.

  • 15.
    Milanic, Matija
    et al.
    Norwegian University of Science and Technology, Norway.
    Bjorgan, Asgeir
    Norwegian University of Science and Technology, Norway.
    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.
    Lyngsnes Randeberga, Lise
    Norwegian University of Science and Technology, Norway.
    Detection of hypercholesterolemia using hyperspectral imaging of human skin2015In: CLINICAL AND BIOMEDICAL SPECTROSCOPY AND IMAGING IV, SPIE - International Society for Optical Engineering, 2015, Vol. 9537, no 95370CConference paper (Refereed)
    Abstract [en]

    Hypercholesterolemia is characterized by high blood levels of cholesterol and is associated with increased risk of atherosclerosis and cardiovascular disease. Xanthelasma is a subcutaneous lesion appearing in the skin around the eyes. Xanthelasma is related to hypercholesterolemia. Identifying micro-xanthelasma can thereforeprovide a mean for early detection of hypercholesterolemia and prevent onset and progress of disease. The goal of this study was to investigate spectral and spatial characteristics of hypercholesterolemia in facial skin. Optical techniques like hyperspectral imaging (HSI) might be a suitable tool for such characterization as it simultaneously provides high resolution spatial and spectral information. In this study a 3D Monte Carlo model of lipid inclusions in human skin was developed to create hyperspectral images in the spectral range 400-1090 nm. Four lesions with diameters 0.12-1.0 mm were simulated for three different skin types. The simulations were analyzed using three algorithms: the Tissue Indices (TI), the two layer Diffusion Approximation (DA), and the Minimum Noise Fraction transform (MNF). The simulated lesions were detected by all methods, but the best performance was obtained by the MNF algorithm. The results were verified using data from 11 volunteers with known cholesterol levels. The face of the volunteers was imaged by a LCTF system (400-720 nm), and the images were analyzed using the previously mentioned algorithms. The identified features were then compared to the known cholesterol levels of the subjects. Significant correlation was obtained for the MNF algorithm only. This study demonstrates that HSI can be a promising, rapid modality for detection of hypercholesterolemia.

  • 16.
    Ewerlöf, Maria
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Salerud, E. Göran
    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.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Estimating skin blood saturation by selecting a subset of hyperspectral imaging data2015In: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XIII / [ed] Daniel L. Farkas; Dan V. Nicolau; Robert C. Leif, SPIE, 2015, Vol. 9328Conference paper (Refereed)
    Abstract [en]

    Skin blood haemoglobin saturation (𝑠b) can be estimated with hyperspectral imaging using the wavelength (λ) range of 450-700 nm where haemoglobin absorption displays distinct spectral characteristics. Depending on the image size and photon transport algorithm, computations may be demanding. Therefore, this work aims to evaluate subsets with a reduced number of wavelengths for 𝑠b estimation. White Monte Carlo simulations are performed using a two-layered tissue model with discrete values for epidermal thickness (𝑇epi) and the reduced scattering coefficient (μ's ), mimicking an imaging setup. A detected intensity look-up table is calculated for a range of model parameter values relevant to human skin, adding absorption effects in the post-processing. Skin model parameters, including absorbers, are; μ's (λ), 𝑇epi, haemoglobin saturation (𝑠b), tissue fraction blood (𝑐b) and tissue fraction melanin (𝑐mel). The skin model paired with the look-up table allow spectra to be calculated swiftly. Three inverse models with varying number of free parameters are evaluated: A(𝑠b, 𝑐b), B(𝑠b, 𝑐b, 𝑐mel) and C(all parameters free). Fourteen wavelength candidates are selected by analysing the maximal spectral sensitivity to 𝑠b and minimizing the sensitivity to 𝑐b. All possible combinations of these candidates with three, four and 14 wavelengths, as well as the full spectral range, are evaluated for estimating 𝑠b for 1000 randomly generated evaluation spectra. The results show that the simplified models A and B estimated 𝑠b accurately using four wavelengths (mean error 2.2% for model B). If the number of wavelengths increased, the model complexity needed to be increased to avoid poor estimations.

