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  • 1.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    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 Radiation Physics.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 101, p. 20-25Article in journal (Refereed)
    Abstract [en]

    Background: : Venous occlusion in the skin is difficult to detect by existing measurement techniques. Our aim was to find out whether Tissue Viability Imaging (TiVi) was better at detecting venous occlusion by comparing it with results of laser Doppler flowmetry (LDF) during graded arterial and venous stasis in human forearm skin. Methods: : Arterial and venous occlusions were simulated in 10 healthy volunteers by inflating a blood pressure cuff around the upper right arm. Changes in the concentration of red blood cells (RBC) were measured using TiVi, while skin perfusion and concentration of moving red blood cells (CMBC) were measured using static indices of LDF during exsanguination and subsequent arterial occlusion, postocclusive reactive hyperaemia, and graded increasing and decreasing venous stasis. Results: : During arterial occlusion there was a significant reduction in the mean concentration of RBC from baseline, as well as in perfusion and CMBC (p less than 0.008). Venous occlusion resulted in a significant 28% increase in the concentration of RBC (p = 0.002), but no significant change in perfusion (mean change -14%) while CMBC decreased significantly by 24% (p = 0.02). With stepwise increasing occlusion pressures there was a significant rise in the TiVi index and reduction in perfusion (p = 0.008), while the reverse was seen when venous flow was gradually restored. Conclusion: : The concentration of RBC measured with TiVi changes rapidly and consistently during both total and partial arterial and venous occlusions, while the changes in perfusion, measured by LDF, were less consistent This suggests that TiVi could be a more useful, non-invasive clinical monitoring tool for detecting venous stasis in the skin than LDF.

  • 2.
    Bergkvist, Max
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Zötterman, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Iredahl, Fredrik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Vascular Occlusion in a Porcine Flap Model: Effects on Blood Cell Concentration and Oxygenation.2017In: Plastic and reconstructive surgery. Global open, ISSN 2169-7574, Vol. 5, no 11, article id e1531Article in journal (Refereed)
    Abstract [en]

    Background: Venous congestion in skin flaps is difficult to detect. This study evaluated the ability of tissue viability imaging (TiVi) to measure changes in the concentration of red blood cells (CRBC), oxygenation, and heterogeneity during vascular provocations in a porcine fasciocutaneous flap model.

    Methods: In 5 pigs, cranial gluteal artery perforator flaps were raised (8 flaps in 5 pigs). The arterial and venous blood flow was monitored with ultrasonic flow probes. CRBC, tissue oxygenation, and heterogeneity in the skin were monitored with TiVi during baseline, 50% and 100% venous occlusion, recovery, 100% arterial occlusion and final recovery, thereby simulating venous and arterial occlusion of a free fasciocutaneous flap. A laser Doppler probe was used as a reference for microvascular perfusion in the flap.

    Results: During partial and complete venous occlusion, increases in CRBC were seen in different regions of the flap. They were more pronounced in the distal part. During complete arterial occlusion, CRBC decreased in all but the most distal parts of the flap. There were also increases in tissue oxygenation and heterogeneity during venous occlusion.

    Conclusions: TiVi measures regional changes in CRBC in the skin of the flap during arterial and venous occlusion, as well as an increase in oxygenated hemoglobin during venous occlusion that may be the result of reduced metabolism and impaired delivery of oxygen to the tissue. TiVi may provide a promising method for measuring flap viability because it is hand-held, easy to-use, and provides spatial information on venous congestion.

  • 3.
    Droog Tesselaar, Erik
    et al.
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert E.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects2004In: Microvascular research, ISSN 0026-2862, Vol. 67, no 2, p. 197-202Article in journal (Refereed)
    Abstract [en]

    Iontophoresis of vasoactive substances is a promising tool for studying pharmacological aspects of the (patho)physiology of the microvasculature. However, nonspecific microvascular responses are a common problem in most protocols used. We studied the effect of current density (mA/cm2), charge density (mC/cm2), drug concentration (mass %) and vehicle concentration (M) on the nonspecific vasodilatation during iontophoresis of sodium chloride, acetylcholine (ACh) and sodium nitroprusside (SNP).

    We found that nonspecific vasodilatation depended on current density and charge density in both anodal and cathodal iontophoresis. The responses to ACh and SNP were dependent on current density, charge density and drug concentration. We found that by limiting current density (<0.01 mA/cm2) and charge density (<7.8 mC/cm2) and with adjusted concentrations for drugs and vehicles, it is possible to prevent nonspecific effects during iontophoresis of ACh and SNP, while maximum drug effects (plateaus in the dose–response curves) are still obtained. These new findings are important for future iontophoresis studies in which vasoactive drugs are used to assess microvascular function because the presented approach has advantages compared to older techniques, which mainly have attempted to suppress or compensate for the nonspecific responses during iontophoresis by the use of local anaesthetics or the measurement of drug-minus-vehicle responses, both of which present well-known experimental shortcomings.

  • 4.
    Farnebo, Simon
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Thorfinn, Johan
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times2010In: MICROVASCULAR RESEARCH, ISSN 0026-2862, Vol. 80, no 3, p. 412-416Article in journal (Refereed)
    Abstract [en]

    Tissue occlusion and the hyperaemic response upon reperfusion can be used as a tool to assess microvascular function in various vascular diseases. Currently, laser Doppler flowmetry (LDF) is applied most often to measure hyperaemic responses. In this study, we have applied tissue viability imaging (TiVi) and LDF to measure the change in red blood cell concentration and perfusion in the skin after occlusions of the forearm with increasing duration. We have found that there is a strong correlation between the changes in perfusion and red blood cell (RBC) concentration during post-occlusive hyperaemia (perfusion: r = 0.80; RBC concentration: r = 0.94). This correlation increases with longer occlusion durations (1, 5 and 10 min). Furthermore, for both perfusion and RBC concentration, the maximum responses (perfusion: r(2) = 0.59; RBC concentration: r(2) = 0.78) and the recovery times (perfusion: r(2) = 0.62; RBC concentration: r(2) = 0.91) increase linearly with the duration of the occlusion. Maximum responses and recovery times were more reproducible for RBC concentration (as measured with TiVi) than for perfusion (as measured with LDF). These results show that perfusion and RBC concentration are related during post-occlusive hyperaemia and that TiVi can be used as a tool in the assessment of hyperaemic responses that has advantages in terms of reproducibility, sensitivity and ease of use.

  • 5.
    Glasin, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Faculty of Medicine and Health Sciences.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Wireless vitals: Proof of concept for wireless patient monitoring in an emergency department setting2019In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 12, no 4, article id e201800275Article in journal (Refereed)
    Abstract [en]

    Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 +/- 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring.

