1. In vivo monitoring of oxygen state and hemoglobin concentration
in course of tumor model development
by optical diffuse spectroscopy
A. Orlovaa,b, M. Kirillina*, A. Volovetskyb, N. Shilyaginab, E. Sergeevaa, G. Golubiatnikova, and I. Turchina
a Institute of Applied Physics RAS, Nizhny Novgorod, Russia, bN.I. Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russia
SFM 2016, Saratov, Russia, September, 2016

2. Motivation
Tumor oxygen status is important for choice of treatment strategy
Evolution of tumor blood saturation and hemoglobin content allow to conclude on tumor progression and response to treatment
Significant difference in absorption spectra of oxy- and deoxyhemoglobin in visible and NIR ranges indicates high efficiency of optical spectroscopy in monitoring blood oxygenation
Optical diffuse spectroscopy monitoring of oxygen status and hemoglobin content in tumor and in normal tissue in course of tumor development

3. Scattering coefficient Absorption coefficient
Optical Diffuse Reflectometry
Main tissue chromophores
ODR measurements
Diffusion approximation
Lipids, water
deoxyhemoglobin (HHb),
oxyhemoglobin (HbO2)
Scattering coefficient
Absorption coefficient
Tissue structure
Tissue content
Blood saturation (StO2) StO2=[HbO2]/[HHb+HbO2]
ODR principle
source
detector
measurement volume
Tissue blood content
tHb
Tissue oxygen consumption
Blood outflow rate
НHb
Tissue oxygen delivery
HbO2
Torricelli A., et al, Optics Express, 2003, V 11
De Blasi et all, 1993; Lu et all, 2004
Phan T.G., Bullen A., Immunol Cell Biol (4) 3

4. Dynamics of tumor growth*
Mice Balb/c-nude (n = 6) SKBR-3 tumor model
Asterisk (*) indicates statistically significant differences with the initial level at the beginning of monitoring period (p < 0.05).

5. Reconstructed absorption spectra
Normalized reflectance spectra
tumor muscle
Reconstructed spectra of absorption coefficient
tumor muscle

6. Dynamics of blood oxygen saturation level
Asterisk (*) indicates statistically significant differences with the initial level (p < 0.05). Hash (#) indicates statistically significant differences between the tumor and muscle (p < 0.05).

7. Oxygen saturation (StO2) versus pO2 values
Measurements from 12th, 16th, 19th, and 22th days of tumor growth
r is the Pearson's correlation coefficient

8. Dynamics of hemoglobin concentrationμ * #
tHb
HbO2 μ
HHb
Asterisk (*) indicates statistically significant differences with the initial level (p < 0.05).
Hash (#) indicates statistically significant differences between the tumor and muscle (p < 0.05).

9. Values of tHb, StO2, HbO2, HHb
versus tumor volume for entire monitoring period b)
p-value = 0.11
StO2 μ c)
p-value < 0.01
HbO2 μ a)
p-value < 0.01
tHb μ d)
p-value < 0.01
HHb
p-value is the significance level from х2-test.

10. Conclusion
Using DOS technique differences in the level of oxygenation and hemoglobin concentration between experimental tumor and normal tissue were revealed.
Rapid decrease of tumor oxygenation level preceded the acceleration of its growth during which oxygen state has remained low.
Increase of tumor volume was accompanied by the gradual elevation of total hemoglobin concentration (increase of blood content).
The main contribution to blood content increase was made by deoxyhemoglobin (increase of tissue oxygen consumption and decreased blood outflow rate).
The proposed approach is useful for diagnosis of tumors as well as for study of changes in tumor models blood flow parameters when monitoring tumor response to therapy.

11. Acknowledgements Anna Maslennikova Maksim Prudnikov
Russian Foundation for Basic Research (projects )
Targeted Federal Program of the Ministry of Education and Science of the Russian Federation, Grant No (RFMEFI57814X0030).
Anna Maslennikova Maksim Prudnikov
Kristina Kuznetsova Vladimir Plekhanov
Ilya Fiks

12. Thank you for your interest!
Questions?