  • 17.
    Milanic, Matija
    et al.
    Norwegian University of Science and Technology, Norway.
    Bjorgan, Asgeir
    Norwegian University of Science and Technology, Norway.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Marraccini, Paolo
    CNR, Italy.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Randeberg, Lyngsnes
    Norwegian University of Science and Technology, Norway.
    Hyperspectral imaging for detection of cholesterol in human skin2015In: OPTICAL DIAGNOSTICS AND SENSING XV: TOWARD POINT-OF-CARE DIAGNOSTICS, Society of Photo-optical Instrumentation Engineers (SPIE) , 2015, Vol. 9332, no 93320WConference paper (Refereed)
    Abstract [en]

    Hypercholesterolemia is characterized by high levels of cholesterol in the blood and is associated with an increased risk of atherosclerosis and coronary heart disease. Early detection of hypercholesterolemia is necessary to prevent onset and progress of cardiovascular disease. Optical imaging techniques might have a potential for early diagnosis and monitoring of hypercholesterolemia. In this study, hyperspectral imaging was investigated for this application. The main aim of the study was to identify spectral and spatial characteristics that can aid identification of hypercholesterolemia in facial skin. The first part of the study involved a numerical simulation of human skin affected by hypercholesterolemia A literature survey was performed to identify characteristic morphological and physiological parameters. Realistic models were prepared and Monte Carlo simulations were performed to obtain hyperspectral images. Based on the simulations optimal wavelength regions for differentiation between normal and cholesterol rich skin were identified Minimum Noise Fraction transformation (MNF) was used for analysis. In the second part of the study, the simulations were verified by a clinical study involving volunteers with elevated and normal levels of cholesterol. The faces of the volunteers were scanned by a hyperspectral camera covering the spectral range between 400 nm and 720 nm, and characteristic spectral features of the affected skin were identified Processing of the images was done after conversion to reflectance and masking of the images. The identified features were compared to the known cholesterol levels of the subjects. The results of this study demonstrate that hyperspectral imaging of facial skin can be a promising, rapid modality for detection of hypercholesterolemia

  • 18.
    Andreu-Cabedo, Yasmina
    et al.
    University of Central Lancashire, England.
    Castellano, Pedro
    University of Central Lancashire, England.
    Colantonio, Sara
    National Research Council Italy, Italy.
    Coppini, Giuseppe
    National Research Council Italy, Italy.
    Favilla, Riccardo
    National Research Council Italy, Italy.
    Germanese, Danila
    National Research Council Italy, Italy.
    Giannakakis, Giorgos
    Fdn Research and Technology, Greece.
    Giorgi, Daniela
    National Research Council Italy, Italy.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Marraccini, Paolo
    National Research Council Italy, Italy.
    Martinelli, Massimo
    National Research Council Italy, Italy.
    Matuszewski, Bogdan
    University of Central Lancashire, England.
    Milanic, Matijia
    Norvegian University of Science and Technology, Norway.
    Pascali, Mariantonietta
    National Research Council Italy, Italy.
    Pediaditis, Mattew
    Fdn Research and Technology, Greece.
    Raccichini, Giovanni
    National Research Council Italy, Italy.
    Randeberg, Lise
    Norvegian University of Science and Technology, Norway.
    Salvetti, Ovidio
    National Research Council Italy, Italy.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    MIRROR MIRROR ON THE WALL... AN INTELLIGENT MULTISENSORY MIRROR FOR WELL-BEING SELF-ASSESSMENT2015In: 2015 IEEE INTERNATIONAL CONFERENCE ON MULTIMEDIA and EXPO (ICME), IEEE , 2015Conference paper (Refereed)
    Abstract [en]

    The face reveals the healthy status of an individual, through a combination of physical signs and facial expressions. The project SEMEOTICONS is translating the semeiotic code of the human face into computational descriptors and measures, automatically extracted from videos, images, and 3D scans of the face. SEMEOTICONS is developing a multisensory platform, in the form of a smart mirror, looking for signs related to cardio-metabolic risk. The goal is to enable users to self-monitor their well-being status over time and improve their life-style via tailored user guidance. Building the multisensory mirror requires addressing significant scientific and technological challenges, from touch-less data acquisition, to real-time processing and integration of multimodal data.

  • 19.
    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.

