Fluorescence Imaging System for Biological Tissues Diagnosis: Phantom and Animal Studies
Currently, optical biopsy is a promising area of diagnosing the state of tissues in real time during the surgical treatment of oncological diseases. The important part of this direction is the development of fluorescence imaging systems and ensuring the accuracy of the calibration of optical measurements. The article describes the development of fluorescence imaging system to define tumor surgical resection margins of abdominal organs. In this study, we proposed of low-cost optical tissue-mimicking phantom combining solid base and liquid part that suitable for quick calibration of fluorescence imaging systems depending on the target endogenous fluorophores. The results of two series of experimental measurements are described. The first measurements of the optical phantom with riboflavin mononucleotide (imitating flavin adenine dinucleotide) and protoporphyrin IX demonstrated the sensitivity of the developed device to proportionally changing concentrations of target fluorophores. The second part of the study included in vivomeasurements of liver tumors modeled in mice. The obtained results showed the ability of the developed fluorescence imaging system to register changes in fluorescence due to carcinogenesis.
1. R. F. Bray, J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. Jemal, “Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries,” CA: A Cancer Journal for Clinicians 68(6), 394–424 (2018).
2. S. Lin, K. Hoffmann, and P. Schemmer, “Treatment of hepatocellular carcinoma: a systematic review,” Liver cancer 1(3–4), 144–158 (2012).
3. N. Coburn, R. Cosby, L. Klein, G. Knight, R. Malthaner, J. Mamazza, C. D. Mercer, and J. Ringash, “Staging and surgical approaches in gastric cancer: A systematic review,” Cancer Treatment Reviews 63, 104–115 (2018).
4. K. D. Miller, L. Nogueira, A. B. Mariotto, J. H. Rowland, K. R. Yabroff, C. M. Alfano, A. Jemal, J. L. Kramer, and R. L. Siegel, “Cancer treatment and survivorship statistics, 2019,” CA: A Cancer Journal for Clinicians 69(5), 363–385 (2019).
5. K. J. Chambers, S. Kraft, and K. Emerick, “Evaluation of frozen section margins in high‐risk cutaneous squamous cell carcinomas of the head and neck,” Laryngoscope 125(3), 636–639 (2015).
6. E. L. Rosenthal, J. M. Warram, E. de Boer, J. P. Basilion, M. A. Biel, M. Bogyo, M. Bouvet, B. E. Brigman, Y. L. Colson, S. R. DeMeester, G. C. Gurtner, T. Ishizawa, P. M. Jacobs, S. Keereweer, J. C. Liao, Q. T. Nguyen, J. M. Olson, K. D. Paulsen, D. Rieves, B. D. Sumer, M. F. Tweedle, A. L. Vahrmeijer, J. P. Weichert, B. C. Wilson, M. R. Zenn, K. R. Zinn, and G. M. van Dam, “Successful translation of fluorescence navigation during oncologic surgery: a consensus report,” Journal of Nuclear Medicine 57(1), 144–150 (2016).
7. I. J. Bigio, J. R. Mourant, “Optical biopsy,” in Encyclopedia of Optical Engineering, CRC Press, Boca Raton, 1577–1593 (2003).
8. T. D. Wang, J. Van Dam, “Optical biopsy: A new frontier in endoscopic detection and diagnosis,” Clinical Gastroenterology and Hepatology 2(9), 744–753 (2004).
9. G. T. Kennedy, O. T. Okusanya, J. J. Keating, D. F. Heitjan, C. Deshpande, L. A. Litzky, S. M. Albelda, J. A. Drebin, S. Nie, P. S. Low, and S. Singhal, “The optical biopsy: A novel technique for rapid intraoperative diagnosis of primary pulmonary adenocarcinomas,” Annals of Surgery 262(4), 602–609 (2015).
10. A. C. Croce, A. Ferrigno, G. Bottiroli, and M. Vairetti, “Autofluorescence‐based optical biopsy: An effective diagnostic tool in hepatology,” Liver International 38(7), 1160–1174 (2018).
