Deep Tissue Hemodynamic Monitoring Using Diffuse Optical Probes

  • Jing Dong
  • Renzhe Bi
  • Kijoon LeeEmail author
Part of the Progress in Optical Science and Photonics book series (POSP, volume 3)


To see what is happening under our skin using light would have been a dream, as there are many strong absorbers and scatterers that act as hindrances for imaging purpose. Although light penetrates the skin a little and it is possible to image and monitor superficial blood flow using light illumination, it remains as a challenge to probe deep tissue (roughly 0.1 ~ 3.0 cm) using light alone. In this chapter, we describe the challenges and recent achievements of diffuse optical methods to probe deep tissue, running the gamut from diffuse optical spectroscopy (DOS) and diffuse optical tomography (DOT) to recently developed diffuse speckle contrast analysis (DSCA). Diffuse optics has opened up a new possibility of non-invasive diagnosis of lesions in deep tissue. In addition, the usage of light makes diffuse optics-based device compatible with other conventional medical devices such as CT and MRI as well as some implanted device such as pace maker. Moreover, diffuse optics-based device is relatively cost-effective and portable. These merits could limitlessly extend its application to primary care unit, bedside monitoring, and operation theater as an optimal modality for probing hemodynamic parameters in microvasculature in deep tissue.


Blood Perfusion Deep Tissue Diffuse Optical Imaging Optical Intrinsic Signal Bedside Monitoring 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    R. Bright, Diseases of the Brain and Nervous System (Longman, London, 1831)Google Scholar
  2. 2.
    M. Cutler, Transillumination of the breast. Surg. Gynecol. Obstet. 48, 721 (1929)Google Scholar
  3. 3.
    F.F. Jobsis, Noninvasive infrared monitoring of cerebral and myocardial sufficiency and circulatory parameters. Science 198, 1264 (1977)CrossRefGoogle Scholar
  4. 4.
    D.B. Jakubowski, A.E. Cerussi, F.d.r. Bevilacqua, N. Shah, D. Hsiang, J. Butler, B.J. Tromberg, Monitoring neoadjuvant chemotherapy in breast cancer using quantitative diffuse optical spectroscopy: a case study. J. Biomed. Opt. 9, 230–238 (2004)Google Scholar
  5. 5.
    R. Choe, A. Corlu, K. Lee, T. Durduran, S.D. Konecky, M. Grosicka-Koptyra, S.R. Arridge, B.J. Czerniecki, D.L. Fraker, A. DeMichele, B. Chance, M.A. Rosen, A.G. Yodh, Diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study with comparison to MRI. Med. Phys. 32, 1128–1139 (2005)CrossRefGoogle Scholar
  6. 6.
    A. Cerussi, D. Hsiang, N. Shah, R. Mehta, A. Durkin, J. Butler, B.J. Tromberg, Predicting response to breast cancer neoadjuvant chemotherapy using diffuse optical spectroscopy. Proc. Natl. Acad. Sci. U.S.A. 104, 4014–4019 (2007)CrossRefGoogle Scholar
  7. 7.
    S.D. Jiang, B.W. Pogue, C.M. Carpenter, S.P. Poplack, W.A. Wells, C.A. Kogel, J.A. Forero, L.S. Muffly, G.N. Schwartz, K.D. Paulsen, P.A. Kaufman, Evaluation of breast tumor response to neoadjuvant chemotherapy with tomographic diffuse optical spectroscopy: case studies of tumor region-of-interest changes. Radiology 252, 551–560 (2009)CrossRefGoogle Scholar
  8. 8.
    Y. Hoshi, Functional near-infrared optical imaging: utility and limitations in human brain mapping. Psychophysiology 40, 511–520 (2003)CrossRefGoogle Scholar
  9. 9.
    D.A. Boas, A.M. Dale, M.A. Franceschini, Diffuse optical imaging of brain activation: approaches to optimizing image sensitivity, resolution, and accuracy. NeuroImage 23, S275–S288 (2004)CrossRefGoogle Scholar
  10. 10.
