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Quantitative Laser Doppler Flowmetry
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.ORCID iD: 0000-0002-3454-6576
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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

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

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

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

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

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

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

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2009. , 78 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1269
National Category
Medical Laboratory and Measurements Technologies
Identifiers
URN: urn:nbn:se:liu:diva-19947ISBN: 978-91-7393-547-0 (print)OAI: oai:DiVA.org:liu-19947DiVA: diva2:234437
Public defence
2009-10-02, Berzeliussalen, Campus US, Linköpings Universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2009-09-18 Created: 2009-08-18 Last updated: 2016-08-31Bibliographically approved
List of papers
1. Absolute flow velocity components in laser Doppler flowmetry
Open this publication in new window or tab >>Absolute flow velocity components in laser Doppler flowmetry
2006 (English)In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 6094, 60940A- p.Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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