1. |
- Ajan, Aida, et al.
(author)
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Reproducibility of Laser Doppler Flowmetry in gingival microcirculation. A study on six different protocols
- 2024
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In: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 153
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Journal article (peer-reviewed)abstract
- Objectives: Laser Doppler Flowmetry (LDF) is a non-invasive technique for the assessment of tissue blood flow, but increased reproducibility would facilitate longitudinal studies. The aim of the study was to assess the interday reproducibility of Laser Doppler Flowmetry (LDF) at rest, at elevated local temperatures, and with the use of the vasodilator Methyl Nicotinate (MN) in six interconnected protocols for the measurement of the blood supply to the microvascular bed of the gingiva. Methods: Ten healthy volunteers were included. Interweek LDF measurements with custom-made acrylic splints were performed. Six protocols were applied in separate regions of interest (ROI): 1; basal LDF, 2; LDF with thermoprobe 42 degrees C, 3; LDF with thermoprobe 45 degrees C, 4; LDF with thermoprobe 42 degrees C and MN, 5; LDF with thermoprobe 45 C and MN and 6; LDF with MN. Results: Intra-individual reproducibility was assessed by the within -subject coefficient of variation (wCV) and the intraclass correlation coefficient (ICC). Basal LDF measurements demonstrated high reproducibility with wCV 11.1 in 2 min and 10.3 in 5 min. ICC was 0.9 and 0.92. wCV after heat and MN was 4.9-10.3 and ICC 0.82-0.93. The topically applied MN yielded increased blood flow. Conclusion: This is the first study evaluating the reproducibility of basal LDF compared to single or multiple vasodilatory stimuli in gingiva. Multiple collector fibers probe and stabilizing acrylic splints are recommended. Vasodilatory stimulation showed a tendency toward higher reproducibility. Furthermore, MN yields vasodilation in gingiva.
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2. |
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3. |
- Bergstrand, Sara, et al.
(author)
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Association between cardiovascular risk profile and impaired microvascular function in a Swedish middle-aged cohort (the SCAPIS study)
- 2024
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In: European Journal of Preventive Cardiology. - : OXFORD UNIV PRESS. - 2047-4873 .- 2047-4881.
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Journal article (peer-reviewed)abstract
- Aims The aim was to investigate the relationship between microvascular function, cardiovascular risk profile, and subclinical atherosclerotic burden. Methods and results The study enrolled 3809 individuals, 50-65 years old, participating in the population-based observational cross-sectional Swedish CArdioPulmonary bioImage Study. Microvascular function was assessed in forearm skin using an arterial occlusion and release protocol determining peak blood oxygen saturation (OxyP). Cardiovascular risk was calculated using the updated Systematic Coronary Risk Evaluation [SCORE2; 10-year risk of fatal and non-fatal cardiovascular disease (CVD) events]. The OxyP was compared with coronary artery calcification score (CACS) and to plaques in the carotid arteries. Individuals with OxyP values in the lowest quartile (Q1; impaired microvascular function) had a mean SCORE2 of 5.8% compared with 3.8% in those with the highest values of OxyP (Q4), a relative risk increase of 53%. The risk of having a SCORE2 > 10% was five times higher for those in Q1 (odds ratio: 4.96, 95% confidence interval: 2.76-8.93) vs. Q4 when adjusting for body mass index and high-sensitivity C-reactive protein. The OxyP was lower in individuals with CACS > 0 and in those with both carotid plaques and CACS > 0, compared with individuals without subclinical atherosclerotic burdens (87.5 +/- 5.6% and 86.9 +/- 6.0%, vs. 88.6 +/- 5.8%, P < 0.01). Conclusion In a population without CVD or diabetes mellitus, impaired microvascular function is associated with cardiovascular risk profiles such as higher SCORE2 risk and CACS. We suggest that OxyP may serve as a microcirculatory functional marker of subclinical atherosclerosis and CVD risk that is not detected by structural assessments.
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4. |
- Elawa, Sherif, et al.
(author)
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Skin perfusion and oxygen saturation after mastectomy and radiation therapy in breast cancer patients
- 2024
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In: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 75
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Journal article (peer-reviewed)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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5. |
- Engström, Ingemar, 1952-, et al.
(author)
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Relational continuity may give better clinical outcomes in patients with serious mental illness - a systematic review
- 2023
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In: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Research review (peer-reviewed)abstract
- BackgroundContinuity of care is considered important for results of treatment of serious mental illness (SMI). Yet, evidence of associations between relational continuity and different medical and social outcomes is sparse. Research approaches differ considerably regarding how to best assess continuity as well as which outcome to study. It has hitherto been difficult to evaluate the importance of relational continuity of care. The aim of this systematic review was to investigate treatment outcomes, including effects on resource use and costs associated with receiving higher relational continuity of care for patients with SMI.MethodsEleven databases were searched between January 2000 and February 2021 for studies investigating associations between some measure of relational continuity and health outcomes and costs. All eligible studies were assessed for study relevance and risk of bias by at least two independent reviewers. Only studies with acceptable risk of bias were included. Due to study heterogeneity the synthesis was made narratively, without meta-analysis. The certainty of the summarized result was assessed using GRADE. Study registration number in PROSPERO: CRD42020196518.ResultsWe identified 8 916 unique references and included 17 studies comprising around 300 000 patients in the review. The results were described with regard to seven outcomes. The results indicated that higher relational continuity of care for patients with serious mental illness may prevent premature deaths and suicide, may lower the number of emergency department (ED) visits and may contribute to a better quality of life compared to patients receiving lower levels of relational continuity of care. The certainty of the evidence was assessed as low or very low for all outcomes. The certainty of results for the outcomes hospitalization, costs, symptoms and functioning, and adherence to drug treatment was very low with the result that no reliable conclusions could be drawn in these areas.ConclusionsThe results of this systematic review indicate that having higher relational continuity of care may have beneficial effects for patients with severe mental illness, and no results have indicated the opposite relationship. There is a need for better studies using clear and distinctive measures of exposure for relational continuity of care.
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6. |
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7. |
- Fredriksson, Ingemar, et al.
(author)
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Absolute flow velocity components in laser Doppler flowmetry
- 2006
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In: Proceedings of SPIE, the International Society for Optical Engineering. - : IEEE. - 0277-786X .- 1996-756X. ; 6094, s. 60940A-
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Journal article (peer-reviewed)abstract
- A method to separate a Doppler power spectrum into a number of flow velocity components, measured in absolute units (mm/s), is presented. A Monte Carlo software was developed to track each individual Doppler shift, to determine the probability, p(n), for a photon to undergo n Doppler shifts. Given this shift distribution, a mathematical relationship was developed and used to calculate a Doppler power spectrum originating from a certain combination of velocity components. The non linear Levenberg-Marquardt optimization method could thus be used to fit the calculated and measured Doppler power spectra, giving the true set of velocity components in the measured sample. The method was evaluated using a multi tube flow phantom perfused with either polystyrene microspheres or undiluted/diluted human blood (hct = 0.45). It estimated the velocity components in the flow phantom well, during both low and high concentrations of moving scatterers (microspheres or blood). Thus, further development of the method could prove to be a valuable clinical tool to differentiate capillary blood flow.
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8. |
- Fredriksson, Ingemar, et al.
(author)
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Accuracy of vessel diameter estimated from a vessel packaging compensation in diffuse reflectance spectroscopy
- 2011
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In: Clinical and Biomedical Spectroscopy and Imaging II. - : SPIE - International Society for Optical Engineering. - 9780819486837 ; , s. 8087 1M-1-8087 1M-8
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Conference paper (other academic/artistic)abstract
- Light absorption in tissue is generally decreased when chromophores are spatially concentrated rather than being homogeneously distributed. In tissue, this applies to hemoglobin located in blood vessels (vessel packaging). In this paper, the diffusely reflected light from 41 tissue models with discrete blood vessels with diameters ranging from 6.25 to 100 μm were simulated using the Monte Carlo technique. A reverse engineering approach was then utilized to find the model that had an optimal spectral fit to each of the simulated models. The average vessel diameter was one fitting parameter in the adaptive model. The estimated vessel diameter from the optimal fit model was compared to the known diameter from the simulated models. Two different methods to calculate the vessel packaging effect were used, one existing based on a simple analytic expression and a new method based on path length distributions. Both methods had similar performance. For the new method, the absolute RMS deviation of the estimated vessel diameter was 5.5 μm for vessel diameters ≤ 25 μm, and the relative RMS deviation was 21 % for vessel diameters > 25 μm.
