Characterizing Metabolic Shifts in Septic Murine Kidney Tissue Using 2P-FLIM for Early Sepsis Detection

被引：0
作者：
Greiner, Stella [1 ,2 ,3 ]
Ebrahimi, Mahyasadat [1 ,2 ,3 ]
Rodewald, Marko [4 ]
Urbanek, Annett [1 ]
Meyer-Zedler, Tobias [1 ,2 ,3 ]
Schmitt, Michael [1 ]
Neugebauer, Ute [1 ,2 ,3 ,5 ,6 ]
Popp, Juergen [1 ,2 ,3 ]
机构：
[1] Leibniz Inst Photon Technol Leibniz IPHT, Leibniz Ctr Photon Infect Res LPI Jena, Res Alliance Leibniz Hlth Technol, Albert Einstein Str 9, D-07745 Jena, Germany
[2] Friedrich Schiller Univ Jena, Inst Phys Chem, Helmholtzweg 4, D-07743 Jena, Germany
[3] Friedrich Schiller Univ Jena, Abbe Ctr Photon, Helmholtzweg 4, D-07743 Jena, Germany
[4] Politecn Milan, Dipartimento Fis, Piazza Leonardo Vinci 32, I-20133 Milan, Italy
[5] Jena Univ Hosp, Ctr Sepsis Control & Care, Klinikum 1, D-07747 Jena, Germany
[6] Jena Univ Hosp, Dept Anaesthesiol & Intens Care Med, Klinikum 1, D-07747 Jena, Germany
来源：
BIOENGINEERING-BASEL | 2025年 / 12卷 / 02期
基金：
欧盟地平线“2020”;
关键词：
metabolic non-linear imaging; FLIM; sepsis; kidney;
D O I：
10.3390/bioengineering12020170
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
In this study, thin mouse kidney sections from healthy mice and those infected leading to acute and chronic sepsis were examined with two-photon excited fluorescence lifetime imaging (2P-FLIM) using the endogenous fluorescent coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD). The results presented show that this approach is a powerful tool for investigating cell metabolism in thin tissue sections. An adapted measurement routine was established for these samples by performing a spectral scan, identifying a combination of two excitation wavelengths and two detection ranges suitable for detailed scan images of NADH and FAD. Selected positions in thin slices of the renal cortex of nine mice (three healthy, three with chronic sepsis, and three with acute sepsis) were studied using 2P-FLIM. In addition, overview images were obtained using two-photon excited fluorescence (2PEF) intensity. This study shows that healthy kidney slices differ considerably from those with acute sepsis with regard to their fluorescence lifetime signatures. The latter shows a difference in metabolism between the inner and outer cortex, indicating that outer cortical tubular cells switch their metabolism from oxidative phosphorylation to glycolysis in kidneys from mice with acute sepsis and back in later stages, as seen for mice with chronic infections. These findings suggest that 2P-FLIM could serve as a powerful tool for early-stage sepsis diagnosis and monitoring metabolic recovery during treatment.
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页数：17
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  • [1] Singer M., Deutschman C.S., Seymour C.W., Shankar-Hari M., Annane D., Bauer M., Bellomo R., Bernard G.R., Chiche J.-D., Coopersmith C.M., Et al., The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), JAMA, 315, pp. 801-810, (2016)
  • [2] Cecconi M., Evans L., Levy M., Rhodes A., Sepsis and septic shock, Lancet, 392, pp. 75-87, (2018)
  • [3] Rudd K.E., Johnson S.C., Agesa K.M., Shackelford K.A., Tsoi D., Kievlan D.R., Colombara D.V., Ikuta K.S., Kissoon N., Finfer S., Et al., Global, regional, and national sepsis incidence and mortality, 1990–2017: Analysis for the Global Burden of Disease Study, Lancet, 395, pp. 200-211, (2020)
  • [4] Global Report on the Epidemiology and Burden of Sepsis
  • [5] Krafft C., Popp J., Opportunities of optical and spectral technologies in intraoperative histopathology, Optica, 10, (2023)
  • [6] Shaked N.T., Boppart S.A., Wang L.V., Popp J., Label-free biomedical optical imaging, Nat. Photonics, 17, pp. 1031-1041, (2023)
  • [7] Kim J.A., Wales D.J., Yang G.-Z., Optical spectroscopy for in vivo medical diagnosis—A review of the state of the art and future perspectives, Prog. Biomed. Eng, 2, (2020)
  • [8] Liang W., Chen D., Guan H., Park H.-C., Li K., Li A., Li M.-J., Gannot I., Li X., Label-Free Metabolic Imaging In Vivo by Two-Photon Fluorescence Lifetime Endomicroscopy, ACS Photonics, 9, pp. 4017-4029, (2022)
  • [9] Wang X.F., Periasamy A., Herman B., Coleman D.M., Fluorescence Lifetime Imaging Microscopy (FLIM): Instrumentation and Applications, Crit. Rev. Anal. Chem, 23, pp. 369-395, (1992)
  • [10] Luu P., Fraser S.E., Schneider F., More than double the fun with two-photon excitation microscopy, Commun. Biol, 7, (2024)
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