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  • 101.
    Fredriksson, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
    Ilias, Michail
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    New mechanical device for effective removal of skin tags in routine health care2009In: Dermatologi Online, ISSN 1087-2108, E-ISSN 1087-2108, Vol. 15, no 2, article id 9Article in journal (Refereed)
    Abstract [en]

    Skin tags (acrochordons) are exceedingly common benign skin lesions. A novel medical device in the form of a flat adhesive patch applies pressure to the base of a skin tag, leading to its removal within 3-6 days. The device was used in a clinical trial to treat and remove skin tags of the neck, upper torso, and axillae in volunteers. In this study, a total of 177 skin tags were treated in 32 individuals. One hundred seventy-two lesions fulfilled intention to treat (ITT) criteria. A majority of ITT lesions (90%) reached final assessment. Successful outcome was highest (90%) for lesions up to 1 mm in base. For lesions up to 2 mm, the rate of successful outcome was 76 percent. The desired outcome was seen in 65 percent of all ITT lesions. The cosmetic outcome after removal was excellent. Discomfort was assessed as minimal during all stages of the procedure. Analysis of data on blood flow in the skin tags during the treatment showed that the outcome was influenced by whether a decrease in blood flow was achieved immediately after application and at 2-3 days, but that the degree of occlusion was not critical. The results of this study illustrate that the device presents a new option for the management of unmet needs in the treatment of skin tags.

  • 102.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Quantitative Laser Doppler Flowmetry2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Laser Doppler flowmetry (LDF) is virtually the only non-invasive technique, except for other laser speckle based techniques, that enables estimation of the microcirculatory blood flow. The technique was introduced into the field of biomedical engineering in the 1970s, and a rapid evolvement followed during the 1980s with fiber based systems and improved signal analysis. The first imaging systems were presented in the beginning of the 1990s.

    Conventional LDF, although unique in many aspects and elegant as a method, is accompanied by a number of limitations that may have reduced the clinical impact of the technique. The analysis model published by Bonner and Nossal in 1981, which is the basis for conventional LDF, is limited to measurements given in arbitrary and relative units, unknown and non-constant measurement volume, non-linearities at increased blood tissue fractions, and a relative average velocity estimate.

    In this thesis a new LDF analysis method, quantitative LDF, is presented. The method is based on recent models for light-tissue interaction, comprising the current knowledge of tissue structure and optical properties, making it fundamentally different from the Bonner and Nossal model. Furthermore and most importantly, the method eliminates or highly reduces the limitations mentioned above.

    Central to quantitative LDF is Monte Carlo (MC) simulations of light transport in tissue models, including multiple Doppler shifts by red blood cells (RBC). MC was used in the first proof-of-concept study where the principles of the quantitative LDF were tested using plastic flow phantoms. An optically and physiologically relevant skin model suitable for MC was then developed. MC simulations of that model as well as of homogeneous tissue relevant models were used to evaluate the measurement depth and volume of conventional LDF systems. Moreover, a variance reduction technique enabling the reduction of simulation times in orders of magnitudes for imaging based MC setups was presented.

    The principle of the quantitative LDF method is to solve the reverse engineering problem of matching measured and calculated Doppler power spectra at two different source-detector separations. The forward problem of calculating the Doppler power spectra from a model is solved by mixing optical Doppler spectra, based on the scattering phase functions and the velocity distribution of the RBC, from various layers in the model and for various amounts of Doppler shifts. The Doppler shift distribution is calculated based on the scattering coefficient of the RBC:s and the path length distribution of the photons in the model, where the latter is given from a few basal MC simulations.

    When a proper spectral matching is found, via iterative model parameters updates, the absolute measurement data are given directly from the model. The concentration is given in g RBC/100 g tissue, velocities in mm/s, and perfusion in g RBC/100 g tissue × mm/s. The RBC perfusion is separated into three velocity regions, below 1 mm/s, between 1 and 10 mm/s, and above 10 mm/s. Furthermore, the measures are given for a constant output volume of a 3 mm3 half sphere, i.e. within 1.13 mm from the light emitting fiber of the measurement probe.