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9. |
- Fredriksson, Ingemar, et al.
(author)
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Evaluation of a multi-layer diffuse reflectance spectroscopy system using optical phantoms
- 2017
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In: DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES X. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510605534 - 9781510605541
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Conference paper (peer-reviewed)abstract
- A fiber probe-based device for assessing microcirculatory parameters, especially red blood cell (RBC) tissue fraction, their oxygen saturation and speed resolved perfusion, has been evaluated using state-of-the-art multi-layer tissue simulating phantoms. The device comprises both diffuse reflectance spectroscopy (DRS) at two source-detector separations (0.4 and 1.2 mm) and laser Doppler flowmetry (LDF) and use an inverse Monte Carlo method for identifying the parameters of a multi-layered tissue model. First, model parameters affecting scattering, absorption and geometrical parameters are fitted to measured DRS spectra, then speed parameters are fitted to LDF spectra. In this paper, the accuracy of the spectral parameters is evaluated. The measured spectral shapes at the two source-detector separations were in good agreement with forward calculated spectral shapes. In conclusion, the multi-layer skin model based on spectral features of the included chromophores, can reliably estimate the tissue fraction of RBC, its oxygen saturation and the reduced scattering coefficient spectrum of the tissue. Furthermore, it was concluded that some freedom in the relative intensity difference between the two DRS channels is necessary in order to compensate for non-modeled surface structure effects.
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10. |
- Fredriksson, Ingemar, et al.
(author)
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Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms
- 2017
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In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 22:11
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Journal article (peer-reviewed)abstract
- A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (f(RBC)), oxygen saturation (S-O2), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source-detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The rootmean-square (RMS) deviations for f(RBC) for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for SO2 was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (mus), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter (D) was 1 mu m. In conclusion, the skin microcirculation parameters fRBC and SO2, as well as, mu(s) and D are estimated with reasonable accuracy. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.
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11. |
- Fredriksson, Ingemar, et al.
(author)
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Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations
- 2009
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In: JOURNAL OF BIOPHOTONICS. - : Wiley. - 1864-063X .- 1864-0648. ; 2:3, s. 178-184
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Journal article (peer-reviewed)abstract
- Two forced detection (FD) variance reduction Monte Carlo algorithms for image simulations of tissue-embedded objects with matched refractive index are presented. The principle of the algorithms is to force a fraction of the photon weight to the detector at each and every scattering event. The fractional weight is given by the probability for the photon to reach the detector without further interactions. Two imaging setups are applied to a tissue model including blood vessels, where the ID algorithms produce identical results as traditional brute force simulations, while being accelerated with two orders of magnitude. Extending the methods to include refraction mismatches is discussed. The principle of forced detection; a part of the photon weight. based on the probability of reaching the detector without further interactions, is forced to the detector at each and every scattering event.
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12. |
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13. |
- Fredriksson, Ingemar, et al.
(author)
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Improved calibration procedure for laser Doppler perfusion monitors
- 2011
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In: Optical Diagnostics and SensingXI: Toward Point-of-CareDiagnostics; and Design andPerformance Validation ofPhantoms Used in Conjunctionwith Optical Measurement ofTissue III. - : SPIE - International Society for Optical Engineering. - 9780819484437 ; , s. 790602-1-790602-7
-
Conference paper (other academic/artistic)abstract
- Commercial laser Doppler perfusion monitors are calibrated using the perfusion value, i.e. the first order moment of the Doppler power spectrum, from a measurement in a standardized microsphere colloidal suspension under Brownian motion. The calibration perfusion value depends on several parameters of the suspension that are difficult to keep constant with adequate accuracy, such as the concentration, temperature and the microsphere size distribution. The calibration procedure itself may therefore introduce significant errors in the measured values.An altered calibration procedure, where the zero order moment is used is described and demonstrated in this paper. Since the above mentioned parameters only affect the frequency content of the Doppler power spectrum and not the total power, the zero order moment will be independent of those parameters. It is shown that the variation in the calibration value, as given by measurements on different scattering liquids with a wide range of scattering properties and temperatures, is only a few percent using the proposed method. For the conventional calibration procedure, this variation corresponds to an error introduced by merely a 1°C variation in the reference liquid temperature. The proposed calibration method also enables absolute level comparisons between measured and simulated Doppler power spectra.
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14. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry
- 2013
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In: Journal of Biomedical Optics. - Bellingham, WA, United States : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 18:12, s. 127004-1-127004-14
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Journal article (peer-reviewed)abstract
- The tissue fraction of red blood cells (RBCs) and their oxygenation and speed-resolved perfusion areestimated in absolute units by combining diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry(LDF). The DRS spectra (450 to 850 nm) are assessed at two source–detector separations (0.4 and 1.2 mm), allowingfor a relative calibration routine, whereas LDF spectra are assessed at 1.2mmin the same fiber-optic probe. Data areanalyzed using nonlinear optimization in an inverse Monte Carlo technique by applying an adaptive multilayeredtissue model based on geometrical, scattering, and absorbing properties, as well as RBC flow-speed information.Simulations of 250 tissue-like models including up to 2000 individual blood vessels were used to evaluatethe method. The absolute root mean square (RMS) deviation between estimated and true oxygenation was 4.1percentage units, whereas the relative RMS deviations for the RBC tissue fraction and perfusion were 19% and23%, respectively. Examples of in vivo measurements on forearm and foot during common provocations arepresented. The method offers several advantages such as simultaneous quantification of RBC tissue fractionand oxygenation and perfusion from the same, predictable, sampling volume. The perfusion estimate is speedresolved, absolute (% RBC × mm∕s), and more accurate due to the combination with DRS.
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15. |
- Fredriksson, Ingemar, et al.
(author)
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Inverse Monte Carlo method in a multilayered tissue model for diffuse reflectance spectroscopy
- 2012
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In: Journal of Biomedical Optics. - 1083-3668 .- 1560-2281. ; 17:4, s. 047004-
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Journal article (peer-reviewed)abstract
- Model based data analysis of diffuse reflectance spectroscopy data enables the estimation of optical and structural tissue parameters. The aim of this study was to present an inverse Monte Carlo method based on spectra from two source-detector distances (0.4 and 1.2 mm), using a multilayered tissue model. The tissue model variables include geometrical properties, light scattering properties, tissue chromophores such as melanin and hemoglobin, oxygen saturation and average vessel diameter. The method utilizes a small set of presimulated Monte Carlo data for combinations of different levels of epidermal thickness and tissue scattering. The path length distributions in the different layers are stored and the effect of the other parameters is added in the post-processing. The accuracy of the method was evaluated using Monte Carlo simulations of tissue-like models containing discrete blood vessels, evaluating blood tissue fraction and oxygenation. It was also compared to a homogeneous model. The multilayer model performed better than the homogeneous model and all tissue parameters significantly improved spectral fitting. Recorded in vivo spectra were fitted well at both distances, which we previously found was not possible with a homogeneous model. No absolute intensity calibration is needed and the algorithm is fast enough for real-time processing.
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16. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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Laser doppler flowmetry
- 2012
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In: Microcirculation imaging. - Weinheim : Wiley-VCH Verlagsgesellschaft. - 3527328947 - 9783527328949 - 9783527651238 ; , s. 67-86
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Book chapter (other academic/artistic)abstract
- Adopting a multidisciplinary approach with input from physicists, researchers and medical professionals, this is the first book to introduce many different technical approaches for the visualization of microcirculation, including laser Doppler and laser speckle, optical coherence tomography and photo-acoustic tomography. It covers everything from basic research to medical applications, providing the technical details while also outlining the respective strengths and weaknesses of each imaging technique. Edited by an international team of top experts, this is the ultimate handbook for every clinician and researcher relying on microcirculation imaging.
