A pulsed photoacoustic technique for studying red blood cell sedimentation

Matti Kinnunen (Login required)
Optoelectronics and Measurement Techniques Laboratory, University of Oulu, Finland

Paper #1990 received 2014.11.22; revised manuscript received 2015.01.20; accepted for publication 2015.01.20; published online 2015.03.28.

DOI: 10.18287/jbpe-2015-1-1-81


This study shows the capability of a pulsed photoacoustic (PA) technique to measure red blood cell sedimentation and aggregation processes in vitro. Red blood cells are the main source of absorption in blood. The PA signal is proportional to the sample’s optical absorption coefficient, and hence, dynamic changes in the sample can be monitored by analyzing the PA pulse amplitude and pulse arrival time. Optical coherence tomography (OCT) is used as a parallel method for comparison. Diluted whole blood and different concentrations of washed red blood cells were used as samples. The pulsed PA technique is suitable for monitoring changes in sedimentation velocity when dextran is added to the sample. When the measurement section with the fastest sedimentation rate was selected for analysis, a more than 10-fold increase in the sedimentation rate, induced by dextran, was found with both the PA and OCT techniques. The PA pulse delay was found to be a more reliable measure of changes in the sample than the PA signal amplitude.


blood sedimentation; red blood cell aggregation; dextran; pulsed photoacoustic technique; optical coherence tomography

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1. S. E. Bedell, and B. T. Bush, “Erythrocyte sedimentation rate. From folklore to facts,” Am. J. Med. 78, 1001-1009 (1985). Crossref

2. T. L. Fabry, “Mechanism of erythrocyte aggregation and sedimentation,” Blood 70(5), 1572-1576 (1987).

3. A. V. Priezzhev, N. F. Nikolai, and J. Lademann, “Light backscattering diagnostics of red blood cell aggregation in whole blood samples,” Handbook of optical biomedical diagnostics, Tuchin V. V. Ed., SPIE Press, Bellingham (2002).

4. B. Neu, R. Wendy, and H. J. Meiselman, “Effects of dextran molecular weight on red blood cell aggregation,” Biophys. J. 95, 3059-3065 (2008). Crossref

5. A. Westergren, “Studies of the Suspension Stability of the Blood in Pulmonary Tuberculosis,” Acta Medica Scandinavica 54, 247–282 (1921). Crossref

6. L. E. Böttiger, and C. A. Svedberg, “Normal erythrocyte sedimentation rate and age,” Brit. Med. J. 2, 85-87 (1967). Crossref

7. M. L. Bridgen, “Clinical utility of the erythrocyte sedimentation rate,” Am. Fam. Physician 60(5), 1443-1450 (1999).

8. J. M. Jou, S. M. Lewis, C. Briggs, S.-H. Lee, B. de la Salle, and S. McFadden, “ICSH review of the measurement of the erythrocyte sedimentation rate,” Int. Jnl. Lab. Hem. 33, 125-132 (2011). Crossref

9. A. V. Priezzhev, O. M. Ryaboshapka, N. N. Firsov, and I. V. Sirko, “Aggregation and disaggregation of erythrocytes in whole blood: study by backscattering technique,” J. Biomed. Opt. 4(1), 76-84 (1999). Crossref

10. C. V. L. Pop, and S. Neamtu, “Aggregation of red blood cells in suspension: study by light-scattering technique at small angles,” J. Biomed. Opt. 13(4), 041308 (2008). Crossref

11. X. Xu, L. Yu, and Z. Chen, “Velocity variation assessment of red blood cell aggregation with spectral domain Doppler optical coherence tomography,” Ann. Biomed. Eng. 38, 3210-3217 (2010). Crossref

12. F. T. H. Yu, and G. Cloutier, “Experimental ultrasound characterization of red blood cell aggregation using the structure factor size estimator (SFSE),” J. Acoust. Soc. Am. 122, 645-656 (2007). Crossref

13. E. Franceschini, F. T. H. Yu, F. Destrempes, and G. Cloutier, “Ultrasound characterization of red blood cell aggregation with interventing attenuation tissue mimicking phantoms using structure factor size and attenuation estimator,” J. Acoustic Soc. Am. 127, 1104-1115 (2010). Crossref

14. S. J. Lee, H. Ha, and K.-H. Nam, “Measurement of red blood cell aggregation using X-ray phase contrast imaging,” Opt. Express 18, 26052-26061 (2010). Crossref

15. Z. Zhao, X. Wang, and J. F. Stoltz, “Comparision of three optical methods to study erythrocyte aggregation,” Clinical Hemorheology and Microcirculation 21, 297-302 (1999).

