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Model-based quantitative assessment of skin microcirculatory blood flow and oxygen saturation
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The microcirculation, involving the smallest vessels in the body, is where the oxygen transport to all tissue occurs. Evaluating microcirculatory parameters is, therefore, important and involves the quantification of oxygen content of red blood cells (RBCs), the amount of RBCs and their speed.

Diffuse reflectance spectroscopy (DRS) can be used to estimate blood oxygen saturation and fraction of RBCs in tissue since oxygenated and deoxygenated blood have different light absorption characteristics. By illuminating the skin with white light and detecting the spectrum of the backscattered light, tissue absorption and scattering can be assessed. Laser Doppler flowmetry (LDF) is a technique to measure blood flow in tissue. When laser light encounter moving objects in tissue, i.e. RBCs, the light is Doppler shifted, which can be detected and used to calculate tissue perfusion (the fraction of moving RBCs times their speed). With a small distance between light source and detector, both techniques measure superficially where most vessels are microcirculatory vessels. Photon transport in tissue can be simulated with Monte Carlo techniques and the simulations form the basis of modeled DRS and LDF spectra. The estimated microcirculatory parameters are given by the model that best describe measured DRS and LDF data.

This thesis describes the development and the evaluation of an optical method to simultaneously measure oxygen saturation, RBC tissue fraction and speed resolved perfusion in absolute units by integrating DRS and LDF. By combining DRS and LDF into one system with a common tissue model, the two modalities can benefit from each other’s strengths. Different calibration methods and model assumptions for the system were evaluated in optical phantoms and in skin measurements. A simple calibration method with two detector distances for DRS was found adequate to accurately estimate absorption and scattering in optical phantoms. It was also necessary to model blood located in vessels, rather than homogeneously distributed in the skin, to obtain accurate parameter estimates. The system was evaluated in healthy subjects during standard provocations, where the parameters were in agreement with other studies and followed an expected pattern during the provocations. In patients with diabetes type 2, tissue fraction of RBCs and nutritive blood flow were reduced in baseline compared to healthy controls. These differences were not related to prevalence of microalbuminuria, a marker sign of microvascular complications in the kidneys.

A combined system with DRS and LDF enables a more comprehensive assessment of the microcirculation by measuring oxygen saturation, RBC tissue fraction and speed resolved perfusion simultaneously and in absolute units. This system has clinical potential to assist in the evaluation of the microcirculation both in healthy and diseased individuals.

Abstract [sv]

Mikrocirkulationen innefattar de minsta kärlen i kroppen och det är här syretransporten till all vävnad i kroppen sker. Det är därför viktigt att kunna utvärdera mikrocirkulatoriska parametrar såsom syresättningen hos de röda blodkropparna, mängden röda blodkroppar samt deras hastighet.

Diffus reflektansspektroskopi (DRS) kan användas för att beräkna syresättningen i blodet och mängden röda blodkroppar eftersom syresatt blod har ett karaktäristiskt sätt att absorbera ljus. Absorptionen och spridningen i vävnaden kan skattas genom att belysa huden med vitt ljus och mäta spektrumet från det tillbakaspridda ljuset. Laserdopplerbaserad flödesmätning (LDF) är en teknik som mäter blodflöde i vävnad. När laserljus träffar objekt i vävnaden som rör sig, t.ex. röda blodkroppar, så uppstår Dopplerskift. Dessa Dopplerskift kan detekteras och ett perfusionmått för vävnaden (mängden röda blodkroppar i rörelse gånger deras hastighet) kan beräknas. Med små avstånd mellan ljuskälla och detektor kan båda teknikerna mäta ytligt där den största delen av kärlen tillhör mikrocirkulationen. Fotontransporten i vävnad kan simuleras med Monte Carlo-teknik och simuleringarna ligger till grund för att modellera DRS- och LDF-spektra. De mikrocirkulatoriska parametrarna ges från den modellen som bäst passar DRS- och LDF-data.

Avhandlingen beskriver utvecklingen och utvärderingen av en optisk metod för att simultant mäta syresättningen, mängden röda blodkroppar och hastighetsupplöst perfusion i absoluta enheter genom att integrera DRS och LDF. Genom att kombinera DRS och LDF i ett system med en gemensam hudmodell kan de två modaliteterna dra nytta av varandras styrkor. Olika kalibreringsmetoder och modellantaganden för systemet utvärderades i optiska fantomer och i hudmätningar. En enkel kalibreringsmetod med två detektoravstånd för DRS visade sig vara tillräckligt för att kunna skatta absorption och spridning i optiska fantomer. Det var också nödvändigt att modellera blod i kärl istället för homogent fördelat i huden för att uppnå noggranna parameterskattningar. Systemet utvärderades under standardprovokationer på friska försökspersoner där parametrarna stämde överens med andra studier och följde ett förväntat mönster under provokationerna. Hos patienter med diabetes typ 2 sågs en minskad mängd röda blodkroppar och kapillärt blodflöde i oprovocerad hud jämfört med friska kontroller. Skillnaden var inte kopplad till förekomsten av mikroalbuminuri, ett tecken på mikrovaskulära komplikationer i njurarna.