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17. |
- Fredriksson, Ingemar, et al.
(author)
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Machine learning for direct oxygen saturation and hemoglobin concentration assessment using diffuse reflectance spectroscopy
- 2020
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In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 25:11
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Journal article (peer-reviewed)abstract
- Significance: Diffuse reflectance spectroscopy (DRS) is frequently used to assess oxygen saturation and hemoglobin concentration in living tissue. Methods solving the inverse problem may include time-consuming nonlinear optimization or artificial neural networks (ANN) determining the absorption coefficient one wavelength at a time. Aim: To present an ANN-based method that directly outputs the oxygen saturation and the hemoglobin concentration using the shape of the measured spectra as input. Approach: A probe-based DRS setup with dual source-detector separations in the visible wavelength range was used. ANNs were trained on spectra generated from a three-layer tissue model with oxygen saturation and hemoglobin concentration as target. Results: Modeled evaluation data with realistic measurement noise showed an absolute root-mean-square (RMS) deviation of 5.1% units for oxygen saturation estimation. The relative RMS deviation for hemoglobin concentration was 13%. This accuracy is at least twice as good as our previous nonlinear optimization method. On blood-intralipid phantoms, the RMS deviation from the oxygen saturation derived from partial oxygen pressure measurements was 5.3% and 1.6% in two separate measurement series. Results during brachial occlusion showed expected patterns. Conclusions: The presented method, directly assessing oxygen saturation and hemoglobin concentration, is fast, accurate, and robust to noise. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
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18. |
- Fredriksson, Ingemar, et al.
(author)
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Machine learning in multiexposure laser speckle contrast imaging can replace conventional laser Doppler flowmetry
- 2019
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In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 24:1
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Journal article (peer-reviewed)abstract
- Laser speckle contrast imaging (LSCI) enables video rate imaging of blood flow. However, its relation to tissue blood perfusion is nonlinear and depends strongly on exposure time. By contrast, the perfusion estimate from the slower laser Doppler flowmetry (LDF) technique has a relationship to blood perfusion that is better understood. Multiexposure LSCI (MELSCI) enables a perfusion estimate closer to the actual perfusion than that using a single exposure time. We present and evaluate a method that utilizes contrasts from seven exposure times between 1 and 64 ms to calculate a perfusion estimate that resembles the perfusion estimate from LDF. The method is based on artificial neural networks (ANN) for fast and accurate processing of MELSCI contrasts to perfusion. The networks are trained using modeling of Doppler histograms and speckle contrasts from tissue models. The importance of accounting for noise is demonstrated. Results show that by using ANN, MELSCI data can be processed to LDF perfusion with high accuracy, with a correlation coefficient R = 1.000 for noise-free data, R = 0.993 when a moderate degree of noise is present, and R = 0.995 for in vivo data from an occlusion-release experiment. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
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19. |
- Fredriksson, Ingemar, et al.
(author)
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Measurement depth and volume in laser Doppler flowmetry
- 2009
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In: Microvascular Research. - : Elsevier BV. - 0026-2862 .- 1095-9319. ; 78:1, s. 4-13
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Journal article (peer-reviewed)abstract
- A new method for estimating the measurement depth and volume in laser Doppler flowmetry (LDF) is presented. The method is based on Monte Carlo simulations of light propagation in tissue. The contribution from each individual Doppler shift is calculated and thereby multiple Doppler shifts are handled correctly. Different LDF setups for both probe based (0.0, 0.25, 0.5, and 1.2 mm source-detector separation) and imaging systems (0.5 and 2.0 mm beam diameter) are considered, at the wavelengths 543 nm, 633 nm, and 780 nm. Non-linear speckle pattern effects are accounted for in the imaging system setups. The effects of tissue optical properties, blood concentration, and blood oxygen saturation are evaluated using both homogeneous tissue models and a layered skin model. The results show that the effect on the measurement depth of changing tissue properties is comparable to the effect of changing the system setup, e.g. source-detector separation and wavelength. Skin pigmentation was found to have a negligible effect on the measurement depth. Examples of measurement depths are (values are given for a probe based system with 0.25 mm source-detector separation and an imaging system with a 0.5 mm beam diameter, respectively, both operating at 780 nm): muscle - 0.55/0.79 mm; liver - 0.40/0.53 mm; gray matter - 0.48/0.68 mm; white matter - 0.20/0.20 mm; index finger pulp - 0.41/0.53 mm; forearm skin - 0.53/0.56 mm; heat provoked forearm skin - 0.66/0.67 mm.
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20. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetry
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Other publication (other academic/artistic)abstract
- The response to local heating (44oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume. A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.
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21. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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Model-based quantification of skin microcirculatory perfusion
- 2015. - 1
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In: Computational biophysics of the skin. - Boca Raton : CRC Press. - 9789814463843 - 9789814463850 ; , s. 395-418
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Book chapter (other academic/artistic)abstract
- During the last decades new tools, such as magnetic resonance imaging and Doppler ultra sound imaging, have rapidly been taken into clinical practice for studying the flow dynamics of the macrocirculation. M eanw hile, techniques for quantifying the microcirculation have struggled to become clinically accepted. This includes the use of laser Doppler flow metry (LDF), an optical technique that is capable of monitoring either spatial or temporal changes in the microcirculation by analyzing the backscattered Doppler shifted light from a laser illuminated tissue. Until now , LDF has only been capable of producing non-absolute relative measures, w hich has limited its cl inical acceptance. With a model based analysis approach, as presented here, this can be overcome, and objective diagnosis of the microcirculation may finally be a part of everyday clinical praxis. The most important advantages w ith the proposed method are that a quantitative perfusion estimate (% RBC × mm/ s) can be extracted, and that this measure can be resolved into different speed regions.
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22. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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Model-based quantitative laser Doppler flowmetry in skin
- 2010
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In: Journal of Biomedical Optics. - : Society of Photo-optical Instrumentation Engineers. - 1083-3668 .- 1560-2281. ; 15:5
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Journal article (peer-reviewed)abstract
- Laser Doppler Flowmetry (LDF) can be used for assessing the microcirculatory perfusion. However, conventional LDF (cLDF) gives only a relative perfusion estimate in an unknown measurement volume. To overcome these limitations a model-based analysis method for quantitative LDF (qLDF) is proposed. The method uses an inverse Monte Carlo technique with an adaptive three layer skin model. By analyzing the optimal model where measured and simulated LDF spectra using two different source-detector separations match, the absolute microcirculatory perfusion for a specified velocity region in a predefined volume is determined. The robustness of the qLDF method and how much it is affected by physiologically relevant variations in optical properties were evaluated using additional Monte Carlo simulations. When comparing qLDF to cLDF, a much smaller deviation from the true perfusion was attained. For physiologically relevant variations in the optical properties of static tissue and blood absorption, qLDF displayed errors <12%. Variations in the scattering properties of blood displayed larger errors (<58%). Evaluations on inhomogeneous models containing small blood vessels, hair and sweat glands displayed errors <5%. For extremely inhomogeneous models containing larger blood vessels, the error increased substantially, but this was detected by analyzing the qLDF model residual. The qLDF algorithm was applied to an in vivo local heat provocation. The perfusion increase was higher with qLDF than cLDF, due to non-linear effects in the latter. The qLDF showed that the perfusion increase was due to an increased amount of blood cells with a velocity > 1 mm/s.
