1. Experimental modeling of local laser hyperthermia using thermosensitive nanoparticles absorbing in NIR
Grachev P.V., Romanishkin I.D., Pominova D.V., Burmistrov I.A., Kaldvee K., Sildos I., Vanetsev A.S., Orlovskaya E.O., Orlovskii Yu.V., Loschenov V.B., Ryabova A.V.
Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow, Russia
Institute of Physics, University of Tartu, Tartu, Estonia
This work was supported by MES RF: RFMEFI61615X0064

2. Hyperthermia therapy
At the moment, there exist several ways of using hyperthermia as treatment of cancers. The use of systemic and regional hyperthermia increases the effectiveness of chemotherapy and radiotherapy techniques. The method of local laser hyperthermia can be used independently, and have a direct effect on individual tumor cells and organelles.

3. Localized hyperthermia
Pulse time from pico- to nanoseconds
The use of special thermal agents helps minimizing the overheating of the healthy tissue as well as maximizing the destruction of tumor. Such agents can be magnetic and plasmon nanoparticles, nanoparticles doped with rare earth ions, and quantum dots.
As a result of local heating, the apoptotic mechanism of cell death could be triggered, leading to a gradual replacement of the dying tumor cells with healthy tissue. τ τ
τ∼ps
τ∼ns
Biomolecule
Dy3+
Tm3+
Nd3+
Biostructure
Visualization of the nanoparticle pulse laser excitation with subsequent environment heating

4. nanoparticles, biomolecules
Heat localization
The use of pulse laser excitation results in more localized heating
The temperature distribution surrounding a gold nanoparticle (calculations)
Pulse length
Effective radius
Target types
1 sec
350 mm
1 ms
10 mm
cells, capillaries
1 us
0.35 mm
cell organelles
1 ns
10 nm
nanoparticles, biomolecules
1 ps
0.3 nm
clusters
1 fs
0.1 A
molecules
Spatial distribution of temperature in the gold nanoparticle environment depending on the excitation pulse length [1]
The depth of thermal effect depending on the excitation pulse length (calculations)
1 Hüttmann et al. High precision cell surgery with nanoparticles? Medical Laser Application, 2002

5. The main disadvantage of existing devices for temperature determination – that temperature is measured from the surface while the temperature in the tissue depth remains unknown.

6. Light transfer in media
Scheme of light propagation in a scattering medium
Main absorbers in biotissue

7. Composite nanosystems based in the crystalline nanoparticles doped with plasmonic nanoparicles and Dy3+ и Nd3+ rare-earth ions for photohyperthermia with the capability for fluorescent navigation and non-invasive temperature determination based on their spectral characteristics
Plasmon Nanoparticle
YPO4:Dy3+
LaF3:Nd3+
Particles were synthesized in Institute of Physics, University of Tartu, Estonia
YPO4:Dy3+

8. Fiber-optic probe with cooling
Fiber-optic probe 3D-model
The experimental setup for optical phantom temperature measurements
The distance between the receiving fiber and the probe center: 1.5 – 2.5 см
Receiving fiber angle of incidence to the phantom surface: 0˚, 30˚, 45˚

9. Rare-earth luminescence spectrum registration
LFT BIOSPEC laser system (Biospec, Russia) with fiber-optic delivery light
Raman-HR-Tec fiber-optic spectrometer (StellarNet, США)
YPO4:Nd3+ nanoparticle luminescence spectrum with decomposition into Stark components

10. Temperature registration
Simultaneously, the temperature of the biotissue phantoms was been measured using the thermal IR camera JADE MWIR SC7300M (CEDIP, France).
The data obtained with the thermal camera was compared with calculated from luminescence spectra

11. Mathematical modeling of light propagation
Scattering pattern of laser radiation with a wavelength of 805 nm in pseudocolor. The distance between the fibers is 5 mm, the angle is 45 degrees relative to the normal to the surface of the tissue
Sounding depth, mm
The plot of the depth of sounding from the angle of inclination of the fibers relative to the normal to the biotissue at a fixed distance between the fibers of 20 mm, the wavelength of the laser radiation is 810 nm.
Angle, ˚

12. The most probable photon path (red color)
Scattered laser (805 nm)
The most probable photon path (red color)
Sounding depth, mm
Distance between fibers, mm

13. Scattered laser light intensity
Intensity, a.u.
Intensity, a.u.
Lipofundin concentration, %
Distance, mm
Dependence on the concentration of the scattering medium for different positions of the receiving fiber
Dependence on the distance between fibers for different concentration of the scattering medium

14. Luminescence and scattered laser light intensity
Интенсивность лазерного излучения планируется использовать для оценки степени коагуляции
Lipofundin concentration 0.4%
The distance between illuminating and receiving fibers was 25 mm

15. Spectroscopic evaluation of Nd3+ nanoparticles local temperature
Temperature values obtained using IR thermal camera
Temperature values calculated from the luminescence spectra

16. Temperature values obtained using IR thermal camera
Temperature values calculated from the luminescence spectra

17. Summary
A fiber-optic probe with cooling has been developed, which makes it possible to obtain a luminescent signal from various depths by changing the position and angle of inclination of the receiving optical fiber, and also cause laser-induced heating of optical models of tumors.
The optimal position and angle of inclination of the receiving optical fiber for different depths of the tumor model are determined.
Demonstrated mismatch between the temperature measured from the surface using thermal IR camera and the actual temperature at the depth measured spectroscopically.

18. Thank you for your attention