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Sökning: WFRF:(Tesselaar Erik)

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1.
  • Samuelsson, Anders, et al. (författare)
  • Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline
  • 2012
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 38:7, s. 975-983
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support. less thanbrgreater than less thanbrgreater thanMethod: Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded. less thanbrgreater than less thanbrgreater thanResults: Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine. less thanbrgreater than less thanbrgreater thanConclusion: These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.
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2.
  • Bergkvist, Max, et al. (författare)
  • Assessment of microcirculation of the skin using Tissue Viability Imaging: A promising technique for detecting venous stasis in the skin
  • 2015
  • Ingår i: Microvascular Research. - : Elsevier. - 0026-2862 .- 1095-9319. ; 101, s. 20-25
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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3.
  • Bergkvist, Max, et al. (författare)
  • Assessment of oxygenation with polarized light spectroscopy enables new means for detecting vascular events in the skin
  • 2020
  • Ingår i: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 130
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Impaired oxygenation in the skin may occur in disease states and after reconstructive surgery. We used tissue viability imaging (TiVi) to measure changes in oxygenation and deoxygenation of haemoglobin in an in vitro model and in the dermal microcirculation of healthy individuals. Materials and methods: Oxygenation was measured in human whole blood with different levels of oxygenation. In healthy subjects, changes in red blood cell concentration (C-RBC,(TiVi)), oxygenation (Delta C-OH,(TiVi)) and deoxygenation (Delta C-DOH,(TiVi)) of haemoglobin were measured during and after arterial and venous occlusion using TiVi and were compared with measurements from the enhanced perfusion and oxygen saturation system (EPOS). Results: During arterial occlusion, C-RBC,(TiVi) remained unchanged while Delta C-OH,(TiVi) decreased to -44.2 (10.4) AU (p = 0.04), as compared to baseline. After release, C-RBC,C-TiVi increased to 39.2 (18.8) AU (p < 0.001), Delta C-OH,C-TiVi increased to 38.5. During venous occlusion, C-RBC,C-TiVi increased to 28.9 (11.2) AU (p < 0.001), Delta C-OH,C-TiVi decreased to -52.2 (46.1) AU (p < 0.001) compared to baseline after 5 min of venous occlusion. There was a significant correlation between the TiVi Oxygen Mapper and EPOS, for arterial (r = 0.92, p < 0.001) and venous occlusion (r = 0.87, p < 0.001), respectively. Conclusion: This study shows that TiVi can measure trends in oxygenation and deoxygenation of haemoglobin during arterial and venous stasis in healthy individuals.
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4.
  • Bergkvist, Max, 1976- (författare)
  • Studies on Polarised Light Spectroscopy
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis project focuses on measurements of dermal microcirculation during vascular provocations with polarised light spectroscopy. This is done with a non-invasive method commercially available as Tissue viability imaging (TiVi) which measures concentration and oxygenation of red blood cells in the papillary dermis. Three studies were done with human subjects and one with an animal model, to validate and compare the TiVi technique with laser Doppler flowmetry, which is an established method of measuring dermal microcirculation.The TiVi consists of a digital camera with polarisation filters in front of the flash and lens, with software for analysis of the picture. When taking a picture with the TiVi, the polarised light that is reflected on the skin surface is absorbed by the second filter over the lens (which is perpendicular to the first filter) but a portion of light penetrates the surface of the skin and is scattered when it is reflected on tissue components. This makes the light depolarised, passes the second filter, and produces a picture for analysis. The red blood cell (RBC) has a distinct absorption pattern that differs between red and green colour compared to melanin and other components of tissue. This difference is used by the software that calculates differences in each picture element and produces a measure of output which is proportional to the concentration of red blood cells. The oxygenation of RBC can also be calculated, as there is a difference in absorption depending on oxygen state.The first paper takes up possible sources of error such as ambient light, and the angle and distance of the camera. The main experiment was to investigate how the local heating reaction is detected with TiVi compared to LDF.In the second paper arterial and venous stasis are examined in healthy subjects with TiVi.The Third paper is an animal study where skin flaps were raised on pigs, and the vascular pedicle is isolated to enable control of inflow and outflow of blood.The measurements were made during partial venous, total venous, and total arterial occlusion. The TiVi recorded changes in the concentration of RBC, oxygenation and heterogeneity and the results were compared with those of laser Doppler flowmetry.In the fourth paper oxygenation and deoxygenation of RBC: s was studied. Studies were made on the forearms of healthy subjects who were exposed to arterial and venous occlusion. Simultaneous measurements were made with TiVi and Enhanced perfusion and oxygen saturation or EPOS, which is a new device that combines laser Doppler flowmetry and diffuse reflectance spectroscopy in one probe.With TiVi, one can measure RBC concentration and oxygenation in the area of an entire picture or in one or multiple user defined regions of interest (ROI). Methods such as laser Doppler flowmetry makes single point measurements, which is a potential source of error both because of the heterogeneity of the microcirculation, and that the circulation be insufficient in the margins of the investigated area. TiVi has been able to measure venous stasis more accurately than laser Doppler flowmetry, and venous stasis is the more common reason for flaps to fail.The TiVi is an accurate way to measure the concentration of RBC and trends in oxygenation of the dermal microcirculation. It has interesting possible applications for microvascular and dermatological research, monitoring of flaps, and diagnosis of peripheral vascular disease. Future clinical studies are needed as well as development of the user interface.  
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5.
  • Bergkvist, Max, 1976-, et al. (författare)
  • Vascular Occlusion in a Porcine Flap Model : Effects on Blood Cell Concentration and Oxygenation.
  • 2017
  • Ingår i: Plastic and Reconstructive Surgery - Global Open. - : Wolters Kluwer. - 2169-7574. ; 5:11
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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6.
  • Booij, Ronald, et al. (författare)
  • Assessment of visibility of bone structures in the wrist using normal and half of the radiation dose with photon-counting detector CT
  • 2023
  • Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 159
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To quantitatively and qualitatively assess the visibility of bone structures in the wrist on photon-counting detector computed tomography (PCD-CT) images compared to state-of-the-art energy-integrating de-tector CT (EID-CT).Method: Four human cadaveric wrist specimens were scanned with EID-CT and PCD-CT at identical CTDIvolof 12.2 mGy and with 6.1 mGy (half dose PCD-CT). Axial images were reconstructed using the thinnest possible slice thickness, i.e. 0.4 mm on EID-CT and 0.2 mm on PCD-CT, with the largest image matrix size possible using reconstruction kernels optimized for bone (EID-CT: Ur68, PCD-CT: Br92). Quantitative evaluation was performed to determine contrast-noise ratio (CNR) of bone/ fat, cortical and trabecular sharpness. An observer study using visual grading characteristics (VGC) analysis was performed by six observers to assess the visibility of nutrient canals, trabecular architecture, cortical bone and the general image quality.Results: At equal dose, images obtained with PCD-CT had 39 +/- 6 % lower CNR (p = 0.001), 71 +/- 57 % higher trabecular sharpness in the radius (p = 0.02) and 42 +/- 8 % (p < 0.05) sharper cortical edges than those obtained with EID-CT. This was confirmed by VGC analysis showing a superior visibility of nutrient canals, trabeculae and cortical bone area under the curve (AUC) > 0.89) for PCD-CT, even at half dose.Conclusions: Despite a lower CNR and increased noise, the trabecular and cortical sharpness were twofold higher with PCD-CT. Visual grading analysis demonstrated superior visibility of cortical bone, trabeculae, nutrient canals and an overall improved image quality with PCD-CT over EID-CT. At half dose, PCD-CT also yielded superior image quality, both in quantitative measures and as evaluated by radiologists.
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7.
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8.