    The quantitative LDF method was used in a study on microcirculatory changes in type 2 diabetes. It was concluded that the perfusion response to a local increase in skin temperature, a response that is reduced in diabetes, is a process involving only intermediate and high flow velocities and thus relatively large vessels in the microcirculation. The increased flow in higher velocities was expected, but could not previously be demonstrated with conventional LDF. The lack of increase in low velocity flow indicates a normal metabolic demand during heating. Furthermore, a correlation between the perfusion at low and intermediate flow velocities and diabetes duration was found. Interestingly, these correlations were opposites (negative for the low velocity region and positive for the mediate velocity region). This finding is well in line with the increased shunt flow and reduced nutritive capillary flow that has previously been observed in diabetes.

    List of papers
    1. Absolute flow velocity components in laser Doppler flowmetry
    Open this publication in new window or tab >>Absolute flow velocity components in laser Doppler flowmetry
    2006 (English)In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 6094, p. 60940A-Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    IEEE, 2006
    Keywords
    Laser Doppler flowmetry, LDF, Monte Carlo simulations, flow phantom, blood perfusion, scattering phase
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-11703 (URN)10.1117/12.659206 (DOI)
    Note
    Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Absolute flow velocity components in laser Doppler flowmetry, 2006, Proceedings of SPIE -- Volume 6094 Optical Diagnostics and Sensing VI. http://dx.doi.org/10.1117/12.659206. Copyright 2006 Society of Photo-Optical Instrumentation Engineers. This paper was published in Proceedings of SPIE -- Volume 6094 Optical Diagnostics and Sensing VI and is made available as an electronic reprint with permission of SPIE. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2017-12-13Bibliographically approved
    2. Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry
    Open this publication in new window or tab >>Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry
    2008 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 1, p. 14015-Article in journal (Refereed) Published
    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.

    Keywords
    laser Doppler velocimetry, simulations, biomedical optics, Doppler
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-11700 (URN)10.1117/1.2854691 (DOI)
    Note
    Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry, 2008, Journal of Biomedical Optics, (13), 1, 14015. http://dx.doi.org/10.1117/1.2854691. Copyright 2008 Society of Photo-Optical Instrumentation Engineers. This paper was published in Journal of Biomedical Optics and is made available as an electronic reprint with permission of SPIE. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2017-12-13
    3. Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations
    Open this publication in new window or tab >>Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations
    2009 (English)In: JOURNAL OF BIOPHOTONICS, ISSN 1864-063X, Vol. 2, no 3, p. 178-184Article in journal (Refereed) Published
    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.

    Keywords
    Monte Carlo simulations, diffuse scattering, variance reduction, Image simulation
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-17749 (URN)10.1002/jbio.200810048 (DOI)
    Note
    This is the pre-peer reviewed version of the following article: Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations, 2009, JOURNAL OF BIOPHOTONICS, (2), 3, 178-184. which has been published in final form at: http://dx.doi.org/10.1002/jbio.200810048 Copyright: Wiley-Blackwell Available from: 2009-04-18 Created: 2009-04-17 Last updated: 2016-08-31Bibliographically approved
    4. Measurement depth and volume in laser Doppler flowmetry
    Open this publication in new window or tab >>Measurement depth and volume in laser Doppler flowmetry
    2009 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 78, no 1, p. 4-13Article in journal (Refereed) Published
    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.

    Keywords
    Laser Doppler flowmetry, Laser Doppler perfusion monitoring, Laser Doppler perfusion imaging, Source-detector separation, Measurement volume, Sampling depth, Monte Carlo simulations, Tissue model, Multiple Doppler shifts
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-19656 (URN)10.1016/j.mvr.2009.02.008 (DOI)
    Note
    Original Publication: Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Measurement depth and volume in laser Doppler flowmetry, 2009, Microvascular Research, (78), 1, 4-13. http://dx.doi.org/10.1016/j.mvr.2009.02.008 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-07-10 Created: 2009-07-10 Last updated: 2017-12-13Bibliographically approved
    5. Model-based quantitative laser Doppler flowmetry in skin
    Open this publication in new window or tab >>Model-based quantitative laser Doppler flowmetry in skin
    2010 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 5Article in journal (Refereed) Published
    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.

    Place, publisher, year, edition, pages
    Society of Photo-optical Instrumentation Engineers, 2010
    Keywords
    laser Doppler flowmetry, microcirculation, tissue modeling, inverse Monte Carlo, quantitative measures, flow speed differentiation
    National Category
    Medical Laboratory and Measurements Technologies
    Identifiers
    urn:nbn:se:liu:diva-20445 (URN)10.1117/1.3484746 (DOI)000284837400046 ()
    Available from: 2009-09-08 Created: 2009-09-08 Last updated: 2017-12-13Bibliographically approved
    6. Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetry
    Open this publication in new window or tab >>Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetry
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The response to local heating (44oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume.