    A.T. Eggebrecht, S.L. Ferradal, A. Robichaux-Viehoever, M.S. Hassanpour, H. Dehghani, A.Z. Snyder, T. Hershey, J.P. Culver, Mapping distributed brain function and networks with diffuse optical tomography. Nat Photon 8, 448–454 (2014)CrossRefGoogle Scholar
  11. 11.
    A. Maki, Y. Yamashita, H. Koizumi, Wavelength dependence of the precision of noninvasive optical measurement of oxy-, deoxy- and total-hemoglobin concentration. Med. Phys. 28, 1108 (2001)Google Scholar
  12. 12.
    M.A. Franceschini, G. Strangman, D.A. Boas, Factors affecting the accuracy of near-infrared spectroscopy concentration calculations for focal changes in oxygenation parameters. Neuroimage 18, 865 (2003)CrossRefGoogle Scholar
  13. 13.
    T. Durduran, R. Choe, W.B. Baker, A.G. Yodh, Diffuse optics for tissue monitoring and tomography. Rep. Prog. Phys. 73, 076701 (2010)Google Scholar
  14. 14.
    T.J. Farrell, M.S. Patterson, B. Wilson, A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the noninvasive determination of tissue optical properties in vivo. Med. Phys. 19, 879 (1992)CrossRefGoogle Scholar
  15. 15.
    J. Ripoll, Light diffusion in turbid media with biomedical applications, Universidad Autonoma de Madrid, 2000Google Scholar
  16. 16.
    D.A. Boas, Diffuse photon probes of structural and dynamical properties of turbid media theory and biomedical applications, University of Pennsylvania, 1996Google Scholar
  17. 17.
    M.A. O’Leary, Imaging with diffuse photon density waves. University of Pennsylvania, 1996Google Scholar
  18. 18.
    D.R. Leff, O.J. Warren, L.C. Enfield, A. Gibson, T. Athanasiou, D.K. Patten, J. Hebden, G.Z. Yang, A. Darzi, Diffuse optical imaging of the healthy and diseased breast: a systematic review. Breast Cancer Res. Treat. 108, 9–22 (2008)CrossRefGoogle Scholar
  19. 19.
    T. Durduran, R. Choe, J.P. Culver, L. Zubkov, M.J. Holboke, J. Giammarco, B. Chance, A.G. Yodh, Bulk optical properties of healthy female breast tissue. Phys. Med. Biol. 47, 2847 (2002)CrossRefGoogle Scholar
  20. 20.
    T. Yates, J.C. Hebden, A. Gibson, N. Everdell, S.R. Arridge, M. Douek, Optical tomography of the breast using a multi-channel time-resolved imager. Phys. Med. Biol. 50, 2503 (2005)CrossRefGoogle Scholar
  21. 21.
    M.L. Flexman, M.A. Khalil, R. Al Abdi, H.K. Kim, C.J. Fong, E. Desperito, D.L. Hershman, R.L. Barbour, A.H. Hielscher, Digital optical tomography system for dynamic breast imaging. J. Biomed. Opt. 16, 076014–076016 (2011)Google Scholar
  22. 22.
    X. Intes, S. Djeziri, Z. Ichalalene, N. Mincu, Y. Wang, P. St.-Jean, F.d.r. Lesage, D. Hall, D.A. Boas, M. Polyzos, Time-domain optical mammography Softscan: initial results on detection and characterization of breast tumors, pp. 188–197 (2004)Google Scholar
  23. 23.
    Q. Zhu, M. Huang, N. Chen, K. Zarfos, B. Jagjivan, M. Kane, P. Hedge, S.H. Kurtzman, Ultrasound-guided optical tomographic imaging of malignant and benign breast lesions: initial clinical results of 19 cases. Neoplasia 5, 379 (2003)CrossRefGoogle Scholar
  24. 24.
    N. Chen, Q. Zhu, S.H. Kurtzman, Imaging tumor angiogenesis by use of combined near-infrared diffusive light and ultrasound. Opt. Lett. 28, 337 (2003)CrossRefGoogle Scholar
  25. 25.
