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Quantitative diffuse reflectance spectroscopy: myocardial oxygen transport from vessel to mitochondria
Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In the field of biomedical optics, diffuse reflectance spectroscopy (DRS) is a frequently used technique for obtaining information about the optical properties of the medium under investigation. The method utilizes spectral difference between incident and backscattered light intensity for quantifying the underlying absorption and scattering processes that affects the light-medium interaction.

In this thesis, diffuse reflectance spectroscopy (DRS) measurements have been combined with an empirical photon migration model in order to quantify myocardial tissue chromophore content and status. The term qDRS (quantitative DRS) is introduced in the thesis to emphasize the ability of absolute quantification of tissue chromophore content. To enable this, the photon migration models have been calibrated using liquid optical phantoms. Methods for phantom characterization in terms of scattering coefficient, absorption coefficient, and phase function determination are also presented and evaluated. In-vivo qDRS measurements were performed on both human subjects undergoing routine coronary artery bypass grafting (CABG), and on bovine heart during open-chest surgery involving hemodynamic and respiratory provocations. The application of a hand-held fiber-optic surface probe (human subjects) proved the clinical applicability of the technique as the results were in agreement with other studies. However, problems with non-physiological variations in detected intensity due to intermittent probe-tissue discontact were observed. Also, systematic deviations between modeled and measured spectra were found. By model inclusion of additional chromophores revealing the mitochondrial oxygen uptake ability, an improved model fit to measured data was achieved. Measurements performed with an intramuscular probe (animal subjects) diminished the influence of probe-tissue discontact on the detected intensity. It was demonstrated that qDRS could quantify variations in myocardial oxygenation induced by physiological provocations, and that absolute quantification of tissue chromophore content could be obtained.

The suggested qDRS method has the potential of becoming a valuable tool in clinical practice, as it has the unique ability of monitoring both the coronary vessel oxygen delivery and the myocardial mitochondrial oxygen uptake ability. This makes qDRS suitable for directly measuring the result of different therapies, which can lead to a paradigm shift in the monitoring during cardiac anesthesia.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2009. , 92 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1276
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:liu:diva-25587ISBN: 978-91-7393-522-7 (print)OAI: oai:DiVA.org:liu-25587DiVA: diva2:246012
Public defence
2009-10-30, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2009-10-15 Created: 2009-10-08 Last updated: 2016-08-31Bibliographically approved
List of papers
1. Reduced scattering coefficient determination by non-contact oblique angle illumination: methodological considerations
Open this publication in new window or tab >>Reduced scattering coefficient determination by non-contact oblique angle illumination: methodological considerations
2007 (English)In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 6435, 64350I-1-64350I-12 p.Article in journal (Refereed) Published
Abstract [en]

The reduced scattering coefficient, µs, was determined using oblique angle illumination and imaging backscattered light intensity. The distance r between the point of light incidence (hot-spot) and the circular symmetric diffuse reflectance centre, is ~1/µ. Previously, r was obtained analyzing a 1D strip aligned with the laser beam. We improved this method by calculating a 2D intensity image with extended dynamic range by assessing camera linearity, superimposing images with multiple integration times, and compensating for lens vignetting. The hot-spot algorithm utilises several images to minimize speckle variations and account for laser beam shape. Diffuse centre position is obtained by filtering the superimposed image with decreasing thresholds using momentum analysis to determine circular symmetry. The method was evaluated on 18 optical liquid phantoms with µs[1.5, 3.0] mm-1 and µs[0.01, 0.16] mm-1. The 2D method had better linearity with µs and smaller variations due to more stable hot-spot detection, than the 1D method. The anisotropy factor g was obtained by fitting measured and Monte Carlo simulated spatially resolved intensity decays and verified with a laser Doppler flowmetry technique. With an optimal compensation for the µa dependence, the rms error in µ estimation was 2.9%.