  • 20.
    Colantonio, Sara
    et al.
    CNR, Italy.
    Germanese, Danila
    CNR, Italy.
    Moroni, Davide
    CNR, Italy.
    Giorgi, Daniela
    CNR, Italy.
    Pascali, Mariantonietta
    CNR, Italy.
    Righi, Marco
    CNR, Italy.
    Coppini, Giuseppe
    CNR, Italy.
    Aurora Morales, Maria
    CNR, Italy.
    Chiarugi, Franco
    FORTH, Greece.
    Pediaditis, Mattew
    FORTH, Greece.
    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.
    Henriquez, Pedro
    University of Central Lancashire, England.
    Matuszewski, Bogdan
    University of Central Lancashire, England.
    Milanic, Matijia
    Norwegian University of Science and Technology, Norway.
    Randeberg, Lise
    Norwegian University of Science and Technology, Norway.
    SEMEOTICONS - READING THE FACE CODE OF CARDIO-METABOLIC RISK2015In: 2015 INTERNATIONAL WORKSHOP ON COMPUTATIONAL INTELLIGENCE FOR MULTIMEDIA UNDERSTANDING (IWCIM), IEEE , 2015Conference paper (Refereed)
    Abstract [en]

    What if you could discover your health status by looking at yourself in the mirror? Since November 2013, the EU FP7 Project SEMEOTICONS is working to make this possible. The Project is building a multi-sensory device, having the form of a conventional mirror, able to read the semeiotic code of the face and detect possible evidence of the onset of cardio-metabolic diseases. The device, called Wize Mirror, integrates unobtrusive imaging sensors used to capture videos, images and 3D scans of the face. These are processed to assess the risk of a cardio-metabolic disease and thereby suggest possible strategies to prevent its onset.

  • 21.
    Strömberg, Tomas
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Laser Doppler Perfusion Monitoring and Imaging.2014In: Biomedical Photonics Handbook, CRC Press, 2014Chapter in book (Refereed)
  • 22.
    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.

  • 23.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Model-Based Quantification of Skin Microcirculatory Perfusion2014In: Computational Biophysics of the Skin / [ed] Bernard Querleux, Singapore: Pan Stanford Publishing, 2014, 1, p. 395-420Chapter in book (Other academic)
  • 24.
    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)
  • 25.
    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.

  • 26.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Perimed AB, Järfälla, Sweden.
    Burdakov, Oleg
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 12, p. 127004-1-127004-14Article in journal (Refereed)
    Abstract [en]

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

  • 27.
    Briers, David
    et al.
    University of Kingston, England .
    Duncan, Donald D.
    Portland State University, OR USA .
    Hirst, Evan
    Callaghan Innovat, New Zealand .
    Kirkpatrick, Sean J.
    Michigan Technology University, MI USA .
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Steenbergen, Wiendelt
    University of Twente, Netherlands .
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Thompson, Oliver B.
    Callaghan Innovat, New Zealand .
    Laser speckle contrast imaging: theoretical and practical limitations2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 6Article in journal (Refereed)
    Abstract [en]

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

  • 28.
    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.

  • 29.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo method in a multilayered tissue model for diffuse reflectance spectroscopy2012In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 17, no 4, p. 047004-Article in journal (Refereed)
    Abstract [en]

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

  • 30.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Laser Doppler flowmetry2012In: Microcirculation imaging / [ed] Martin J. Leahy, Weinheim: Wiley-Blackwell, 2012, , p. 411p. 67-84Chapter in book (Other academic)
    Abstract [en]

    Adopting a multidisciplinary approach with input from physicists, researchers and medical professionals, this is the first book to introduce many different technical approaches for the visualization of microcirculation, including laser Doppler and laser speckle, optical coherence tomography and photo-acoustic tomography. It covers everything from basic research to medical applications, providing the technical details while also outlining the respective strengths and weaknesses of each imaging technique. Edited by an international team of top experts, this is the ultimate handbook for every clinician and researcher relying on microcirculation imaging.

  • 31.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Accuracy of vessel diameter estimated from a vessel packaging compensation in diffuse reflectance spectroscopy2011In: Clinical and Biomedical Spectroscopy and Imaging II / [ed] Nirmala Ramanujam, Jurgen Popp, SPIE - International Society for Optical Engineering, 2011, Vol. 8087, p. 8087 1M-1-8087 1M-8Conference paper (Other academic)
    Abstract [en]

     Light absorption in tissue is generally decreased when chromophores are spatially concentrated rather than being homogeneously distributed. In tissue, this applies to hemoglobin located in blood vessels (vessel packaging). In this paper, the diffusely reflected light from 41 tissue models with discrete blood vessels with diameters ranging from 6.25 to 100 μm were simulated using the Monte Carlo technique. A reverse engineering approach was then utilized to find the model that had an optimal spectral fit to each of the simulated models. The average vessel diameter was one fitting parameter in the adaptive model. The estimated vessel diameter from the optimal fit model was compared to the known diameter from the simulated models. Two different methods to calculate the vessel packaging effect were used, one existing based on a simple analytic expression and a new method based on path length distributions. Both methods had similar performance. For the new method, the absolute RMS deviation of the estimated vessel diameter was 5.5 μm for vessel diameters ≤ 25 μm, and the relative RMS deviation was 21 % for vessel diameters > 25 μm.