  • Detert, Hedvig, et al. (författare)
  • Microcirculatory response to cold stress test in the healthy hand
  • 2023
  • Ingår i: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 148
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Cold sensitivity of the fingers is common in several conditions. It has been linked to digital vasospasm, microvascular dysfunction, and neural mechanisms. This study aimed to investigate the normal digital micro-vascular response to a cold stress test in healthy individuals using Laser Speckle Contrast Imaging (LSCI).Methods: Twenty-six healthy individuals, mean age 31 (SD 9) years were included. Skin perfusion of digits II-V was measured using Laser Speckle Contrast Imaging before and after a standardized cold stress test. Changes in skin perfusion from baseline were analyzed between hands, digits, and sexes.Results: Skin perfusion was significantly (p < 0.0001) affected by cold provocation in both the cold exposed and the contralateral hands in all participants of the study. This effect was significantly different between the radial (digit II and III) and the ulnar (digit V) side of the hands (p < 0.001). There was a trend towards a larger decrease in perfusion in men (ns), and a faster recovery to baseline values in women (ns). A larger inter subject variability was seen in perfusion values in women.Conclusions: The normal microvascular response to cold provocation may involve both centrally and regionally mediated processes. When exposing one hand to a cold stress test, the contralateral hand responds with simul-taneous but smaller decreases in perfusion.
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9.
  • Droog Tesselaar, Erik, et al. (författare)
  • A protocol for iontophoresis of acetylcholine and sodium nitroprusside that minimises nonspecific vasodilatory effects
  • 2004
  • Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 197-202
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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10.
  • Droog Tesselaar, Erik, 1977- (författare)
  • Assessment of microvascular function by use of transdermal iontophoresis : methodological aspects
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Assessment of the microcirculation is of major importance in understanding the physiology of the vasculature and in assessing te vascular effects of pathological conditions such as diabetes, hypertension and sepsis. Transdermal iontophoresis can be used to non‐invasively introduce vasoactive drugs into the skin. The response to these drugs of the local cutaneous microvasculature can be measured by laser Doppler flowmetry methods. Although these techniques have been used together for over two decades, there are still important methodological issues to be resolved. This work is aimed at optimizing transdermal iontophoresis as a tool for microvascular assessment by focusing on the main methdological issues: non‐specific vasodilatation, drug delivery protocols and analysis of blood flow data.Non‐specific vasodilatation, an increase blood flow during iontophoresis of non‐vasoactive compounds, is an important problem as it interferes with the response to the administered drug. By investigating this effect in healthy volunteers, we found that the extent of the non‐specific response differs between the positive and negative electrode and that it is dependent on the voltage over the skin andon the ionic strength of the vehicle in which the drug is dissolved. We also found that the extent of the non‐specific response could be reduced by applying local anesthetics and by pre‐treatment with antihistamine drugs. These results suggest that non‐specific effects could be mediated by depolarization or hyperpolarisation of cells, triggering neural and histamine related mechanisms that finally lead to vasodilatation of the local microvasculature.To prevent non‐specific effects from occurring during the experiments, our results show that the current strength and the total electric charge during iontophoresis should be limited to 0.02 mA and12 mC, respectively. Furthermore, drug solutions at physiological ionic strengths should be used. Under these conditions, adequate responses to the most commonly used drugs, acetylcholine (ACh) and sodium nitroprusside (SNP), are obtained while no significant non‐specific vasodilatation occurs.The results of our investigations show that blood responses to ACh and SNP applied by a single iontophoretic pulse can well be escribed by conventional dose‐response models, which enables a more powerful analysis and comparison between drugs or possibly patient groups as compared with conventional aalysis methods. Finally, we have incorporated drug transport and physiological response to the local drug concentration during iontophoresis of vasoactve drugs into a single model. Validation of this model using measured responses to ACh and SNP shows that the commonly used assumption that the local drug concentration during iontophoresis is linearly proportional to the electric charge may not be valid.
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11.
  • Droog Tesselaar, Erik, 1977-, et al. (författare)
  • Changes in skin microcirculation during radiation therapy for breast cancer
  • 2017
  • Ingår i: Acta Oncologica. - Oxfordshire : Taylor & Francis. - 0284-186X .- 1651-226X. ; 56:8, s. 1072-1080
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The majority of breast cancer patients who receive radiation treatment are affected by acute radiation-induced skin changes. The assessment of these changes is usually done by subjective methods, which complicates the comparison between different treatments or patient groups. This study investigates the feasibility of new robust methods for monitoring skin microcirculation to objectively assess and quantify acute skin reactions during radiation treatment.MATERIAL AND METHODS: Laser Doppler flowmetry, laser speckle contrast imaging, and polarized light spectroscopy imaging were used to measure radiation-induced changes in microvascular perfusion and red blood cell concentration (RBC) in the skin of 15 patients undergoing adjuvant radiation therapy for breast cancer. Measurements were made before treatment, once a week during treatment, and directly after the last fraction.RESULTS: In the treated breast, perfusion and RBC concentration were increased after 1-5 fractions (2.66-13.3 Gy) compared to baseline. The largest effects were seen in the areola and the medial area. No changes in perfusion and RBC concentration were seen in the untreated breast. In contrast, Radiation Therapy Oncology Group (RTOG) scores were increased only after 2 weeks of treatment, which demonstrates the potential of the proposed methods for early assessment of skin changes. Also, there was a moderate to good correlation between the perfusion (r = 0.52) and RBC concentration (r = 0.59) and the RTOG score given a week later.CONCLUSION: We conclude that radiation-induced microvascular changes in the skin can be objectively measured using novel camera-based techniques before visual changes in the skin are apparent. Objective measurement of microvascular changes in the skin may be valuable in the comparison of skin reactions between different radiation treatments and possibly in predicting acute skin effects at an earlier stage.
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12.
  • Droog Tesselaar, Erik, et al. (författare)
  • Nonspecific vasodilatation during transdermal iontophoresis : the effect of voltage over the skin
  • 2003
  • Ingår i: Microvascular research. - 0026-2862. ; 65:3, s. 172-178
  • Tidskriftsartikel (refereegranskat)abstract
    • We used laser Doppler perfusion imaging (LDPI) to study nonspecific vasodilatation during iontophoresis. In iontophoresis studies, nonspecific vasodilatation occurs as a result either of galvanic currents or of the applied voltage over the skin. We made dose–response measurements to study the effect of ionic strength of the vehicle on the nonspecific vasodilatation during iontophoresis of sodium chloride and deionized water, while we monitored the voltage over the skin. We found that anodal and cathodal ionotophoresis induced a voltage over the skin that was dependent on the ionic strength of the test solution. The nonspecific vasodilatation during anodal iontophoresis was less pronounced than during cathodal iontophoresis, and was independent of the voltage over the skin. The nonspecific vasodilatation in cathodal iontophoresis was related to the voltage over the skin, and was possibly mediated by depolarization of local sensory nerves. In experiments using cathodal iontophoresis, therefore, the ionic strengths of the vehicle and the drug are important when vasoactive drugs are examined, as the nonspecific vasodilatation needs to be controlled for. As the vasodilatation that we observed was heterogeneously distributed within the area of iontophoresis, LDPI may provide more accurate measurements than conventional laser Doppler perfusion monitoring.
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13.
  • Elawa, Sherif, et al. (författare)
  • Microcirculatory changes in the skin after postmastectomy radiotherapy in women with breast cancer
  • 2024
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Postmastectomy radiotherapy (PMRT) increases the risk for complications after breast reconstruction. The pathophysiological mechanism underlying this increased risk is not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion in the skin directly after, and at 2 and 6 months after PMRT and to assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate-MN) after PMRT. Skin microvascular responses after PMRT were measured on two sites in the irradiated chest wall of 22 women before, immediately after, and at 2 and 6 months after unilateral PMRT with the contralateral breast as a control. A significant increase in basal skin perfusion was observed in the irradiated chest wall immediately after RT (p < 0.0001). At 2 and 6 months after RT, there was no longer a difference in basal skin perfusion compared to the contralateral breast and compared to baseline. Similarly, the blood flow response in the skin after application of MN was stronger immediately after RT compared to before RT (p < 0.0001), but there was no difference at later time points. These results indicate that the increased risk for complications after surgical procedures are not directly related to changes in skin perfusion and microvascular responsiveness observed after postmastectomy RT.
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14.
