Asian Journal of Physics Vol 30, No 12 (2021) 1627-1635

Measurement of blood oxygen saturation using a single wavelength photoacoustic Z-scan technique

Albert Kamanzi1†, Helena Rudolph2, Sumit Agrawal2, Sri Rajasekhar Kothapalli2,3 and Chandra S Yelleswarapu1
1Department of Physics, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA
2Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA
3Penn State Cancer institute, The Pennsylvania State University, Hershey, PA 17033, USA.

The paper is dedicated to Prof D V G L N Rao

Measuring and monitoring oxygen saturation (SO2) levels in the blood is very important in medicine. Low oxygen levels in the blood is an early warning sign for immediate medical care as it can be related to a wide variety of chronic illnesses, including viral infections. Also, mapping of SO2 values by performing a raster scan across the region of interest in vivo is essential in clinical and research settings, such as evaluating the therapeutic effects of treatment and monitoring wound healing. Conveniently, the two main derivatives of hemoglobin, oxyhemoglobin and deoxyhemoglobin, work as strong natural optical contrast agents with distinct spectral profiles. The differential optical absorption of oxy- and deoxy hemoglobins has been exploited by non-invasive optical sensing methods, such as pulse oximetry, to quantify blood SO2 levels. However, the accuracy of conventional optical methods is affected by skin color and strong optical scattering of biological tissue. Overcoming the optical scattering limits, photoacoustic imaging has shown great promise in mapping deep tissue SO2 levels. However, bulky and multiwavelength lasers are used in conventional photoacoustic imaging, limiting the portability, affordability and widespread use of the technology. In this work, we quantify the blood oxygen saturation by measuring the nonlinear absorption coefficient (β) of blood samples using a single wavelength photoacoustic Z-scan (PAZ) technique. Results demonstrate a linear dependency between β and blood SO2 levels. In future the PAZ scan could pave the way for many in vivo biomedical applications. © Anita Publications. All rights reserved.
Keywords: Blood oxygenation, Z-scan technique, Photoacoustics, Nonlinear optical studies of blood.

Peer Review Information
Method: Single- anonymous; Screened for Plagiarism? Yes
Buy this Article in Print © Anita Publications. All rights reserve