     

  • 32.
    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.

  • 33.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Linköping University, Faculty of Health Sciences.
    Salomonsson, Fredrik
    Perimed AB, Järfälla-Stockholm, Sweden.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Improved calibration procedure for laser Doppler perfusion monitors2011In: Optical Diagnostics and SensingXI: Toward Point-of-CareDiagnostics; and Design andPerformance Validation ofPhantoms Used in Conjunctionwith Optical Measurement ofTissue III / [ed] Robert J. Nordstrom; Gerard L. Coté, SPIE - International Society for Optical Engineering, 2011, p. 790602-1-790602-7Conference paper (Other academic)
    Abstract [en]

    Commercial laser Doppler perfusion monitors are calibrated using the perfusion value, i.e. the first order moment of the Doppler power spectrum, from a measurement in a standardized microsphere colloidal suspension under Brownian motion. The calibration perfusion value depends on several parameters of the suspension that are difficult to keep constant with adequate accuracy, such as the concentration, temperature and the microsphere size distribution. The calibration procedure itself may therefore introduce significant errors in the measured values.

    An altered calibration procedure, where the zero order moment is used is described and demonstrated in this paper. Since the above mentioned parameters only affect the frequency content of the Doppler power spectrum and not the total power, the zero order moment will be independent of those parameters. It is shown that the variation in the calibration value, as given by measurements on different scattering liquids with a wide range of scattering properties and temperatures, is only a few percent using the proposed method. For the conventional calibration procedure, this variation corresponds to an error introduced by merely a 1°C variation in the reference liquid temperature. The proposed calibration method also enables absolute level comparisons between measured and simulated Doppler power spectra.

  • 34.
    Lindbergh, Tobias
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Häggblad, Erik
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Ahn, Henrik
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Salerud, Göran
    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.
    Improved model for myocardial diffuse reflectance spectra by including mitochondrial cytochrome aa3, methemoglobin, and inhomogenously distributed RBC2011In: Journal of Biophotonics, ISSN 1864-063X, Vol. 4, no 4, p. 268-276Article in journal (Refereed)
    Abstract [en]

    Hemo- and myoglobin oxygen saturation and cytochrome aa3 oxidation was locally assessed using calibrated diffuse reflectance spectroscopy in fourteen patients undergoing coronary artery bypass grafting. Diffuse spectral reflectance data, recorded with a handheld fiberoptic probe with a single source-detector separation, was analyzed using an empirical light transport model relating the absorption and reduced scattering coefficients to the measured spectrum. The absorption coefficient has previously been modeled as a sum of hemoglobin and myoglobin, fat, and water. In this study, inclusion of cytochrome aa3 and the sum of methemoglobin and metmyoglobin improved the spectral fit, especially in the wavelength regions where their absorption is prominent. On average, the extended model increased the mean R2 from 0.96 to 0.99 and displayed 4% units higher saturation levels. After aorta cross-clamping, the sum of hemo- and myoglobin oxygen saturation increased while cytochrome aa3 oxidation decreased slightly. Opposite trends were observed during cardiac arrest. At reperfusion, the saturation increased compared to the levels found at cardiac arrest, and the cytochrome aa3 oxidation was restored. The estimated tissue chromophore fractions, saturation and oxidation, were in agreement with other studies.

  • 35.
    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)
  • 36.
    Lindbergh, Tobias
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Casimir-Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Thoracic Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Intramyocardial oxygen transport by quantitative diffuse reflectance spectroscopy in calves2010In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 2Article in journal (Refereed)
    Abstract [en]

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

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

  • 37.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Model-based quantitative laser Doppler flowmetry in skin2010In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 5Article in journal (Refereed)
    Abstract [en]

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

  • 38.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences, Internal Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences, Physiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Johan Östgren, Carl
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Finspång, Primary Health Care Centre.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Reduced Arteriovenous Shunting Capacity After Local Heating and Redistribution of Baseline Skin Blood Flow in Type 2 Diabetes Assessed With Velocity-Resolved Quantitative Laser Doppler Flowmetry2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 7, p. 1578-1584Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS-The skin blood flow response to local heating (44 degrees C for 20 mm) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity X concentration), in a physiologically relevant unit (grams RBC per 100 g tissue X millimeters per second) in a fixed output volume, separated into three velocity regions: v less than1 mm/s, v 1-10 mm/s, and v greater than10 mm/s. RESULTS-The increased blood flow occurs in vessels with a velocity greater than1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v greater than10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v greater than10 mm/s, whereas no significant increase was found for v less than1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS-The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio.