    A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.

    National Category
    Medical Laboratory and Measurements Technologies Biomedical Laboratory Science/Technology Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-20447 (URN)
    Available from: 2009-09-08 Created: 2009-09-08 Last updated: 2010-01-14Bibliographically approved
  • 103.
    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.

  • 104.
    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.

  • 105.
    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.

  • 106.
    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. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology .
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology .
    Östgren, Carl Johan
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, West County Primary Health Care.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetryManuscript (preprint) (Other academic)
    Abstract [en]

    The response to local heating (44oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume.

    A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.

  • 107.
    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.

  • 108.
    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)
  • 109.
    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.

  • 110.
    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.

     

  • 111.
    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.

  • 112.
    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)
  • 113.
    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.

  • 114.
    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.

  • 115.
    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.

  • 116.
    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)
  • 117.
    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.

  • 118.
    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.

  • 119.
    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)
  • 120.
    Fullerton, A.
    et al.
    Leo Pharmaceutical Products Ltd.
    Stücker, M.
    Ruhr Universitet Bochum.
    Wilhelm, K-P.
    proDERM Institute for Applied Derm. Res. GmbH.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, C.
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Fisher, T.
    National Institute of Working Life, Solna.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Serup, J.
    Leo Pharmaceutical Products Ltd.
    Guidelines for visualisation of cutaneous blood flow by laser Doppler imaging2002In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 46, no 3, p. 129-140Article in journal (Refereed)
    Abstract [en]

    This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

  • 121.
    Fytagoridis, A.
    et al.
    Department of Pharmacology and Clinical Neuroscience, Section of Neurosurgery, Umeå University, Sweden; Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Blomstedt, P.
    Department of Pharmacology and Clinical Neuroscience, Section of Neurosurgery, Umeå University, Sweden.
    Stimulation-induced side effects in the posterior subthalamic area: distribution, characteristics and visualization2013In: Clinical neurology and neurosurgery (Dutch-Flemish ed. Print), ISSN 0303-8467, E-ISSN 1872-6968, Vol. 15, no 1, p. 65-71Article in journal (Refereed)
    Abstract [en]

    Objective: The posterior subthalamic area (PSA) is an emerging but relatively unexplored target for DBS treatment of tremor. The aim of the study was to explore the area further by evaluating the spatial distribution and the characteristics of stimulation-induced side effects in this area. Methods: Twenty-eight patients with essential tremor (ET) implanted with 33 DBS electrodes were evaluated concerning stimulation-induced side effects by testing each contact separately one year after surgery. The location of the side effects were plotted on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the area for visualization was created. Results: Visualization of the contacts eliciting stimulation-induced side effects demonstrated that identical responses can be elicited from various points in the PSA and its vicinity. The majority of contacts inducing muscular affection and cerebellar symptoms, including dysarthria, could not be attributed to an effect on the internal capsule. Paresthesias, affecting various body parts were elicited throughout the area without a clear somatotopic pattern. Conclusion: Stimulation-induced side effects in the PSA and its vicinity are difficult to attribute to certain anatomical areas as the same response can be induced from various locations, and are thus of limited localizing value.

  • 122.
    Fytagoridis, Anders
    et al.
    Karolinska University Hospital.
    Sandvik, Ulrika
    Umeå University.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Bergenheim, Tommy
    Umeå University.
    Blomstedt, Patric
    Umeå University.
    Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor2012In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 83, no 3, p. 258-262Article in journal (Refereed)
    Abstract [en]

    Purpose The ventral intermediate nucleus of thalamus is the standard target for deep brain stimulation (DBS) in essential tremor (ET). However, favourable data have recently highlighted the caudal zona incerta (cZi) as an alternative target. Reports concerning the long-term results are however lacking, and we have therefore evaluated the long-term effects in our patients with ET and cZi DBS. less thanbrgreater than less thanbrgreater thanMethods 18 patients were evaluated using the Essential Tremor Rating Scale (ETRS) before and on-/off-stimulation at 1 and 3-5 years after surgery (mean 48.5+/-10.6 months). Two patients were operated on bilaterally but all electrodes were evaluated separately. The stimulation parameters were recorded and the stimulation strength calculated. less thanbrgreater than less thanbrgreater thanResults A baseline total ETRS mean score of 46.0 decreased to 21.9 (52.4%) at the final evaluation. On the treated side, tremor of the upper extremity (item 5 or 6) improved from 6.1 to 0.5 (91.8%) and hand function (items 11-14) improved from 9.3 to 2.0 (78.0%). Activities of daily living improved by 65.8%. There was no increase in stimulation strength over time. less thanbrgreater than less thanbrgreater thanConclusion cZi DBS is a safe and effective treatment for the long term suppression of ET.