  1. Reinhart K, Kuhn H J, Hartog C, Bredle D L, Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill, Intensive Care Med, 30(2004)1572–1578.
  2. Lee M, Assessment of oxidative stress and antioxidant property using electron spin resonance (ESR) spectroscopy, J Clin Biochem Nutr, 52(2013)1–8.
  3. Blockley N P, Griffeth V E, Simon A B, Buxton R B, A review of calibrated blood oxygenation level-dependent (BOLD) methods for the measurement of task-induced changes in brain oxygen metabolism, NMR Biomed, 26(2013)987–1003.
  4. Culver J P, Durduran T, Furuya D, Cheung C, Greenberg J H, Yodh A G, Diffuse optical tomography of cerebral blood flow, oxygenation, and metabolism in rat during focal ischemia, J Cerebral Blood Flow & Metabolism, 23(2003)911–924.
  5. Leyba K A, Vasudevan S, O’Sullivan T D, Goergen C J, Evaluation of Hemodynamics in a Murine Hindlimb Ischemia Model Using Spatial Frequency Domain Imaging, Lasers Surg Med, 53(2021)557–566.
  6. Roche-Labarbe N, Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates, Neuroimage, 85(2014)279–286.
  7. Li M, Hu J, Miao Y, Shen H, Tao D, Yang Z, Li Q, Xuan Y S, Raza W, Alzubaidi S, Haacke E M, In vivo measurement of oxygenation changes after stroke using susceptibility weighted imaging filtered phase data, PLoS One, 8(2013)e63013; doi.
  8. Das B P, Sharma M, Bansal S, Philip M, Umamaheswara Rao G S, Prognostic value of tissue oxygen monitoring and regional cerebral oxygen saturation monitoring and their correlation in neurological patients with sepsis: a preliminary, prospective, observational study, J Neurosurg Anesthesiol, 32(2020)77–81.
  9. Chen J, Zhang Y, He L, Liang Y, Wang L, Wide-field polygon-scanning photoacoustic microscopy of oxygen saturation at 1-MHz A-line rate, Photoacoustics, 20(2020)100195; doi. org/10.1016/j.pacs.2020.100195.
  10. Agrawal S, Singh M K, Yang X, Albahrani H, Dangi A, Kothapalli S R, Functional, molecular and structural imaging using LED-based photoacoustic and ultrasound imaging system, Photons Plus Ultrasound: Imaging and Sensing, 11240(2020)112405A;
  11. Foo S S, Abbott D F, Lawrentschuk N, Scott A M, Functional imaging of intratumoral hypoxia, Mol Imaging Biol, 6(2004)291–305.
  12. Rebling J, Estrada H, Gottschalk S, Sela G, Zwack M, Wissmeyer G, Ntziachristos V, Razansky D, Dual-wavelength hybrid optoacoustic-ultrasound biomicroscopy for functional imaging of large-scale cerebral vascular networks, J biophotonics, 11(2018)e201800057;
  13. Ueda S, Saeki T, Osaki A, Yamane T, Kuji I, Bevacizumab induces acute hypoxia and cancer progression in patients with refractory breast cancer: multimodal functional imaging and multiplex cytokine analysis, Clin Cancer Res, 23(2017)5769–5778.
  14. Nishiyama K, Ito N, Orita T, Hayashida K, Arimoto H, Beppu S, Abe M, Unoki T, Endo T, Murai A, Hatada T, Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: a prospective, observational, multicentre study, Resuscitation, 96(2015)135–141.
  15. Rivers EP, Ander DS, Powell D, Central venous oxygen saturation monitoring in the critically ill patient, Curr Opin Crit Care, 7(2001)204–211.
  16. Medikonda R, Ong C S, Wadia R, Goswami D, Schwartz J, Wolff L, Hibino N, Vricella L, Barodka V, Steppan J, A review of goal-directed cardiopulmonary bypass management in pediatric cardiac surgery, World J Pediatr Congenit Heart Surg, 9(2018)565–572.
  17. Kovarova L, Valerianova A, Kmentova T, Lachmanova J, Hladinova Z, Malik J, Low cerebral oxygenation is associated with cognitive impairment in chronic hemodialysis patients, Nephron, 139(2018)113–119.
  18. Alvarez D, Hornero R, Marcos JV, del Campo F, Multivariate analysis of blood oxygen saturation recordings in obstructive sleep apnea diagnosis, IEEE Trans Biomed Eng, 57(2010)2816–2824.
  19. Li T, Lin Y, Shang Y, He L, Huang C, Szabunio M, Yu G, Simultaneous measurement of deep tissue blood flow and oxygenation using noncontact diffuse correlation spectroscopy flow-oximeter, Sci Rep, 3, 1358(2013);
  20. “Pneumonia.” World Health Organization. World Health Organization. Accessed March 27, 2020.
  21. Harris M, Clark J, Coote, Fletcher P, Harnden A, McKean M, Thomson A, British Thoracic Society guidelines for the management of community acquired pneumonia in children: update 2011, Thorax, 66(2011)ii1-ii23;
  22. Jacques S L, Optical properties of biological tissues: a review, Phys Med Bio, 58(2013)R37;
  23. Sjoding M W, Dickson R P, Iwashyna T J, Gay S E, Valley T S, Racial Bias in Pulse Oximetry Measurement, N Engl J Med, 383(2020)2477–2478.
  24. Tiba M H, Awad A B, Pennington A, Fung C M, Napolitano L M, Park P K, Machado-Aranda D A, Gunnerson K J, Romfh P, Ward K R, Resonance Raman spectroscopy derived tissue hemoglobin oxygen saturation in critically ill and injured patients, Shock, 56(2021)92–97.
  25. Rinia H, Bonn M, Vartiainen E E, Schaffer C B, Mueller M, Spectroscopic analysis of the oxygenation state of hemoglobin using coherent anti-Stokes Raman scattering, J Biomed Opt, 11(2006)0505021;
  26. Poddar R, Basu M, Characterization and oxygen saturation study of human retinal blood vessels evaluated by spectroscopic optical coherence tomography angiography, Opt Laser Technol, 122(2020):1058861;
  27. O’Connor J P, Robinson S P, Waterton J C. Imaging tumour hypoxia with oxygen-enhanced MRI and BOLD MRI, Brit J Radiol, 92(2019)201806421-12;
  28. Eklund A, Nichols TE, Knutsson H, Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates, Proc Natl Acad Sci. (S.A), 113(2016)7900–7905.
  29. Bok T, Hysi E, Kolios M C, In vivo photoacoustic assessment of the oxygen saturation changes in the human radial artery: a preliminary study associated with age, J Biomed Opt, 26(2021)036006;
  30. Lin L, Hu P, Shi J, Appleton C M, Maslov K, Li L, Zhang R, Wang L V, Single-breath-hold photoacoustic computed tomography of the breast, Nat Commun, 9(2018)1–9.
  31. Knieling F, Neufert C, Hartmann A, Claussen J, Urich A, Egger C, Vetter M, Fischer S, Pfeifer L, Hagel A, Kielisch C, Multispectral optoacoustic tomography for assessment of Crohn’s disease activity, N Engl J Med, 376(2017) 1292–1294.
  32. Reber J, Willershäuser M, Karlas A, Paul-Yuan K, Diot G, Franz D, Fromme T, Ovsepian S V, Bézière N, Dubikovskaya E, Karampinos D C, Holzapfel C, Hauner H, Klingenspor M, Ntziachristos V, Non-invasive measurement of brown fat metabolism based on optoacoustic imaging of hemoglobin gradients, Cell Metab, 27(2018)689–701.
  33. Yelleswarapu C S, Kothapalli S R, Nonlinear photoacoustics for measuring the nonlinear optical absorption coefficient, Opt Express, 18(2010)9020–9025.
  34. OMLC website,
  35. Agrawal S, Suresh T, Garikipati A, Dangi A, Kothapalli S R, Modeling combined ultrasound and photoacoustic imaging: Simulations aiding device development and artificial intelligence, Photoacoustics, 24(2021)100304;
  36. Frenette M, Hatamimoslehabadi M, Bellinger-Buckley S, Laoui S, La J, Bag S, Mallidi S, Hasan T, Bouma B, Yelleswarapu C, Rochford J, Shining light on the dark side of imaging: excited state absorption enhancement of a bis-styryl BODIPY photoacoustic contrast agent, J Am Chem Soc, 136(2014)15853-15856.
  37. Kislyakov I M, Yelleswarapu C S, Nonlinear scattering studies of carbon black suspensions using photoacoustic Z-scan technique, Appl Phys Lett, 103(2013)151104;
  38. Yasin A, Nair V S, Aravindh S A, Sarkar SM, Hatamimoslehabadi M, Mitra S, Rahim M H, La J, Roqan I S, Yusoff M M, Yelleswarapu C S, Rajan J, Meso-Zn (ii) porphyrins of tailored functional groups for intensifying the photoacoustic signal, J Mat Chem C, 8(2020)8546–8559.
  39. Sheik-Bahae M, Said A A, Wei T H, Hagan D J, Van Stryland E W, Sensitive measurement of optical nonlinearities using a single beam, IEEE J Quant Elect, 26(1990)760–769.