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23. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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On the equivalence and differencesbetween laser Doppler flowmetry andlaser speckle contrast analysis
- 2016
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In: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 21:12
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Journal article (peer-reviewed)abstract
- Laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LASCA) both utilize the spatiotemporalproperties of laser speckle patterns to assess microcirculatory blood flow in tissue. Although the techniquesanalyze the speckle pattern differently, there is a close relationship between them. We present atheoretical overview describing how the LDF power spectrum and the LASCA contrast can be calculatedfrom each other, and how both these can be calculated from an optical Doppler spectrum containing variousdegrees of Doppler shifted light. The theoretical relationships are further demonstrated using time-resolvedspeckle simulations. A wide range of Monte Carlo simulated tissue models is then used to show how perfusionestimates for LDF and LASCA are affected by changes in blood concentration and speed distribution, as well asby geometrical and optical properties. We conclude that perfusion estimates from conventional single exposuretime LASCA are in general more sensitive to changes in optical and geometrical properties and are less accuratein the prediction of real perfusion changes, especially speed changes. Since there is a theoretical one-to-onerelationship between Doppler power spectrum and contrast, one can conclude that those drawbacks with theLASCA technique can be overcome using a multiple exposure time setup.
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24. |
- Fredriksson, Ingemar, et al.
(author)
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Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry
- 2008
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In: Journal of Biomedical Optics. - : SPIE-Intl Soc Optical Eng. - 1083-3668 .- 1560-2281. ; 13:1, s. 14015-
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Journal article (peer-reviewed)abstract
- An optical microvascular skin model, valid at 780 nm, was developed. The model consisted of six layers with individual optical properties, and variable thicknesses and blood concentrations at three different blood flow velocities. Monte Carlo simulations were used to evaluate the impact of various model parameters on the traditional Laser Doppler flowmetry (LDF) measures. A set of reference Doppler power spectra was generated by simulating 7,000 configurations, varying the thickness and blood concentrations. Simulated spectra, at two different source detector separations, were compared with in vivo recorded spectra, using a non-linear search algorithm for minimizing the deviation between simulated and measured spectra. The model was validated by inspecting the thickness and blood concentrations which generated the best fit. These four parameters followed a priori expectations for the measurement situations, and the simulated spectra agreed well with the measured spectra for both detector separations. Average estimated dermal blood concentration was 0.08% at rest and 0.63% during heat provocation (44°C) on the volar side of the forearm, and 1.2% at rest on the finger pulp. The model is crucial for developing a technique for velocity-resolved absolute LDF measurements with known sampling volume, and can also be useful for other bio-optical modalities.
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25. |
- Fredriksson, Ingemar, 1980-
(author)
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Quantitative Laser Doppler Flowmetry
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Laser Doppler flowmetry (LDF) is virtually the only non-invasive technique, except for other laser speckle based techniques, that enables estimation of the microcirculatory blood flow. The technique was introduced into the field of biomedical engineering in the 1970s, and a rapid evolvement followed during the 1980s with fiber based systems and improved signal analysis. The first imaging systems were presented in the beginning of the 1990s.Conventional LDF, although unique in many aspects and elegant as a method, is accompanied by a number of limitations that may have reduced the clinical impact of the technique. The analysis model published by Bonner and Nossal in 1981, which is the basis for conventional LDF, is limited to measurements given in arbitrary and relative units, unknown and non-constant measurement volume, non-linearities at increased blood tissue fractions, and a relative average velocity estimate.In this thesis a new LDF analysis method, quantitative LDF, is presented. The method is based on recent models for light-tissue interaction, comprising the current knowledge of tissue structure and optical properties, making it fundamentally different from the Bonner and Nossal model. Furthermore and most importantly, the method eliminates or highly reduces the limitations mentioned above.Central to quantitative LDF is Monte Carlo (MC) simulations of light transport in tissue models, including multiple Doppler shifts by red blood cells (RBC). MC was used in the first proof-of-concept study where the principles of the quantitative LDF were tested using plastic flow phantoms. An optically and physiologically relevant skin model suitable for MC was then developed. MC simulations of that model as well as of homogeneous tissue relevant models were used to evaluate the measurement depth and volume of conventional LDF systems. Moreover, a variance reduction technique enabling the reduction of simulation times in orders of magnitudes for imaging based MC setups was presented.The principle of the quantitative LDF method is to solve the reverse engineering problem of matching measured and calculated Doppler power spectra at two different source-detector separations. The forward problem of calculating the Doppler power spectra from a model is solved by mixing optical Doppler spectra, based on the scattering phase functions and the velocity distribution of the RBC, from various layers in the model and for various amounts of Doppler shifts. The Doppler shift distribution is calculated based on the scattering coefficient of the RBC:s and the path length distribution of the photons in the model, where the latter is given from a few basal MC simulations.When a proper spectral matching is found, via iterative model parameters updates, the absolute measurement data are given directly from the model. The concentration is given in g RBC/100 g tissue, velocities in mm/s, and perfusion in g RBC/100 g tissue × mm/s. The RBC perfusion is separated into three velocity regions, below 1 mm/s, between 1 and 10 mm/s, and above 10 mm/s. Furthermore, the measures are given for a constant output volume of a 3 mm3 half sphere, i.e. within 1.13 mm from the light emitting fiber of the measurement probe.The quantitative LDF method was used in a study on microcirculatory changes in type 2 diabetes. It was concluded that the perfusion response to a local increase in skin temperature, a response that is reduced in diabetes, is a process involving only intermediate and high flow velocities and thus relatively large vessels in the microcirculation. The increased flow in higher velocities was expected, but could not previously be demonstrated with conventional LDF. The lack of increase in low velocity flow indicates a normal metabolic demand during heating. Furthermore, a correlation between the perfusion at low and intermediate flow velocities and diabetes duration was found. Interestingly, these correlations were opposites (negative for the low velocity region and positive for the mediate velocity region). This finding is well in line with the increased shunt flow and reduced nutritive capillary flow that has previously been observed in diabetes.
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26. |
- Fredriksson, Ingemar, et al.
(author)
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Reduced Arteriovenous Shunting Capacity After Local Heating and Redistribution of Baseline Skin Blood Flow in Type 2 Diabetes Assessed With Velocity-Resolved Quantitative Laser Doppler Flowmetry
- 2010
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In: Diabetes. - : American Diabetes Association Inc / American Diabetes Association; 1999. - 0012-1797 .- 1939-327X. ; 59:7, s. 1578-1584
-
Journal article (peer-reviewed)abstract
- OBJECTIVE-To compare the microcirculatory velocity distribution in type 2 diabetic patients and nondiabetic control subjects at baseline and after local heating. RESEARCH DESIGN AND METHODS-The skin blood flow response to local heating (44 degrees C for 20 mm) was assessed in 28 diabetic patients and 29 control subjects using a new velocity-resolved quantitative laser Doppler flowmetry technique (qLDF). The qLDF estimates erythrocyte (RBC) perfusion (velocity X concentration), in a physiologically relevant unit (grams RBC per 100 g tissue X millimeters per second) in a fixed output volume, separated into three velocity regions: v less than1 mm/s, v 1-10 mm/s, and v greater than10 mm/s. RESULTS-The increased blood flow occurs in vessels with a velocity greater than1 mm/s. A significantly lower response in qLDF total perfusion was found in diabetic patients than in control subjects after heat provocation because of less high-velocity blood flow (v greater than10 mm/s). The RBC concentration in diabetic patients increased sevenfold for v between 1 and 10 mm/s, and 15-fold for v greater than10 mm/s, whereas no significant increase was found for v less than1 mm/s. The mean velocity increased from 0.94 to 7.3 mm/s in diabetic patients and from 0.83 to 9.7 mm/s in control subjects. CONCLUSIONS-The perfusion increase occurs in larger shunting vessels and not as an increase in capillary flow. Baseline diabetic patient data indicated a redistribution of flow to higher velocity regions, associated with longer duration of diabetes. A lower perfusion was associated with a higher BMI and a lower toe-to-brachial systolic blood pressure ratio.
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27. |
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28. |
- Fredriksson, Ingemar, 1980-, et al.