  • 6.
    Haridass, Isha N.
    et al.
    Curtin Univ, Australia; Univ Queensland, Australia.
    Wei, Jonathan C. J.
    Univ Queensland, Australia; Delft Univ Technol, Netherlands.
    Mohammed, Yousuf H.
    Univ Queensland, Australia.
    Crichton, Michael L.
    Heriot Watt Univ, Scotland.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Sanchez, Washington Y.
    Univ Queensland, Australia.
    Meliga, Stefano C.
    Univ Queensland, Australia.
    Grice, Jeffrey E.
    Univ Queensland, Australia.
    Benson, Heather A. E.
    Curtin Univ, Australia.
    Kendall, Mark A. F.
    Australian Natl Univ, Australia; Univ Queensland, Australia.
    Roberts, Michael S.
    Univ Queensland, Australia; Univ South Australia, Australia.
    Cellular metabolism and pore lifetime of human skin following microprojection array mediation2019In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 306, p. 59-68Article in journal (Refereed)
    Abstract [en]

    Skin-targeting microscale medical devices are becoming popular for therapeutic delivery and diagnosis. We used cryo-SEM, fluorescence lifetime imaging microscopy (FLIM), autofluorescence imaging microscopy and inflammatory response to study the puncturing and recovery of human skin ex vivo and in vivo after discretised puncturing by a microneedle array (Nanopatch (R)). Pores induced by the microprojections were found to close by similar to 25% in diameter within the first 30 min, and almost completely close by similar to 6 h. FLIM images of ex vivo viable epidermis showed a stable fluorescence lifetime for unpatched areas of similar to 1000 ps up to 24 h. Only the cells in the immediate puncture zones (in direct contact with projections) showed a reduction in the observed fluorescence lifetimes to between similar to 518-583 ps. The ratio of free-bound NAD(P)H (alpha 1/alpha 2) in unaffected areas of the viable epidermis was similar to 2.5-3.0, whereas the ratio at puncture holes was almost double at similar to 4.2-4.6. An exploratory pilot in vivo study also suggested similar closure rate with histamine administration to the forearms of human volunteers after Nanopatch (R) treatment, although a prolonged inflammation was observed with Tissue Viability Imaging. Overall, this work shows that the pores created by the microneedle-type medical device, Nanopatch (R), are transient, with the skin recovering rapidly within 1-2 days in the epidermis after application.

  • 7.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Assessment of microvascular effects of vasoactive drugs: Methodological in vivo studies in humansbased on iontophoresis2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease is the leading cause of death in western societies and endothelial dysfunction is one of the earliest signs seen in the development of such conditions. Thedevelopment of prognostic tools to aid in the prediction of micro- and macrovascular diseasebased on assessment of vascular reactivity is therefore of paramount importance.

    Transdermal iontophoresis offers a quick, non-invasive and relatively straightforward way todeliver vasoactive substances in order to provoke a vascular response in man. When combined with either laser Doppler flowmetry (LDF) or tissue viability imaging (TiVi) for quantification of these responses the methodology offers a potentially powerful tool forvascular investigations. The technique has, however, not been established in clinical practice yet and is mostly used in experimental settings. The lack of consensus in what data analysistechnique to use, uncertainty concerning the actual drug dose applied, and the difficulties associated with the assessment of responses to vasoconstrictors may have contributed to thisfact. The aim of this thesis is therefore to address these issues and thus facilitate the use and improve the applicability of transdermal iontophoresis for assessment of cutaneous microvascular function.

    More specifically, a non-linear dose-response model (Emax-model) that is commonly used in in vitro investigations of vascular function was applied to the iontophoresis data. The resultsshow that the Emax-model accurately describes the cutaneous vascular responses totransdermally iontophoresed acetylcholine (ACh) and, sodium nitroprusside (SNP). The Emaxmodelgenerates variables that can be used for quantitative statistical analysis of data andenables a more powerful analysis compared to the methods presently used. It is furtherdemonstrated that the maximal dose effect and vascular responses vary between differentprotocols with the same total iontophoretic charge but with different current strengths anddurations. This finding implies that the assumption that the local drug dose is linearlyproportional to the iontophoretic charge (used for estimation of delivered drug dose to themicrovascular bed) may be inaccurate in in vivo investigations and that there is need for amore refined model.

    It is also demonstrated that in a vasoconstrictive setting (iontophoresis of noradrenaline andphenylephrine) TiVi is the favourable technique for measuring vascular responses as it issensitive enough to generate data that can be fitted to the Emax-model even without predilatationof the vessels.

    List of papers
    1. Assessment of microvascular function by study of the dose‐response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside): Methods and comparison with in vitro studies
    Open this publication in new window or tab >>Assessment of microvascular function by study of the dose‐response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside): Methods and comparison with in vitro studies
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    2007 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 73, no 2, p. 143-149Article in journal (Refereed) Published
    Abstract [en]

    Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose–response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge.

    We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis.

    Dose–response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose–response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive.

    The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose–response curves that picture the vascular effects of vasoactive drugs.

    Keywords
    Microvascular circulation, Endothelium, Dose–response, Iontophoresis, Laser doppler
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14459 (URN)10.1016/j.mvr.2006.10.004 (DOI)
    Available from: 2007-05-04 Created: 2007-05-04 Last updated: 2017-12-13Bibliographically approved
    2. Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation
    Open this publication in new window or tab >>Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation
    Show others...
    2007 (English)In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 13, no 4, p. 472-484Article in journal (Refereed) Published
    Abstract [en]

    Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non-invasive, more user-independent and objective methods are available today. Limited portability, high cost, lack of robustness and non-specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy-to-use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

    Methods: The use of orthogonal linear polarization filters over both the flash source and the detector array removes the polarization-retaining light reflected from the epidermal layer. Only the depolarized light backscattered from the papillary dermal matrix reaches the detector array. By separating the RGB color planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the chromophores in the dermal tissue can be attained. If the algorithm is based on a differential principle in which the normalized differences between the individual values of the red and green color plane are calculated, tissue components with similar spectral signature in both planes are suppressed, while components with different spectral signatures such as RBCs are enhanced.

    Results: In vitro fluid models compare well with theory and computer simulations in describing a linear relationship between the imager output signal termed the tissue viability index (TiVi index) and RBC concentration in the physiological range of 0-4% RBC fraction of tissue volume (cc=0.997, n=20). The influence of oxygen saturation on the calculated RBC concentration is limited to within -3.9% for values within the physiological range (70-100% oxygen saturation). Monte Carlo simulations provide information about the sampling depth (about 0.5mm on the average) of the imaging system. In vivo system evaluation based on iontophoresis of acetylcholine displays a heterogeneous pattern of vasodilatation appearing inside the electrode area after about 10min. Topical application of methyl nicotinate and clobetasol propionate further demonstrates the capacity to document the extent and intensity of both an increase (erythema) and a decrease (blanching) in the skin RBC concentration without movement artifact and with compensation for irregularity in pigmentation.

    Conclusions: Polarization light spectroscopy imaging for assessment of RBC concentration in the skin microvasculature is a robust and accessible technique for the clinical setting. Additionally, the technique has pre-clinical research applications for investigation of the spatial and temporal aspects of skin erythema and blanching as well as a potential role in drug development, skin care product development and skin toxicological assessment.