16. M. R. Hardeman, J. G. G. Dobbe, and C. Ince, “The laser-assisted optical rotational cell analyzer (LORCA) as red blood cell aggregometer,” Clinical Hemorheology and Microcirculation 25, 1-11 (2001).

17. I. Y. Kuo, and K. K. Shung, “High frequency ultrasonic baskscatter from erythrocyte suspension,” IEEE Trans. Biomed. Eng. 41(1), 29-34 (1994). Crossref

18. M. S. van der Heiden, M. G. M. de Kroon, N. Bom, and C. Borst, “Ultrasound backscatter at 30 MHz from human blood: influence of rouleau size affected by blood modification and shear rate,” Ultrasound in Med. & Biol. 21(6), 817-826 (1995).

19. A. A. Oraevsky, S. L. Jacques, F. K. Tittel, “Measurement of tissue optical properties by time-resolved detection of laser-induced transient stress,” Appl. Opt. 36, 402-415 (1997). Crossref

20. J. S. Antoniow, J. Egèe, M. Chirtoc, C. Bissieux, and G. Potron, “Real time analysis of erythrocyte sedimentation by photothermal methods,” Journal de Physique IV, CT-469 – C7-472 (1994).

21. A. Landa, and J. J. Alvarado-Gil, “Photoacoustic monitoring of real time blood and hemolymph sedimentation,” Rev. Sci. Instrum. 74(1), 377-379 (2003). Crossref

22. P. Helander, and I. Lundström, “Whole blood – a sedimenting sample studied by photoacoustic spectroscopy,” J. Photoacoust. 1(2), 203-215 (1982).

23. S. Oka, “A physical theory of erythrocyte sedimentation,” Biorheology 22, 315-321 (1985).

24. E. I. Galanzha, and V. P. Zharov, “In vivo photoacoustic and photothermal cytometry for monitoring multiple blood rheology parameters,” Cytometry Part A 79 A, 746-757 (2011).

25. H. Schmid-Schönbein, H. Malotta, and F. Striesow, “Erythrocyte aggregation: causes, consequence and methods of assessment”, J. Netherlands Soc. Clin. Chem. 15, 88-97 (1990).

26. J. K. Armstrong, R. B. Wendy, H. J. Meiselman, and T. C. Fisher, “The hydrodynamic radii of macromolecules and their effect on red blood cell aggregation,” Biophys. J. 87, 4259-4270 (2004). Crossref

27. X. Xu, R. K. Wang, J. B. Elder, and V. V. Tuchin, “Effect of dextran-induced changes in refractive index and aggregation on optical properties of whole blood,” Phys. Med. Biol. 48, 1205-1221 (2003). Crossref

28. V. V. Tuchin, X. Xu, and R. K. Wang, “Dynamic optical coherence tomography in studies of optical clearing, sedimentation, and aggregation of immersed blood,” Appl. Opt. 41(1), 258-271 (2002). Crossref

29. V. V. Tuchin, R. K. Wang, E. I. Galanzha, J. B. Elder, and D. M. Zhestkov, “Monitoring of glycated hemoglobin by OCT measurements of refractive index,” Proc. SPIE 5316, 66-77 (2004). Crossref

30. X. Xu, V. V. Tuchin, and R. K. Wang, “Immersion technique as a tool for in depth OCT imaging trough human blood and body’s interior tissues,” Proc. SPIE 4251, 89-96 (2001). Crossref

31. V. V. Tuchin, R. K. Wang, and X. Xu, “Whole blood and RBC sedimentation and aggregation study using OCT,” Proc. SPIE 4263, 143-149 (2001). Crossref

32. X. Xu, L. Yu, and Z. Chen, “Effect of erythrocyte aggregation on hematocrit measurement using spectral-domain optical coherence tomography,” IEEE Trans. Biomed. Eng. 55(12) 2753-2758 (2008). Crossref

33. V. V. Tuchin, Optical clearing of tissues and blood, SPIE press, Washington, Bellingham, USA, 2006.

34. M. Yu Kirillin, A. V. Priezzhev, V. V. Tuchin, R. K. Wang, and R. Myllylä, “Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples,” J. Phys. D: Appl. Phys. 38, 2582-2589 (2005). Crossref

35. V. V. Tuchin, D. M. Zhestkov, A. N. Bashkatov, and E. A. Genina, “Theoretical study of immersion optical clearing of blood in vessels at local hemolysis,” Opt. Express 12(13), 2966-2971 (2004). Crossref