Ett kombinerat system med DRS och LDF ger en mer fullständig bild av mikrocirkulationen genom att samtidigt och i absoluta enheter mäta syresättningen, mängden röda blodkroppar och hastighetsupplöst perfusion. Systemet kan användas för att utvärdera mikrocirkulationen både hos friska och sjuka individer.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. , 80 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1753
National Category
Medical Engineering
Identifiers
URN: urn:nbn:se:liu:diva-127691DOI: 10.3384/diss.diva-127691ISBN: 978-91-7685-801-1 (print)OAI: oai:DiVA.org:liu-127691DiVA: diva2:926511
Public defence
2016-06-10, Berzeliussalen, Campus US, Linköping, 13:00 (English)
Opponent
Supervisors
Funder
VINNOVAEuropean Science Foundation (ESF)
Available from: 2016-05-24 Created: 2016-05-08 Last updated: 2016-05-24Bibliographically approved
List of papers
1. Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?
Open this publication in new window or tab >>Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?
2011 (English)In: Optical Tomography and Spectroscopy of Tissue IX / [ed] Robert R. Alfano; Bruce J. Tromberg; Arjun G. Yodh; Mamoru Tamura; Eva M. Sevick-Muraca, SPIE - International Society for Optical Engineering, 2011, Vol. 7896, 78962Y-78962Y-9 p.Conference paper, Published paper (Other academic)
Abstract [en]

Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2011
Series
Proceedings of SPIE - International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X ; 7896
Keyword
diffuse reflectance spectroscopy, light transport, Monte Carlso simulation, tissue moedeling, vessel packaging, skin
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:liu:diva-81240 (URN)10.1117/12.873134 (DOI)
Conference
Optical Tomography and Spectroscopy of Tissue IX Conference, San Francisco, California, January 22, 2011
Available from: 2012-09-14 Created: 2012-09-10 Last updated: 2017-02-10Bibliographically approved
2. Inverse Monte Carlo for estimation of scattering and absorption in liquid optical phantoms
Open this publication in new window or tab >>Inverse Monte Carlo for estimation of scattering and absorption in liquid optical phantoms
2012 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 20, no 11, 12233-12246 p.Article in journal (Refereed) Published
Abstract [en]

A spectroscopic probe with multiple detecting fibers was used for quantifying absorption and scattering in liquid optical phantoms. The phantoms were mixtures of Intralipid and red and blue food dyes. Intensity calibration for the detecting fibers was undertaken using either a microsphere suspension (absolute calibration) or a uniform detector illumination (relative calibration between detectors). Two different scattering phase functions were used in an inverse Monte Carlo algorithm. Data were evaluated for residual spectra (systematic deviations and magnitude) and accuracy in estimation of scattering and absorption. Spectral fitting was improved by allowing for a 10% intensity relaxation in the optimization algorithm. For a multi-detector setup, non-systematic residual spectrum was only found using the more complex Gegenbauer-kernel phase function. However, the choice of phase function did not influence the accuracy in the estimation of absorption and scattering. Similar estimation accuracy as in the multi-detector setup was also obtained using either two relative calibrated detectors or one absolute calibrated detector at a fiber separation of 0.46 mm.

Place, publisher, year, edition, pages
Optical Society of America, 2012
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-78815 (URN)10.1364/OE.20.012233 (DOI)000304403100070 ()
Note

Funding Agencies|VINNOVA||Perimed AB|2008-00149|ResearchGrow program|2011-03074|European Union||Linkoping University through the Center for Excellence NIMED-CBDP (Center for Biomedical Data Processing)||

Available from: 2012-06-21 Created: 2012-06-21 Last updated: 2017-12-07Bibliographically approved
3. Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry
Open this publication in new window or tab >>Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry
Show others...
2014 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 19, no 5, 057002- p.Article in journal (Refereed) Published
Abstract [en]

Microvascular assessment would benefit from co-registration of blood flow and hemoglobin oxygenation dynamics during stimulus response tests. We used a fiber-optic probe for simultaneous recording of white light diffuse reflectance (DRS; 475-850 nm) and laser Doppler flowmetry (LDF; 780 nm) spectra at two source-detector distances (0.4 and 1.2 mm). An inverse Monte Carlo algorithm, based on a multiparameter three-layer adaptive skin model, was used for analyzing DRS data. LDF spectra were conventionally processed for perfusion. The system was evaluated on volar forearm recordings of 33 healthy subjects during a 5-min systolic occlusion protocol. The calibration scheme and the optimal adaptive skin model fitted DRS spectra at both distances within 10%. During occlusion, perfusion decreased within 5 s while oxygenation decreased slowly (mean time constant 61 s; dissociation of oxygen from hemoglobin). After occlusion release, perfusion and oxygenation increased within 3 s (inflow of oxygenized blood). The increased perfusion was due to increased blood tissue fraction and speed. The supranormal hemoglobin oxygenation indicates a blood flow in excess of metabolic demands. In conclusion, by integrating DRS and LDF in a fiber-optic probe, a powerful tool for assessment of blood flow and oxygenation in the same microvascular bed has been presented.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-107715 (URN)10.1117/1.JBO.19.5.057002 (DOI)000338334600033 ()24788373 (PubMedID)
Available from: 2014-06-19 Created: 2014-06-19 Last updated: 2017-12-05Bibliographically approved
4. Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment
Open this publication in new window or tab >>Oxygen saturation, red blood cell tissue fraction and speed resolved perfusion — A new optical method for microcirculatory assessment
Show others...
2015 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 102, 70-77 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Academic Press, 2015
Keyword
Diffuse reflectance spectroscopy; Hemoglobin oxygen saturation; Laser Doppler flowmetry; Microcirculation; Skin blood flow
National Category
Medical Laboratory and Measurements Technologies
Identifiers
urn:nbn:se:liu:diva-121774 (URN)10.1016/j.mvr.2015.08.006 (DOI)000362310700010 ()26279347 (PubMedID)
Note

Funding text:  VINNOVA (Swedens innovation agency); Perimed AB through the SamBIO research collaboration program [2008-00149]; Research&Grow program (VINNOVA) [2011-03074]; NovaMedTech - European Union Regional Development Fund [68737, 160382]

Available from: 2015-10-05 Created: 2015-10-05 Last updated: 2017-12-01

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