    Keywords
    Biomedical optics, Blanching, Erythema, Microcirculation, Polarizationspectroscopy
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-48066 (URN)10.1111/j.1600-0846.2007.00253.x (DOI)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13Bibliographically approved
    3. Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
    Open this publication in new window or tab >>Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Laser-Doppler flowmetry (LDF) is an attractive method to assess blood flow responses butlacks sensitivity to accurately measure low perfusion values during iontophoresis of vasoconstricting drugs without predilatation of the microvascular bed.

    The aim of this study was to develop a protocol for iontophoresis of noradrenaline (NA) andphenylephrine (Phe) in the skin, using local heating to predilate the microvascular bed andLDF to measure blood flow responses. Three protocols with the same electrical charge (12mC) but different durations and current strengths (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x0.04 mA) were used to study the effect of pulse duration and current strength on the responses.

    Skin perfusion decreased to 68-78% of the predilatated state with both NA and Phe. Doseresponse plateaus were not obtained with any protocol. The extent of the vasoconstriction depended on the protocol used.

    These results suggest that predilatation by local heating appears less suitable duringiontophoresis of NA and Phe, due to limited vascular responses and especially absence of response plateaus, even at high current strengths. The latter leads to difficulties in performing proper dose response analyses. Another interesting finding was that the actual dose of NA and Phe given to the tissue was affected not only by the size of the electrical charge, but local blood flow as well.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-50639 (URN)
    Available from: 2009-10-13 Created: 2009-10-13 Last updated: 2010-01-14Bibliographically approved
    4. Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis
    Open this publication in new window or tab >>Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis
    Show others...
    2009 (English)In: Microvascular Research, ISSN 0026-2862, Vol. 78, no 2, p. 199-205Article in journal (Refereed) Published
    Abstract [en]

    When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging.

    Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED50-values with narrow confidence intervals and acceptable r2 values. Mean ED50-values for the TiVi did not differ significantly from similar values obtained using laser Doppler.

    Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

    Keywords
    Cutaneous microcirculation; Iontophoresis; Laser Doppler; Tissue viability imager
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-21238 (URN)10.1016/j.mvr.2009.04.008 (DOI)
    Note
    Original Publication: Joakim Henricson, Anders Nilsson, Erik Tesselaar, Gert Nilsson and Folke Sjöberg, Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis, 2009, Microvascular Research, (78), 2, 199-205. http://dx.doi.org/10.1016/j.mvr.2009.04.008 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-09-30 Created: 2009-09-30 Last updated: 2009-10-30Bibliographically approved
  • 8.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Baiat, Yashma
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Surgery.
    Local Heating as a Predilatation Method for Measurement of Vasoconstrictor Responses with Laser-Doppler Flowmetry2011In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 18, no 3, p. 214-220Article in journal (Refereed)
    Abstract [en]

    Studying microvascular responses to iontophoresis of vasoconstricting drugs contributes to a better understanding of the regulatory mechanisms of cutaneous vessels, but measuring these responses with laser-Doppler flowmetry at basal blood flow conditions is technically challenging. This study aimed to investigate whether the measurement of cutaneous vasoconstrictor responses to noradrenaline (NA) and phenylephrine (PE), delivered by iontophoresis, is facilitated by predilatation of the microvascular bed using local heating. We used different drug delivery rates (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x 0.04 mA) to investigate whether predilatation affects the local drug dynamics by an increased removal of drugs from the skin. In a predilatated vascular bed, iontophoresis of NA and PE resulted in a significant decrease in perfusion from the thermal plateau (p andlt; 0.001). The decrease was 25-33%, depending on drug delivery rate. In unheated skin, a significant vasoconstriction was observed (p andlt; 0.001), with 17% and 14% decrease from baseline for NA and PE, respectively. These results indicate that predilatating the cutaneous vascular bed by local heating facilitates measurement of vasoconstriction with laser-Doppler flowmetry and does not seem to significantly affect the result by an increased removal of drugs from the skin.

  • 9.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Baiat, Y
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery and Burns.
    Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetryManuscript (preprint) (Other academic)
    Abstract [en]

    Laser-Doppler flowmetry (LDF) is an attractive method to assess blood flow responses butlacks sensitivity to accurately measure low perfusion values during iontophoresis of vasoconstricting drugs without predilatation of the microvascular bed.

    The aim of this study was to develop a protocol for iontophoresis of noradrenaline (NA) andphenylephrine (Phe) in the skin, using local heating to predilate the microvascular bed andLDF to measure blood flow responses. Three protocols with the same electrical charge (12mC) but different durations and current strengths (100 s x 0.12 mA, 200 s x 0.06 mA, 300 s x0.04 mA) were used to study the effect of pulse duration and current strength on the responses.

    Skin perfusion decreased to 68-78% of the predilatated state with both NA and Phe. Doseresponse plateaus were not obtained with any protocol. The extent of the vasoconstriction depended on the protocol used.

    These results suggest that predilatation by local heating appears less suitable duringiontophoresis of NA and Phe, due to limited vascular responses and especially absence of response plateaus, even at high current strengths. The latter leads to difficulties in performing proper dose response analyses. Another interesting finding was that the actual dose of NA and Phe given to the tissue was affected not only by the size of the electrical charge, but local blood flow as well.

  • 10.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Persson, Karin
    Linköping University, Department of Medicine and Health Sciences, Pharmacology . Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Assessment of microvascular function by study of the dose‐response effects of iontophoretically applied drugs (acetylcholine and sodium nitroprusside): Methods and comparison with in vitro studies2007In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 73, no 2, p. 143-149Article in journal (Refereed)
    Abstract [en]

    Current knowledge about vascular function stems mainly from pharmacological in vitro studies using mounted vascular strips on a strain gauge. We know of no paper that has systematically examined the possibility of assessing the conventional dose–response effects of iontophoresis and laser Doppler investigation of vasoactive substances and compared those relations to data obtained from strips mounted on a strain gauge.

    We used the vasoactive substances acetylcholine (endothelium dependent) and sodium nitroprusside (endothelium independent) and an antagonist (atropine) to enable further investigations in the receptor physiology of iontophoresis.

    Dose–response curves from the iontophoresis experiments showed close similarity to those obtained by vascular strips mounted on a strain gauge. The coefficient of variation (CV) of the dose–response factors found in iontophoresis (both inter and intra experimental variability) was low. The iontophoretic effective dose of 50% (ED50) for acetylcholine and nitroprusside had only CVs of 25% and 26%, respectively, compared with 71% and 77% for the vascular strips. Acetylcholine-induced response was antagonized by iontophoresis of atropine. Contrary to expectations, this antagonism was not competitive.

    The results show that iontophoresis in combination with laser Doppler technology produces reproducible and reliable dose–response curves that picture the vascular effects of vasoactive drugs.