36. C. Li, and L. V. Wang, “Photoacoustic tomography and sensing in biomedicine,” Phys. Med. Biol. 54, R59-R97 (2009).

37. J. Laufer, C. Elwell, D. Delpy, and P. Beard, “In vitro measurements of absolute blood oxygen saturation using pulsed near-infrared photoacoustic spectroscopy: accuracy and resolution,” Phys. Med. Biol. 50, 4409-4428 (2005). Crossref

38. J. Laufer, D. Delpy, C.Elwell, and P. Beard, “Quantitative spatially resolved measurement of tissue chromophore concentrations using photoacoustic spectroscopy: application to the measurement of blood oxygenation and haemoglobin concentration,” Phys. Med. Biol. 52, 141-168 (2007). Crossref

39. R. K. Saha, and M. C. Kolios, “A simulation study on photoacoustic signals from red blood cells,” J. Acoust. Soc. Am. 129(5), 2935-2943 (2011). Crossref

40. E. Hysi, R. K. Saha and M. C. Kolios, "On the potential of using photoacoustic spectroscopy to monitor red blood cell aggregation", Proc. SPIE 8222, 82220Q (2012)

41. G. Barshtein, I. Tamir, and S. Yedgar, “Red blood cell rouleaux formation in dextran solution: dependence on polymer conformation,” Eur. Biophys. J. 27, 177-181 (1998). Crossref

42. M. Kinnunen, and R. Myllylä, ”Application of Optical Coherence Tomography, Pulsed Photoacoustic Technique and Time-of-flight Technique to Detect Changes in the Scattering Properties of a Tissue-simulating Phantom,” J. Biomed. Opt. 13(2), 024005-(1-9) 2008. Crossref

43. G. J. Diebold, and T. Sun, “Properties of photoacoustic waves in one, two, and three dimensions,” Acustica 80, 339-351 (1994).

44. M. Kinnunen, "Monitoring the effect of dextran on blood sedimentation using a pulsed photoacoustic technique", Proc. SPIE 8222, 82221E (2012).

45. F. A. Duck, Physical properties of tissue: a comprehensive reference book, Academic Press Inc., San Diego (1990).

46. M. Meinke, G. Müller, J. Helfmann, and M. Friebel, “Optical properties of platelets and blood plasma and their influence on the optical behavior of whole blood in the visible to near infrared wavelength range,” J. Biomed. Opt. 12(1), 014024 (2007). Crossref

47. A. B. Karpiouk, S. R. Aglyamov, S. Mallidi, J. Shah, W. G. Scott, J. M. Rubin, and S. Y. Emelianov, “Combined ultrasound and photoacoustic imaging to detect and stage deep vein thrombosis: phantom and ex vivo studies, “ J. Biomed. Opt. 13(5), 054061 (2008). Crossref

48. R. D. Eastham, “The erythrocyte sedimentation rate and the plasma viscosity,” J. Clin. Path. 7, 164-167 (1954). Crossref

49. S. Kim, S. Yang, and D. Lim, “Effect of dextran on rheological properties of rat blood,” Journal of Mechanical Science and Technology, 23, 868-873 (2009). Crossref

50. M. Kinnunen, Z. Zhao, and R. Myllylä, ”Glucose-induced changes in the optical properties of Intralipid,” Optics and Spectroscopy, 101(1), 54-59 (2006). Crossref

51. B. E. Treeby, E. Z. Zhang, A. S. Thomas, and B. T. Cox, “Measurement of the ultrasound attenuation and dispersion in whole human blood and its components from 0-70 MHz,” Ultrasound in Med. & Biol. 37(2), 289-300 (2011). Crossref

52. H.-J. Lim, Y.-J. Lee, J.-H. Nam, S. Chung, and S. Shin, “Temperature-dependent threshold shear stress of red blood cell aggregation,” Journal of Biomechanics, 43, 546-550 (2010). Crossref

53. D. J. Faber, F. J. van der Meer, M. C. G. Aalders, and T. G. van Leeuwen, “Quantitative measurement of attenuation coefficients of weakly scattering media using optical coherence tomography,” Opt. Express 12(19), 4353-4365 (2004). Crossref

54. Z. Zhao, S. Nissilä, O. Ahola, and R. Myllylä, ”Production and detection theory of pulsed photoacoustic wave with maximum amplitude and minimum distortion in absorbing liquid,” IEEE Transaction on Instrumentation and Measurement, 47(2), 578-583 (1998). Crossref

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