  • 123.
    Fytagoridis, Anders
    et al.
    Umeå University, Sweden .
    Sjoberga, Rickard L.
    Umeå University, Sweden .
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fredricks, Anna
    Umeå University, Sweden .
    Nyberg, Lars
    Umeå University, Sweden .
    Blomstedt, Patric
    Umeå University, Sweden .
    Effects of Deep Brain Stimulation in the Caudal Zona Incerta on Verbal Fluency2013In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 91, no 1, p. 24-29Article in journal (Refereed)
    Abstract [en]

    Background: Deep brain stimulation (DBS) of the caudal zona incerta (cZi) is a relatively unexplored and promising treatment in patients with severe essential tremor (ET). Preliminary data further indicate that the ability to produce language may be slightly affected by the treatment. Objective: To evaluate the effects on verbal fluency following cZi DBS in patients with ET. Method: Seventeen consecutive patients who had undergone DBS of the cZi for ET were tested regarding verbal fluency before surgery, 3 days after surgery and after 1 year. Ten patients were also evaluated by comparing performance on versus off stimulation after 1 year. Results: The total verbal fluency score decreased slightly, but significantly, from 22.7 (SD = 10.9) before surgery to 18.1 (SD = 7.5) 3 days after surgery (p = 0.036). After 1 year the score was nonsignificantly decreased to 20.1 (SD = 9.7, p = 0.2678). There was no detectable difference between stimulation on and off after 1 year. Conclusion: There was a tendency of an immediate and mostly transient postoperative decline in verbal fluency following cZi DBS for ET. In some of the patients this reduction was, however, more pronounced and also sustained over time.

  • 124.
    Fytagoridis, Anders
    et al.
    Department of Pharmacologyand Clinical Neuroscience, Section of Neurosurgery, Umeå University, Umeå, Sweden.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Samuelsson, Jörgen
    Unit of Functional and Stereotactic Neurosurgery, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Blomstedt, Patric
    Department of Pharmacology and Clinical Neuroscience, Division of Neurosurgery, Umeå University, Umeå, Sweden.
    Deep Brain Stimulation of the Caudal Zona Incerta: Tremor Control in Relation to the Location of Stimulation Fields2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 6, p. 363-370Article in journal (Refereed)
    Abstract [en]

    Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.

  • 125.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, Faculty of Science & Engineering. Imperial Coll London, England.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Silesian Technical University, Poland.
    de Muinck, Ebo
    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 Cardiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Los, Marek Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Pomeranian Medical University, Poland.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Direct Mechanical Stimulation of Stem Cells: A Beating Electromechanically Active Scaffold for Cardiac Tissue Engineering2016In: Advanced Healthcare Materials, ISSN 2192-2640, E-ISSN 2192-2659, Vol. 5, no 12, p. 1471-1480Article in journal (Refereed)
    Abstract [en]

    The combination of stem cell therapy with a supportive scaffold is a promising approach to improving cardiac tissue engineering. Stem cell therapy can be used to repair nonfunctioning heart tissue and achieve myocardial regeneration, and scaffold materials can be utilized in order to successfully deliver and support stem cells in vivo. Current research describes passive scaffold materials; here an electroactive scaffold that provides electrical, mechanical, and topographical cues to induced human pluripotent stem cells (iPS) is presented. The poly(lactic-co-glycolic acid) fiber scaffold coated with conductive polymer polypyrrole (PPy) is capable of delivering direct electrical and mechanical stimulation to the iPS. The electroactive scaffolds demonstrate no cytotoxic effects on the iPS as well as an increased expression of cardiac markers for both stimulated and unstimulated protocols. This study demonstrates the first application of PPy as a supportive electroactive material for iPS and the first development of a fiber scaffold capable of dynamic mechanical actuation.