  • 11.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Lassus, J.
    Sterisol AB, Vadstena, Sweden.
    Eklund, J.
    Sterisol AB, Vadstena, Sweden.
    Lassus, S.
    Cosmetox AB, Linkoping, Sweden.
    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.
    Avoidance of dermal exposure to preservatives by packaging2010In: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 802-802, Pharmaceutical Press , 2010, Vol. 62, no 6, p. 802-802Conference paper (Refereed)
    Abstract [en]

    Dermal exposure to chemicals in cosmetics and hygiene products (e.g. moisturising creams, soaps, shampoos) is increasingly recognized as an important area for risk assessment and regulation. The contents of such products is regulated by classification of exposure types (e.g. stay on/wash off) and regulatory concepts based on toxicological studies and manufacturing or market experience. Positive lists, negative lists or establishment of recommendations on concentration and exposure form a basis for consumer safety. Common problem areas are perfumes, preservatives and the formation of oxidation products after manufacture.

    A new patented system, suitable for packages from 100 ml to 5 l, with collapsible plastic bags and unique dosage valves prevents bacteria and air from entering the packaging. Thus the use of preservatives can be avoided.

    This may lead to a reduced risk of individual reactions to specific preservatives as well as cross-allergy reactions. The consumer no longer needs to hunt for strange names on small ingredient labels. Also, it could prevent the prospective development of allergy. The avoidance of oxidation products is another advantage.

  • 12.
    Henricson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, A.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Sub-epidermal imaging using polarized light spectroscopy for assessment of cutaneous microvascular function during iontophoresis of nor-adrenaline and phenylephrine2007In: 8th World Congress for microcirculation,2007, 2007Conference paper (Refereed)
  • 13.
    Henricson, Joakim
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Anders
    Berzelius Clinical Research Center AB.
    Tesselaar, Erik
    Berzelius Clinical Research Center AB.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Tissue viability imaging: Microvascular response to vasoactive drugs induced by iontophoresis2009In: Microvascular Research, ISSN 0026-2862, Vol. 78, no 2, p. 199-205Article in journal (Refereed)
    Abstract [en]

    When one is studying the physiology of the cutaneous microcirculation there is a need for relevant non-invasive and versatile techniques. In this study we used a new optical device, the tissue viability imager (TiVi), to map changes in cutaneous microvascular concentrations of red blood cells during iontophoresis of vasoactive substances (noradrenaline (NA) and phenylephrine (Phe) for vasoconstriction and acetylcholine (ACh) and sodium nitroprusside (SNP) for vasodilatation). We aimed to present data both individually and pooled, using a four-variable logistic dose response model that is commonly used in similar in vitro vascular studies. The accuracy of the TiVi was also investigated by calculating the coefficient of variation and comparing it with similar tests previously done using laser Doppler imaging.

    Tests were also performed using the TiVi and LDPI simultaneously to further compare the two methods. Results showed that the TiVi is capable of quantifying vascular responses to iontophorised noradrenaline and phenylephrine without the need to increase background flow first. Fitting the TiVi data to the dose response model resulted in ED50-values with narrow confidence intervals and acceptable r2 values. Mean ED50-values for the TiVi did not differ significantly from similar values obtained using laser Doppler.

    Results further seem to suggest that when the blood perfusion increases during vasodilatation in skin the initial phase relies mainly on an increase in red blood cell concentration whereas the further perfusion increase is due to an increase in red blood cell velocity.

  • 14.
    Henricson, Joakim
    et al.
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Microvascular response to iontophoretically applied acetylcholine investigated by Tissue Viability Imaging2006Conference paper (Other academic)
  • 15.
    Henricson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    The polarization scectroscopic camera allows assessment of vasoconstriction after topical application of clobetasol2007In: 16th congress of the European Academy of Dermatology and Venerology,2007, 2007Conference paper (Refereed)
  • 16.
    Henricson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Toll John, Rani
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Diffuse Reflectance Spectroscopy: Getting the Capillary Refill Test Under Ones Thumb2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 130, article id e56737Article in journal (Refereed)
    Abstract [en]

    The capillary refill test was introduced in 1947 to help estimate circulatory status in critically ill patients. Guidelines commonly state that refill should occur within 2 s after releasing 5 s of firm pressure (e.g., by the physicians finger) in the normal healthy supine patient. A slower refill time indicates poor skin perfusion, which can be caused by conditions including sepsis, blood loss, hypoperfusion, and hypothermia. Since its introduction, the clinical usefulness of the test has been debated. Advocates point out its feasibility and simplicity and claim that it can indicate changes in vascular status earlier than changes in vital signs such as heart rate. Critics, on the other hand, stress that the lack of standardization in how the test is performed and the highly subjective nature of the naked eye assessment, as well as the tests susceptibility to ambient factors, markedly lowers the clinical value. The aim of the present work is to describe in detail the course of the refill event and to suggest potentially more objective and exact endpoint values for the capillary refill test using diffuse polarization spectroscopy.

    The full text will be freely available from 2019-12-02 09:45
  • 17.
    Horiuchi, Yoshihito
    et al.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Droog Tesselaar, Erik
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Wikström, Thore
    Linköping University, Department of Clinical and Experimental Medicine, Disaster Medicine and Traumatology. Linköping University, Faculty of Health Sciences.
    Lennquist, Sten
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis2004In: Microvascular research, ISSN 0026-2862, Vol. 67, no 2, p. 192-196Article in journal (Refereed)
    Abstract [en]

    Nonspecific vasodilatation during iontophoresis is an important confounding factor in experimental pharmacology. In this investigation, we studied the involvement of sensory nerves and histamine-related reactions in causing nonspecific vasodilatation in a model of anodal and cathodal iontophoresis of sodium chloride. Firstly, we applied a mixture of local anesthetic (EMLA) cream to confirm its suppressive effect on nonspecific vasodilatation and to measure its efficacy in three different dosages (duration: 1, 2, and 3 h). We then investigated the role of histamine in nonspecific vasodilatation by giving an oral antihistamine drug (cetirizine) to subjects who had and had not been given EMLA. We found substantial suppression of the nonspecific vasodilatation in all EMLA-treated groups (all dosages) compared with untreated controls (with suppression rates of 60–65%). Dosage had no significant effect. A further suppression of nonspecific vasodilatation was seen after oral cetirizine during anodal and cathodal iontophoresis in both EMLA-treated and untreated groups. The antihistamine effect was most pronounced during anodal iontophoresis. These results suggest a histaminergic increase in perfusion that may be independent of neurogenic mechanisms and depend on polarity (anode or cathode). Local nerve blocks (EMLA) together with cetirizine may therefore be used to reduce nonspecific vasodilatation in both anodal and cathodal iontophoresis.