Keyword
Reduced scattering coefficient, absorption coefficient, anisotropy factor, optical properties, oblique angle illumination, optical phantoms, Monte Carlo simulations
National Category
Other Industrial Biotechnology
Identifiers
urn:nbn:se:liu:diva-25582 (URN)10.1117/12.698903 (DOI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
2. Myocardial tissue oxygenation estimated with calibrated diffuse reflectance spectroscopy during coronary artery bypass grafting
Open this publication in new window or tab >>Myocardial tissue oxygenation estimated with calibrated diffuse reflectance spectroscopy during coronary artery bypass grafting
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2008 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 5, 054030- p.Article in journal (Refereed) Published
Abstract [en]

We present a study using a method able to assess tissue oxygenation, taking into account the absorption and the level of scattering in myocardial tissue using a calibrated fiber optic probe. With this method, interindividual comparisons of oxygenation can be made despite varying tissue optical properties during coronary artery bypass grafting (CABG). During CABG, there are needs for methods allowing continuous monitoring and prediction of the metabolism in the myocardial tissue. 14 patients undergoing CABG are investigated for tissue oxygenation during different surgical phases using a handheld fiber optic spectroscopic probe with a source-detector distance of less than 1 mm. The probe is calibrated using a light transport model, relating the absorption and reduced scattering coefficients (mu(a) and mu()(s)) to the measured spectra. By solving the inverse problem, absolute measures of tissue oxygenation are evaluated by the sum of oxygenized hemoglobin and myoglobin. Agreement between the model and measurements is obtained with an average correlation coefficient R-2 of 0.96. Oxygenation is found to be significantly elevated after aorta cross-clamping and cardioplegic infusion, as well as after reperfusion, compared to a baseline (p < 0.05). Tissue oxygenation decreases during cardiac arrest and increases after reperfusion.

Keyword
diffuse reflectance spectroscopy, oxygenation, myocardium, tissue, coronary artery bypass grafting
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16251 (URN)10.1117/1.2976433 (DOI)
Note

Original Publication: Erik Häggblad, Tobias Lindbergh, Daniel Karlsson, Henrik Casimir-Ahn, Göran Salerud and Tomas Strömberg, Myocardial tissue oxygenation estimated with calibrated diffuse reflectance spectroscopy during coronary artery bypass grafting, Journal of Biomedical Optics, (13), 5, 054030, 2008. http://dx.doi.org/10.1117/1.2976433 Copyright 2008 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, 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: 2009-01-12 Created: 2009-01-09 Last updated: 2017-05-23Bibliographically approved
3. Improved model for myocardial diffuse reflectance spectra by including mitochondrial cytochrome aa3, methemoglobin, and inhomogenously distributed RBC
Open this publication in new window or tab >>Improved model for myocardial diffuse reflectance spectra by including mitochondrial cytochrome aa3, methemoglobin, and inhomogenously distributed RBC
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2011 (English)In: Journal of Biophotonics, ISSN 1864-063X, Vol. 4, no 4, 268-276 p.Article in journal (Refereed) Published
Abstract [en]

Hemo- and myoglobin oxygen saturation and cytochrome aa3 oxidation was locally assessed using calibrated diffuse reflectance spectroscopy in fourteen patients undergoing coronary artery bypass grafting. Diffuse spectral reflectance data, recorded with a handheld fiberoptic probe with a single source-detector separation, was analyzed using an empirical light transport model relating the absorption and reduced scattering coefficients to the measured spectrum. The absorption coefficient has previously been modeled as a sum of hemoglobin and myoglobin, fat, and water. In this study, inclusion of cytochrome aa3 and the sum of methemoglobin and metmyoglobin improved the spectral fit, especially in the wavelength regions where their absorption is prominent. On average, the extended model increased the mean R2 from 0.96 to 0.99 and displayed 4% units higher saturation levels. After aorta cross-clamping, the sum of hemo- and myoglobin oxygen saturation increased while cytochrome aa3 oxidation decreased slightly. Opposite trends were observed during cardiac arrest. At reperfusion, the saturation increased compared to the levels found at cardiac arrest, and the cytochrome aa3 oxidation was restored. The estimated tissue chromophore fractions, saturation and oxidation, were in agreement with other studies.

