Article

Real-time intraoperative monitoring of blood coagulability via coherence-gated light scattering

  • Nature Biomedical Engineering 1, Article number: 0028 (2017)
  • doi:10.1038/s41551-017-0028
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Abstract

When characterizing dynamic processes, ergodicity—that is, the equivalence of time averages and of averages over a system’s possible microstates—is often invoked. Yet many complex social, economic and material systems are such that practical observations cannot survey the entire ensemble of microstates. In the case of non-ergodic fluids, their slow structural dynamics makes such an approach prohibitive. Blood is a prominent example of a non-ergodic, complex fluid for which today’s standards for coagulation tests in vivo are chemically induced offline assays. Here, we show that heterodyne amplification—that is, amplification of a signal by frequency conversion—combined with suitable control of spatiotemporal coherence permits measurements of non-stationary dynamics in non-ergodic, complex media. By taking advantage of this approach, we developed an optical-fibre-based tool that can be directly incorporated into standard vascular-access devices for real-time monitoring of blood coagulability in the operating room.

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References

  1. 1.

    , & Colloidal gelation and non-ergodicity transitions. J. Phys. Condens. Matter 12, 6575–6583 (2000).

  2. 2.

    & Nonergodicity transitions in colloidal suspensions with attractive interactions. Phys. Rev. E 59, 5706–5715 (1999).

  3. 3.

    Colloidal glasses. Curr. Opin. Colloid Interface Sci. 6, 479–483 (2001).

  4. 4.

    & Slow dynamics in glasses, gels and foams. Curr. Opin. Colloid Interface Sci. 7, 228–234 (2002).

  5. 5.

    The glass paradigm for colloidal glasses, gels, and other arrested states driven by attractive interactions. Curr. Opin. Colloid Interface Sci. 7, 218–227 (2002).

  6. 6.

    , & Nonergodic states of charged colloidal suspensions: repulsive and attractive glasses and gels. Phys. Rev. E 69, 031404 (2004).

  7. 7.

    & Colloidal gels—low-density disordered solid-like states. Curr. Opin. Colloid Interface Sci. 8, 494–500 (2004).

  8. 8.

    , & Anomalous diffusion and ergodicity breaking in heterogeneous diffusion processes. New J. Phys. 15, 083039 (2013).

  9. 9.

    , & Particle invasion, survival, and non-ergodicity in 2D diffusion processes with space-dependent diffusivity. Soft Matter 10, 1591–1601 (2014).

  10. 10.

    & Nonergodicity, fluctuations, and criticality in heterogeneous diffusion processes. Phys. Rev. E 90, 012134 (2014).

  11. 11.

    , & Scaled Brownian motion: a paradoxical process with a time dependent diffusivity for the description of anomalous diffusion. Phys. Chem. Chem. Phys. 16, 15811–15817 (2014).

  12. 12.

    et al. Nonergodic subdiffusion from Brownian motion in an inhomogeneous medium. Phys. Rev. Lett. 112, 150603 (2014).

  13. 13.

    et al. Anomalous diffusion models and their properties: non-stationarity, non-ergodicity, and ageing at the centenary of single particle tracking. Phys. Chem. Chem. Phys. 16, 24128–24164 (2014).

  14. 14.

    & Ergodicity breaking and particle spreading in noisy heterogeneous diffusion processes. J. Chem. Phys. 142, 144105 (2015).

  15. 15.

    & Ergodicity breaking, ageing, and confinement in generalized diffusion processes with position and time dependent diffusivity. J. Stat. Mech. 2015, P05010 (2015).

  16. 16.

    et al. Anomalous diffusion in living yeast cells. Phys. Rev. Lett. 93, 078102 (2004).

  17. 17.

    et al. Fast and slow dynamics of the cytoskeleton. Nat. Mater. 5, 636–640 (2006).

  18. 18.

    & Physical nature of bacterial cytoplasm. Phys. Rev. Lett. 96, 098102 (2006).

  19. 19.

    et al. Transient anomalous diffusion of telomeres in the nucleus of mammalian cells. Phys. Rev. Lett. 103, 018102 (2009).

  20. 20.

    et al. In vivo anomalous diffusion and weak ergodicity breaking of lipid granules. Phys. Rev. Lett. 106, 048103 (2011).

  21. 21.

    et al. Ergodic and non-ergodic processes coexist in the plasma membrane as observed by single-molecule tracking. Proc. Natl Acad. Sci. USA 108, 6438–6443 (2011).

  22. 22.

    & Anomalous transport in the crowded world of biological cells. Rep. Prog. Phys. 7, 046602 (2013).

  23. 23.

    et al. Intracellular transport of insulin granules is a subordinated random walk. Proc. Natl Acad. Sci. USA 110, 4911–4916 (2013).

  24. 24.

    et al. Weak ergodicity breaking of receptor motion in living cells stemming from random diffusivity. Phys. Rev. X 5, 011021 (2015).

  25. 25.