  • 18.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Högstedt, Alexandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    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 Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load2016In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, p. 597-605Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

    METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

    RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

    CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

  • 19. Leahy, M.
    et al.
    ODoherty, J.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Tissue Viability Imaging: A new modality for microcirculation imaging2006In: Imaging Technology in Drug Discovery Development,2006, 2006Conference paper (Refereed)
  • 20.
    Leahy, Martin J.
    et al.
    Department of Physics, University of Limerick Limerick, Ireland.
    O'Doherty, Jim
    Department of Physics, University of Limerick Limerick, Ireland.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, The Institute of Technology.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Anderson, Chris
    Linköping University, Department of Biomedicine and Surgery, Dermatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology UHL.
    A new method for visualizing red blood cell content in the microcirculation2007In: Progress in Biomedical Optics and Imaging, ISSN 1605-7422, E-ISSN 1042-4687Article in journal (Other academic)
    Abstract [en]

    n/a

  • 21.
    Leahy, MJ.
    et al.
    Department of Physics, University of Limerick, National Technological Park, Ireland.
    ODoherty, J.
    Department of Physics, University of Limerick, National Technological Park, Ireland.
    McNamara, P.
    Department of Physics, University of Limerick, National Technological Park, Ireland.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Diffuse reflection imaging of sub-epidermal tissue haematocrit using a simple RGB camera2007In: Optical Technologies in Biophysics and Medicine VIII / [ed] Valery V. Tuchin, SPIE - International Society for Optical Engineering, 2007, Vol. 6535, p. 653503-1-653503-17Conference paper (Other academic)
    Abstract [en]

    This paper describes the design and evaluation of a novel easy to use, tissue viability imaging system (TiVi). The system is based on the methods of diffuse reflectance spectroscopy and polarization spectroscopy. The technique has been developed as an alternative to current imaging technology in the area of microcirculation imaging, most notably optical coherence tomography (OCT) and laser Doppler perfusion imaging (LDPI). The system is based on standard digital camera technology, and is sensitive to red blood cells (RBCs) in the microcirculation. Lack of clinical acceptance of both OCT and LDPI fuels the need for an objective, simple, reproducible and portable imaging method that can provide accurate measurements related to stimulus vasoactivity in the microvasculature. The limitations of these technologies are discussed in this paper. Uses of the Tissue Viability system include skin care products, drug development, and assessment spatial and temporal aspects of vasodilation (erythema) and vasoconstriction (blanching).

  • 22. Leahy, MJ.
    et al.
    ODoherty, J.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    A new method for visualizing red blood cell content in the microcirculation. SPIE newsroom2006In: The International Society for Optical Engineering,2006, 2006Conference paper (Refereed)
  • 23.
    Magnusson, B.M.
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Nilsson, Gert
    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.
    Intra- and inter-individual variability in the development of erythema after application of methyl nicotinate evaluated by polarization spectroscopy imaging2010In: JOURNAL OF PHARMACY AND PHARMACOLOGY, vol 62, issue 6, pp 801-801, ISSN: 002-3573, Pharmaceutical Press , 2010, Vol. 62, no 6, p. 801-801Conference paper (Refereed)
    Abstract [en]

    The concept that the time to onset of erythema after the application of the rubefacient and urticant substance methyl nicotinate (MN) indicates skin barrier competence was introduced 30 years ago. MN produces a dose-dependent erythema on topical application to intact skin, the nature of which is known to be fast moving (in the order of minutes) and variable. Using tissue viability imaging (TiVi) the time course and degree of the reaction can be conveniently followed and analysed. Inter-individual variability can be quite marked but intra-individual variability is less pronounced. At the upper end of provocation (higher doses, more sensitive individuals) urtication can occur, which decreases blood flow by increasing pressure on and thus emptying capillaries. The TiVi system can quantitate urtication and inherent (blanched) skin colour. The utility of MN application in the study of individual barrier function and microvascular reactivity is increased by the use of the TiVi system for collection and analysis of data.

  • 24.
    Mernelius, S.
    et al.
    Ryhov County Hospital, Jönköping, Sweden.
    Carlsson, E.
    Ryhov County Hospital, Jönköping, Sweden.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Löfgren, S.
    Ryhov County Hospital, Jönköping, Sweden.
    Lindgren, Per-Eric
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Jönköping, Sweden.
    Ehricht, R.
    Alere Technology GmbH, Germany; InfectoGnostics, Germany.
    Monecke, S.
    Alere Technology GmbH, Germany; InfectoGnostics, Germany.
    Matussek, A.
    Ryhov County Hospital, Jönköping, Sweden.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Staphylococcus aureus colonization related to severity of hand eczema2016In: European Journal of Clinical Microbiology and Infectious Diseases, ISSN 0934-9723, E-ISSN 1435-4373, Vol. 35, no 8, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    Knowledge on Staphylococcus aureus colonization rates and epidemiology in hand eczema is limited. The aim of this study was to clarify some of these issues. Samples were collected by the "glove juice" method from the hands of 59 patients with chronic hand eczema and 24 healthy individuals. Swab samples were taken from anterior nares and throat from 43 of the 59 patients and all healthy individuals. S. aureus were spa typed and analysed by DNA-microarray-based genotyping. The extent of the eczema was evaluated by the hand eczema extent score (HEES). The colonization rate was higher on the hands of hand eczema patients (69 %) compared to healthy individuals (21 %, p amp;lt; 0.001). This was also seen for bacterial density (p = 0.002). Patients with severe hand eczema (HEES a parts per thousand yen 13) had a significantly higher S. aureus density on their hands compared to those with milder eczema (HEES = 1 to 12, p = 0.004). There was no difference between patients and healthy individuals regarding colonization rates in anterior nares or throat. spa typing and DNA-microarray-based genotyping indicated certain types more prone to colonize eczematous skin. Simultaneous colonization, in one individual, with S. aureus of different types, was identified in 60-85 % of the study subjects. The colonization rate and density indicate a need for effective treatment of eczema and may have an impact on infection control in healthcare.

  • 25.
    Nilsson, Gert
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Leahy, J.
    ODoherty, J.
    Polarization Spectroscopy camera: a new technique for mapping redness2007In: 16th congress of the European Academy of Dermatology and Venerology,2007, 2007Conference paper (Refereed)
  • 26.
    Nilsson, Gert
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Leahy, J.
    ODoherty, J.
    Tissue Viability Imaging in Dermatology2007In: 21th World congress of Dermatology,2007, 2007Conference paper (Refereed)
  • 27.
    Nilsson, Gert
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Leahy, M.
    Department of Physics University of Limeric, Ireland.
    O´Doherty, J.
    Department of Physics University of Limerick, Ireland.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Assessment of tissue viability by polarization spectroscopy2008In: Opto-Electronics Review, ISSN 1230-3402, E-ISSN 1896-3757, Vol. 16, no 3, p. 309-313Article in journal (Refereed)
    Abstract [en]

    A new and versatile method for tissue viability imaging based on polarization spectroscopy of blood in superficial tissue structures such as the skin is presented in this paper. Linearly polarized light in the visible wavelength region is partly reflected directly by the skin surface and partly diffusely backscattered from the dermal tissue matrix. Most of the directly reflected light preserves its polarization state while the light returning from the deeper tissue layers is depolarized. By the use of a polarization filter positioned in front of a sensitive CCD-array, the light directly reflected from the tissue surface is blocked, while the depolarized light returning from the deeper tissue layers reaches the detector array. By separating the colour planes of the detected image, spectroscopic information about the amount of red blood cells (RBCs) in the microvascular network of the tissue under investigation can be derived. A theory that utilizes the differences in light absorption of RBCs and bloodless tissue in the red and green wavelength region forms the basis of an algorithm for displaying a colour coded map of the RBC distribution in a tissue. Using a fluid model, a linear relationship (cc. = 0.99) between RBC concentration and the output signal was demonstrated within the physiological range 0–4%. In-vivo evaluation using transepidermal application of acetylcholine by the way of iontophoresis displayed the heterogeneity pattern of the vasodilatation produced by the vasoactive agent. Applications of this novel technology are likely to be found in drug and skin care product development as well as in the assessment of skin irritation and tissue repair processes and even ultimately in a clinic case situation.