11. I. Georgakoudi, M. S. Feld, “The combined use of fluorescence, reflectance, and light-scattering spectroscopy for evaluating dysplasia in Barrett’s esophagus,” Gastrointestinal Endoscopy Clinics of North America 14(3), 519–537 (2004).
12. S. Y. Lee, W. R. Lloyd, M. Chandra, R. H. Wilson, B. McKenna, D. Simeone, J. Scheiman, and M.-A. Mycek, “Characterizing human pancreatic cancer precursor using quantitative tissue optical spectroscopy,” Biomedical Optics Express 4(12), 2828–2834 (2013).
13. A. Gisbrecht, E. Borisova, T. Genova-Hristova, P. Troyanpva, E. Pavlova, N. Penkov, I. Bratchenko, V. Zakharov, I. Lihachova, I. Kuzmina, and J. Spigulis, “Multispectral autoflourescence detection of skin neoplasia using steady-state techniques,” Proceeding of SPIE 11047, 1104704 (2019).
14. Y. A. Khristoforova, I. A. Bratchenko, O. O. Myakinin, D. N. Artemyev, A. A. Moryatov, A. E. Orlov, S. V. Kozlov, and V. P. Zakharov, “Portable spectroscopic system for in vivo skin neoplasms diagnostics by Raman and autofluorescence analysis,” Journal of Biophotonics 12(4), e201800400 (2019).
15. K. Kandurova, V. Dremin, E. Zherebtsov, E. Potapova, A. Alyanov, A. Mamoshin, Y. Ivanov, A. Borsukov, and A. Dunaev, “Fiber-optic system for intraoperative study of abdominal organs during minimally invasive surgical interventions,” Applied Sciences 9(2), 217 (2019).
16. V. R. Kolli, A. R. Shaha, H. E. Savage, P. G. Sacks, M. A. Casale, and S. P. Schantz, “Native cellular fluorescence can identify changes in epithelial thickness in-vivo in the upper aerodigestive tract,” The American Journal of Surgery 170(5), 495–498 (1995).
17. B. Hill, S. F. Lam, P. Lane, C. MacAulay, L. Fradkin, and M. Follen, “Established and emerging optical technologies for the real-time detection of cervical neoplasia: a review,” Journal of Cancer Therapy 8(13), 1241–1278 (2017).
18. K. He, L. Zhao, Y. Chen, X. Huang, Y. Ding, H. Hua, L. Liu, X. Wang, M. Wang, Y. Zhang, and Z. Fan, “Label‐free multiphoton microscopic imaging as a novel real‐time approach for discriminating colorectal lesions: A preliminary study,” Journal of Gastroenterology and Hepatology 34(12), 2144–2151 (2019).
19. T. Nagaya, Y. A. Nakamura, P. L. Choyke, and H. Kobayashi, “Fluorescence-guided surgery,” Frontiers in Oncology 7, 314 (2017).
20. K. Koenig, H. Schneckenburger, “Laser-induced autofluorescence for medical diagnosis,” Journal of Fluorescence 4(1), 17–40 (1994).
21. S. Palmer, K. Litvinova, A. Dunaev, J. Yubo, D. McGloin, and G. Nabi, “Optical redox ratio and endogenous porphyrins in the detection of urinary bladder cancer: A patient biopsy analysis,” Journal of Biophotonics 10(8), 1062–1073 (2017).
22. T. Vo-Dinh, Biomedical photonics handbook: biomedical diagnostics, CRC press, Boca Raton (2014).
23. K. T. Moesta, B. Ebert, T. Handke, D. Nolte, C. Nowak, W. E. Haensch, R. K. Pandey, T. J. Dougherty, H. Rinneberg, and P. M. Schlag, “Protoporphyrin IX occurs naturally in colorectal cancers and their metastases,” Cancer Research 61(3), 991–999 (2001).
