NONINVASIVE ESTIMATION OF THE LOCAL TEMPERATURE OF BIOTISSUES HEATING UNDER THE ACTION OF LASER IRRADIATION FROM THE LUMINESCENCE SPECTRA OF Nd3+ IONS

Laser hyperthermia is one of the promising methods for treatment of oncological diseases. For routine clinical use of hyperthermia, it is necessary to control the uniformity and localization of heat within the tumor. Local heating can be achieved by using special thermal agents, such as nanoparticles doped with rare-earth ions. Measurement of the temperature of the thermal agents will allow timely regulation of the applied laser radiation excitation power and optimization of the hyperthermia process.

The paper presents the results of a study on the non-invasive determination of the YPO₄ nanoparticles doped with Nd³+ temperature with sensitivity of 0.2% °С^-1 in 30-60°С temperature range. The temperature of the nanoparticles was calculated from the Nd³+ luminescence spectra in the 800-1000 nm range under excitation into ⁴F_5/2 energy state by 805 nm laser. A calibration procedure for recalculating the ratio of the luminescence intensities from the Stark sublevels of the ⁴F_3/2 Nd³+ state into the values of the real NP temperature in accordance with the Boltzmann distribution is given. An algorithm for calculating luminescence intensities for individual Stark components is proposed. After calculating the intensities corresponding to each individual Stark component, all the intensities related to the transition from the upper and lower Stark sublevels of the ⁴F_3/2 state are summed, and then their ratio is calculated. The resulting ratio is normalized to the value of the ratio at room temperature and, in accordance with the calibration dependence, is recalculated into the NP heating temperature. It was demonstrated that the investigated 1%Nd³+:YPO₄ nanoparticles can be used as "primary” thermometers that do not require additional recalibration to evaluate the temperature in the range used for hyperthermia.

1. Issels R., Kampmann E., Kanaar R., Lindner L.H. Hallmarks of hyperthermia in driving the future of clinical hyperthermia as targeted therapy: translation into clinical application, International Journal of Hyperthermia, 2016, Vol. 32(1), pp. 89-95. doi:10.3109/02656736.2015.1119317

2. Chichel A., Skowronek J., Kubaszewska M., Kanikowski M. Hyperthermia - description of a method and a review of clinical applications, Reports of Practical Oncology & Radiotherapy, 2007, Vol. 12(5), pp. 267-275. doi: 10.1016/S1507-1367(10)60065-X

3. Myerson R.J., Moros E.G., Diederich C.J., Haemmerich D., Hurwitz M.D., Hsu I.C., Mc Gough R.J., Nau W.H., Straube W.L., Turner P.F., Vujaskovic Z., Stauffer P.R. Components of a hyperthermia clinic: recommendations for staffing, equipment, and treatment monitoring, International Journal of Hyperthermia, 2014, Vol. 30(1), pp. 1-5. doi:10.3109/02656736.2013.861520

4. Helmchen F., Denk W. Deep tissue two-photon microscopy, Nature Methods, 2005, Vol. 2, pp. 932-940. doi:10.1038/nmeth818

5. Leitgeb N., Omerspahic A., Niedermayr F. Exposure of non-target tissues in medical diathermy, Bioelectromagnetics, 2010, Vol. 31(1), pp. 12-19. doi:10.1002/bem.20521

6. Kaur P., Aliru M.L., Chadha A.S., Asea A., Krishnan S. Hyperthermia using nanoparticles - promises and pitfalls, International Journal of Hyperthermia, 2016, Vol. 32(1), pp. 76-88. doi:10.3109/02656736.2015.1120889

7. Wust P., Cho C., Hildebrant B., Gellermann J. Thermal monitoring: invasive, minimal-invasive and non-invasive approaches, International Journal of Hyperthermia, 2006, Vol. 22(3), pp. 255-262. doi: 10.1080/02656730600661149

8. Rocha U., Hu J., Rodriguez E.M., Vanetsev A.S., Rahn M., Sam- melselg V., Orlovskii Y.V., Sole J.G., Jaque D., Ortgies D.H. Subtissue imaging and thermal monitoring of gold nanorods through joined encapsulation with Nd-doped infrared-emitting nanoparticles, Small, 2016, Vol. 12(39), pp. 5394-5400. doi:10.1002/smll.201600866

9. Escudero A., Carrillo-Carrion C., Zyuzin M.V., Parak W.J. Luminescent rare-earth-based nanoparticles: a summarized overview of their synthesis, functionalization, and applications, Top Curr Chem (Cham), 2016, Vol. 374(4), p. 48. doi:10.1007/s41061-016-0049-8

10. Carrasco E., del Rosal B., Sanz-Rodriguez F., de la Fuente A.J., Gonzalez P.H., Rocha U., Kumar K.U., Jacinto C., Sole J.G., Jaque D. Intratumoral thermal reading during photo-thermal therapy by multifunctional fluorescent nanoparticles, Advanced Functional Materials, 2015, Vol. 25(4), p. 615. doi:10.1002/adfm.201403653

11. Quintanilla M., Benayas A., Naccache R., Vetrone F. Chapter 5. Luminescent nanothermometry with lanthanide-doped nanoparticles in book Thermometry at the Nanoscale: Techniques and Selected Applications. The Royal Society of Chemistry, 2016. pp. 124-166. doi:10.1039/9781782622031-00124

12. Wang Z., Zhang P., Yuan Q., Xu X., Lei P., Liu X., Su Y., Dong L., Feng J., Zhang H. Nd3+-sensitized NaLuF4 luminescent nanoparticles for multimodal imaging and temperature sensing under 808 nm excitation, Nanoscale, 2015, Vol. 7(42), pp. 17861-17870. doi:10.1039/C5NR04889C