  • 28.
    Nyman, Erika
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Rakar, Jonathan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences.
    Olausson, Patrik
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Ghafouri, Bijar
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Kratz, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Exogenous hyaluronic acid induces accelerated re-epithelialization and altered protein expression in adult human skin wounds in vivoManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Hyaluronic acid, a large glycosaminoglycan involved in proliferation, migration, and tissue repair, is suggested to play an important role in ideal scarless fetal wound healing. This study aimed to investigate the effect of exogenous hyaluronic acid intradermal during deep dermal wound healing. Study parameters were erythema, re-epithelialization, and protein expression examined by using a previously described, minimally invasive in vivo human wound model in combination with tissue viability imaging, histology, and proteomics.

    Methods

    Standardized deep dermal wounds were created in the ventral forearm in ten healthy volunteers using blood collection lancets. The wound sites were injected with hyaluronic acid or saline solution, prior to wounding, or were left untreated. To quantify changes in red blood cell concentration as a measurement of inflammation, the study sites were photographed daily for two weeks using a tissue viability imaging system. At 24 hours and after 14 days, biopsy specimens were taken for histology and proteomics analysis.

    Results

    The inflammatory response was not affected by the injection of hyaluronic acid, as measured by tissue viability imaging. Hyaluronic acid significantly induced (p < 0.05) accelerated reepithelialization at 24 hours, and wounds treated with hyaluronic acid showed an altered protein expression.

    Conclusion

    The results from the present study are in concordance with  previous in vitro findings and suggest that exogenous hyaluronic acid has a  positive effect on the healing process of cutaneous wounds. We conclude that hyaluronic acid injected intradermally induces accelerated re-epithelialization and alters protein expression in vivo in human deep dermal skin wounds.

  • 29. ODoherty, J.
    et al.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Leahy, MJ.
    O'Doherty Investigation of Microvascular Red Blood Cell Proliferation in Dermal Tissue2006In: Institute of Physics IOP Ireland Annual Spring Meeting,2006, 2006Conference paper (Refereed)
  • 30.
    O'doherty, Jim
    et al.
    Department of Physics, University of Limerick, Plassey Technological Park, Limerick, Ireland.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine.
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology . Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Leahy, Martin J.
    Department of Physics, University of Limerick, Plassey Technological Park, Limerick, Ireland.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Sub-epidermal imaging using polarized light spectroscopy for assessment of skin microcirculation2007In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 13, no 4, p. 472-484Article in journal (Refereed)
    Abstract [en]

    Background/aims: Many clinical conditions that affect the microcirculation of the skin are still diagnosed and followed up by observational methods alone in spite of the fact that non-invasive, more user-independent and objective methods are available today. Limited portability, high cost, lack of robustness and non-specificity of findings are among the factors that have hampered the implementation of these methods in a clinical setting. The aim of this study is to present and evaluate a new, portable and easy-to-use imaging technology for investigation of the red blood cell (RBC) concentration in the skin microvasculature based on the method of polarization light spectroscopy using modified standard digital camera technology.

    Methods: The use of orthogonal linear polarization filters over both the flash source and the detector array removes the polarization-retaining light reflected from the epidermal layer. Only the depolarized light backscattered from the papillary dermal matrix reaches the detector array. By separating the RGB color planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the chromophores in the dermal tissue can be attained. If the algorithm is based on a differential principle in which the normalized differences between the individual values of the red and green color plane are calculated, tissue components with similar spectral signature in both planes are suppressed, while components with different spectral signatures such as RBCs are enhanced.

    Results: In vitro fluid models compare well with theory and computer simulations in describing a linear relationship between the imager output signal termed the tissue viability index (TiVi index) and RBC concentration in the physiological range of 0-4% RBC fraction of tissue volume (cc=0.997, n=20). The influence of oxygen saturation on the calculated RBC concentration is limited to within -3.9% for values within the physiological range (70-100% oxygen saturation). Monte Carlo simulations provide information about the sampling depth (about 0.5mm on the average) of the imaging system. In vivo system evaluation based on iontophoresis of acetylcholine displays a heterogeneous pattern of vasodilatation appearing inside the electrode area after about 10min. Topical application of methyl nicotinate and clobetasol propionate further demonstrates the capacity to document the extent and intensity of both an increase (erythema) and a decrease (blanching) in the skin RBC concentration without movement artifact and with compensation for irregularity in pigmentation.

    Conclusions: Polarization light spectroscopy imaging for assessment of RBC concentration in the skin microvasculature is a robust and accessible technique for the clinical setting. Additionally, the technique has pre-clinical research applications for investigation of the spatial and temporal aspects of skin erythema and blanching as well as a potential role in drug development, skin care product development and skin toxicological assessment.

  • 31.
    O'Doherty, Jim
    et al.
    Royal Surrey County Hospital, Guildford, United Kingdom.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Enfield, Joey
    University of Limerick, Ireland.
    Nilsson, Gert E
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Leahy, Martin J.
    University of Limerick, Ireland.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Tissue viability imaging (TiVi) in the assessment of divergent beam UV-B provocation2011In: Archives of Dermatological Research, ISSN 0340-3696, E-ISSN 1432-069X, Vol. 303, no 2, p. 79-87Article in journal (Refereed)
    Abstract [en]

    In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 μm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.

  • 32.
    ODoherty, Jim
    et al.
    St Thomas Hospital, England .
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Dermatology and Venerology.
    Correcting for possible tissue distortion between provocation and assessment in skin testing: The divergent beam UVB photo-test2013In: Skin research and technology, ISSN 0909-752X, E-ISSN 1600-0846, Vol. 19, no 4, p. 368-374Article in journal (Refereed)
    Abstract [en]

    BackgroundIn tissue viability imaging (TiVi), an assessment method for skin erythema, correct orientation of skin position from provocation to assessment optimizes data interpretation. Image processing algorithms could compensate for the effects of skin translation, torsion and rotation realigning assessment images to the position of the skin at provocation. less thanbrgreater than less thanbrgreater thanMethodsA reference image of a divergent, UVB phototest was acquired, as well as test images at varying levels of translation, rotation and torsion. Using 12 skin markers, an algorithm was applied to restore the distorted test images to the reference image. less thanbrgreater than less thanbrgreater thanResultsThe algorithm corrected torsion and rotation up to approximately 35 degrees. The radius of the erythemal reaction and average value of the input image closely matched that of the reference images true value. less thanbrgreater than less thanbrgreater thanConclusionThe image de-warping procedure improves the robustness of the response image evaluation in a clinical research setting and opens the possibility of the correction of possibly flawed images performed away from the laboratory setting by the subject/patient themselves. This opportunity may increase the use of photo-testing and, by extension, other late response skin testing where the necessity of a return assessment visit is a disincentive to performance of the test.