  • Elawa, Sherif, 1988- (författare)
  • Microvascular Function Assessment after Mastectomy and Radiation Therapy in Breast Cancer Patients : From Methodology to Clinical Application
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Post-mastectomy radiotherapy (PMRT) is an important part of the treatment of breast cancer. It reduces the risk of recurrence and improves overall survival. Scaring and fibrotization of the skin and subcutaneous tissue of the chest wall or remaining breast are among its side-effects. These late side-effects of PMRT may in turn affect skin microcirculation and oxygenation, although this connection is not completely established. In patients that later require breast reconstruction, it is difficult as a plastic surgeon to evaluate if the microcirculatory changes have been affected by PMRT, and how such effects should have an impact on the choice of reconstructive method. In the work presented in this thesis, laser speckle contrast imaging (LSCI), laser-doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) have been used with a strong vasodilator, methyl nicotinate (MN) to study the microcirculatory changes after PMRT.In studies I and II, we aimed to find the optimal concentration of MN and its main mechanisms of action. In healthy volunteers, the microvascular response to different concentrations of MN was evaluated on the forearm using LSCI. It was found that a concentration of 20 mmol/l resulted in a quick vasodilatory response with a long plateau phase, minimal tissue edema and no non-responders. In study II, we utilized locally administered drugs to block the three main pathways responsible for skin vasodilation. Subsequently, we provoked the skin with MN and assessed its effect with LSCI. From this study we could conclude that MN’s mechanism of action is largely mediated by prostaglandins and partly by local sensory nerves.In study III, we examined the skin microcirculatory response in breast cancer patients before, immediately after, and at two and six months following unilateral PMRT, using the contralateral breast as a control. A significant increase in basal skin perfusion and perfusion after application of MN was observed on the irradiated chest wall immediately after RT compared to the contralateral breast and compared to before RT. At six months after RT, there was no longer a difference in basal skin perfusion or after application of MN in the irradiated chest wall compared to the contralateral breast and compared to before RT was given. The results from this study concluded that skin perfusion in the irradiated chest wall had returned to normal when measured six months after RT.In study IV, the late effects on skin microvascular function were studied in women who had undergone mastectomy and PMRT several years prior to the study. Skin perfusion and oxygen saturation was measured with white light diffuse reflectance spectroscopy (DRS) combined with Laser Doppler Flowmetry (LDF) before and after application of MN on the irradiated chest wall with the contralateral non-irradiated breast as control. In this study we found that skin perfusion and oxygenation in the breast are affected several years after radiotherapy and that our method could be a valuable clinical tool prior to deciding surgical procedures after PMRT.To conclude, MN can be topically applied to the skin to reliably assess microvascular function and the microvascular capacity. LSCI and LDF have different strengths and drawbacks, with LSCI having the advantage of having a large spatial resolution that allows for measurements of control areas in the same field of view as the provoked areas. LDF in combination with DRS enabled us to further assess perfusion and oxygenation simultaneously which could be an advantage in fibrotic skin where skin perfusion and oxygen saturation may not correlate with each other. Although the study groups differed between the study examining the early effects of PMRT with the late effects of PMRT, we have been able to non-invasively visualize changes in microcirculation in relation to the acute and chronic phase after PMRT. Future studies are needed to investigate the value of pre-operative measurements with MN provocation for predicting surgical outcome.
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15.
  • Elawa, Sherif, et al. (författare)
  • Skin blood flow response to topically applied methyl nicotinate: Possible mechanisms
  • 2020
  • Ingår i: Skin research and technology. - : WILEY. - 0909-752X .- 1600-0846. ; 26:3, s. 343-348
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be valuable as a local provocation in the assessment of microcirculation and skin viability. The mechanisms through which MN mediates its vascular effect are not fully known. The aim of this study was to characterize the vasodilatory effects of topically applied MN and to study the involvement of nitric oxide (NO), local sensory nerves, and prostaglandin-mediated pathways. Methods MN was applied on the skin of healthy subjects in which NO-mediated (L-NMMA), nerve-mediated (lidocaine/prilocaine), and cyclooxygenase-mediated (NSAID) pathways were selectively inhibited. Microvascular responses in the skin were measured using laser speckle contrast imaging (LSCI). Results NSAID reduced the MN-induced perfusion increase with 82% (P < .01), whereas lidocaine/prilocaine reduced it with 32% (P < .01). L-NMMA did not affect the microvascular response to MN. Conclusion The prostaglandin pathway and local sensory nerves are involved in the vasodilatory actions of MN in the skin.
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16.
  • Elawa, Sherif, et al. (författare)
  • Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients
  • 2024
  • Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 75
  • Tidskriftsartikel (refereegranskat)abstract
    • The pathophysiological mechanism behind complications associated with postmastectomy radiotherapy (PMRT) and subsequent implant-based breast reconstruction are not completely understood. The aim of this study was to examine if there is a relationship between PMRT and microvascular perfusion and saturation in the skin after mastectomy and assess if there is impaired responsiveness to a topically applied vasodilator (Methyl nicotinate - MN). Skin microvascular perfusion and oxygenation >2 years after PMRT were measured using white light diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) in the irradiated chest wall of 31 women with the contralateral breast as a control. In the non-irradiated breast, the perfusion after application of MN (median 0.84, 25th-75th centile 0.59-1.02 % RBC × mm/s) was higher compared to the irradiated chest wall (median 0.51, 25th-75th centile 0.21-0.68 % RBC × mm/s, p < 0.001). The same phenomenon was noted for saturation (median 91 %, 25th-75th centile 89-94 % compared to 89 % 25th-75th centile 77-93 %, p = 0.001). Eight of the women (26%) had a ≥10 % difference in skin oxygenation between the non-irradiated breast and the irradiated chest wall. These results indicate that late microvascular changes caused by radiotherapy of the chest wall significantly affect skin perfusion and oxygenation.
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17.
  • Elawa, Sherif, et al. (författare)
  • The microvascular response in the skin to topical application of methyl nicotinate : Effect of concentration and variation between skin sites
  • 2019
  • Ingår i: Microvascular Research. - : Academic Press. - 0026-2862 .- 1095-9319. ; 124, s. 54-60
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundMethyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be used as a local provocation in the assessment of microcirculation and skin viability. The aims were to measure the effects of increasing doses of MN, to find the concentration that yields the most reproducible effect from day to day and between sites, and to study the variation between skin sites.MethodsMicrovascular responses to topically applied MN at different concentrations were measured in 12 subjects on separate days and on contralateral sides, using laserspeckle contrast imaging (LSCI). MN effects were measured in four different body sites.ResultsAt 20 mmol/L, the response to MN was most reproducible day-to-day and site-to-site, and resulted in a plateau response between 5 and 20 min after application.The skin region of the lower back had a lower perfusion value compared to the epigastric region (p = 0.007). When responses were compared to nearby, unprovoked areas, a significantly larger increase in perfusion was seen in the forearm, compared to all other anatomical sites (p < 0.03).ConclusionA concentration of 20 mmol/L MN generated the most reproducible microvascular response in the skin. The response varies between different body sites.
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18.
  • Elgström, Henrik, et al. (författare)
  • Signal-To-Noise Ratio Rate Measurement in Fluoroscopy For Quality Control and Teaching Good Radiological Imaging Technique
  • 2021
  • Ingår i: Radiation Protection Dosimetry. - : Oxford University Press. - 0144-8420 .- 1742-3406. ; 195:3-4, s. 407-415
  • Tidskriftsartikel (refereegranskat)abstract
    • Visibility of low-contrast details in fluoroscopy and interventional radiology is important. Assessing detail visibility with human observers typically suffers from large observer variances. Objective, quantitative measurement of low-contrast detail visibility using a model observer, such as the square of the signal-to-noise ratio rate (SNR2rate), was implemented in MATLAB™ and evaluated. The expected linear response of SNR2rate based on predictions by the so-called Rose model and frame statistics was verified. The uncertainty in the measurement of SNR2rate for a fixed imaging geometry was 6% based on 16 repeated measurements. The results show that, as expected, reduced object thickness and x-ray field size substantially improved SNR2rate/PKA,rate with PKA,rate being the air kerma area product rate. The measurement precision in SNR2rate/PKA,rate (8–9%) is sufficient to detect small but important improvements, may guide the selection of better imaging settings and provides a tool for teaching good radiological imaging techniques to clinical staff.
