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3Optoacoustic angiography and diffuse optical spectroscopy to study tumor vascularization and oxygenation dynamics
A. Orlova1*, A. Glyavina12, K. Akhmedzhanova12, A. Kurnikov1, D. Khochenkov3, Yu. Khochenkova3, A. Maslennikova12, A. Korobov14, I.V. Turchin1, P.V. Subochev1
1-A.V Gaponov-Grekhov Institute of Applied Physics RAS, 46 Ulyanov Street, Nizhny Novgorod, Russia 2- Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Avenue, Nizhny Novgorod, Russia 3- N.N. Blokhin National Medical Research Center of Oncology, 23 Kashirskoye Highway, Moscow, Russia 4- Skolkovo Institute of Science and Technology, 30 Bolshoy Boulevard, Moscow, Russia
The study of tumor angiogenesis and the oxygen state is crucial for understanding the role of the circulatory system in the mechanisms of neoplasm growth and its response to therapy [1]. In this study, we utilized complementary optoacoustic (OA) imaging and diffuse optical spectroscopy (DOS) to compare the characteristics of vascular networks in different tumor models and assess their response to antiangiogenic and radiation therapies. OA imaging [2] provides label-free optical-contrast angiography with ultrasonic resolution at optical penetration depths. DOS relies on the detection of multiply scattered diffuse light that has passed through a biological tissue, allowing for the reconstruction of the concentrations of key tissue chromophores, such as oxy- and deoxyhemoglobin [3].
For OA we used a raster-scan system equipped with a pulsed laser (532 nm; 1 ns; 2 kHz) and a wideband PVDF detector, achieving a lateral spatial resolution of less than 50 ^m. For DOS we utilized a fiber-optic-based system in a reflectance geometry, featuring a broadband LED as the light source and a spectrometer for detection.
As a first step of the work, we compared vascularity across tumor models of human renal cell carcinoma SN-12C, human colon carcinoma HCT-116, and Colo320. OA and DOS studies were conducted when the average tumor volume reached 700 mm3. Next, the study on the effects of the antiangiogenic therapy was performed on Colo320, with axitinib administered to animals at a dose of 50 mg/kg, five days per week for four weeks. Finally, the investigation of tumor responses to radiation therapy was conducted on murine colon carcinoma CT26, with assessments before and at intervals of 1-3 days following irradiation at single doses of 6, 12, and 18 Gy.
OA revealed the highest values of vessel size and fraction in Colo320 tumors. DOS indicated an increased content of deoxyhemoglobin, leading to reduced blood oxygen saturation level in Colo320 compared to other tumor models [4]. Axitinib treatment resulted in a gradual reduction in vessel segment sizes by more than two times compared to the control. This reduction was accompanied by a transient increase in blood oxygen saturation level.
Experiments evaluating the response of tumors to irradiation showed a decrease in density and an increase in fragmentation of small vessels, while large vessels exhibited the opposite reaction. The duration of the vascular response increased with higher radiation doses. Radiation-induced reoxygenation was detected only at high doses, occurring despite the incomplete recovery of vascular damage [5].
The combination of OA and DOS methods for in vivo analysis of vessel structure and oxygenation in experimental tumors has been demonstrated. This approach can be used to identify the features of blood vessel structure and their influence on tumor oxygenation, as well as to monitor the vascular response to treatment.
The study was supported by the Center of Excellence "Center of Photonics" funded by the Ministry of Science and Higher Education of the Russian Federation, Contract No. 075-15-2022-316.
[1] J. Brown and W. Wilson, Exploiting tumour hypoxia in cancer treatment, Nat. Rev. Cancer, 4, pp. 437-447, (2004).
[2] L. Wang and S. Hu, Photoacoustic tomography: in vivo imaging from organelles to organs, Science, 335, pp. 1458-1462, (2012).
[3] T. Durduran, R. Choe, W. Baker, A. Yodh, Diffuse Optics for Tissue Monitoring and Tomography, Rep Prog Phys., 73, p. 076701, (2010).
[4] K. Akhmedzhanova, A. Kurnikov, D. Khochenkov, Yu. Khochenkova, A. Glyavina, V. Kazakov, A. Yudintsev, A. Maslennikova, I. Turchin, P. Subochev, A. Orlova, In vivo monitoring of vascularization and oxygenation of tumor xenografts using optoacoustic microscopy and diffuse optical spectroscopy, BOE, 13, pp. 5695-5708, (2022).
[5] A. Orlova, K. Pavlova, A. Kurnikov, A. Maslennikova, M. Myagcheva, E. Zakharov, D. Skamnitskiy, V. Perekatova, A. Khilov, A. Kovalchuk, A. Moiseev, I. Turchin, D. Razansky, P. Subochev, Noninvasive optoacoustic microangiography reveals dose and size dependency of radiation-induced deep tumor vasculature remodeling, Neoplasia, 26, p. 100778, (2022).