  • 39.
    Draijer, Matthijs J
    et al.
    University of Twente.
    Hondebrink, Erwin
    University of Twente.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    G van Leeuwen, Ton
    University of Twente.
    Steenbergen, Wiendelt
    University of Twente.
    Relation between the contrast in time integrated dynamic speckle patterns and the power spectral density of their temporal intensity fluctuations2010In: OPTICS EXPRESS, ISSN 1094-4087, Vol. 18, no 21, p. 21883-21891Article in journal (Refereed)
    Abstract [en]

    Scattering fluid flux can be quantified with coherent light, either from the contrast of speckle patterns, or from the moments of the power spectrum of intensity fluctuations. We present a theory connecting these approaches for the general case of mixed static-dynamic patterns of boiling speckles without prior assumptions regarding the particle dynamics. An expression is derived and tested relating the speckle contrast to the intensity power spectrum. Our theory demonstrates that in speckle contrast the concentration of moving particles dominates over the contribution of speed to the particle flux. Our theory provides a basis for comparison of both approaches when used for studying tissue perfusion.

  • 40.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations2009In: JOURNAL OF BIOPHOTONICS, ISSN 1864-063X, Vol. 2, no 3, p. 178-184Article in journal (Refereed)
    Abstract [en]

    Two forced detection (FD) variance reduction Monte Carlo algorithms for image simulations of tissue-embedded objects with matched refractive index are presented. The principle of the algorithms is to force a fraction of the photon weight to the detector at each and every scattering event. The fractional weight is given by the probability for the photon to reach the detector without further interactions. Two imaging setups are applied to a tissue model including blood vessels, where the ID algorithms produce identical results as traditional brute force simulations, while being accelerated with two orders of magnitude. Extending the methods to include refraction mismatches is discussed.

    The principle of forced detection; a part of the photon weight. based on the probability of reaching the detector without further interactions, is forced to the detector at each and every scattering event.

  • 41.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Measurement depth and volume in laser Doppler flowmetry2009In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 78, no 1, p. 4-13Article in journal (Refereed)
    Abstract [en]

    A new method for estimating the measurement depth and volume in laser Doppler flowmetry (LDF) is presented. The method is based on Monte Carlo simulations of light propagation in tissue. The contribution from each individual Doppler shift is calculated and thereby multiple Doppler shifts are handled correctly. Different LDF setups for both probe based (0.0, 0.25, 0.5, and 1.2 mm source-detector separation) and imaging systems (0.5 and 2.0 mm beam diameter) are considered, at the wavelengths 543 nm, 633 nm, and 780 nm. Non-linear speckle pattern effects are accounted for in the imaging system setups. The effects of tissue optical properties, blood concentration, and blood oxygen saturation are evaluated using both homogeneous tissue models and a layered skin model. The results show that the effect on the measurement depth of changing tissue properties is comparable to the effect of changing the system setup, e.g. source-detector separation and wavelength. Skin pigmentation was found to have a negligible effect on the measurement depth. Examples of measurement depths are (values are given for a probe based system with 0.25 mm source-detector separation and an imaging system with a 0.5 mm beam diameter, respectively, both operating at 780 nm): muscle - 0.55/0.79 mm; liver - 0.40/0.53 mm; gray matter - 0.48/0.68 mm; white matter - 0.20/0.20 mm; index finger pulp - 0.41/0.53 mm; forearm skin - 0.53/0.56 mm; heat provoked forearm skin - 0.66/0.67 mm.