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19.
  • Elmasry, Moustafa, 1981-, et al. (författare)
  • Laser speckle contrast imaging in children with scalds : Its influence on timing of intervention, duration of healing and care, and costs
  • 2019
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 45:4, s. 798-804
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundScalds are the most common type of burn injury in children, and the initial evaluation of burn depth is a problem. Early identification of deep dermal areas that need excision and grafting would save unnecessary visits and stays in hospital. Laser speckle contrast imaging (LSCI) shows promise for the evaluation of this type of burn. The aim of this study was to find out whether perfusion measured with LSCI has an influence on the decision for operation, duration of healing and care period, and costs, in children with scalds.MethodsWe studied a group of children with scalds whose wounds were evaluated with LSCI on day 3–4 after injury during the period 2012–2015. Regression (adjustment for percentage total body surface area burned (TBSA%), age, and sex) was used to analyse the significance of associations between degree of perfusion and clinical outcome.ResultsWe studied 33 children with a mean TBSA% of 6.0 (95% CI 4.4–7.7)%. Lower perfusion values were associated with operation (area under the receiver-operating characteristic curve 0.86, 95% CI 0.73–1.00). The perfusion cut-off with 100% specificity for not undergoing an operation was ≥191 PU units (66.7% sensitivity and 72.7% accurately classified). Multivariable analyses showed that perfusion was independently associated with duration of healing and care period.ConclusionLower perfusion values, as measured with LSCI, are associated with longer healing time and longer care period. By earlier identification of burns that will be operated, perfusion measurements may further decrease the duration of care of burns in children with scalds.
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20.
  • Engstrand, Fredrik, et al. (författare)
  • Validation of a smartphone application and wearable sensor for measurements of wrist motions
  • 2021
  • Ingår i: Journal of Hand Surgery, European Volume. - : Sage Publications. - 1753-1934 .- 2043-6289. ; 46:10, s. 1057-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • We developed a smartphone application to measure wrist motion using the mobile devices built-in motion sensors or connecting it via Bluetooth to a wearable sensor. Measurement of wrist motion with this method was assessed in 33 participants on two occasions and compared with those obtained with a standard goniometer. The test-retest reproducibility in healthy individuals ranged from good to excellent (intraclass correlation (ICC) 0.76-0.95) for all motions, both with and without the wearable sensor. These results improved to excellent (ICC 0.90-0.96) on the second test day, suggesting a learning effect. The day-to-day reproducibility was overall better with the wearable sensor (mean ICC 0.87) compared with the application without using sensor or goniometer (mean ICC 0.82 and 0.60, respectively). This study suggests that smartphone-based measurements of wrist range of motion are feasible and highly accurate, making it a powerful tool for outcome studies after wrist surgery.
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21.
  • Ericsson, Elin, et al. (författare)
  • Effect of Electrode Belt and Body Positions on Regional Pulmonary Ventilation- and Perfusion-Related Impedance Changes Measured by Electric Impedance Tomography
  • 2016
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:6, s. e0155913-
  • Tidskriftsartikel (refereegranskat)abstract
    • Ventilator-induced or ventilator-associated lung injury (VILI/VALI) is common and there is an increasing demand for a tool that can optimize ventilator settings. Electrical impedance tomography (EIT) can detect changes in impedance caused by pulmonary ventilation and perfusion, but the effect of changes in the position of the body and in the placing of the electrode belt on the impedance signal have not to our knowledge been thoroughly evaluated. We therefore studied ventilation-related and perfusion-related changes in impedance during spontaneous breathing in 10 healthy subjects in five different body positions and with the electrode belt placed at three different thoracic positions using a 32-electrode EIT system. We found differences between regions of interest that could be attributed to changes in the position of the body, and differences in impedance amplitudes when the position of the electrode belt was changed. Ventilation-related changes in impedance could therefore be related to changes in the position of both the body and the electrode belt. Perfusion-related changes in impedance were probably related to the interference of major vessels. While these findings give us some insight into the sources of variation in impedance signals as a result of changes in the positions of both the body and the electrode belt, further studies on the origin of the perfusion-related impedance signal are needed to improve EIT further as a tool for the monitoring of pulmonary ventilation and perfusion.
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22.
  • Farnebo, Simon, et al. (författare)
  • Hyperaemic changes in forearm skin perfusion and RBC concentration after increasing occlusion times
  • 2010
  • Ingår i: MICROVASCULAR RESEARCH. - : Elsevier Science B.V., Amsterdam. - 0026-2862. ; 80:3, s. 412-416
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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23.
  • Folkesson, Tchou, et al. (författare)
  • A human vascular model based on microdialysis for the assessment of the vasoconstrictive dose-response effects of noradrenaline and vasopressin in skin : in JOURNAL OF VASCULAR RESEARCH, vol 48, pp 320-320
  • 2011
  • Ingår i: JOURNAL OF VASCULAR RESEARCH. - : Karger. ; , s. 320-320
  • Konferensbidrag (refereegranskat)abstract
    • Microdialysis is a well-established technique for continuous sampling of small, water-soluble molecules within the extracellular fluid space in vivo. It also allows the use of microdoses of drugs, and the simultaneous evaluation of their related effects at the site of action. The present study was an experimental, randomized microdose trial to develop a human vascular model of dose response. We aimed to evaluate a microdialysis dosing method using urea clearance as a marker of druginduced changes in dermal blood flow and metabolism (glucose and lactate) in 12 healthy volunteers. We found that asymptomatic vasoconstriction can be detected by continuous microdialysis measurements of urea clearance in dermal tissue. More importantly, dose-effect relations using the Emax model could be constructed using the corresponding data on drug doses and both the urea clearance-based flow estimates and the changes in concentrations of tissue metabolites. This in vivo human experimental skin model offers an interesting tool with which both the dose-response effects on blood flow and concentrations of tissue metabolites of potent vasoactive substances can be evaluated.
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24.
  • Fredäng Kämmerling, Nina, et al. (författare)
  • A comparative study of image quality and diagnostic confidence in diagnosis and follow-up of scaphoid fractures using photon-counting detector CT and energy-integrating detector CT
  • 2024
  • Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 173
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Scaphoid fractures in patients and assessment of healing using PCD-CT have, as far as we know, not yet been studied. Therefore, the aim was to compare photon counting detector CT (PCD-CT) with energy integrating detector CT (EID-CT) in terms of fracture visibility and evaluation of fracture healing. Method: Eight patients with scaphoid fracture were examined with EID-CT and PCD-CT within the first week posttrauma, and with additional scans at 4, 6 and 8 weeks. Our clinical protocol for wrist examination with EID-CT was used (CTDIvol 3.1 +/- 0.1 mGy, UHR kernel Ur77). For PCD-CT matched radiation dose, reconstruction kernel Br89. Quantitative analyses of noise, CNR, trabecular and cortical sharpness, and bone volume fraction were conducted. Five radiologists evaluated the images for fracture visibility, fracture gap consolidation and image quality, and rated their confidence in the diagnosis. Results: The trabecular and cortical sharpness were superior in images obtained with PCD-CT compared with EIDCT. A successive reduction in trabecular bone volume fraction during the immobilized periods was found with both systems. Despite higher noise and lower CNR with PCD-CT, radiologists rated the image quality of PCD-CT as superior. The visibility of the fracture line within 1 -week post -trauma was rated higher with PCD-CT as was diagnostic confidence, but the subsequent assessments of fracture gap consolidation during healing process and the confidence in diagnosis were found equivalent between both systems. Conclusion: PCD-CT offers superior visibility of bone microstructure compared with EID-CT. The evaluation of fracture healing and confidence in diagnosis were rated equally with both systems, but the radiologists found primary fracture visibility and overall image quality superior with PCD-CT.
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25.