    L. Enfield, G. Cantanhede, M. Douek, V. Ramalingam, A. Purushotham, J. Hebden, A. Gibson, Monitoring the response to neoadjuvant hormone therapy for locally advanced breast cancer using three-dimensional time-resolved optical mammography. J. Biomed. Opt. 18, 056012–056012 (2013)CrossRefGoogle Scholar
  26. 26.
    C.H. Schmitz, M. Löcker, J.M. Lasker, A.H. Hielscher, R.L. Barbour, Instrumentation for fast functional optical tomography. Rev. Sci. Instrum. 73, 429–439 (2002)CrossRefGoogle Scholar
  27. 27.
    S. Srinivasan, C.M. Carpenter, H.R. Ghadyani, S.J. Taka, P.A. Kaufman, R.M. DiFlorio-Alexander, W.A. Wells, B.W. Pogue, K.D. Paulsen, Image guided near-infrared spectroscopy of breast tissue in vivo using boundary element method. J. Biomed. Opt. 15, 061703–061703–061703–061708 (2010)CrossRefGoogle Scholar
  28. 28.
    H. Soliman, A. Gunasekara, M. Rycroft, J. Zubovits, R. Dent, J. Spayne, M.J. Yaffe, G.J. Czarnota, Functional imaging using diffuse optical spectroscopy of neoadjuvant chemotherapy response in women with locally advanced breast cancer. Clin. Cancer Res. 16, 2605–2614 (2010)CrossRefGoogle Scholar
  29. 29.
    B.J. Tromberg, A.E. Cerussi, Imaging breast cancer chemotherapy response with light. Clin. Cancer Res. 16, 2486–2488 (2010)CrossRefGoogle Scholar
  30. 30.
    A. Villringer, J. Planck, C. Hock, L. Schleinkofer, U. Dirnagl, Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults. Neurosci. Lett. 154, 101–104 (1993)CrossRefGoogle Scholar
  31. 31.
    Y. Hoshi, M. Tamura, Detection of dynamic changes in cerebral oxygenation coupled to neuronal function during mental work in man. Neurosci. Lett. 150, 5–8 (1993)CrossRefGoogle Scholar
  32. 32.
    T. Kato, A. Kamei, S. Takashima, T. Ozaki, Human visual cortical function during photic stimulation monitoring by means of near-infrared spectroscopy. J. Cereb. Blood Flow Metab. 13, 516–520 (1993)CrossRefGoogle Scholar
  33. 33.
    J.H. Meek, M. Firbank, C.E. Elwell, J. Atkinson, O. Braddick, J.S. Wyatt, Regional hemodynamic responses to visual stimulation in awake infants. Pediatr. Res. 43, 840–843 (1998)CrossRefGoogle Scholar
  34. 34.
    Y. Hoshi, B.H. Tsou, V.A. Billock, M. Tanosaki, Y. Iguchi, M. Shimada, T. Shinba, Y. Yamada, I. Oda, Spatiotemporal characteristics of hemodynamic changes in the human lateral prefrontal cortex during working memory tasks. NeuroImage 20, 1493–1504 (2003)CrossRefGoogle Scholar
  35. 35.
    F. Okada, Y. Tokumitsu, Y. Hoshi, M. Tamura, Impaired interhemispheric integration in brain oxygenation and hemodynamics in schizophrenia. Eur. Arch. Psychiatry Clin. Nuerosci. 244, 17–25 (1994)CrossRefGoogle Scholar
  36. 36.
    A.J. Fallgatter, W.K. Strik, Reduced frontal functional asymmetry in schizophrenia during a cued continuous performance test assessed with near-infrared spectroscopy. Schizophr. Bull. 26, 913–919 (2000)CrossRefGoogle Scholar
  37. 37.
    T. Shinba, M. Nagano, N. Kariya, K. Ogawa, T. Shinozaki, S. Shimosato, Y. Hoshi, Near-infrared spectroscopy analysis of frontal lobe dysfunction in schizophrenia. Biol. Psychiatry 55, 154–164 (2004)Google Scholar
  38. 38.
    T. Suto, M. Fukuda, M. Ito, T. Uehara, M. Mikuni, Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study. Biol. Psychiatry 55, 501–511 (2004)Google Scholar
  39. 39.