(author)
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Vasomotion analysis of speed resolved perfusion, oxygen saturation, red blood cell tissue fraction, and vessel diameter : Novel microvascular perspectives
- 2022
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In: Skin research and technology. - : Wiley-Blackwell Publishing Inc.. - 0909-752X .- 1600-0846. ; 28:1, s. 142-152
-
Journal article (peer-reviewed)abstract
- BackgroundVasomotion is the spontaneous oscillation in vascular tone in the microcirculation and is believed to be a physiological mechanism facilitating the transport of blood gases and nutrients to and from tissues. So far, Laser Doppler flowmetry has constituted the gold standard for in vivo vasomotion analysis.Materials and methodsWe applied vasomotion analysis to speed-resolved perfusion, oxygen saturation, red blood cell tissue (RBC) tissue fraction, and average vessel diameter from five healthy individuals at rest measured by the newly developed Periflux 6000 EPOS system over 10 minutes. Magnitude scalogram and the time-averaged wavelet spectra were divided into frequency intervals reflecting endothelial, neurogenic, myogenic, respiratory, and cardiac function.ResultsRecurrent high-intensity periods of the myogenic, neurogenic, and endothelial frequency intervals were found. The neurogenic activity was considerably more pronounced for the oxygen saturation, RBC tissue fraction, and vessel diameter signals, than for the perfusion signals. In a correlation analysis we found that changes in perfusion in the myogenic, neurogenic, and endothelial frequency intervals precede changes in the other signals. Furthermore, changes in average vessel diameter were in general negatively correlated to the other signals in the same frequency intervals, indicating the importance of capillary recruitment.ConclusionWe conclude that vasomotion can be observed in signals reflecting speed resolved perfusion, oxygen saturation, RBC tissue fraction, and vessel diameter. The new parameters enable new aspects of the microcirculation to be observed.
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29. |
- Fredriksson, Ingemar, et al.
(author)
-
Vessel packaging effect in laser speckle contrast imaging and laser Doppler imaging
- 2017
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In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 22:10
-
Journal article (peer-reviewed)abstract
- Laser speckle-based techniques are frequently used to assess microcirculatory blood flow. Perfusion estimates are calculated either by analyzing the speckle fluctuations over time as in laser Doppler flowmetry (LDF), or by analyzing the speckle contrast as in laser speckle contrast imaging (LSCI). The perfusion estimates depend on the amount of blood and its speed distribution. However, the perfusion estimates are commonly given in arbitrary units as they are nonlinear and depend on the magnitude and the spatial distribution of the optical properties in the tissue under investigation. We describe how the spatial confinement of blood to vessels, called the vessel packaging effect, can be modeled in LDF and LSCI, which affect the Doppler power spectra and speckle contrast, and the underlying bio-optical mechanisms for these effects. As an example, the perfusion estimate is reduced by 25% for LDF and often more than 50% for LSCI when blood is located in vessels with an average diameter of 40 aem, instead of being homogeneously distributed within the tissue. This significant effect can be compensated for only with knowledge of the average diameter of the vessels in the tissue. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.
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30. |
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31. |
- Fredriksson, Jakob, 1973, et al.
(author)
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Numerical Investigation of a Loop-Scavenged Two-Stroke Free Piston Engine
- 2006
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In: JSAE Annual Spring Congress.
-
Conference paper (peer-reviewed)abstract
- In this study, the KIVA-3V CFD code was used to investigate the effect of ports and port angles on the scavenging behaviour of a loop-scavenged free piston engine. A dynamic SIMULINK model that takes into account all forces acting on the piston was used in order to obtain the piston motion. Detailed chemistry combustion simulations using a 3-D sector mesh have been performed for combustion validation purposes. It is shown that low emissions of soot and NOx combined with a decent combustion efficiency are attainable. The scavenging process for different port layouts and port timings has been investigated using the same CFD code, indicating reasonable scavenging characteristics, but these can be further improved.
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32. |
- Fredriksson, Jakob, 1973, et al.
(author)
-
Simulation of a Two-Stroke Free Piston Energy Converter
- 2003
-
In: Joint Meeting of the Scandinavian-Nordic and Italian Section of the Combustion Institute.
-
Conference paper (other academic/artistic)abstract
- In a free piston engine, the piston motion is not prescribed by a crank mechanism, but is the result of the equilibrium of forces acting on the piston. The linear motion of the pistons is directly converted to electricity in an alternator and a compact energy converter is the result.The lack of a crank mechanism gives means to easily vary the compression ratio, and it is possible to run the engine on a multitude of fuels in HCCI combustion mode.In this paper the effect of different fuels on the performance of the free piston engine has been studied. It is shown that both efficiency and power increase, but not dramatically, with higher octane rating.
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33. |
- Fredriksson, Jakob, 1973, et al.
(author)
-
Simulation of a Two-Stroke Free Piston Engine
- 2004
-
In: SAE 2004 Spring Fuels & Lubricants Conference in Toulouse. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0768013194
-
Conference paper (peer-reviewed)abstract
- The free piston internal combustion engine used inconjunction with a linear alternator offers an interestingchoice for use in hybrid vehicles. The linear motion ofthe pistons is directly converted to electricity by thealternator, and the result is a compact and efficientenergy converter that has only one moving part. Themovement of the pistons is not prescribed by a crankmechanism, but is the result of the equilibrium of forcesacting on the pistons, and the engine will act like amass-spring system. This feature is one of the mostprominent advantages of the FPE (Free Piston Engine),as the lack of mechanical linkage gives means ofvarying the compression ratio in simple manners,without changing the hardware of the engine. By varyingthe compression ratio, it is also it possible to run on amultitude of different fuels and to use HCCI(Homogeneous Charge Compression Ignition)combustion. Furthermore, the reduction of the number ofmoving parts will decrease engine friction and thusincrease efficiency.In this paper, BOOST and SENKIN have been used toinvestigate engine performance for different fuels. Adynamic model of the complete free piston engine wascreated that predicts the piston motion and frequency.The gas exchange was simulated with the commercial 1-D code BOOST, which solves the gas dynamicequations. The high-pressure cycle of the commercial 1-D code BOOST was replaced by detailed chemistrycalculations in the SENKIN code. For combustionreduced mechanisms of Diesel (n-heptane and toluene),gasoline (iso-octane, toluene and n-heptane), naturalgas (methane, ethane, propane and n-butane) andhydrogen have been used. All mechanisms consisted ofabout 60-100 species. The results show that adecreased cetane number requires higher compressionratios in order to position the ignition properly. Thehigher compression ratios give an increase in enginespeed, power and efficiency.
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34. |
- Hultman, Martin, et al.
(author)
-
A 15.6 frames per second 1 megapixel Multiple Exposure Laser Speckle Contrast Imaging setup
- 2018
-
In: Journal of Biophotonics. - : Wiley-VCH Verlagsgesellschaft. - 1864-063X .- 1864-0648. ; 11:2
-
Journal article (peer-reviewed)abstract
- A multiple exposure laser speckle contrast imaging (MELSCI) setup for visualizing blood perfusion was developed using a field programmable gate array (FPGA), connected to a 1000 frames per second (fps) 1-megapixel camera sensor. Multiple exposure time images at 1, 2, 4, 8, 16, 32 and 64 milliseconds were calculated by cumulative summation of 64 consecutive snapshot images. The local contrast was calculated for all exposure times using regions of 4 × 4 pixels. Averaging of multiple contrast images from the 64-millisecond acquisition was done to improve the signal-to-noise ratio. The results show that with an effective implementation of the algorithm on an FPGA, contrast images at all exposure times can be calculated in only 28 milliseconds. The algorithm was applied to data recorded during a 5 minutes finger occlusion. Expected contrast changes were found during occlusion and the following hyperemia in the occluded finger, while unprovoked fingers showed constant contrast during the experiment. The developed setup is capable of massive data processing on an FPGA that enables processing of MELSCI data in 15.6 fps (1000/64 milliseconds). It also leads to improved frame rates, enhanced image quality and enables the calculation of improved microcirculatory perfusion estimates compared to single exposure time systems.
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35. |
- Hultman, Martin, 1992-, et al.