  • Hackethal, Johannes, et al. (författare)
  • Microvascular effects of microneedle application
  • 2021
  • Ingår i: Skin research and technology. - : WILEY. - 0909-752X .- 1600-0846. ; 27, s. 121-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The efficiency of transdermal drug delivery may be increased by pretreating the skin with microneedles, but distinct effects of microneedles and the microneedle-enhanced delivery of vasoactive drugs on the skin microvasculature are still not well investigated. Materials and Methods In eight healthy human subjects, we measured the microvascular response to microneedle-induced microtraumas in the skin microvasculature using polarized light spectroscopy imaging (Tissue Viability imaging, TiVi). The microvascular response was assessed for up to 48 hours for three microneedle sizes (300 mu m, 500 mu m, and 750 mu m) and for different pressures and application times. Results In our results, microneedle application increased the local red blood cell (RBC) concentration for up to 24 hours dependent on the needle lengths, applied time, and force. Conclusion Optimization of microneedles size, pressure, and application time should be taken into account for future protocols for drug delivery and experimental provocations.
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26.
  • Henricson, Joakim, 1977- (författare)
  • Assessment of microvascular effects of vasoactive drugs : Methodological in vivo studies in humansbased on iontophoresis
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
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27.
  • Henricson, Joakim, et al. (författare)
  • 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
  • 2007
  • Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 73:2, s. 143-149
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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28.
  • Henricson, Joakim, 1977-, et al. (författare)
  • Assessment of microvascular response to iontophoresis ofnoradrenaline and phenylephrine using local heating andlaser Doppler flowmetry
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • 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.
  •  
29.
  • Henricson, Joakim, et al. (författare)
  • Tissue viability imaging : Microvascular response to vasoactive drugs induced by iontophoresis
  • 2009
  • Ingår i: Microvascular Research. - : Elsevier BV. - 0026-2862. ; 78:2, s. 199-205
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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30.
  • Horiuchi, Yoshihito, et al. (författare)
  • Role of histamine release in nonspecific vasodilatation during anodal and cathodal iontophoresis
  • 2004
  • Ingår i: Microvascular research. - : Elsevier BV. - 0026-2862. ; 67:2, s. 192-196
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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31.
  • Högstedt, Alexandra, et al. (författare)
  • Effect of N-G-monomethyl l-arginine on microvascular blood flow and glucose metabolism after an oral glucose load
  • 2020
  • Ingår i: Microcirculation. - : WILEY. - 1073-9688 .- 1549-8719. ; 27:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The aim of this study was to investigate whether the effects on local blood flow and metabolic changes observed in the skin after an endogenous systemic increase in insulin are mediated by the endothelial nitric oxide pathway, by administering the nitric oxide synthase inhibitor N-G-monomethyl l-arginine using microdialysis. Methods Microdialysis catheters, perfused with N-G-monomethyl l-arginine and with a control solution, were inserted intracutaneously in 12 human subjects, who received an oral glucose load to induce a systemic hyperinsulinemia. During microdialysis, the local blood flow was measured by urea clearance and by laser speckle contrast imaging, and glucose metabolites were measured. Results After oral glucose intake, microvascular blood flow and glucose metabolism were both significantly suppressed in the N-G-monomethyl l-arginine catheter compared to the control catheter (urea clearance: P amp;lt; .006, glucose dialysate concentration: P amp;lt; .035). No significant effect of N-G-monomethyl l-arginine on microvascular blood flow was observed with laser speckle contrast imaging (P = .81). Conclusion Local delivery of N-G-monomethyl l-arginine to the skin by microdialysis reduces microvascular blood flow and glucose delivery in the skin after oral glucose intake, presumably by decreasing local insulin-mediated vasodilation.
  •  
32.
  • Högstedt, Alexandra, et al. (författare)
  • Investigation of proteins important for microcirculation using in vivo microdialysis after glucose provocation : a proteomic study
  • 2021
  • Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin has metabolic and vascular effects in the human body. What mechanisms that orchestrate the effects in the microcirculation, and how the responds differ in different tissues, is however not fully understood. It is therefore of interest to search for markers in microdialysate that may be related to the microcirculation. This study aims to identify proteins related to microvascular changes in different tissue compartments after glucose provocation using in vivo microdialysis. Microdialysis was conducted in three different tissue compartments (intracutaneous, subcutaneous and intravenous) from healthy subjects. Microdialysate was collected during three time periods; recovery after catheter insertion, baseline and glucose provocation, and analyzed using proteomics. Altogether, 126 proteins were detected. Multivariate data analysis showed that the differences in protein expression levels during the three time periods, including comparison before and after glucose provocation, were most pronounced in the intracutaneous and subcutaneous compartments. Four proteins with vascular effects were identified (angiotensinogen, kininogen-1, alpha-2-HS-glycoprotein and hemoglobin subunit beta), all upregulated after glucose provocation compared to baseline in all three compartments. Glucose provocation is known to cause insulin-induced vasodilation through the nitric oxide pathway, and this study indicates that this is facilitated through the interactions of the RAS (angiotensinogen) and kallikrein-kinin (kininogen-1) systems.
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33.
  • Högstedt, Alexandra, 1993- (författare)
  • Microvascular effects of insulin in the skin
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The microcirculation in the skin is essential for skin homeostasis. In instances of altered microvascular function, that may be the result of insulin resistance, tissue morbidity may ensue. The underlying mechanisms are however complex and not fully understood. By studying the physiological effects of insulin in the skin, the understanding of the complex interplay between glucose metabolism and skin microcirculation can be improved. The general aim of this thesis was to develop an experimental in vivo model to study metabolic and microvascular responses to insulin in the skin in healthy subjects. Microdialysis is a suiting technique as it allows for both local delivery of drugs and simultaneous monitoring of the local metabolic and vascular effects in the very same tissue compartment. The effects of local and systemic insulin provocation on skin blood flow and metabolism were investigated using microdialysis urea clearance and laser speckle contrast imaging (paper I). An insulin dependent increase in skin blood flow was observed, presumably induced through the nitric oxide pathway (paper II). Investigating the protein expression during an oral glucose provocation using proteomic approaches however indicates interactions with other pathways, such as the renin-angiotensin system and the kallikrein-kinin system (paper IV). Paper III also investigated methodological concerns regarding the sampling of insulin using microdialysis. This in vivo model can, in the future, be applied to assess the microvascular effects of insulin in the skin in different patient groups, including those with micro-vascular dysfunction due to, for instance, insulin resistance.  
  •  
34.
  • Högstedt, Alexandra, et al. (författare)
  • Sampling insulin in different tissue compartments using microdialysis: methodological aspects
  • 2020
  • Ingår i: Scientific Reports. - : NATURE RESEARCH. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Sampling the concentration of insulin in human skin using microdialysis is challenging because of low intracutaneous concentrations and low recovery, presumably due to adsorption of insulin to the microdialysis system. In this study, we aimed to (1) measure how the concentration of insulin varies in three different tissue compartments (intracutaneous, subcutaneous and intravenous) and (2) to study how much insulin is adsorbed to the microdialysis catheter membranes and tubing during a typical microdialysis experiment, both in vivo and in vitro. We hypothesized that (1) the concentration of insulin decreases from the intravenous compartment to the intracutaneous and subcutaneous tissue, and that (2) adsorption of insulin to the microdialysis membrane and tubing impairs the recovery of insulin from the tissue. In this experimental study, microdialysis catheters were inserted intracutaneously, subcutaneously and intravenously in 11 healthy subjects. Systemic endogenous hyperinsulinemia was induced by intake of an oral glucose load. Insulin concentration was measured in the dialysate and in the extracted samples from the catheter membrane and tubings. In vitro microdialysis was performed to investigate the temporal resolution of the adsorption. After an oral glucose load insulin concentration increased intravenously, but not in the intracutaneous or subcutaneous compartments, while glucose, lactate and pyruvate concentrations increased in all compartments. The adsorption of insulin to the microdialysis membrane in vivo was highest in the intravenous compartment (p=0.01), compared to the intracutaneous and subcutaneous compartments. In vitro, the adsorption to the microdialysis membrane was highest one hour after sampling, then the concentration gradually decreased after three and five hours of sampling. The concentration of insulin in peripheral tissues is low, probably due to decreasing tissue vascularity. Adsorption of insulin to the microdialysis membrane is modest but time-dependent. This finding highlights the importance of a stabilization time for the microdialysis system before sampling tissue analytes.
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35.