24. C. J. Fox, P. S. Hammerman, and C. B. Thompson, “Fuel feeds function: energy metabolism and the T-cell response,” Nature Reviews Immunology 5(11), 844–852 (2005).
25. E. Currie, A. Schulze, R. Zechner, T. C. Walther, and R. V. Farese, “Cellular fatty acid metabolism and cancer,” Cell Metabolism 18(2), 153–161 (2013).
26. Y. Wu , P. Xi, J. Y. Qu, T.-H. Cheung, and M.-Y. Yu, “Depth-resolved fluorescence spectroscopy of normal and dysplastic cervical tissue,” Optics Express 13(2), 382–388 (2005).
27. Y. Wu, J. Y. Qu, “Autofluorescence spectroscopy of epithelial tissues,” Journal of Biomedical Optics 11(5), 054023 (2006).
28. N. Ramanujam, “Fluorescence spectroscopy of neoplastic and non-neoplastic tissues,” Neoplasia 2(1–2), 89–117 (2000).
29. M. M. Lukina, M. V. Shirmanova, T. F. Sergeeva, and E. V. Zagaynova, “Metabolic imaging in the study of oncological processes,” Sovremennye Tehnologii v Medicine 8(4 (eng)), 113–124 (2016).
30. I. Pavlova, K. Sokolov, R. Drezek, A. Malpica, M. Follen, and R. Richards-Kortum, “Microanatomical and Biochemical Origins of Normal and Precancerous Cervical Autofluorescence Using Laser‐scanning Fluorescence Confocal Microscopy,” Photochemistry and Photobiology 77(5), 550–555 (2003).
31. A. C. Croce, G. Santamaria, U. D. Simone, F. Lucchini, I. Freitas, and G. Bottiroli, “Naturally-occurring porphyrins in a spontaneous-tumour bearing mouse model,” Photochemical & Photobiological Sciences 10(7), 1189–1195 (2011)..
32. W. Kemmner, K. Wan, S. Rüttinger, B. Ebert, R. Macdonald, U. Klamm, and K. T. Moesta, “Silencing of human ferrochelatase causes abundant protoporphyrin-IX accumulation in colon cancer,” The FASEB Journal 22(2), 500–509 (2008).
33. M. Sachar, K. E. Anderson, and X. Ma, “Protoporphyrin IX: the good, the bad, and the ugly,” Journal of Pharmacology and Experimental Therapeutics 356(2), 267–275 (2016).
34. E. A. Machinskaya, V. I. Ivanova-Radkevich, “Review of selective accumudation of photosensitizers with different chemical structure in tumor tissue,” Photodynamic therapy and photodyagnosis 2(4), 28–32 (2013). [in Russian]
35. A. Moiyadi, P, Shetty, E. Sridhar, V. Gota, M. Gurjar, G. Saicharan, V. Singh, and S. Srivastava, “Objective assessment of intraoperative tumor fluorescence reveals biological heterogeneity within glioblastomas: a biometric study,” Journal of Neuro-Oncology 146(3), 477–488 (2020).
36. O. Stelmashchuk, E. Zherebtsov, A. Zherebtsova, E. Kuznetsova, A. Vinokurov, A. Dunaev, A. Mamoshin, I. Snimshchikova, A. Borsukov, A. Bykov, and I. Meglinski, “Noninvasive control of the transport function of fluorescent coloured liposomal nanoparticles,” Laser Physics Letters 14(6), 065603 (2017).
37. I. V. Meglinski, S. J. Matcher, “Quantitative assessment of skin layers absorption and skin reflectance spectra simulation in the visible and near-infrared spectral regions,” Physiological Measurement 23(4), 741 (2002).
38. P. Thueler, I. Charvet, F. Bevilacqua, M. St. Ghislain, G. Ory, P. Marquet, P. Meda, B. Vermeulen, and C. Depeursinge, “In vivo endoscopic tissue diagnostics based on spectroscopic absorption, scattering, and phase function properties,” Journal of Biomedical Optics 8(3), 495–504 (2003).