  • 126.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Bioelectronic nanofibre scaffolds for tissue engineering and whole-cell biosensors2014Conference paper (Refereed)
  • 127.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Smart Electroactive Scaffolds for Cardiac Tissue Regeneration2014Conference paper (Refereed)
  • 128.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Actuating electroactive scaffolds for cardiac tissue regeneration2014Conference paper (Refereed)
  • 129.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Zhang, Jiabin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Los, Marek
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Electroactive polymer scaffolds for cardiac tissue engineering2015In: Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015 / [ed] Bar-Cohen, SPIE - International Society for Optical Engineering, 2015, Vol. 9430, p. 94301T-1-94301T-7Conference paper (Refereed)
    Abstract [en]

    By-pass surgery and heart transplantation are traditionally used to restore the heart’s functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

  • 130.
    Gerdle, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Forsgren, Mikael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Bengtsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Sören, B.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Karlsson, Anette
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Health Sciences.
    Brandejsky, Vaslav
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients – A 31P-MRS study2013In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 17, no 8, p. 1205-1215Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND METHODS:

    Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity.

    RESULTS:

    Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities.

    CONCLUSIONS:

    Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.

  • 131. Ghassemifar, M.R.
    et al.
    Tarnuzzer, R.W.
    Salerud, Göran
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Schultz, G.S.
    Franzén, Lennart
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Pathology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Alpha-smooth muscle actin expression in rat and mouse mesenteric wounds after TGF-ß1 treatment1997In: Wound Repair and Regeneration, ISSN 1067-1927, E-ISSN 1524-475X, Vol. 5, p. 339-347Article in journal (Refereed)
  • 132.
    Grönkvist, Mikael
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Emery, M
    Assessment of ventilation distribution in four body positions by single breath vital apacity washouts of SF6 and He in man at 1G1998In: Aerospace Medical Association,1998, 1998Conference paper (Other academic)
  • 133. Gustavsson, U.
    et al.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Lewis, D.H.
    Vasomotion in rat skeletal muscle induced by hemorrhage as recorded by laser Doppler flowmetry1991In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, no 42, p. 224-228Article in journal (Refereed)
  • 134.
    Haj Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Medicine and Health Sciences.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Neurokirurgi.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Optical Guidance for Brain Tumor Stereotactic Biopsy2017Conference paper (Refereed)
  • 135.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence Spectroscopy for Quantitative Demarcation of Glioblastoma Using 5-Aminolevulinic Acid2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Total resection of glioblastoma, the highly malignant brain tumor, is difficult to accomplish due to its diffuse growth and similarity to the surrounding brain tissue. A total resection is proven to increase patient survival. The aim of this thesis was to evaluate fiber-optical based fluorescence spectroscopy for quantitative demarcation of malignant brain tumors during the surgery. Five-aminolevulinic acid (5-ALA) was used as a fluorescence contrast agent that accumulated as protoporphyrin IX (PpIX) in the tumor.

    The method was evaluated at the Department of Neurosurgery, Linköping University Hospital. The patients (n = 22) received an oral dose of 5 mg/kg body weight 5-ALA two hours prior to craniotomy. Measurements with a developed fluorescence spectroscopy system were performed under the general procedure of surgery. The collected fluorescence spectra were quantified by defining a fluorescence ratio and the main challenges of measuring and quantifying spectra were investigated. The fluorescence ratio was compared to visual diagnosis of the surgeon, histopathological examination and ultrasound-based neuronavigation. The main challenges of using a fluorescence spectroscopy system in the operating room were the disturbing ambient light, photobleaching and blood interference which affect the signal quantification. The superimposition of ambient light was removed by modulating the system.

    Using principal component analysis (PCA) the photobleaching sequences could be described by three spectral components of autofluorescence, PpIX fluorescence and blue-shift. To investigate the photobleaching induced prior to the measurements, a dynamic model was developed based on the PCA derived spectral components. Modulation and increased power of the excitation light resulted in a faster photobleaching; however, photobleaching was saturated at higher excitation powers. The system was adjusted to induce minimal photobleaching. In addition, effect of blood absorption on the fluorescence spectrum was investigated experimentally by placing blood drops on skin and theoretically by using Beer-Lambert law. The theoretical model was used to compensate for the distorted fluorescence ratio. According to the theoretical model of blood interference, a total 300 µm blood layer blocked the brain fluorescence signal totally and when the fluorescence signal was partially blocked, the fluorescence ratio was overestimated. The fluorescence ratio was corrected for blood layers thinner than 50 µm.