  • Iredahl, Fredrik, 1988- (författare)
  • Assessment of microvascular and metabolic responses in the skin
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs.In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI.The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide.
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36.
  • Iredahl, Fredrik, et al. (författare)
  • Modeling Perfusion Dynamics in the Skin During Iontophoresis of Vasoactive Drugs Using Single-Pulse and Multiple-Pulse Protocols
  • 2015
  • Ingår i: Microcirculation. - : Informa Healthcare / Wiley: 12 months. - 1073-9688 .- 1549-8719. ; 22:6, s. 446-453
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: After iontophoresis of vasoactive drugs into the skin, a decrease in perfusion is commonly observed. We delivered vasoactive drugs by iontophoresis using different delivery protocols to study how these affect this decrease in perfusion as measured using LDF. Methods: We measured skin perfusion during iontophoresis of (ACh), MCh, andNAusing a single pulse or separate pulses at different skin sites, and during repeated delivery of ACh at the same site. Results: Perfusion half-life was 6.1 (5.6-6.6) minutes for ACh and 41 (29-69) minutes for MCh (p less than 0.001). The maximum response with multiple pulses of ACh iontophoresis was lower than with a single pulse, 30 (22-37) PU vs. 43 (36-50) PU, p less than 0.001. Vasoconstriction to NA was more rapid with a single pulse than with multiple pulses. The perfusion half-life of ACh decreased with repeated delivery of ACh at the same site-first 16 (14-18), second 5.9 (5.1-6-9) and third 3.2 (2.9-3.5) minutes, p less than 0.001. Conclusions: The drug delivery protocol affects microvascular responses to iontophoresis, possibly as a result of differences in the dynamics of local drug concentrations. Perfusion half-life may be used as a measure to quantify the rate of perfusion recovery after iontophoresis of vasoactive drugs.
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37.
  • Iredahl, Fredrik, et al. (författare)
  • Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations
  • 2015
  • Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:8, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques. Method Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi. Results Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9 +/- 6.2 PU; 10-min 100 +/- 25 PU; pless than0.001) and RBC concentration (TiVi: baseline 119 +/- 18; 10-min 150 +/- 41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0 +/- 4.4 PU; 10-min 38.9 +/- 5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6 +/- 11.8 AU; 10-min 54.4 +/- 13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8 +/- 3.6 PU; max 112 +/- 55 PU; pless than0.001, LSCI: baseline 50.8 +/- 8.0 PU; max 151 +/- 22 PU; pless than0.001) and RBC concentration (TiVi: baseline 49.2 +/- 32.9 AU; max 99.3 +/- 28.3 AU; pless than0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: pless than0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (pless than0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses. Conclusion LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline-induced vasoconstriction. LSCI and TiVi show lower inter-subject variability than LDF. These findings are important to consider when choosing measurement techniques for studying skin microvascular responses.
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38.
  • Iredahl, Fredrik, et al. (författare)
  • Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load
  • 2016
  • Ingår i: Microcirculation. - : Wiley-Blackwell. - 1073-9688 .- 1549-8719. ; 23:7, s. 597-605
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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39.
  • Iredahl, Fredrik, et al. (författare)
  • The Microvascular Response to Transdermal Iontophoresis of Insulin is Mediated by Nitric Oxide
  • 2013
  • Ingår i: Microcirculation. - : WILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA. - 1073-9688 .- 1549-8719. ; 20:8, s. 717-723
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveInsulin has direct effects on blood flow in various tissues, most likely due to endothelial NO production. We investigated whether insulin delivered to the skin by iontophoresis increases microvascular perfusion and whether this effect is partly or completely mediated by the release of NO. MethodsIn healthy subjects, regular insulin and monomeric insulin were delivered to the skin by cathodal iontophoresis. The skin was pretreated either with L-NAME or control solution (PBS) using anodal iontophoresis. Microvascular responses were measured using laser Doppler flowmetry. ResultsA dose-dependent increase in perfusion was observed during iontophoresis of regular and monomeric insulin. The maximum perfusion was significantly elevated compared with control after PBS (regular insulin 53.6 (12.7-95.6) PU vs. 4.2 (3.4-4.8) PU, p = 0.002; monomeric insulin 32.6 (8.9-92.6) PU vs. 5.9 (3.4-56.0) PU, p = 0.03). The microvascular response to insulin was abolished after L-NAME (regular insulin: 25.6 (11.6-54.4) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.15; monomeric insulin 10.9 (5.4-56.8) PU vs. control: 4.7 (2.9-11.5) PU, p = 0.22). ConclusionsThe main finding is that iontophoresis of insulin induces a dose-dependent vasodilation in the skin, which could be suppressed after pretreatment with a NO synthase inhibitor. This suggests that vasodilation in the skin after iontophoresis of insulin is mediated by the NO pathway.
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40.
  • Kämmerling, Nina, et al. (författare)
  • Assessment of image quality in photon-counting detector computed tomography of the wrist - An ex vivo study
  • 2022
  • Ingår i: European Journal of Radiology. - : Elsevier Ireland Ltd. - 0720-048X .- 1872-7727. ; 154
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The aim of this study was to evaluate the effect of reconstruction parameters on image quality in wrist imaging using photon-counting detector CT (PCD-CT) and to compare the results with images from an energyintegrating detector CT (EID-CT). Methods: Twelve cadaveric wrist specimens were examined using a prototype PCD-CT and a clinical EID-CT using similar radiation dose. Reconstruction parameters were matched between scanners. Also, sharper reconstruction kernels, a larger matrix size, and smaller slice thicknesses were evaluated for PCD-CT. Image noise, contrast-tonoise ratio (CNR) and image sharpness in trabecular structures were quantitatively measured. Image quality with respect to the visibility of cortical and trabecular bone structures was assessed by six radiologists using visual grading methods.Results: Images obtained with PCD-CT had lower noise (42.6 +/- 3.9 HU vs 75.1 +/- 6.3 HU), higher CNR (38.9 +/- 4.5 vs 19.0 +/- 2.4) and higher trabecular sharpness (63.5 +/- 6.0 vs 53.7 +/- 8.5) than those obtained with EID-CT using similar scan and reconstruction parameters (p < 0.001). The image sharpness in trabecular structures was further improved by using sharper kernels, despite higher noise levels. Radiologists had a strong preference for PCD-CT images both in terms of spatial resolution and suitability for bone imaging. Visual grading analysis showed an improved visibility of cortical bone, trabeculae and nutritive canals (p < 0.005).Conclusion: PCD-CT offers improved image quality regarding bone structures in the wrist relative to EID-CT systems, particularly when sharper reconstruction kernels, smaller slice thickness and a larger image matrix size are used.
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41.
  • Li, Y., et al. (författare)
  • Hyperoxia affects the regional pulmonary ventilation/perfusion ratio : an electrical impedance tomography study
  • 2014
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 58:6, s. 716-725
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The way in which hyperoxia affects pulmonary ventilation and perfusion is not fully understood. We investigated how an increase in oxygen partial pressure in healthy young volunteers affects pulmonary ventilation and perfusion measured by thoracic electrical impedance tomography (EIT). Methods Twelve semi-supine healthy male volunteers aged 21-36 years were studied while breathing room air and air-oxygen mixtures (FiO2) that resulted in predetermined transcutaneous oxygen partial pressures (tcPO2) of 20, 40 and 60kPa. The magnitude of ventilation (Zv) and perfusion (ZQ)-related changes in cyclic impedance variations, were determined using an EIT prototype equipped with 32 electrodes around the thorax. Regional changes in ventral and dorsal right lung ventilation (V) and perfusion (Q) were estimated, and V/Q ratios calculated. Results There were no significant changes in Zv with increasing tcPO2 levels. ZQ in the dorsal lung increased with increasing tcPO2 (P=0.01), whereas no such change was seen in the ventral lung. There was a simultaneous decrease in V/Q ratio in the dorsal region during hyperoxia (P=0.04). Two subjects did not reach a tcPO2 of 60kPa despite breathing 100% oxygen. Conclusion These results indicate that breathing increased concentrations of oxygen induces pulmonary vasodilatation in the dorsal lung even at small increases in FiO2. Ventilation remains unchanged. Local mismatch of ventilation and perfusion occurs in young healthy men, and the change in ventilation/perfusion ratio can be determined non-invasively by EIT.
