Development of the methodology of monitoring experimental tumors using multimodal optical coherence tomography: The choice of an optimal tumor model

Abstract

The objective of the research was to study the features of transplantation, growth and visualization of experimental tumors of animals, using multimodal optical coherence tomography (OCT) to develop the methodology of evaluation of individual tumor response to anti-cancer therapy. Materials and Methods. The research was carried out using an experimental high-speed spectral-domain multimodal OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences (Russia). The technical characteristics of the system are the following: speed of information acquisition, 20,000 А-scans per second; 1.3 μm wavelength; frame size, approximately 4×2 mm; lateral resolution, 25 μm; and depth resolution, 10 μm. We evaluated cross-polarized (CP) and microangiopathic (МА) OCT images. We performed an OCT study of the experimental tumor model of colon adenocarcinoma of mice Colo-26 on BALB/с mice (transplanted by suspension of tumor cells culture) inoculated subcutaneously into the thigh, intradermally into auricle, and in a dorsal skinfold window chamber. In the case of a deep subcutaneous location of a nodule, skin flap over the tumor was surgically opened. CP OCT images were compared with histological preparations (stained using hematoxylin and eosine). Results. It was established that a Colo-26 tumor growing subcutaneously is not suitable with OCT monitoring investigations. Applying of tumor model with opened skin flap made it possible considerably to increase the visualization depth; however, it is not feasible to use this method for everyday OCT monitoring. The tumor grown within a dorsal window chamber is optimal for the visualization of blood vessels by means the OCT. Nevertheless, the inflammation and edema sometimes observed at the tumor site impeded the МА OCT study. Superficial tumors on the auricle are available for OCT investigation throughout their entire depth if the size of nodule does not exceed 1.5 mm. The tumor model on the auricle is convenient for physiological studies of the state of the vessels during the tumor growth. Conclusions. The optimal tumor model for dynamic multimodal OCT observation is a tumor on the auricle. Unlike a tumor located on the thigh it is characterized by a subcutaneous location of the nodule yet one which still remains accessible for visualization. The tumor evolving in the ear can be studied using dynamics which would be impossible for the tumor with opened skin flap. Tumors in the dorsal skin window can also be used for research, but the monitoring of their growth is limited to those that are no larger than 5–7 mm, as the nodule goes beyond the window due to the decreased elasticity of the skin, typical of these mice.