    & Dynamic Light Scattering: With Applications to Chemistry, Biology, and Physics ( Courier Corporation, 1976).

  26. 26.

    et al. Assessing blood coagulation status with laser speckle rheology. Biomed. Opt. Express 5, 817–831 (2014).

  27. 27.

    , & Optical thromboelastography to evaluate whole blood coagulation. J. Biophotonics 8, 372–381 (2015).

  28. 28.

    & Dynamic light scattering by non-ergodic media. Physica A 157, 705–741 (1989).

  29. 29.

    et al. Nonergodicity and light scattering from polymer gels. Phys. Rev. A 46, 6550–6563 (1992).

  30. 30.

    Accuracy of photon correlation measurements on nonergodic samples. Appl. Opt. 32, 3880–3885 (1993).

  31. 31.

    , & Dynamic light scattering by nonergodic media: Brownian particles trapped in polyacrylamide gels. Phys. Rev. A 42, 2161–2175 (1990).

  32. 32.

    , & Nonergodicity parameters of colloidal glasses. Phys. Rev. Lett. 67, 1586–1589 (1991).

  33. 33.

    et al. Diffusing-wave spectroscopy of nonergodic media. Phys. Rev. E 63, 061404 (2001).

  34. 34.

    et al. Multispeckle autocorrelation spectroscopy and its application to the investigation of ultraslow dynamical processes. J. Chem. Phys. 104, 1758–1761 (1996).

  35. 35.

    et al. The glass transition dynamics of polymer micronetwork colloids. A mode coupling analysis. J. Chem. Phys. 106, 3743–3756 (1997).

  36. 36.

    et al. Aging behavior of laponite clay particle suspensions. Europhys. Lett. 52, 73–79 (2000).

  37. 37.

    & Fiber-optic quasielastic light scattering in concentrated latex dispersions: the performance of single-mode vs. multimode fibers. Ber. Bunsenges. Phys. Chem. 96, 1818–1828 (1992).

  38. 38.

    Speckle Phenomena in Optics: Theory and Applications ( Roberts Co., 2007).

  39. 39.

    & in Progress in Optics (ed. Wolf, E.) 146–150 (North-Holland, 1970).

  40. 40.

    in Photon Correlation and Light Beating Spectroscopy (eds Cummins, H. Z. & ) 75–149 ( Springer, 1974).

  41. 41.

    & Multimode theory of graded-core fibers. Bell Syst. Tech. J. 52, 1563–1578 (1973).

  42. 42.

    & Principal modes in multimode waveguides. Opt. Lett. 30, 135–137 (2005).

  43. 43.

    et al. Principal modes in graded-index multimode fiber in presence of spatial-and polarization-mode coupling. J. Lightwave Technol. 27, 1248–1261 (2009).

  44. 44.

    & Statistics of group delays in multimode fiber with strong mode coupling. J. Lightwave Technol. 29, 3119–3128 (2011).

  45. 45.

    et al. In-situ characterization of structural dynamics in swelling hydrogels. Soft Matter 12, 5986–5994 (2016).

  46. 46.

    & The perfect measure of hemostasis: a quest for the holy grail. Thromb. Res. 125, 481–482 (2010).

  47. 47.

    , & Spatially resolved microrheology through a liquid/liquid interface. J. Colloid Interface Sci. 269, 503–513 (2004).

  48. 48.

    et al. Passive optical mapping of structural evolution in complex fluids. RSC Adv. 5, 5357–5362 (2015).

  49. 49.

    Estimating the viscoelastic moduli of complex fluids using the generalized Stokes–Einstein equation. Rheol. Acta 39, 371–378 (2000).

  50. 50.

    , & Superdiffusion in optically controlled active media. Nat. Photon. 6, 834–837 (2012).

  51. 51.

    , & Measurement of diffusive transport at liquid–liquid interfaces. In Frontiers in Optics 2015 (Optical Society of America, 2015).

  52. 52.

    et al. Microrheology and release behaviors of self-assembled steroid hydrogels. J. Mater. Sci. Chem. Eng. 3, 6–15 (2015).

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Acknowledgements

This work was partially supported by the National Institutes of Health and the National Heart, Lung and Blood Institute under grant number 5R21HL124486.

Author information

Affiliations

  1. CREOL, The College of Optics and Photonics, University of Central Florida, Orlando, Florida 32816, USA

    • J. R. Guzman-Sepulveda
    •  & A. Dogariu
  2. Pediatric Cardiothoracic Surgery, The Heart Center, Arnold Palmer Hospital for Children, Orlando, Florida 32806, USA

    • R. Argueta-Morales
    •  & W. M. DeCampli

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Contributions

A.D. and W.M.D.C. planned the project. A.D. and J.R.G.-S. designed the experimental technique. W.M.D.C. and R.A.-M. designed the clinical study and the medical protocols. J.R.G.-S. and R.A.-M. contributed to data collection. J.R.G.-S. and A.D. analysed the data. All authors contributed to interpreting the data and to drafting the article.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to A. Dogariu.

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