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42.
  • Lindahl, Filip, et al. (författare)
  • Assessing paediatric scald injuries using Laser Speckle Contrast Imaging
  • 2013
  • Ingår i: Burns. - : Elsevier. - 0305-4179 .- 1879-1409. ; 39:4, s. 662-666
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundThe use of objective methods for assessment of burns is limited. Laser Speckle Contrast Imaging (LSCI) is a non-invasive technique for instant measurement of tissue perfusion, making it potentially valuable for early prediction of burn wound outcome.AimTo evaluate the influence of technical factors on perfusion and to measure perfusion in burns 0–14 days post-burn and compare this with the outcome of the burn wound at 14 days after burn.MethodThe effect of room light, camera distance and camera angle was studied using a suspension of polystyrene particles. LSCI measurements were performed on 45 scald burns and 32 uninjured areas 0–14 days after burn.ResultTechnical factors had no clinically relevant effect on measured perfusion. Burns that healed within 14 days had a higher perfusion during the first week post-burn than burns that healed after 14 days or underwent surgery. The difference in perfusion was largest 4–7 days after burn.ConclusionLSCI allows for robust, instant measurement of burns and can easily be applied in a clinical setting. Differences in perfusion during the first week post-burn are related to the outcome after 14 days.
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43.
  • Mirdell, Robin, et al. (författare)
  • Accuracy of laser speckle contrast imaging in the assessment of pediatric scald wounds
  • 2018
  • Ingår i: Burns. - : ELSEVIER SCI LTD. - 0305-4179 .- 1879-1409. ; 44:1, s. 90-98
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Changes in microvascular perfusion in scalds in children during the first four days, measured with laser speckle contrast imaging (LSCI), are related to the time to healing and need for surgical intervention. The aim of this study was to determine the accuracy (sensitivity and specificity) of LSCI on different days after injury in the prediction of healing outcome and if the accuracy can be improved by combining an early and a late measurement. Also, the accuracy of LSCI was compared with that of clinical assessment. Methods: Perfusion was measured between 0-24h and between 72-96h using LSCI in 45 children with scalds. On the same occasions, burn surgeons assessed the burns as healing amp;lt; 14days or healing amp;gt; 14days/surgery. Receiver operating characteristic (ROC) curves were constructed for the early and late measurement and for the double measurement (DM) using two different methods. Results: Sensitivity and specificity were 92.3% (95% CI: 64.0-99.8%) and 78.3% (95% CI: 69.985.3%) between 0-24h, 100% (95% CI: 84.6-100%) and 90.4% (95% CI: 83.8-94.9%) between 72-96h, and was 100% (95% CI: 59.0-100%) and 100% (95% CI: 95.1-100%) when combining the two measurements into a modified perfusion trend. Clinical assessment had an accuracy of 67%, Cohens k=0.23. Conclusion: The perfusion in scalds between 72-96h after injury, as measured using LSCI, is highly predictive of healing outcome in scalds when measured. The predictive value can be further improved by incorporating an early perfusion measurement within 24h after injury. (C) 2017 Elsevier Ltd and ISBI. All rights reserved.
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44.
  • Mirdell, Robin, 1989- (författare)
  • Blood Flow Dynamics in Burns
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Objectives:Burns of intermediate thickness are hard to evaluate clinically. This often leads to unnecessary delays of up to 14 days before a surgical decision can be made. To counter this, several objective methods have been developed to determine the healing potential of the wound. Over the years, measurement of perfusion has proven to be the most successful method for evaluation of healing potential. Laser Doppler imaging (LDI) is currently the most used method and can determine surgical need 2 days after injury with an accuracy >90%.  There are however emerging techniques like laser speckle contrast imaging (LSCI), which also measure perfusion. LSCI have several advantages over LDI and is easier to use. LSCI can also investigate aspects of the microcirculation, previously not possible with LDI. The aim of this thesis was to investigate LSCI’s ability to evaluate surgical need in burns of indeterminate partial-thickness.  The first objective was to investigate the dynamics of perfusion the first 14 days after injury. The purpose was to find the optimal time-window for perfusion measurements. The next goal was to determine the accuracy of different perfusion cut-offs. In this second study, the benefit of a subsequent measurement was also investigated. After this, interobserver variation between different profession groups was studied. Both the agreement of perfusion measurements and observer assessments were evaluated. Finally, cardiac vasomotion in combination with perfusion (pulsatility) was investigated as a method to determine surgical need <48 hours after injury.  Methods:Perfusion was measured in a total of 77 patients at the Department of Plastic Surgery, Hand Surgery and Burns at Linköping University Hospital, Sweden. Most of these patients were children and the most common type of burn was scalds. A laser speckle contrast imager (PeriCam PSI System, Perimed AB, Järfälla, Sweden) was used to measure perfusion.  Results:  In the first paper we showed a clear relation between perfusion dynamics and the healing potential of the wound. The changes in perfusion were largest the first 5 days after injury, why this time interval was selected for subsequent papers. Perfusion measurements done day 3-4 after injury could predict surgical need with a sensitivity of 100% (95% CI: 83.9-100%) and a specificity of 90.4% (95% CI: 83.8-94.9%). If two measurements were used, <24 hours and 3-4 days after injury, the accuracy was 100%. Furthermore, we found that different observers could consistently predict perfusion, while there was a large variation in their clinical assessments. This was not improved by extensive burn experience. Finally, pulsatility could be used to predict surgical need the same day as the injury occurred with a sensitivity of 100% (95% CI: 88.1-100%) and a specificity of 98.8% (95% CI: 95.7- 99.9%).  Conclusions:  LSCI is a promising method for evaluation of burns and provides several benefits over LDI. The surgical need of burns can be determined mere hours after injury when pulsatility is measured. However, the benefits of early scald diagnostics in children with LSCI need to be evaluated in a prospective study before the method is ready for routine clinical use.
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45.
  • Mirdell, Robin, 1989-, et al. (författare)
  • Data on microcirculatory perfusion dips in the resting nail bed
  • 2018
  • Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 21, s. 1232-1235
  • Tidskriftsartikel (refereegranskat)abstract
    • This article contains the raw data from the article entitled: "The presence of synchronized perfusion dips in the microcirculation of the resting nail bed" Mirdell et al. (in press). A laser speckle contrast imager (LSCI) was used to make a total of 21 recordings of the perfusion in the resting nail bed of 10 healthy test subjects. The first 10 recordings were acquired after 5?min of acclimatization. An additional 10 recordings were acquired in the same test subjects, after 20?min of acclimatization. In the last recording, a digital nerve block was applied to the left dig III. The data show the presence of highly irregular perfusion variations, a phenomenon we like to call perfusion dips. The data also show how the perfusion dips can be abolished through a digital nerve block. An algorithm for the quantification of the perfusion dips is included in the data.
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46.
  • Mirdell, Robin, et al. (författare)
  • Interobserver reliability of laser speckle contrast imaging in the assessment of burns
  • 2019
  • Ingår i: Burns. - : ELSEVIER SCI LTD. - 0305-4179 .- 1879-1409. ; 45:6, s. 1325-1335
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Laser speckle contrast imaging (LSCI) is an emerging technique for the assessment of burns in humans and interobserver differences have not been studied. The aim of this study was to compare assessments of perfusion images by different professional groups regarding (i) perfusion values and (ii) burn depth assessment. Methods: Twelve observers without LSCI experience were included. The observers were evenly recruited from three professional groups: plastic surgeons with experience in assessing burns, nurses with experience in treating burns, and junior doctors with limited experience of burns. Ten cases were included. Each case consisted of one digital photo of the burn with a pre-marked region of interest (ROI) and two unmarked perfusion images of the same area. The first and the second perfusion image was from 24h and 72-96h after injury, respectively. The perfusion values from both perfusion images were used to generate a LSCI recommendation based on the perfusion trend (the derivative between the two perfusion values). As a last step, each observer was asked to estimate the burn depth using their clinical experience and all available information. Intraclass correlation (ICC) was calculated between the different professional groups and among all observers. Results: Perfusion values and perfusion trends between all observers had an ICC of 0.96 (95% CI 0.91-0.99). Burn depth assessment by all observers yielded an ICC of 0.53 (95% CI: 0.31-0.80) and an accuracy of 0.53 (weighted kappa). LSCI recommendations generated by all observers had an ICC of 0.95 (95% CI: 0.90-0.99). Conclusion: Observers can reliably identify the same ROI, which results in observer-independent perfusion measurements, irrespective of burn experience. Extensive burn experience did not further improve burn depth assessment. The LSCI recommendation was more accurate in all professional groups. Introducing LSCI measurements would be likely improve early assessment of burns. (C) 2019 Elsevier Ltd and ISBI. All rights reserved.