(author)
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Comprehensive imaging of microcirculatory changes in the foot during endovascular intervention - A technical feasibility study
- 2022
-
In: Microvascular Research. - Maryland Heights, MO, United States : Academic Press. - 0026-2862 .- 1095-9319. ; 141
-
Journal article (peer-reviewed)abstract
- Chronic limb-threatening ischemia (CLTI) has a major impact on patient's lives and is associated with a heavy health care burden with high morbidity and mortality. Treatment by endovascular intervention is mostly based on macrocirculatory information from angiography and does not consider the microcirculation. Despite successful endovascular intervention according to angiographic criteria, a proportion of patients fail to heal ischemic lesions. This might be due to impaired microvascular perfusion and variations in the supply to different angiosomes. Non-invasive optical techniques for microcirculatory perfusion and oxygen saturation imaging have the potential to provide the interventionist with additional information in real-time, supporting clinical decisions during the intervention. This study presents a novel multimodal imaging system, based on multi-exposure laser speckle contrast imaging and multi-spectral imaging, for continuous use during endovascular intervention. The results during intervention display spatiotemporal changes in the microcirculation compatible with expected physiological reactions during balloon dilation, with initially induced ischemia followed by a restored perfusion, and local administration of a vasodilator inducing hyperemia. We also present perioperative and postoperative follow-up measurements with a pulsatile microcirculation perfusion. Finally, cases of spatial heterogeneity in the observed oxygen saturation and perfusion are discussed. In conclusion, this technical feasibility study shows the potential of the methodology to characterize changes in microcirculation before, during, and after endovascular intervention.
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36. |
- Hultman, Martin, 1992-, et al.
(author)
-
Evaluation of a high framerate multi-exposure laser speckle contrast imaging setup
- 2018
-
In: High-Speed Biomedical Imaging and Spectroscopy III. - : SPIE - International Society for Optical Engineering. - 9781510614963
-
Conference paper (peer-reviewed)abstract
- We present a first evaluation of a new multi-exposure laser speckle contrast imaging (MELSCI) system for assessing spatial variations in the microcirculatory perfusion. The MELSCI system is based on a 1000 frames per second 1-megapixel camera connected to a field programmable gate arrays (FPGA) capable of producing MELSCI data in realtime. The imaging system is evaluated against a single point laser Doppler flowmetry (LDF) system during occlusionrelease provocations of the arm in five subjects. Perfusion is calculated from MELSCI data using current state-of-the-art inverse models. The analysis displayed a good agreement between measured and modeled data, with an average error below 6%. This strongly indicates that the applied model is capable of accurately describing the MELSCI data and that the acquired data is of high quality. Comparing readings from the occlusion-release provocation showed that the MELSCI perfusion was significantly correlated (R=0.83) to the single point LDF perfusion, clearly outperforming perfusion estimations based on a single exposure time. We conclude that the MELSCI system provides blood flow images of enhanced quality, taking us one step closer to a system that accurately can monitor dynamic changes in skin perfusion over a large area in real-time
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37. |
- Hultman, Martin, et al.
(author)
-
Flowmotion imaging analysis of spatiotemporal variations in skin microcirculatory perfusion
- 2023
-
In: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 146
-
Journal article (peer-reviewed)abstract
- Background: Flowmotion is the rhythmical variations in measured skin blood flow that arise due to global and local regulation of the vessels and can be studied using frequency analysis of time-resolved blood flow signals. It has the potential to reveal clinically useful information about microvascular diseases, but the spatial heteroge-neous nature of the microvasculature makes interpretation difficult. However, recent technological advances in multi-exposure laser speckle contrast imaging (MELSCI) enable new possibilities for simultaneously studying spatial and temporal variations in flowmotion.Aim: To develop a method for flowmotion analysis of MELSCI perfusion images. Furthermore, to investigate the spatial and temporal variations in flowmotion in forearm baseline skin perfusion.Method: In four healthy subjects, forearm skin perfusion was imaged at 15.6 fps for 10 min in baseline. The time -trace signal in each pixel was analyzed using the wavelet transform and summarized in five physiologically relevant frequency intervals, resulting in images of flowmotion. Furthermore, a method for reducing the effect of motion artifacts in the flowmotion analysis was developed.Results: The flowmotion images displayed patterns of high spatial heterogeneity that differed between the fre-quency intervals. The spatial variations in flowmotion, quantified as the coefficient of variation, was between 11 % and 31 % in four subjects. Furthermore, significant temporal variations in flowmotion were also observed, indicating the importance of a spatiotemporal analysis.Conclusion: The new imaging technique reveals significant spatial differences in flowmotion that cannot be ob-tained with single-point measurements. The results indicate that global statistics of flowmotion, such as the mean value in a large region of interest, is more representative of the microcirculation than data measured only in a single point. Therefore, imaging techniques have potential to increase the clinical usefulness of flowmotion analysis.
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38. |
- Hultman, Martin, 1992-
(author)
-
Real-time multi-exposure laser speckle contrast imaging of skin microcirculatory perfusion
- 2021
-
Doctoral thesis (other academic/artistic)abstract
- The microcirculation, the blood flow in the smallest blood vessels in the body, has a vital function as this is where oxygen and nutrients diffuses from the blood to to the surrounding cells. An important quantity is the tissue perfusion, a measure of the microcirculation’s capacity to provide oxygen and nutrients to the cells. Laser speckle contrast imaging (LSCI) is a non-invasive optical technique that captures images of the microcirculatory perfusion by analysing the local contrast in the laser speckle pattern that forms when tissue is illuminated by a laser. LSCI has seen extensive use in clinical research due to the easy and cheap measurement setup, and high spatial and temporal resolution. Despite this, clinical acceptance and routine use remains low. Some of the drawbacks of the technique is a limitation to relative measurements in arbitrary units, as well as high susceptibility to measurement noise and confounding properties of the tissue. This makes comparisons difficult, especially between patients. An extension of LSCI called multi-exposure laser speckle contrast imaging (MELSCI) was proposed to deal with some of these issues, although the more complicated data acquisition and models prevented real-time use. MELSCI has in-stead been used exclusively as an offline technique where data is post-processed, and the clinical use has been non-existent. Furthermore, existing models for LSCI and MELSCI are designed for tissues where individual vessels are visible, such as the surface of the brain or on the retina. For measurements in the diffuse regime, such as on skin tissue, these models are no longer physiologically accurate, resulting in incorrect perfusion estimates.This thesis presents a MELSCI-based perfusion imaging instrument that is simultaneously fast and physiologically accurate for measurements of skin. There are three main parts to this work; development of a real-time MELSCI system, development of perfusion models for skin, and demonstration of the system in a clinical feasibility study.A real-time MELSCI instrument was developed based on a high-speed CMOS camera tightly integrated with algorithms in a field programmable gate array (FPGA). The algorithm was based on synthetic multi-exposure, where a set of 64 individual 1-ms images were digitally added to create multi-exposure images at 1, 2, 4, 8, 16, 32, and 64 ms. The resulting multi-exposure data was demonstrated to have high quality and less susceptibility to measurement noise than previous models. The instrument enabled continuous acquisition and analysis of MELSCI data in real-time at 15.6 frames per second, sufficiently fast to capture the temporal dynamics of the skin perfusion.To enable real-time estimation of accurate and physiologically relevant perfusion from the MELSCI data, two artificial neural networks were trained on synthetic data from a mathematical model of skin. The first estimated perfusion as computed by conventional laser Doppler flowmetry (LDF), demonstrating a high correlation between the two methods. The second estimated true perfusion in absolute units %RBC × mm/s separated into three distinct speed components, 0-1 mm/s, 1-10 mm/s and >10 mm/s. The ANNs removed the need for iterative optimization algorithms, resulting in more than 1000x speed-up over previous methods, and enabled real-time use in an imaging setting.The instrument was demonstrated in controlled experiments on healthy volunteers, using standardized occlusion-release provocations, and in a clinical feasibility study where the foot perfusion was monitored during endovascular interventions in patients with chronic limb-threatening ischemia. The instrument enabled continuous imaging of perfusion, with sufficiently high framerate to capture the pulsatile dynamics, or lack thereof, at each point in time. The necessity for both high spatial and temporal resolution to properly asses the microcirculation was demonstrated.The advancements to MELSCI proposed in this thesis has the potential to improve the clinical viability of the technique, increase interpretability of the results, and might lead to improved treatments based on a better understanding of the complex processes in the microcirculation.
