volume | PIER Journals

Abstract

Raman imaging for a sepsis study is reported here for the first time. We propose a confocal resonance Raman microscopic imager (CRRMI)to measure in vivo the redox state of mitochondria over a surface area of a septic rat. The CRRMI has excellent performance with spectral and spatial resolutions of 0.1 nm and 2 um, respectively. It is found for the first time that the Raman signal related to the mitochondrial dysfunction in sepsis is abnormally large only locally at many points with some random spatial distribution. Our CRRMI can detect the mitochondrial redox state through the skin of a naturally living rat even without the removal of hairs, and overcomes some issues that a pointwise measurement method of Raman signalsmay encounter when monitoring mitochondrial dysfunction of a sepsis rat, such as the fluorescence of hairs, hitting the points without mitochondrial redox metabolic disorder, etc.The present Raman imager can be used for giving an early warning for sepsis. It provides a new method for noninvasive monitoring of mitochondrial redox status in sepsis.

1. Singer, M., C. S. Deutschman, C. W. Seymour, et al. "The third international consensus definitions for sepsis and septic shock (Sepsis-3)," JAMA, Vol. 315, 801-810, 2016.
doi:10.1001/jama.2016.0287 Google Scholar

2. Evans, L., A. Rhodes, W. Alhazzani, et al. "Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021," Intensive Care Med., Vol. 47, 1181-1247, 2021.
doi:10.1007/s00134-021-06506-y Google Scholar

3. Rudd, K. E., S. C. Johnson, K. M. Agesa, et al. "Global, regional, and national sepsis incidence and mortality, 1990-2017: Analysis for the global burden of disease study," Lancet, Vol. 395, 200-211, 2020.
doi:10.1016/S0140-6736(19)32989-7 Google Scholar

4. Cecconi, M., L. Evans, M. Levy, et al. "Sepsis and septic shock," Lancet, Vol. 392, 75-87, 2018.
doi:10.1016/S0140-6736(18)30696-2 Google Scholar

5. Liu, V. X., Y. Lu, K. A. Carey, E. R. Gilbert, M. Afshar, M. Akel, N. S. Shah, J. Dolan, C. Winslow, P. Kipnis, D. P. Edelson, G. J. Escobar, and M. M. Churpek, "Comparison of early warning scoring systems for hospitalized patients with and without infection at risk for in-hospital mortality and transfer to the intensive care unit," JAMA Netw. Open, Vol. 3, e205191, 2020.
doi:10.1001/jamanetworkopen.2020.5191 Google Scholar

6. Reinhart, K., R. Daniels, N. Kissoon, F. R. Machado, R. D. Schachter, and S. Finfer, "Recognizing sepsis as a global health priority --- A WHO resolution," N. Engl. J. Med., Vol. 377, 414-417, 2017.
doi:10.1056/NEJMp1707170 Google Scholar

7. Singer, M., "The role of mitochondrial dysfunction in sepsis-induced multi-organ failure," Virulence, Vol. 5, 66-72, 2014.
doi:10.4161/viru.26907 Google Scholar

8. Fink, M. P., "Cytopathic hypoxia, is oxygen use impaired in sepsis as a result of an acquired intrinsic derangement in cellular respiration?," Crit. Care Clin., Vol. 8, 165-175, 2002.
doi:10.1016/S0749-0704(03)00071-X Google Scholar

9. Galley, H. F., "Oxidative stress and mitochondrial dysfunction in sepsis," Br. J. Anaesth., Vol. 107, 57-64, 2011.
doi:10.1093/bja/aer093 Google Scholar

10. Crouser, E. D., M. W. Julian, J. E. Huff, J. Struck, and C. H. Cook, "Carbamoyl phosphate synthase-1: A marker of mitochondrial damage and depletion in the liver during sepsis," Crit. Care Med., Vol. 34, 2439-2446, 2006.
doi:10.1097/01.CCM.0000230240.02216.21 Google Scholar

11. Carré, J. E., J.-C. Orban, L. Re, K. Felsmann, W. Iffert, M. Bauer, H. B. Suliman, C. A. Piantadosi, T. M. Mayhew, P. Breen, M. Stotz, and M. Singer, "Survival in critical illness is associated with early activation of mitochondrial biogenesis," Am. J. Respir Crit. Care Med., Vol. 182, 745-751, 2010.
doi:10.1164/rccm.201003-0326OC Google Scholar

12. Robert, B., "Resonance Raman spectroscopy," Photosynthesis Research, Vol. 101, 147-155, 2009.
doi:10.1007/s11120-009-9440-4 Google Scholar

13. Spiro, T. G., "Resonance Raman spectroscopy. New structure probe for biological chromophor," Acc. Chem. Res., Vol. 7, 339-344, 1974.
doi:10.1021/ar50082a004 Google Scholar

14. Spiro, T. G. and T. C. Strekas, "Resonance Raman spectra of hemoglobin and cytochrome c: Inverse polarization and vibronic scattering," Proc. Natl. Acad. Sci., Vol. 69, 2622-2626, USA, 1972.
doi:10.1073/pnas.69.9.2622 Google Scholar