    The tissue in and around the tumor was categorized into necrosis, low and high grade tumor and gliosis. The median fluorescence ratio confirmed with histopathological examination (n = 45) had a lower fluorescence ratio for low grade malignancies (0.3) than high grade malignancies (2.4) (p < 0.05). Gliosis (1.6) and necrosis (1.0) showed a moderate fluorescence ratio. Ultrasound-based navigation in combination with fluorescence spectroscopy showed improvement in the results; however, a more extensive study is needed to confirm benefits of the method combination. In conclusion, fluorescence spectroscopy of 5-ALA induced PpIX provided an objective method for differentiating tumor from the healthy tissue intra-operatively. Fluorescence ratios were indicative of tissue type and tumor malignancy degree.

  • 136.
    Haj-Hosseini, Neda
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Optical Coherence Tomography for 3D Cancer Imaging2015Conference paper (Refereed)
    Abstract [en]

    Optical coherence tomography (OCT) is an advanced optical imaging technology for imaging material based on their optical scattering properties. OCT provides high-resolution 2D (en face or cross-sectional) and 3D images from the surface and subsurface tissue microstructures within a few mm depth. The first article on OCT was published in 1991 by D. Huang et. al. [1]. More than 15000 articles have been published since 1991 on different applications of OCT. However, the technique has so far entered the clinical routine only within ophthalmology and cardiovascular imaging in which the majority of the articles have been published [2]. OCT is a capable technology with great potentials for further translational research and implementation in additional clinical fields. One potential application of OCT is within cancer detection intraoperatively or post operatively for providing an on-site fast diagnosis. In this study, OCT’s ability to differentiate histology and pathology for application in tissue identification, pathological diagnosis and cancer staging was investigated.

    Material and Method:

    The technology uses near infrared or infrared light for imaging tissue structures that havedifferent optical scattering properties. The technique is based on low coherence interferometryand measures the backscattered light from the tissue. The scanning dimensions and resolutions are dependent on the type of the OCT system. In this study a TELESTO IITM system (Thorlabs, Inc., NJ, USA) was used. The maximum lateral and axial resolution of the system were 13 and 5.5 μm, respectively. A total of eleven patients undergoing brain, thyroid and parathyroid surgery were included in the study.

    Results:

    Figure 1 shows a 3D scan of the fingertip taken by the described OCT system as an example. The skin layers (epidermis and dermis) including the fingerprint and a sweat gland (the spiral structure) are visible. Various tissue type specimens involved in thyroid and parathyroid surgeries and brain tumor surgery were evaluated.

  • 137.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Lund University.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Evaluation of a Fiber-Optic Based Pulsed Laser System for Fluorescence Spectroscopy2008Conference paper (Refereed)
    Abstract [en]

    A fiber optic based continous wave laser setup has been developed to record the 5-aminolevulinic (5-ALA) induced Protoporfyrin IX (PpIX) fluorescence signals from cerebral gliomas. To reduce the energy delivered to the tissue as well as suppression of the ambient lamp artifact from the recorded spectra, a pulsed laser setup has been developed and evaluated. This setup has been calibrated and first evaluations were performed on the 5-ALA treated skin showing PpIX fluorescence peaks from the ALA treated skin at 635 and 704 nm wavelengths. The system controls laser pulses through a computer interface and labview software package. Pulses as short as 50 ms over a period time of 500 ms are generated and optimally detected. The results from primary measurements on skin show an effective suppression of room fluorescent lamp artifact from the recorded spectra.

  • 138.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Behm, Pascal
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. University of Applied Sciences in Northwest Switzerland.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence spectroscopy using indocyanine green for lymph node mapping2014Conference paper (Refereed)
    Abstract [en]

    The principles of cancer treatment has for years been radical resection of the primary tumor. In the oncologic surgeries where the affected cancer site is close to the lymphatic system, it is as important to detect the draining lymph nodes for metastasis (lymph node mapping). As a replacement for conventional radioactive labeling, indocyanine green (ICG) has shown successful results in lymph node mapping; however, most of the ICG fluorescence detection techniques developed are based on camera imaging. In this work, fluorescence spectroscopy using a fiber-optical probe was evaluated on a tissue-like ICG phantom with ICG concentrations of 6-64 μM and on breast tissue from five patients. Fiber-optical based spectroscopy was able to detect ICG fluorescence at low intensities; therefore, it is expected to increase the detection threshold of the conventional imaging systems when used intraoperatively. The probe allows spectral characterization of the fluorescence and navigation in the tissue as opposed to camera imaging which is limited to the view on the surface of the tissue