  • 42.
    Lindbergh, Tobias
    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.
    Spectral determination of a two-parametric phase function for polydispersive scattering liquids2009In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 17, no 3, p. 1610-1621Article in journal (Refereed)
    Abstract [en]

    A method for determining a two-parametric Gegenbauer-kernel phase function that accurately describes the diffuse reflectance from a polydispersive scattering media at small source-detector separations (0.23 to 1.2 mm), is presented. The method involves spectral collimated transmission measurements, spatially resolved spectral diffuse reflectance (SRDR) measurements, and inverse Monte Carlo technique. Both absolute calibration (using a monodispersive polystyrene microsphere suspension) and relative calibration (eliminating differences between fibers) of SRDR spectra yielded comparable results. When applied to water dilutions of milk, simulated and measured spectra deviated less than 6.5% and 2.5% for the absolute and relative calibration case, respectively, even for the closest fiber separation. Corresponding values for milk including ink as an absorber, were 13.4% and 7.3%.

  • 43.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry2008In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 1, p. 14015-Article in journal (Refereed)
    Abstract [en]

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

  • 44.
    Lindbergh, Tobias
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fredriksson, Ingemar
    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.
    Reduced scattering coefficient determination by non-contact oblique angle illumination: methodological considerations2007In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 6435, p. 64350I-1-64350I-12Article in journal (Refereed)
    Abstract [en]

    The reduced scattering coefficient, µs, was determined using oblique angle illumination and imaging backscattered light intensity. The distance r between the point of light incidence (hot-spot) and the circular symmetric diffuse reflectance centre, is ~1/µ. Previously, r was obtained analyzing a 1D strip aligned with the laser beam. We improved this method by calculating a 2D intensity image with extended dynamic range by assessing camera linearity, superimposing images with multiple integration times, and compensating for lens vignetting. The hot-spot algorithm utilises several images to minimize speckle variations and account for laser beam shape. Diffuse centre position is obtained by filtering the superimposed image with decreasing thresholds using momentum analysis to determine circular symmetry. The method was evaluated on 18 optical liquid phantoms with µs[1.5, 3.0] mm-1 and µs[0.01, 0.16] mm-1. The 2D method had better linearity with µs and smaller variations due to more stable hot-spot detection, than the 1D method. The anisotropy factor g was obtained by fitting measured and Monte Carlo simulated spatially resolved intensity decays and verified with a laser Doppler flowmetry technique. With an optimal compensation for the µa dependence, the rms error in µ estimation was 2.9%.

  • 45.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Absolute flow velocity components in laser Doppler flowmetry2006In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 6094, p. 60940A-Article in journal (Refereed)
    Abstract [en]

    A method to separate a Doppler power spectrum into a number of flow velocity components, measured in absolute units (mm/s), is presented. A Monte Carlo software was developed to track each individual Doppler shift, to determine the probability, p(n), for a photon to undergo n Doppler shifts. Given this shift distribution, a mathematical relationship was developed and used to calculate a Doppler power spectrum originating from a certain combination of velocity components. The non linear Levenberg-Marquardt optimization method could thus be used to fit the calculated and measured Doppler power spectra, giving the true set of velocity components in the measured sample. The method was evaluated using a multi tube flow phantom perfused with either polystyrene microspheres or undiluted/diluted human blood (hct = 0.45). It estimated the velocity components in the flow phantom well, during both low and high concentrations of moving scatterers (microspheres or blood). Thus, further development of the method could prove to be a valuable clinical tool to differentiate capillary blood flow.

  • 46.
    Fredriksson, Ingemar
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Larsson, Marcus
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Separation av shuntat och kapillärt mikrocirkulatoriskt blodflöde med laser Doppler-tekniken2006In: Medicinteknikdagarna,2006, 2006Conference paper (Refereed)
  • 47.
    Larsson, Marcus
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Towards a velocity-resolved microvascular blood flow measure by decomposition of the laser Doppler spectrum2006In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 11, no 1Article in journal (Refereed)
    Abstract [en]

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

  • 48.
    Fredriksson, Ingemar
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Larsson, Marcus
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Absolute blood flow velocity components in Laser Doppler flowmetry2005In: International Graduate Summer School Biophotonics05,2005, 2005Conference paper (Other academic)
  • 49.
    Fredriksson, Ingemar
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Larsson, Marcus
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Hastighetsupplöst blodflödesmätning med Laserdopplertekniken2005In: Medicinteknikdagar MTF,2005, 2005Conference paper (Other academic)
  • 50.
    Häggblad, Erik
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Lindbergh, Tobias
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Larsson, Marcus
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Strömberg, Tomas
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Myocardial blood volume and oxygenation monitoring during thoracic surgery2005Conference paper (Other academic)
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