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47.
  • Mirdell, Robin, et al. (författare)
  • Microvascular blood flow in scalds in children and its relation to duration of wound healing: A study using laser speckle contrast imaging
  • 2016
  • Ingår i: Burns. - : ELSEVIER SCI LTD. - 0305-4179 .- 1879-1409. ; 42:3, s. 648-654
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Microvascular perfusion changes in scalds in children during the first weeks after injury is related to the outcome of healing, and measurements of perfusion, based on laser Doppler imaging, have been used successfully to predict the need for excision and grafting. However, the day-to-day changes in perfusion during the first weeks after injury have not to our knowledge been studied in detail. The aim of this study, based on a conservative treatment model where excision and grafting decisions were delayed to day 14 after injury, was to measure changes in perfusion in scalds using laser speckle contrast imaging (LSCI) during the first three weeks after injury. Methods: We measured perfusion with LSCI in 34 patients at regular intervals between 6 h after injury until complete reepithelialization or surgery. Duration of healing was defined as the time to complete reepithelialization. Results: Less perfusion, between 6 and 96 h after injury, was associated with longer duration of healing with the strongest association occurring between 72 and 96 h. Burns that healed within 14 days had relatively high initial perfusion, followed by a peak and subsequent slow decrease. Both the maximum perfusion and the time-to-peak were dependent on the severity of the burn. Burns that needed excision and grafting had less initial perfusion and a gradual reduction over time. Conclusion: The perfusion in scalds in children shows characteristic patterns during the first weeks after injury depending on the duration of wound healing, the greatest difference between wounds of different severity being on the 4th day. Perfusion should therefore preferably be measured on the fourth day if it is to be used in the assessment of burn depth. (c) 2015 Elsevier Ltd and ISBI. All rights reserved.
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48.
  • Mirdell, Robin, et al. (författare)
  • The presence of synchronized perfusion dips in the microcirculation of the resting nail bed
  • 2019
  • Ingår i: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 121, s. 71-81
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Laser speckle contrast imaging (LSCI) has seen limited use in the study of perfusion dynamics such as vasomotion. The aim of this study was to investigate the effects of a prolonged seated position on perfusion dynamics in the nail bed using LSCI. Methods: Perfusion was recorded in digits II to IV bilaterally for 20 min during two separate sessions in ten healthy volunteers. The acclimatization period was 5 min for the 1st session and 20 min for the 2nd. Perfusion variability and the presence of recurring perfusion dips were analyzed. A digital nerve block was done to verify suspected nervous origin of phenomenon. Results: Synchronized phases of vasoconstriction were observed in all subjects with perfusion dips in all digits bilaterally and simultaneously. Application of a digital nerve block abolished perfusion dips. The frequency of this phenomenon increased by 25.0% (95% CI: 1.6 to 49.2%) in the left-hand digits after a prolonged seated position. Perfusion variability increased by 11.6% (95% CI: 2.6 to 20.3%) in the digits of the left hand. Perfusion changes in right-hand digits did not significantly increase. During the 1st session, temperature increased by 2.7 degrees C (1.1 to 4.2) while it decreased by 1.3 degrees C (0.2 to 2.4) during the 2nd session. Conclusion: The observed perfusion dips are of a centrally mediated nervous origin but are also affected by local factors. They are affected by seating duration and differ between left and right hands, likely because of local micro perfusion dips. This phenomenon seems related to digital thermoregulation.
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49.
  • Mirdell, Robin, et al. (författare)
  • Using blood flow pulsatility to improve the accuracy of laser speckle contrast imaging in the assessment of burns
  • 2020
  • Ingår i: Burns. - : ELSEVIER SCI LTD. - 0305-4179 .- 1879-1409. ; 46:6, s. 1398-1406
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Measurement of perfusion is an establishedmethod to evaluate the depth of burns. However, high accuracy is only achievable >48 h after injury. The aim of the study was to investigate if measurement of blood flow pulsatility, combined with perfusion measurement, can improve early assessment of burn depth using laser speckle contrast imaging (LSCI). Methods: Perfusion and pulsatility were measured with LSCI in 187 regions of interest in 32 patients, between 0 and 5 days after injury. The reproducibility of pulsatility was tested for recording durations between 1 and 12 s. The most reproducible duration was chosen, and receiver operator characteristics were created to find suitable pulsatility cut-offs to predict surgical need. Results: A measurement duration of 8 s resulted in a good reproducibility of the pulsatility (% CV: 15.9%). Longer measurement durations resulted in a small improvement of the accuracy of the assessment. A pulsatility of <1.45 (Perfusion Units)(2) on day 0-2 after injury predicted surgical need with a sensitivity of 100% (95% CI: 83.2-100%), specificity of 100% (95% CI: 95.2-100%), a positive predictive value of 100%, and a negative predictive value of 100%. Pulsatility was not significantly different when comparing measurements done day 0-2 today 3-5. Perfusion was however significantly higher day 3-5 compared today 0-2 for wound shealing with in 3 weeks. Conclusion: Measurement of pulsatility improves the accuracy of the assessment of burns with LSCI and makes it possible to predict the need for surgery during day 0-2 after injury with a high accuracy. (C) 2020 Elsevier Ltd and ISBI. All rights reserved.
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50.
  • Nilsson, Klara, et al. (författare)
  • A Novel Technique to Assess Distal Radioulnar Joint Stability Using Increasing Torque
  • 2019
  • Ingår i: Journal of wrist surgery. - : Thieme Medical Publishers. - 2163-3916 .- 2163-3924. ; 8:4, s. 327-334
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Previous studies on computed tomography (CT) in patients with a suspected triangular fibrocartilage complex (TFCC) injury have not been successful in assessing distal radioulnar joint (DRUJ) laxity. The aim of this study was to develop a novel servomotor-driven device for the assessment of DRUJ by applying increasing torque to the DRUJ in pronation and supination.Methods A custom-built device was designed to function during four-dimensional (4D) CT of the wrist. A torque meter, positioned between the incoming hand holder, and a direct current (DC) servomotor were used for angular positioning and for applying rotational force to the patient's arm. A total of 110 healthy participants were recruited to gather reference values for the range of motion (ROM), maximum torque in neutral and supinated/pronated position, and the ability to withstand an increasing, device-generated torque in these positions. The device was also used during 4D DRUJ CT in five patients with suspected TFCC injuries.Results A gender- and age-relevant reference chart for ROM and torque was created. Men showed a tendency (ns) toward having a larger ROM and increasing strength with increasing age, whereas women showed the opposite. Also, the dominant hand showed a tendency toward having a larger ROM and being stronger than the nondominant hand (ns). A smaller cohort of patients (n = 5) with suspected TFCC injuries showed a significantly decreased ability to withstand increasing torque in both supination (2.1 ± 0.3 vs. 3.1 ± 0.2 s; p < 0.005) and pronation (2.3 ± 0.5 vs. 3.1 ± 0.4 s; p < 0.0005) and also showed a clear laxity on real-time 4D CT image sequences. Decreased strength at all positions was also found (average 74% decrease compared to noninjured side).Conclusion Reference values for torque strength and ability to withstand increasing torque can be used clinically in the assessment of patients with symptoms that could represent ligamentous injuries to the TFCC. The ability to use the device during CT enables radiographic evaluation of instability during increasing torque.Level of Evidence This is a Level II study.
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