    C. Hock, K. Villringer, F. Müller-Spahn, R. Wenzel, H. Heekeren, S. Schuh-Hofer, M. Hofmann, S. Minoshima, M. Schwaiger, U. Dirnagl, A. Villringer, Decrease in parietal cerebral hemoglobin oxygenation during performance of a verbal fluency task in patients with Alzheimer’s disease monitored by means of near-infrared spectroscopy (NIRS)—correlation with simultaneous rCBF-PET measurements. Brain Res. 755, 293–303 (1997)CrossRefGoogle Scholar
  40. 40.
    A.-C. Ehlis, C.G. Bähne, C.P. Jacob, M.J. Herrmann, A.J. Fallgatter, Reduced lateral prefrontal activation in adult patients with attention-deficit/hyperactivity disorder (ADHD) during a working memory task: a functional near-infrared spectroscopy (fNIRS) study. J. Psychiatr. Res. 42, 1060–1067 (2008)Google Scholar
  41. 41.
    H. Obrig, J. Steinbrink, Non-invasive optical imaging of stroke. Philosophical transactions of the royal society a: mathematical, physical and engineering sciences 369, 4470–4494 (2011)CrossRefGoogle Scholar
  42. 42.
    M.N. Kim, T. Durduran, S. Frangos, B.L. Edlow, E.M. Buckley, H.E. Moss, C. Zhou, G.Q. Yu, R. Choe, E. Maloney-Wilensky, R.L. Wolf, M.S. Grady, J.H. Greenberg, J.M. Levine, A.G. Yodh, J.A. Detre, W.A. Kofke, Noninvasive measurement of cerebral blood flow and blood oxygenation using near-infrared and diffuse correlation spectroscopies in critically brain-injured adults. Neurocrit. Care 12, 173–180 (2010)CrossRefGoogle Scholar
  43. 43.
    P.J. Kirkpatrick, J. Lam, P. Al-Rawi, P. Smielewski, M. Czosnyka, Defining thresholds for critical ischemia by using near-infrared spectroscopy in the adult brain. J. Neurosurg. 89, 389–394 (1998)CrossRefGoogle Scholar
  44. 44.
    A. Gallagher, M. Lassonde, D. Bastien, P. Vannasing, F. Lesage, C. Grova, A. Bouthillier, L. Carmant, F. Lepore, R. Béland, D.K. Nguyen, Non-invasive pre-surgical investigation of a 10 year-old epileptic boy using simultaneous EEG–NIRS. Seizure—Eur. J. Epilepsy 17, 576–582 (2008)Google Scholar
  45. 45.
    L.S.L. Arakaki, V. Ntziachristos, B. Chance, J.S. Leigh, J.C. Schotland, Optical diffusion tomography of the exercising human forearm. Biomed. Opt. Spectrosc. Diagn. 38, 374–377 (2000)Google Scholar
  46. 46.
    G.Q. Yu, Y. Shang, Y.Q. Zhao, R. Cheng, L.X. Dong, S.P. Saha, Intraoperative evaluation of revascularization effect on ischemic muscle hemodynamics using near-infrared diffuse optical spectroscopies. J Biomed. Opt. 16, 027004 (2011)Google Scholar
  47. 47.
    Y. Yamada, S. Okawa, Diffuse optical tomography: present status and its future. Opt. Rev. 21, 185–205 (2014)CrossRefGoogle Scholar
  48. 48.
    N. Deliolanis, T. Lasser, D. Hyde, A. Soubret, J. Ripoll, V. Ntziachristos, Free-space fluorescence molecular tomography utilizing 360° geometry projections. Opt. Lett. 32, 382–384 (2007)CrossRefGoogle Scholar
  49. 49.
    M. Solomon, B.R. White, R.E. Nothdruft, W. Akers, G. Sudlow, A.T. Eggebrecht, S. Achilefu, J.P. Culver, Video-rate fluorescence diffuse optical tomography for in vivo sentinel lymph node imaging. Biomed. Opt. Express 2, 3267–3277 (2011)CrossRefGoogle Scholar
  50. 50.
