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Microcirculation assessment using an individualized model for diffuse reflectance spectroscopy and conventional laser Doppler flowmetry
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.ORCID iD: 0000-0003-4377-8544
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. Perimed AB, Järfälla, Sweden.ORCID iD: 0000-0002-3454-6576
Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.ORCID iD: 0000-0002-1680-1000
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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. Vol. 19, no 5, 057002- p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-107715DOI: 10.1117/1.JBO.19.5.057002ISI: 000338334600033PubMedID: 24788373OAI: oai:DiVA.org:liu-107715DiVA: diva2:726948
Available from: 2014-06-19 Created: 2014-06-19 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Model-based quantitative assessment of skin microcirculatory blood flow and oxygen saturation
Open this publication in new window or tab >>Model-based quantitative assessment of skin microcirculatory blood flow and oxygen saturation
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:nbn:se:liu:diva-127691 (URN)10.3384/diss.diva-127691 (DOI)978-91-7685-801-1 (ISBN)
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

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Strömberg, TomasKarlsson, HannaFredriksson, IngemarNyström, Fredrik H.Larsson, Marcus

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Strömberg, TomasKarlsson, HannaFredriksson, IngemarNyström, Fredrik H.Larsson, Marcus
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Department of Biomedical EngineeringThe Institute of TechnologyFaculty of Health SciencesDepartment of EndocrinologyDivision of Cardiovascular Medicine
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