Gastric cancer is one of the leading causes in terms of mortality and the number of diseases throughout the world. It is estimated that in 2018 more than 1,000,000 diseases of the stomach cancer were diagnosed, and the number of deaths reached 783,000 [1
]. Gastric cancer can be removed by the endoscopic resection method or surgical operation. The first one is more painless and safe for the patient, however, it can only be used at the early stages of cancer and after timely endoscopic diagnosis [2
]. For advanced cancer, it is necessary to excise the tumor using surgery. During surgery treatment it is important to discriminate between cancer regions and delineate the boundaries between tumor and normal tissue. Accurate intraoperative diagnosis of cancer improves the efficiency of cancer resection and can save more healthy tissues as well as increase the survival of patients after surgery.
In recent years, terahertz (THz) techniques have been actively studied and applied in many areas, such as communications, security, biomedical diagnosis, health monitoring, quality-control applications, etc. [3
]. Biomedical applications of THz techniques are possible, because THz radiation is very sensitive to polar molecules, such as water, and it is absorbed by them. This feature allows the application of THz methods in the diagnosis of various neoplastic diseases because the water content in tumors is often higher than that in normal tissues. Moreover, chemicals and biological molecules can be identified by their characteristic resonant peaks because of the characteristic energies of molecules’ rotational and vibrational motions that are located in the THz frequency range [4
]. Additionally, in contrast to X-rays, THz radiation has a low photon energy, that allows the performance of harmless diagnostics. Thus, THz spectroscopy and imaging methods have already been successfully used to detect tumors with different morphology and localization [5
]. In recent years, there has been a growing interest in research on digestive system cancer, using THz diagnostic methods [6
], which is related to the demand of clear recognition of boundaries between normal and cancer tissues during surgery or endoscopy treatment. It is expected that these methods are able to replace other gastric cancer diagnosis methods, such as conventional endoscopy, X-ray computer tomography, magnetic resonance imaging (MRI), optical coherence tomography (OCT), and positron emission tomography (PET). In [7
], fresh normal and early gastric cancer tissues of mouse stomach were investigated through peak-to-peak THz imaging. Authors obtained a correlation between THz and pathologically mapped images of samples and found that optical density was increased in the tumors due to the high water content. Additionally, results of the work showed that THz imaging can detect gastric adenocarcinoma from normal mucous tissues but cannot detect signet ring cell carcinoma. In other studies, researchers obtained the difference between normal and cancer paraffin-embedded human gastric tissues, using THz time-domain spectroscopy [8
]. Due to embedding in paraffin blocks, it is possible to except the influence of water to the optical properties of samples, and thus, the obtained results depend only on the morphology of investigated tissues. THz spectroscopy has also been applied to obtain the refractive index and absorption coefficient, and the permittivity of fresh excised gastric tissues consisted of cancer, normal, and pathologically changed areas [10
]. It was shown that the optical density of cancer is higher than those of normal tissues and is close to water. In [11
], authors applied a terahertz spectral unmixing method to detect gastric adenocarcinomas with a different grade of tumor from normal tissue. The potential of this method in identification of gastric cancer through an evaluation of the absorption coefficient of the samples, as well as its applicability and limitations were demonstrated. Additionally, different types of THz endoscopes were created, which made it possible to discriminate between normal and cancer tissues in vivo [12
]. It is expected that further development of THz technologies will make it possible to create new effective and commercially inexpensive devices for the diagnostics of digestive systems, based on the THz methods [14
]. Thus, all of these studies showed a large potential of THz methods in gastric cancer diagnosis.
In the works described above, the authors mainly investigated tumors from mucosa, but it is also important to discriminate cancer from other types of gastric tissues, because invasion of advanced gastric tumors often reaches different membranes of the stomach, such as the submucosa, the muscularis propria, the subserosa, and the serosa [15
]. Widely accepted surgery methods such as laparoscopy require diagnostic procedures of different gastric membranes, including the external membrane that consists of serosa. Recognition of cancer cells that can pull away from a tumor in both mucous and serous gastric membranes is important, because these cells can decrease the efficiency of treatment and cause the disease to reappear in future. Due to the possibility of recognizing small objects such as cells [16
] as well as high spatial resolution, in comparison to other methods [6
], THz spectroscopy is a perspective method for an accurate and effective intraoperative diagnosis of gastric cancer.
In this work, we studied ex vivo fresh mucous, serous, and cancer tissues of the stomach using THz time-domain spectroscopy. The refractive indices and absorption coefficients in the frequency range of 0.2–1 THz are presented. Cancer tissues contained gastric, moderately and poorly differentiated adenocarcinomas, which reached the serous stomach membrane from the mucous one. Thereby, we have investigated tumors localized in both mucosa and serosa and compared it with the corresponding types of normal tissues.