    J. Dong, R. Bi, J.H. Ho, P.S.P. Thong, K.-C. Soo, K. Lee, Diffuse correlation spectroscopy with a fast Fourier transform-based software autocorrelator. J. Biomed. Opt. 17, 097001–097004 (2012)CrossRefGoogle Scholar
  51. 51.
    D.A. Boas, A.G. Yodh, Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation. J. Opt. Soc. Am. A 14, 192–215 (1997)CrossRefGoogle Scholar
  52. 52.
    S.A. Carp, G.P. Dai, D.A. Boas, M.A. Franceschini, Y.R. Kim, Validation of diffuse correlation spectroscopy measurements of rodent cerebral blood flow with simultaneous arterial spin labeling MRI; towards MRI-optical continuous cerebral metabolic monitoring. Biomed Opt Express 1, 553–565 (2010)CrossRefGoogle Scholar
  53. 53.
    G.Q. Yu, T.F. Floyd, T. Durduran, C. Zhou, J.J. Wang, J.A. Detre, A.G. Yodh, Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI. Opt. Express 15, 1064–1075 (2007)CrossRefGoogle Scholar
  54. 54.
    E.M. Buckley, N.M. Cook, T. Durduran, M.N. Kim, C. Zhou, R. Choe, G. Yu, S. Schultz, C.M. Sehgal, D.J. Licht, P.H. Arger, M.E. Putt, H.H. Hurt, A.G. Yodh, Cerebral hemodynamics in preterm infants during positional intervention measured with diffuse correlation spectroscopy and transcranial Doppler ultrasound. Opt. Express 17, 12571–12581 (2009)CrossRefGoogle Scholar
  55. 55.
    R. Bi, J. Dong, K. Lee, Deep tissue flowmetry based on diffuse speckle contrast analysis. Opt. Lett. 38, 1401–1403 (2013)CrossRefGoogle Scholar
  56. 56.
    R. Bi, J. Dong, K. Lee, Multi-channel deep tissue flowmetry based on temporal diffuse speckle contrast analysis. Opt. Express 21, 22854–22861 (2013)CrossRefGoogle Scholar
  57. 57.
    K. Lee, R. Bi, J. Dong, Fast and affordable diffuse optical deep-tissue flowmetry. Opt. Photon. News 24, 32–32 (2013)CrossRefGoogle Scholar
  58. 58.
    Y. Shang, T.B. Symons, T. Durduran, A.G. Yodh, G.Q. Yu, Effects of muscle fiber motion on diffuse correlation spectroscopy blood flow measurements during exercise. Biomed. Opt. Express 1, 500–511 (2010)CrossRefGoogle Scholar
  59. 59.
    T. Durduran, R. Choe, G. Yu, C. Zhou, J.C. Tchou, B.J. Czerniecki, A.G. Yodh, Diffuse optical measurement of blood flow in breast tumors. Opt. Lett. 30, 2915–2917 (2005)CrossRefGoogle Scholar
  60. 60.
    J. Dong, H.J. Toh, P.S. Thong, C.S. Tee, R. Bi, K.-C. Soo, K. Lee, Hemodynamic monitoring of Chlorin e6-mediated photodynamic therapy using diffuse optical measurements. J. Photochem. Photobiol. B Biol. 140, 163–172 (2014) Google Scholar
  61. 61.
    J.H. Ho, J. Dong, K. Lee, Chapter 12. Diffuse optical imaging of the breast: recent progress, in Multimodality Breast Imaging: Diagnosis and Treatment, ed. by E.Y.K. Ng, U.R. Acharya, R.M. Rangayyan, J.S. Suri (SPIE, Washington, 2013)Google Scholar

Copyright information

© Springer Science+Business Media Singapore 2016

Authors and Affiliations

  1. 1.School of Chemical and Biomedical EngineeringNanyang Technological UniversitySingaporeSingapore
  2. 2.Wellman Center for PhotomedicineMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  3. 3.School of Basic ScienceConvergence College, Daegu-Gyeongbuk Institute of Science and TechnologyDaeguKorea

Personalised recommendations