13. Wawrzynczyk D., Bednarkiewicz A., Nyk M., Strek W., Samoc M. Neodymium(III) doped fluoride nanoparticles as non-contact optical temperature sensors, Nanoscale, 2012, Vol. 4(22), pp. 69596961. doi:10.1039/c2nr32203j

14. Rocha U., Silva C.J., Silva W.F., Guedes I., Benayas A., Maestro L.M., Elias M.A, Bovero E., van Veggel F.C.J.M., Sole J.A.G., Jaque Subtissue thermal sensing based on neodymium-doped LaF3 nanoparticles, ACS Nano, 2013, Vol. 7(2), pp. 1188-1199. doi:10.1021/nn304373q

15. Li X., Wang R., Zhang F., Zhou L., Shen D., Yao C., Zhao D. Nd3+ sensitized up/down converting dual-mode nanomaterials for efficient in-vitro and in-vivo bioimaging excited at 800 nm, Sci. Rep, 2013, Vol. 3, p. 3536. doi:10.1038/srep03536

16. Tian X., Wei X., Chen Y., Duan C., Yin M. Temperature sensor based on ladder-level assisted thermal coupling and thermal-enhanced luminescence in NaYF4: Nd3+, Opt Express, 2014, Vol. 22(24), pp. 30333-30345. doi:10.1364/OE.22.030333

17. Rocha U., Kumar K.U., Jacinto C., Ramiro J., Caamano A.J., Sole J.G., Jaque D. Nd3+ doped LaF3 nanoparticles as self-monitored photo-thermal agents, Appl. Phys. Lett., 2014, Vol. 104, 053703. doi:10.1063/1.4862968

18. Basiev T.T., Dergachev A.Yu., Orlovskii Y.V., Prokhorov A.M. Multiphonon nonradiative relaxation from high- lying levels of Nd3+ ion in fluoride and oxide laser materials, Journal of Luminescence, 1992, Vol. 53, pp. 19-23. doi:10.1016/0022-2313(92)90096-R

19. Kolesnikov I.E., Kalinichev A.A., Kurochkin M.A., Mamonova D.V., Kolesnikov E.Y., Kurochkin A.V., Lahderanta E., Mikhailov M.D. New strategy for thermal sensitivity enhancement of Nd 3+-based ratiometric luminescence thermometers, Journal of Luminescence, 2017, Vol. 192, pp. 40-46. doi:10.1016/j.jlumin.2017.06.024

20. Samsonova E., Popov A., Vanetsev A., Keevend K., Orlovskaya, Kiisk V., Lange S., Joost U., Kaldvee K., Maeorg U., Glushkov N., Ryabova A., Sildos I., Osiko V., Steiner R., Loschenov V., Orlovskii Y. Energy transfer kinetics probe for OH- quenchers in the YPO4:Nd3+ nanocrystals suitable for imaging in the biological tissue transparency window, Physical Chemistry Chemical Physics, 2014, Vol. 16, pp. 26806-26815. doi:10.1039/C4CP03774J

21. Levenberg K. A method for the solution of certain non-linear problems in least squares, Quarterly of Applied Mathematics, 1944, Vol. 2, pp. 164-168. doi: 10.1090/qam/10666

22. Marquardt D.W. An algorithm for least-squares estimation of nonlinear parameters, Journal of the Society for Industrial and Applied Mathematics, 1963, Vol. 11(2), pp. 431-441. doi:10.1137/0111030

23. Guillot-Noel O., Kahn-Harari A., Viana B., Vivien D., Antic-Fidancev E., Porcher P. Optical spectra and crystal field calculations of Nd3+ doped Zircon-type YMO4 laser hosts (M=V, P, As), Journal of Physics: Condensed Matter, 1998, Vol. 10(29), pp. 6491-6503. doi:10.1088/0953-8984/10/29/009

24. Rai V.K., Rai S.B. A comparative study of FIR and FL based temperature sensing schemes: an example of Pr3+, Applied Physics B, 2007, Vol. 87, pp. 323-325. doi:10.1007/s00340-007-2592-z

25. Balabhadra S., Debasu M.L., Brites C.D.S., Nunes L.A.O., Malta O.L., Rocha J., Bettinellie M., Carlos L.D. Boosting the sensitivity of Nd3+- based luminescent nanothermometers, Nanoscale, 2015, Vol. 7, pp. 17261-17267. doi:10.1039/C5NR05631D

26. Kolesnikov I.E., Kalinichev A.A., Kurochkin M.A., Golyeva E.V., Kolesnikov E.Yu., Kurochkin A.V., Lahderanta E., Mikhailov M.D. YVO4:Nd3+ nanophosphors as NIR-to-NIR thermal sensors in wide temperature range, Scientific Reports, 2017, Vol. 7, 18002. doi:10.1038/s41598-017-18295-w

27. Kaldvee K., Nefedova A.V., Fedorenko S.G., Vanetsev A.S., Orlovskaya E.O., Puust L., Pars M., Sildos I., Ryabova A.V., Orlovskii Yu.V. Approaches to contactless optical thermometer in the NIR spectral range based on Nd3+ doped crystalline nanoparticles, Journal of Luminescence, 2017, Vol. 183, pp. 478-485.

28. Jacques S.L. Origins of tissue optical properties in the UVA, visible and NIR regions, Advances in Optical Imaging and Photon Migration, 1996, Vol. 2, pp. 364-370.