  • 139.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Kistler, Benjamin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. University of Applied Sciences in Northwest Switzerland.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Development and characterization of a brain tumor mimicking fluorescence phantom   2014In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 8945, p. 1-6, article id 894505Article in journal (Refereed)
    Abstract [en]

    Fluorescence guidance using 5-aminolevulinic acid (5-ALA) for brain tumor resection is a recent technique applied to the highly malignant brain tumors. Five-ALA accumulates as protoporphyrin IX fluorophore in the tumor cells in different concentrations depending on the tumor environment and cell properties. Our group has developed a fluorescence spectroscopy system used with a hand-held probe intra-operatively. The system has shown improvement of fluorescence detection and allows quantification that preliminarily correlates with tumor malignancy grade during surgery. However, quantification of fluorescence is affected by several factors including the initial fluorophore concentration, photobleaching due to operating lamps and attenuation from the blood. Accordingly, an optical phantom was developed to enable controlled fluorescence measurements and evaluation of the system outside of the surgical procedure. The phantom mimicked the optical properties of glioma at the specific fluorescence excitation wavelength when different concentrations of the fluorophore were included in the phantom. To allow evaluation of photobleaching, kinetics of fluorophore molecules in the phantom was restricted by solidifying the phantoms. Moreover, a model for tissue autofluorescence was added. The fluorescence intensity’s correlation with fluorophore concentration in addition to the photobleaching properties were investigated in the phantoms and were compared to the clinical data measured on the brain tumor.

  • 140.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Lowndes, Shannely
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Blood interference in fiber-optical based fluorescence guided resection of glioma using 5-aminolevulinic acid2011In: Photonic Therapeutics and Diagnostics VII / [ed] Nikiforos Kollias; Bernard Choi; Haishan Zeng; Hyun Wook Kang; Bodo E. Knudsen; Brian J. Wong; Justus F. R. Ilgner; Kenton W. Gregory; Guillermo J. Tearney; Laura Marcu; Henry Hirschberg; Steen J. Madsen; Andreas Mandelis; Anita Mahadevan-Jansen; E. Duco Jansen, SPIE - International Society for Optical Engineering, 2011, p. 78833R-1-78833R-10Conference paper (Refereed)
    Abstract [en]

    Fluorescence guidance in brain tumor resection is performed intra-operatively where bleeding is included. When using fiber-optical probes, the transmission of light to and from the tissue is totally or partially blocked if a small amount of blood appears in front of the probe. Sometimes even after rinsing with saline, the remnant blood cells on the optical probe head, disturb the measurements. In such a case, the corresponding spectrum cannot be reliably quantified and is therefore discarded. The optimal case would be to calculate and take out the blood effect systematically from the collected signals. However, the first step is to study the pattern of blood interference in the fluorescence spectrum. In this study, a fiber-optical based fluorescence spectroscopy system with a laser excitation light of 405 nm (1.4 J/cm2) was used during fluorescence guided brain tumor resection using 5-aminolevulinic acid (5-ALA). The blood interference pattern in the fluorescence spectrum collected from the brain was studied in two patients. The operation situation was modeled in the laboratory by placing blood drops from the finger tip on the skin of forearm and the data was compared to the brain in vivo measurements. Additionally, a theoretical model was developed to simulate the blood interference pattern on the skin autofluorescence. The blood affects the collected fluorescence intensity and leaves traces of oxy and deoxy-hemoglobin absorption peaks. According to the developed theoretical model, the autofluorescence signal is considered to be totally blocked by an approximately 500 μm thick blood layer.

  • 141.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Fluorescence spectroscopy and optical coherence tomography for brain tumor detection2016Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.

  • 142.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Milos, Peter
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Faculty of Science & Engineering.
    Hallbeck, Martin
    Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    A Multipurpose Guidance Probe for Stereotactic Biopsy Procedures2016Conference paper (Refereed)
  • 143.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Milos, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Detection of brain tumor using fluorescence and optical coherence tomography2015Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.

    Material and Methods:

    A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.

    Results and Conclusion:

    Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.