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39. |
- Hultman, Martin, et al.
(author)
-
Real-time video-rate perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning
- 2020
-
In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 25:11
-
Journal article (peer-reviewed)abstract
- Significance: Multi-exposure laser speckle contrast imaging (MELSCI) estimates microcirculatory blood perfusion more accurately than single-exposure LSCI. However, the technique has been hampered by technical limitations due to massive data throughput requirements and nonlinear inverse search algorithms, limiting it to an offline technique where data must be postprocessed. Aim: To present an MELSCI system capable of continuous acquisition and processing of MELSCI data, enabling real-time video-rate perfusion imaging with high accuracy. Approach: The MELSCI algorithm was implemented in programmable hardware (field programmable gate array) closely interfaced to a high-speed CMOS sensor for real-time calculation. Perfusion images were estimated in real-time from the MELSCI data using an artificial neural network trained on simulated data. The MELSCI perfusion was compared to two existing single-exposure metrics both quantitatively in a controlled phantom experiment and qualitatively in vivo. Results: The MELSCI perfusion shows higher signal dynamics compared to both single-exposure metrics, both spatially and temporally where heartbeat-related variations are resolved in much greater detail. The MELSCI perfusion is less susceptible to measurement noise and is more linear with respect to laser Doppler perfusion in the phantom experiment (R-2 = 0.992). Conclusions: The presented MELSCI system allows for real-time acquisition and calculation of high-quality perfusion at 15.6 frames per second. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.
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40. |
- Hultman, Martin, et al.
(author)
-
Robust analysis of microcirculatory flowmotion during post-occlusive reactive hyperemia
- 2024
-
In: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 155
-
Journal article (peer-reviewed)abstract
- Background: Flowmotion analysis of the microcirculatory blood flow is a method to extract information about the vessel regulatory function. It has previously shown promise when applied to measurements during a postocclusive reactive hyperemia. However, the reperfusion peak and the following monotonic decline introduces false low frequencies that should not be interpreted as rhythmic vasomotion effect. Aim: To develop and validate a robust method for flowmotion analysis of post-occlusive reactive hyperemia signals. Method: The occlusion-induced reperfusion response contains a typical rapid increase followed by a monotonic decline to baseline. A mathematical model is proposed to detrend this transient part of the signal to enable further flowmotion analysis. The model is validated in 96 measurements on healthy volunteers. Results: Applying the proposed model corrects the flowmotion signal without adding any substantial new false flowmotion components. Conclusion: Future studies should use the proposed method or equivalent when analyzing flowmotion during post-occlusive reactive hyperemia to ensure valid results.
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41. |
- Hultman, Martin, et al.
(author)
-
Speed-resolved perfusion imaging using multi-exposure laser speckle contrast imaging and machine learning
- 2023
-
In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 28:3
-
Journal article (peer-reviewed)abstract
- Significance: Laser speckle contrast imaging (LSCI) gives a relative measure of microcirculatory perfusion. However, due to the limited information in single-exposure LSCI, models are inaccurate for skin tissue due to complex effects from e.g. static and dynamic scatterers, multiple Doppler shifts, and the speed-distribution of blood. It has been demonstrated how to account for these effects in laser Doppler flowmetry (LDF) using inverseMonte Carlo (MC) algorithms. This allows for a speed-resolved perfusion measure in absolute units %RBC x mm/s, improving the physiological interpretation of the data. Until now, this has been limited to a single-point LDF technique but recent advances inmulti-exposure LSCI (MELSCI) enable the analysis in an imaging modality. Aim: To present a method for speed-resolved perfusion imaging in absolute units %RBC x mm/s, computed from multi-exposure speckle contrast images. Approach: An artificial neural network (ANN) was trained on a large simulated dataset of multi- exposure contrast values and corresponding speed-resolved perfusion. The dataset was generated using MC simulations of photon transport in randomized skin models covering a wide range of physiologically relevant geometrical and optical tissue properties. The ANN was evaluated on in vivo data sets captured during an occlusion provocation. Results: Speed-resolved perfusion was estimated in the three speed intervals 0 to 1 mm/s, 1 to 10 mm/s, and > 10 mm/s, with relative errors 9.8%, 12%, and 19%, respectively. The perfusion had a linear response to changes in both blood tissue fraction and blood flow speed and was less affected by tissue properties compared with single-exposure LSCI. The image quality was subjectively higher compared with LSCI, revealing previously unseen macro- and microvascular structures. Conclusions: The ANN, trained on modeled data, calculates speed-resolved perfusion in absolute units from multi-exposure speckle contrast. This method facilitates the physiological interpretation of measurements using MELSCI and may increase the clinical impact of the technique. (c) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.
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42. |
- Johansson, Johannes D., 1977-, et al.
(author)
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Simulation of reflected light intensity changes during navigation and radio frequency lesioning in the brain
- 2009
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In: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 14:044040
-
Journal article (peer-reviewed)abstract
- An electrode with adjacent optical fibers for measurements during navigation and radio frequency lesioning in the brain was modeled for Monte Carlo simulations of light transport in brain tissue. Relative reflected light intensity at 780 nm, I780, from this electrode and probes with identical fiber configuration were simulated using the intensity from native white matter as reference. Models were made of homogeneousnative and coagulated gray, thalamus, and white matter as well as blood. Dual layermodels, including models with a layer of cerebrospinal fluid between the fibers andthe brain tissue, were also made. Simulated I780 was 0.16 for gray matter, 0.67 forcoagulate gray matter, 0.36 for thalamus, 0.39 for coagulated thalamus, unity forwhite matter, 0.70 for coagulated white matter and 0.24 for blood. Thalamic matterhas also been found to reflect more light than gray matter and less than white matterin clinical studies. In conclusion the reflected light intensity can be used todifferentiate between gray and white matter during navigation. Furthermore,coagulation of light gray tissue, such as the thalamus, might be difficult to detectusing I780, but coagulation in darker gray tissue should result in a rapid increase of I780.
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44. |
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45. |
- Jonasson, Hanna, et al.
(author)
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Absorption and reduced scattering coefficients in epidermis and dermis from a Swedish cohort study
- 2023
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In: Journal of Biomedical Optics. - : SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS. - 1083-3668 .- 1560-2281. ; 28:11
-
Journal article (peer-reviewed)abstract
- Significance Knowledge of optical properties is important to accurately model light propagation in tissue, but in vivo reference data are sparse.Aim The aim of our study was to present in vivo skin optical properties from a large Swedish cohort including 3809 subjects using a three-layered skin model and spatially resolved diffuse reflectance spectroscopy (Periflux PF6000 EPOS).Approach Diffuse reflectance spectra (475 to 850 nm) at 0.4 and 1.2 mm source-detector separations were analyzed using an inverse Monte Carlo method. The model had one epidermis layer with variable thicknesses and melanin-related absorptions and two dermis layers with varying hemoglobin concentrations and equal oxygen saturations. The reduced scattering coefficient was equal across all layers.Results Median absorption coefficients (mm (- 1)) in the upper dermis ranged from 0.094 at 475 nm to 0.0048 at 850 nm and similarly in the lower dermis from 0.059 to 0.0035. The reduced scattering coefficient (mm( - 1)) ranged from 3.22 to 1.20, and the sampling depth (mm) ranged from 0.23 to 0.38 (0.4 mm separation) and from 0.49 to 0.68 (1.2 mm separation). There were differences in optical properties across sex, age groups, and BMI categories.Conclusions Reference material for skin optical properties is presented.
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46. |
- Jonasson, Hanna, et al.