15. Perry, D. A., J. W. Salvin, P. Romfh, P. L. Chen, K. Krishnamurthy, L. M. Thomson, B. D. Polizzotti, F. X. McGowan, D. Vakhshoori, and J. N. K, "Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest," Sci. Transl. Med., Vol. 9, eaan0117, 2017.
doi:10.1126/scitranslmed.aan0117 Google Scholar

16. Carré, J. E., J.-C. Orban, L. Re, K. Felsmann, W. Iffert, M. Bauer, H. B. Suliman, C. A. Piantadosi, T. M. Mayhew, P. Breen, M. Stotz, and M. Singer, "Survival in critical illness is associated with early activation of mitochondrial biogenesis," Am. J. Respir Crit. Care Med., Vol. 182, 745-751, 2010.
doi:10.1164/rccm.201003-0326OC Google Scholar

17. Lalonde, J. W., G. D. Noojin, N. J. Pope, S. M. Powell, V. V. Yakovlev, and M. L. Denton, "Continuous assessment of metabolic activity of mitochondria using resonance Raman microspectroscopy," Journal of Biophotonics, Vol. 14, e202000384, 202. Google Scholar

18. Morimoto, T., L. D. Chiu, H. Kanda, H. Kawagoe, T. Ozawa, M. Nakamura, K. Nishida, K. Fujita, and T. Fujikado, "Using redox-sensitive mitochondrial cytochrome Raman bands for label-free detection of mitochondrial dysfunction," Analyst, Vol. 144, 2531-2540, 2019.
doi:10.1039/C8AN02213E Google Scholar

19. Brazhe, N. A., M. Treiman, B. Faricelli, J. H. Vestergaard, and O. Sosnovtseva, "In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart," PLoS One, Vol. 8, e70488, 2013.
doi:10.1371/journal.pone.0070488 Google Scholar

20. Rittirsch, D., M. S. Huber-Lang, M. A. Flierl, and P. A. Ward, "Immunodesign of experimental sepsis by cecal ligation and puncture," Nat. Protoc., Vol. 4, 31-36, 2009.
doi:10.1038/nprot.2008.214 Google Scholar

21. Brazhe, N. A., M. Treiman, A. R. Brazhe, N. L. Find, G. V. Maksimov, and O. V. Sosnovtseva, "Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy," PLoS One, Vol. 7, e41990, 2012.
doi:10.1371/journal.pone.0041990 Google Scholar

22. Chen, Z., J. Liu, L. Tian, Q. Zhang, Y. Guan, L. Chen, G. Liu, H.-Q. Yu, Y. Tian, and Q. Huang, "Raman micro-spectroscopy monitoring of cytochrome c redox state in Candida utilis during cell death under low-temperature plasma-induced oxidative stress," Analyst, Vol. 145, 2020. Google Scholar

23. Brückner, M., K. Becker, J. Popp, and T. Frosch, "Fiber array based hyperspectral Raman imaging for chemical selective analysis of malaria-infected red blood cells," Analytica Chimica Acta, Vol. 894, 76-84, 2015.
doi:10.1016/j.aca.2015.08.025 Google Scholar

24. Luo, J., S. Li, E. Forsberg, and S. He, "4D surface shape measurement system with high spectral resolution and great depth accuracy," OE, Vol. 29, 13048-13070, 2021.
doi:10.1364/OE.423755 Google Scholar

25. Luo, J., Z. Lin, Y. Xing, E. Forsberg, C. Wu, X. Zhu, T. Guo, G. Wang, B. Bian, D. Wu, and S. He, "Portable 4D snapshot hyperspectral imager for fast spectral and surface morphology measurements," Progress In Electromagnetics Research, Vol. 173, 25-36, 2022.
doi:10.2528/PIER22021702 Google Scholar

26. Li, J., F. Cai, Y. Dong, Z. Zhu, X. Sun, H. Zhang, and S. He, "A portable confocal hyperspectral microscope without any scan or tube lens and its application in uorescence and Raman spectral imaging," Optics Communications, Vol. 392, 1-6, 2017.
doi:10.1016/j.optcom.2017.01.031 Google Scholar

27. Shen, F., H. Deng, L. Yu, and F. Cai, "Open-source mobile multispectral imaging system and its applications in biological sample sensing," Spectrochimica Acta, Part A: Molecular and Biomolecular Spectroscopy, Vol. 280, 121504, 2022.
doi:10.1016/j.saa.2022.121504 Google Scholar

28. Xu, Z., Y. Jiang, J. Ji, E. Forsberg, Y. Li, and S. He, "Classification, identification, and growth stage estimation of microalgae based on transmission hyperspectral microscopic imaging and machine learning," OE, Vol. 28, 30686, 2020.
doi:10.1364/OE.406036 Google Scholar

29. Xu, Z., Y. Jiang, and S. He, "Multi-mode microscopic hyperspectral imager for the sensing of biological samples," Applied Sciences, Vol. 10, 4876, 2020.
doi:10.3390/app10144876 Google Scholar

Mr. Changwei Jiao

Mr. Zijian Lin

Dr. Yinghe Xu

Prof. Sailing He