  • 33.
    O'Doherty, Jim
    et al.
    Physics Department, University of Limerick, National Technological Park, Limerick, Ireland.
    Henricson, Joakim
    Östergötlands Läns Landsting.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, Chris
    Östergötlands Läns Landsting.
    Leahy, Martin J.
    Physics Department, University of Limerick, National Technological Park, Limerick, Ireland.
    Real time diffuse reflectance polarisation spectroscopy imaging to evaluate skin microcirculation2007In: Novel Optical Instrumentationfor Biomedical Applications III / [ed] Christian D. Depeursinge, SPIE - International Society for Optical Engineering, 2007, p. 66310O-1-66310O-10Conference paper (Refereed)
    Abstract [en]

    This article describes the theoretical development and design of a real-time microcirculation imaging system, an extension from a previously technology developed by our group. The technology utilises polarisation spectroscopy, a technique used in order to selectively gate photons returning from various compartments of human skin tissue, namely from the superficial layers of the epidermis, and the deeper backscattered light from the dermal matrix. A consumer-end digital camcorder captures colour data with three individual CCDs, and a custom designed light source consisting of a 24 LED ring light provides broadband illumination over the 400 nm - 700 nm wavelength region. Theory developed leads to an image processing algorithm, the output of which scales linearly with increasing red blood cell (RBC) concentration. Processed images are displayed online in real-time at a rate of 25 frames s(-1), at a frame size of 256 x 256 pixels, and is limited only by computer RAM memory and processing speed. General demonstrations of the technique in vivo display several advantages over similar technology.

  • 34. O'Doherty, Jim
    et al.
    Leahy, Martin J.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery, Division of surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Polarized Light Spectroscopy for the Non-Invasive Investigation of Microvascular Red Blood Cell Proliferation in Dermal Tissue2006In: Biomedical Topical Meeting (BIO), Optical Society of America, 2006Conference paper (Other academic)
    Abstract [en]

    This paper describes the construction and testing of a novel non-invasive imaging system based on the method of polarization spectroscopy. Computer simulations of the algorithm, Monte Carlo studies and in vivo testing have been performed.

  • 35.
    ODoherty, Jim
    et al.
    Dept of Physics University of Limerick, Ireland.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Leahy, Martin J
    Dept of Physics University of Limerick, Ireland.
    Tissue viability for assessment of microvascular events2005In: Optical Society of America Conference,2005, Munic: SPIE , 2005, p. 125-Conference paper (Refereed)
  • 36.
    ODoherty, Jim
    et al.
    Dept of Physics University of Limerick, Ireland.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Leahy, Martin J
    Dept of Physics University of Limerick, Ireland.
    Tissue viability imaing for assessment of red blood cell concentration in skin tissue.2005In: Irish Institute of Physics Conference,2005, 2005Conference paper (Refereed)
  • 37.
    Pettersson, Erik
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Henricsson, Joachim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Validation of phototesting for estimation of individual skin ultraviolet sensitivity based on a lengthwise attenuating ultraviolet B field.2015In: Journal of Medical Engineering & Technology, ISSN 0309-1902, E-ISSN 1464-522X, Vol. 39, no 2, p. 91-8Article in journal (Refereed)
    Abstract [en]

    Conventional skin UV-sensitivity phototesting is based on semi-quantitative assessment of minimal erythema dose (MED). This study demonstrates a method for quantitative MED determination, using a lengthwise attenuating UVB-field combined with tissue viability imaging (TiVi). The study aim was to investigate the agreement between MED acquired by traditional phototest and by the new method. Forty-seven voluntary subjects underwent phototesting with a traditional phototest and with the new technique. Test reading, carried out after 24 h, showed moderate agreement between the methods when assessed with TiVi (Kappa value=0.46) and visually (Kappa value=0.48). For the new method, no systematic differences were seen between outcomes assessed with TiVi or visually (95% CI for the mean difference=-1.6-2.0). In conclusion, the results give promising support for the concept of achieving a more precise MED estimation by combining continuous attenuating UV fields with new available bioengineering technology.

  • 38.
    Rousseau, Andreas
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Department of Plastic Surgery, Hand surgery UHL. Östergötlands Läns Landsting, Sinnescentrum, Department of Anaesthesiology and Surgery UHL.
    Prostaglandins and Radical Oxygen Species Are Involved in Microvascular Effects of Hyperoxia2010In: JOURNAL OF VASCULAR RESEARCH, ISSN 1018-1172, Vol. 47, no 5, p. 441-450Article in journal (Refereed)
    Abstract [en]

    Hyperoxia causes vasoconstriction in most tissues, by mechanisms that are not fully understood. We investigated microvascular effects of breathing 100% oxygen in healthy volunteers, using iontophoresis to deliver acetylcholine (ACh) and sodium nitroprusside (SNP). Aspirin and vitamin C were used to test for involvement of prostaglandins and radical oxygen species. Forearm skin perfusion was measured using laser Doppler perfusion imaging. Results were analysed using dose-response modelling. The response to ACh was reduced by 30% during oxygen breathing compared to air breathing [0.98 (0.81-1.15) PU vs. 1.45 (1.30-1.60) PU, p andlt; 0.001]. ED50 values were unchanged [2.25 (1.84-2.75) vs. 2.21 (1.79-2.74), not significant]. Aspirin pre-treatment abolished the difference in response between oxygen breathing and air breathing [maximum: 1.03 (0.90-1.16) vs. 0.89 (0.77-1.01), not significant; ED50: 1.83 (1.46-2.30) vs. 1.95 (1.65-2.30), not significant]. ACh-mediated vasodilatation during 100% oxygen breathing was partially restored after pre-treatment with vitamin C. Breathing 100% oxygen did not change the microvascular response to SNP [1.45 (1.28-1.62) vs. 1.40 (1.26-1.53), not significant]. These results favour the hypothesis that hyperoxic vasoconstriction is mediated by inhibition of prostaglandin synthesis. Radical oxygen species may be involved as vitamin C, independently of aspirin, partially restored ACh-mediated vasodilatation during hyperoxia.

  • 39.
    Rousseau, Andréas
    et al.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Hyperoxia inhibits production of endothelial nitric oxide in humansManuscript (preprint) (Other academic)
    Abstract [en]

    Hypceoxia causes vasoconstriction in most tissues, but the mechanisms have yet to be elucidated. One hypothesis is that hyperoxia affects the production of free oxygen radicals (ROS), which reduce the concentration of the vasorelaxing agent nitric oxide (NO). It is not clear whether ROS reduce the synthesis of NO or inactivate NO that is already present. We investigated the effects of breathing 100% oxygen on NO-mediated vasodilation. Iontophoresis was used to deliver acetylcholine (ACh) (which stimulates endothelium-dependent production of NO) and sodium nitroprusside (SNP) (a NO-donor) through the skin of healthy volunteers (n=9). The blood flow in the skin was measured with a laser Doppler perfusion imager and dose-response curves were plotted. The drug dose at which 50% of the total perfusion increase was reached was calculated (ED50). The ED50 was significantly higher (right-shifted curve) while breathing oxygen compared with breathing air, when ACh was given by iontophoresis (95% CI 0.26 to 2.2). When ACh iontophoresis was preceded by oral intake of vitamin C (2.5 g daily for 3 days), this effect was abolished. Hyperoxla had no effect on vasodilation after iontophoresis with SNP. These results favour the hypothesis that hyperoxic vasoconstriction is mediated through inhibition of synthesis of NO by free oxygen radicals inside the endothelial cells.