(author)
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Assessment of the microcirculation using combined model based diffuse reflectance spectroscopy and laser Doppler flowmetry
- 2015
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In: 16th Nordic-Baltic Conference on Biomedical Engineering. - Cham : Springer. - 9783319129662 - 9783319129679 ; , s. 52-54
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Conference paper (peer-reviewed)abstract
- By using a combined inverse model for diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) the tissue fraction of red blood cells (RBCs), their oxygenation and speed-resolved perfusion are estimated in absolute units. DRS spectra (450 to 850 nm) are measured at two source-detector distances; 0.4 and 1.2 mm. LDF spectra are measured at 1.2 mm, integrated in the same fiber-optic probe. Inverse Monte Carlo technique and an adaptive tissue model is used to quantify the microcirculatory parameters. Measurements were done during venous occlusion of the tissue. The model fitting yields a good spectral fit for the two DRS spectra and the LDF spectrum. The physiological responses regarding for example which speed regions respond to provocations follows a priori expectations. The combined model gives quantitative measures of RBC tissue fraction, oxygenation and speed resolved perfusion from the same sampling volume which gives new opportunities to interpret data.
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47. |
- Jonasson, Hanna, 1981-, et al.
(author)
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In vivo characterization of light scattering properties of human skin in the 475- to 850-nm wavelength range in a Swedish cohort
- 2018
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In: Journal of Biomedical Optics. - : SPIE - International Society for Optical Engineering. - 1083-3668 .- 1560-2281. ; 23:12
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Journal article (peer-reviewed)abstract
- We have determined in vivo optical scattering properties of normal human skin in 1734 subjects, mostly with fair skin type, within the Swedish CArdioPulmonary bioImage Study. The measurements were performed with a noninvasive system, integrating spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical, and absorbing properties of the tissue. The reduced scattering coefficient was found to decrease from 3.16 ± 0.72 to 1.13 ± 0.27 mm-1 (mean ± SD) in the 475- to 850-nm wavelength range. There was a negative correlation between the reduced scattering coefficient and age, and a significant difference between men and women in the reduced scattering coefficient as well as in the fraction of small scattering particles. This large study on tissue scattering with mean values and normal variation can serve as a reference when designing diagnostic techniques or when evaluating the effect of therapeutic optical systems.
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48. |
- Jonasson, Hanna, et al.
(author)
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Normative data and the influence of age and sex on microcirculatory function in a middle-aged cohort: results from the SCAPIS study
- 2020
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In: American Journal of Physiology. Heart and Circulatory Physiology. - : AMER PHYSIOLOGICAL SOC. - 0363-6135 .- 1522-1539. ; 318:4, s. H908-H915
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Journal article (peer-reviewed)abstract
- The objective of this study was to assess normative values for comprehensive forearm skin microcirculatory function: oxygen saturation, tissue fraction of red blood cells (RBCs), and speed-resolved perfusion. Furthermore, to examine the influence of age and sex on microcirculatory function. Measurements were performed using a noninvasive probe-based system, including diffuse reflectance spectroscopy and laser-Doppler flowmetry, yielding output data in absolute units. The study was conducted within the Swedish CArdioPulmonary BioImage Study (SCAPIS) and included 1,765 men and women aged 50-65 yr from the Linkoping general population. Normative values are given at baseline, at the end of a 5-min occlusion of the brachial artery and during hyperemia after occlusion release. We found a consistent age distribution, in which the oldest individuals had the lowest peak oxygen saturation (P < 0.001) and the highest baseline low-speed perfusion (P < 0.001). Women had higher peak oxygen saturation (P < 0.001), lower RBC tissue fraction, in general (P < 0.001), lower baseline perfusion in all speed regions (P = 0.01). and lower peak high-speed perfusion at hyperemia (P < 0.001). The normative data can be used as reference values in future studies of disease-specific populations. The results show that age and sex are important aspects to consider in studies of microvascular function. Women and younger age were factors associated with higher peak oxygen saturation after ischemia. This is a novel parameter that reflects overall microcirculatory function associated with vascular dilation capacity. NEW & NOTEWORTHY This study expands experimental microcirculatory research to clinical use by providing normative values on microcirculatory function in a large population-based cohort. Women and younger age were factors associated with higher peak oxygen saturation after ischemia, which implies that age and sex are important aspects to consider in studies of micmvascular function. This study is the first step toward using microcirculatory assessment as a tool to improve diagnosis. prognosis. and treatment in disease-specific populations.
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49. |
- Jonasson, Hanna, et al.
(author)
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Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment
- 2015
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In: Microvascular Research. - : Academic Press. - 0026-2862 .- 1095-9319. ; 102, s. 70-77
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Journal article (peer-reviewed)abstract
- We have developed a new fiber-optic system that combines diffuse reflectance spectroscopy (DRS) and laser Doppler Flowmetry (LDF) for a multi-modal assessment of the microcirculation. Quantitative data is achieved with an inverse Monte Carlo algorithm based on an individually adaptive skin model. The output parameters are calculated from the model and given in absolute units: hemoglobin oxygen saturation (%), red blood cell (RBC) tissue fraction (%), and the speed resolved RBC perfusion separated into three speed regions; 0–1 mm/s, 1–10 mm/s and above 10 mm/s (% mm/s). The aim was to explore microcirculatory parameters using the new optical method, integrating DRS and LDF in a joint skin model, during local heating of the dorsal foot and venous and arterial occlusion of the forearm in 23 healthy subjects (age 20–28 years). There were differences in the three speed regions in regard to blood flow changes due to local heating, where perfusion for high speeds increased the most. There was also a high correlation between changes in oxygenation and changes in perfusion for higher speeds. Oxygen saturation at baseline was 44% on foot, increasing to 83% at plateau after heating. The larger increase in perfusion for higher speeds than for lower speeds together with the oxygenation increase during thermal provocation, shows a local thermoregulatory blood flow in presumably arteriolar dermal vessels. In conclusion, there are improved possibilities to assess microcirculation using integrated DRS and LDF in a joint skin model by enabling both oxygenation and speed resolved blood flow assessment simultaneously and in the same skin site. Output parameters in absolute units may also yield new insights about the microcirculatory system.
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50. |
- Jonasson, Hanna, et al.
(author)
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Post-ischemic skin peak oxygen saturation is associated with cardiovascular risk factors: a Swedish cohort study
- 2022
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In: Microvascular Research. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0026-2862 .- 1095-9319. ; 140
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Journal article (peer-reviewed)abstract
- The objective of this study was to explore the associations between skin microcirculatory function and established cardiovascular risk factors in a large Swedish cohort. As part of the Swedish CArdioPulmonary bioImage Study (SCAPIS), microcirculatory data were acquired at Linko center dot ping University hospital, Linko center dot ping, Sweden during 2016-2017. The subjects, aged 50-64 years, were randomly selected from the national population register. Microcirculatory reactivity was assessed using a 5-min arterial occlusion-release protocol. Comprehensive skin microcirculatory data were continuously acquired by using a fiberoptic probe placed on the lower right arm. After exclusion of missing data (208), 1557 subjects were remaining. Among the parameters, skin microcirculatory peak oxygen saturation after occlusion release, had the strongest relationship to the cardiovascular risk factors. The linear associations between peak oxygen saturation and cardiovascular risk factors were analyzed adjusted for age and sex. We found a negative association with peak oxygen saturation (standardized regression coefficient) for blood pressure (systolic-0.05 (95% CI:-0.10;-0.003) and diastolic-0.05 (-0.10;-0.003)), BMI-0.18 (-0.23;-0.13), waist circumference (males-0.20 (-0.32;-0.16), females-0.18 (-0.25;-0.11)), prevalent diabetes-0.31 (-0.49;-0.12), hypertension-0.30 (-0.42;-0.18), dyslipidemia-0.24 (-0.40;-0.09), fasting glucose level-0.06 (-0.12;-0.01), HbA1c-0.07 (-0.12;-0.02), triglyceride level-0.09 (-0.14;-0.04), hsCRP-0.12 (-0.17;-0.07), and current smoker versus never smoked-0.50 (-0.67;-0.34). A positive association with peak oxygen saturation was found for cholesterol level 0.05 (0.005; 0.11) and HDL 0.11 (0.06; 0.17). This is the first study showing that post-ischemic skin microvascular peak oxygen saturation is associated with virtually all established cardiovascular risk factors in a population-based middle-aged cohort.
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