  • 144.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Petersson, Pernilla
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Gimm, Oliver
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Shabo, Ivan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Optical Coherence Tomography for Pathological Analysis of Thyroid2016Conference paper (Refereed)
  • 145.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Andersson-Engel, Stefan
    Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence guided resection of glioblastoma multiforme using an optical touch pointer-Clinical evaluation2010Conference paper (Refereed)
  • 146.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Department of Physics, Lund University.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fiber optic based fluorescence guided cerebral glioma resection using a pulsed laser setup2008Conference paper (Refereed)
  • 147.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Lund University of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fiber optic based fluorescence spectroscopy on glioblastoma multiforme using 5-aminolevulinic acid - Preliminary clinical results2009Conference paper (Other academic)
  • 148.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Optical Touch Pointer for Fluorescence Guided Glioblastoma Resection Using 5-Aminolevulinic Acid2010In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 42, no 1, p. 9-14Article in journal (Refereed)
    Abstract [en]

    Background and Objective

    Total tumor resection in patients with glioblastoma multiforme (GBM) is difficult to achieve due to the tumor's infiltrative way of growing and morphological similarity to the surrounding functioning brain tissue. The diagnosis is usually subjectively performed using a surgical microscope. The objective of this study was to develop and evaluate a hand-held optical touch pointer using a fluorescence spectroscopy system to quantitatively distinguish healthy from malignant brain tissue intraoperatively.

    Study Design/Materials and Methods

    A fluorescence spectroscopy system with pulsed modulation was designed considering optimum energy delivery to the tissue, minimal photobleaching of PpIX and omission of the ambient light background in the operating room (OR). 5-Aminolevulinic acid (5-ALA) of 5 mg/kg body weight was given to the patients with a presumed GBM prior to surgery. During the surgery a laser pulse at 405 nm was delivered to the tissue. PpIX in glioblastoma tumor cells assigned with peaks at 635 and 704 nm was detected using a fiber optical probe.

    Results/Conclusion

    By using the pulsed fluorescence spectroscopy, PpIX fluorescence is quantitatively detected in the GBM. An effective suppression of low power lamp background from the recorded spectra in addition to a significant reduction of high power surgical lights is achieved.

  • 149.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery.
    Andersson-Engels, Stefan
    Dept. of Physics, Lund University, Lund, Sweden.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Photobleaching behavior of protoporphyrin IX during 5-aminolevulinic acid marked glioblastoma detection2009In: Photonic Therapeutics and Diagnostics V / [ed] Nikiforos Kollias; Bernard Choi; Haishan Zeng; Reza S. Malek; Brian J. Wong; Justus F. R. Ilgner; Kenton W. Gregory; Guillermo J. Tearney; Laura Marcu; Henry Hirschberg; Steen J. Madsen, SPIE - International Society for Optical Engineering, 2009, p. 716131-1-716131-8Conference paper (Other academic)
    Abstract [en]

    The highly malignant brain tumor, glioblastoma multiforme (GBM), is difficult to fully delineate during surgical resection due to its infiltrative ingrowth and morphological similarities to surrounding functioning brain tissue. Selectiveness of GBM to 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) is reported by other researchers to visualize tumor margins under blue light microscopy. To allow objective detection of GBM, a compact and portable fiber optic based fluorescence spectroscopy system is developed. This system is able to deliver excitation laser light (405 nm) in both the continuous and pulsed mode. PpIX fluorescence peaks are detected at 635 and 704 nm, using a fiber-coupled spectrometer. It is necessary to optimize the detection efficiency of the system as the PpIX quickly photobleaches during the laser illumination. A light dose of 2.5 mJ (fluence rate = 9 mJ/mm2) is experimentally approved to excite an acceptable level of fluourescence signal arising from glioblastoma. In pulsed illumination mode, an excitation dose of 2.5 mJ, with a dark interval of 0.5 s (duty cycle 50%) shows a significantly shorter photobleaching time in comparison to the continuous illumination mode with the same laser power (p < 0.05). To avoid photobleaching (the remaining signal is more than 90% of its initial value) when measuring with 2.5 mJ delivered energy, the time for continuous and pulsed illumination should be restricted to 2.5 and 1.1 s, respectively.

  • 150.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery2015In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 12, no 2, p. 209-214Article in journal (Refereed)
    Abstract [en]

    Background

    Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kg b.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance.

    Methods

    A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. (n = 15) dissolved in orange juice or 20 mg/kg b.w. (n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements.

    Results

    The binominal comparison of the diagnostic performance parameters showed no significant statistical difference (p > 0.05). The median fluorescence values in tumor were 2-3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14).

    Conclusions

    Application of 5 mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients.

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