Place, publisher, year, edition, pages
John Wiley & Sons, 2011
National Category
Industrial Biotechnology
Identifiers
urn:nbn:se:liu:diva-25583 (URN)10.1002/jbio.201000048 (DOI)000289716000007 ()
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-02-09Bibliographically approved
4. Intramyocardial oxygen transport by quantitative diffuse reflectance spectroscopy in calves
Open this publication in new window or tab >>Intramyocardial oxygen transport by quantitative diffuse reflectance spectroscopy in calves
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2010 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 2Article in journal (Refereed) Published
Abstract [en]

Intramyocardial oxygen transport was assessed during open-chest surgery in calves by diffuse reflectance spectroscopy using a small intramuscular fiber-optic probe. The sum of hemo- and myoglobin tissue fraction and oxygen saturation, the tissue fraction and oxidation of cytochrome aa3, and the tissue fraction of methemoglobin, were estimated using a calibrated empirical light transport model. Increasing the oxygen content in the inhaled gas; 21%-50%-100%, in five calves (group A) gave an oxygen saturation of 19+/-4%, 24+/-5% and 28+/-8%, and mean tissue fractions of 1.6% (cytochrome aa3), and 1.1% (hemo- and myoglobin). Cardiac arrest in two calves gave an oxygen saturation lower than 5%. In two calves (group B) a left ventricular assistive device (LVAD pump) was implanted. Group B animals displayed similar trends in hemo- and myoglobin oxygen saturation as in group A, but at higher levels (maxima of 38% (B1) and 44% (B2)). The cytochrome aa3 oxidation level was above 96% in both group A and B calves, including the two cases involving cardiac arrest.

In conclusion, the estimated tissue fractions and oxygenation/oxidation levels of the myocardial chromophores during respiratory and hemodynamic provocations where in agreement with previously presented results, demonstrating the potential of the method.

Keyword
bio-optics, biotransport, blood vessels, cardiovascular system, diseases, fibre optic sensors, haemodynamics, molecular biophysics, muscle, oxidation, oxygen, prosthetics, proteins, reflectivity, respiratory protection, statistical analysis, surgery; Hemodynamics, Biomedical engineering, Fluid mechanics and rheology, Fluid transport and rheology, Pneumodyamics, respiration, Muscles
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25585 (URN)10.1117/1.3374050 (DOI)000278465300069 ()
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
5. Spectral determination of a two-parametric phase function for polydispersive scattering liquids
Open this publication in new window or tab >>Spectral determination of a two-parametric phase function for polydispersive scattering liquids
2009 (English)In: Optics Express, ISSN 1094-4087, E-ISSN 1094-4087, Vol. 17, no 3, 1610-1621 p.Article in journal (Refereed) Published
Abstract [en]

A method for determining a two-parametric Gegenbauer-kernel phase function that accurately describes the diffuse reflectance from a polydispersive scattering media at small source-detector separations (0.23 to 1.2 mm), is presented. The method involves spectral collimated transmission measurements, spatially resolved spectral diffuse reflectance (SRDR) measurements, and inverse Monte Carlo technique. Both absolute calibration (using a monodispersive polystyrene microsphere suspension) and relative calibration (eliminating differences between fibers) of SRDR spectra yielded comparable results. When applied to water dilutions of milk, simulated and measured spectra deviated less than 6.5% and 2.5% for the absolute and relative calibration case, respectively, even for the closest fiber separation. Corresponding values for milk including ink as an absorber, were 13.4% and 7.3%.

National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-18841 (URN)10.1364/OE.17.001610 (DOI)
Available from: 2009-06-05 Created: 2009-06-05 Last updated: 2017-12-13Bibliographically approved

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