39. M. Anastasopoulou, D. Gorpas, M. Koch, E. Liapis, S. Glasl, U. Klemm, A. Karlas, T. Lasser, and V. Ntziachristos, “Fluorescence imaging reversion using spatially variant deconvolution,” Scientific Reports 9(1), 1–11 (2019).
40. L. H. Luthjens, T. Yao, and J. M. Warman, “A polymer-gel eye-phantom for 3D fluorescent imaging of millimetre radiation beams,” Polymers 10(11), 1195 (2018).
41. H. Lu, F. Floris, M. Rensing, and S. Andersson-Engels, “Fluorescence spectroscopy study of protoporphyrin IX in tissue-like phantoms,” Proceeding of SPIE 11190, 111901S (2019).
42. Y. Xie, E. Maneas, S. Islam, W. Peveler, J. Shapey, W. Xia, S. Ourselin, I. P. Parkin, A. E. Desjardins, and T. Vercauteren, “Soft optically tuneable fluorescence phantoms based on gel wax and quantum dots: a tissue surrogate for fluorescence imaging validation,” Proceeding of SPIE 10862, 108621F (2019).
43. U. Resch-Genger, M. Grabolle, S. Cavaliere-Jaricot, R. Nitschke, and T. Nann, “Quantum dots versus organic dyes as fluorescent labels,” Nature Methods 5(9), 763–775 (2008).
44. M. Anastasopoulou, M. Koch, V. Ntziachristos, D. Gorpas, P. B. Garcia-Allende, U. Klemm, and A. Karlas, “Multiparameter solid phantom for fluorescence imaging standardization,” Proceeding of SPIE 10411, 104110J (2017).
45. B. W. Pogue, M. S. Patterson, “Review of tissue simulating phantoms for optical spectroscopy, imaging and dosimetry,” Journal of Biomedical Optics 11(4), 041102 (2006).
46. B. Leh, R. Siebert, H. Hamzeh, L. Menard, M.-A. Duval, Y. Charon, and D. A. Haidar, “Optical phantoms with variable properties and geometries for diffuse and fluorescence optical spectroscopy,” Journal of Biomedical Optics 17(10), 108001 (2012).
47. K. B. Nivetha, N. Sujatha, “Development of thin skin mimicking bilayer solid tissue phantoms for optical spectroscopic studies,” Biomedical Optics Express 8(7), 3198–3212 (2017).
48. P. Drössler, W. Holzer, A. Penzkofer, and P. Hegemann, “pH dependence of the absorption and emission behaviour of riboflavin in aqueous solution,” Chemical Physics 282(3), 429–439 (2002).
49. A. Aliverti, B. Curti, and M. A. Vanoni, “Identifying and quantitating FAD and FMN in simple and in iron-sulfur-containing flavoproteins,” in Flavoprotein Protocols, S. K. Chapman, G. A. Reid (eds.), Springer, New York, 9–23 (1999).
50. M. L. Dean, T. A. Miller, and C. Brückner, “Egg-citing! Isolation of protoporphyrin IX from brown eggshells and its detection by optical spectroscopy and chemiluminescence,” Journal of Chemical Education 88(6), 788–792 (2011).
51. OECD Series on Principles of Good Laboratory Practice (GLP) and Compliance Monitoring, Organisation for Economic Co-operation and Development, Paris, France, 1998–2019 (accessed 14.02.2020).
52. E. Zherebtsov, V. Dremin, A. Popov, A. Doronin, D. Kurakina, M. Kirillin, I. Meglinski, and A. Bykov, “Hyperspectral imaging of human skin aided by artificial neural networks,” Biomedical Optics Express 10(7), 3545–3559 (2019).
© 2014-2023 Samara National Research University. All Rights Reserved.
Public Media Certificate (RUS). 12+