  • 40.
    Tesselaar (Droog), Erik
    et al.
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Henricson, Joakim
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences.
    Jonsson, Susanne
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Biomedicine and Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    A time–response model for analysis of drug transport and blood flow response during iontophoresis of acetylcholine and sodium nitroprusside2009In: Journal of Vascular Research, ISSN 1018-1172, E-ISSN 1423-0135, Vol. 46, no 4, p. 270-277Article in journal (Refereed)
    Abstract [en]

    Background/Aims: The analysis of blood flow responses to iontophoresis of vasoactive drugs is often limited to evaluation of maximum responses. In this study, a time-response model is proposed for the blood flow responses to vasoactive drugs applied by iontophoresis.

    Methods: The microvascular bed is represented as a single compartment with a zero-order influx of the drugs from the electrode and a first-order clearance due to diffusion and blood flow. The blood flow response to the local drug dose is described using the Emax model.

    Results: The model accurately describes the blood flow responses to acetylcholine and sodium nitroprusside during a single iontophoretic current pulse. There is a significant clearance out of the microvascular bed during iontophoresis which depends on the type of drug administered.

    Conclusion: The model enables an accurate estimation of response parameters such as ED50 and maximum response, even if the true maximum blood flow is not obtained. The results suggest that due to clearance from the microvascular bed, the local drug dose during a single pulse of current is not linearly proportional to current strength multiplied by pulse duration.

  • 41.
    Toll John, Rani
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Junker, Johan
    Region Östergötland, Center for Disaster Medicine and Traumatology. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences.
    Jonson, Carl-Oscar
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Disaster Medicine and Traumatology. Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. WheelsBridge AB, Linköping, Sweden.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris D
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    A cool response: the influence of ambient temperature on capillary refill time2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 6Article in journal (Refereed)
    Abstract [en]

    Objective

    To describe the effect of low ambient temperature on skin temperature and capillary refill (CR) time in forehead, sternum and finger pulp.

    Methods

    An observational, nonrandomized experimental study on 15 healthy subjects (6 females) in a cold room (8°C). Outcome measures were skin temperature and quantified CR test after application of a standardized blanching pressure (9 N/cm2) using digital photographic polarization spectroscopy to generate CR times.

    Results

    The finger pulp showed marked temperature fall and prolonged CR times (>10 seconds). The CR registrations of the forehead and sternum were more comparable to curves observed in a control material at room temperature, and skin temperature falls were less marked. CR times were not prolonged in forehead measurements. At the sternum, some individuals showed CR times beyond guideline recommendations despite only a marginal reduction in skin temperature.

    Conclusions

    Low ambient temperature is a strong independent factor for CR time at peripheral sites. Reservation about sternum as a site of measurement is warranted since cold provocation produced prolonged CR times in some individuals. We found that the forehead is the most thermostable of the 3 sites and thus the preferred site to avoid ambient temperature artifact in measuring CR time.

  • 42.
    Toll John, Rani
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Nilsson, Gert E.
    WheelsBridge AB, Linköping, Sweden.
    Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Reflectance spectroscopy: to shed new light on the capillary refill test2018In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 11, no 1, article id e201700043Article in journal (Refereed)
    Abstract [en]

    To use Bioengineering methodology is used to achieve, at five anatomical sites, a detailed, quantitative assessment of the return of blood content to the blanched area, during the Capillary Refill (CR) test. An observational, non-randomized, experimental study on 23 healthy subjects (14 females) was performed in our climate controlled skin physiology laboratory. Our main outcome measures were based on the chronological assessment and quantification of red blood cell concentration (RBC) after the release of blanching pressure in the CR test, using Tissue Viability Imaging (TiVi), a digital photographic technique based on polarisation spectroscopy. TiVi enabled collection of detailed data on skin RBC concentration during the CR test. The results were shown as curves with skin blood concentration (TiVi-value) on the y-axis and the time on the x-axis. Quantitative CR responses showed site and temperature variability. We also suggest possible objective endpoint values from the capillary refill curve. Detailed data on skin RBC concentration during the CR test is easily obtained and allows objective determination of end points not possible to achieve by naked eye assessment. These findings have the potential to place the utility of the CR test in a clinical setting in a new light. Picture: Regular photograph and TiVi Image showing CR test and corresponding graph for the CR response. [GRAPHICS] .

  • 43.
    Toll, Rani
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Anderson, Chris
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology.
    Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
    Man versus machine: comparison of naked-eye estimation and quantified capillary refill2019In: Emergency Medicine Journal, ISSN 1472-0205, E-ISSN 1472-0213, Vol. 36, no 8, p. 465-471Article in journal (Refereed)
    Abstract [en]

    Background Capillary refill (CR) time is traditionally assessed by naked-eye inspection of the return to original colour of a tissue after blanching pressure. Few studies have addressed intra-observer reliability or used objective quantification techniques to assess time to original colour. This study compares naked-eye assessment with quantified CR (qCR) time using polarisation spectroscopy and examines intra-observer and interobserver agreements in using the naked eye. Method A film of 18 CR tests (shown in a random fixed order) performed in healthy adults was assessed by a convenience sample of 14 doctors, 15 nurses and 19 secretaries (Department of Emergency Medicine, Linkoping University, September to November 2017), who were asked to estimate the time to return to colour and characterise it as fast, normal or slow. The qCR times and corresponding naked-eye time assessments were compared using the Kruskal-Wallis test. Three videos were shown twice without observers knowledge to measure intra-observer repeatability. Intra-observer categorical assessments were compared using Cohens Kappa analysis. Interobserver repeatability was measured and depicted with multiple-observer Bland-Altman plotting. Differences in naked-eye estimation between professions were analysed using ANOVA. Results Naked-eye assessed CR time and qCR time differ substantially, and agreement for the categorical assessments (naked-eye assessment vs qCR classification) was poor (Cohens kappa 0.27). Bland-Altman intra-observer repeatability ranged from 6% to 60%. Interobserver agreement was low as shown by the Bland-Altman plotting with a 95% limit of agreement with the mean of +/- 1.98 s for doctors, +/- 1.6 s for nurses and +/- 1.75 s for secretaries. The difference in CR time estimation (in seconds) between professions was not significant. Conclusions Our study suggests that naked-eye-assessed CR time shows poor reproducibility, even by the same observers, and differs from an objective measure of CR time.

  • 44. Wood, K
    et al.
    Henricson, Joakim
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery.
    Nilsson, Gert
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Sjöberg, Folke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of surgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Assessment of microvascular response in vivo by local warming and the effects of iontophoritically-applied vasoconstrictive drugs2006Report (Other academic)
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