OCT is a newly developed technology with real-time imaging in vivo. Researches about OCT have been conducted in various fields of medicine , especially in ophthalmology, cardiovascular and digestive tract diseases. OCT outperformed CT and ultrasound with its high resolution and non-radiation process, indicating its potential clinical application.
At present, OCT has been applied in respiratory diseases such as COPD, bronchial asthma and lung cancerbased on the principle that tissue images can be constructed by computer processing after infrared scattering, and the microstructure of bronchial wall can be recognized in real time. Unlike ultrasound, light waves of OCT do not need liquid medium for propagation, indicating that OCT is more suitable to be used in airway imaging. Moreover, OCT does not require a catheter to contact the tissue, which in turn minimizes adverse reactions that are commonly seen in invasive examination procedures. There is also no risk of exposing to infrared light in a short period of time. In addition, the OCT catheter probe reaches the end of the bronchoscope through the working channel of the bronchoscope and then is further sent to the lesion. During the operation, there might be adverse reactions caused by the catheter touching the bronchial wall or the lesions, so scholars have listed OCT examination as one of the "minimally invasive" examinations . The adverse events were consistent with the above study, and there were no adverse reactions directly related to OCT examination. Only several cases of mild bleeding or cough were noticed. The adverse reactions were improved and did not affect the continuation of OCT examination after short observation or local administration of a small amount of hemostatic drugs. In this study, the analysts for OCT image features consisted of a professional OCT image analyst and a trained respiratory physician, pathologist and thoracic surgeon which were of great significance for judging the histological features of lung cancer, evaluating OCT image features and imaging artifacts, and assessing whether OCT imaging can be evaluated in real time during the examination. In addition, although the real-time scanning location of OCT catheter was close to that of biopsy, it was not completely consistent in vivo, so the OCT images could not match the images of tissue pathological sections under microscope, and the one by one comparative analysis was not available, therefore the clinical value of OCT images was evaluated based on the results of histopathology. The OCT examination takes only a few minutes and the tissue microstructure of bronchus such as mucous membrane, submucosa, cartilage and adventitia were imaged with high resolution without contact with the bronchus in our study, these data are consistent with the findings in other literatures [20, 21]. It is worth noting that it is recommended to increase local topical anesthesia for the target lesions and its adjacent bronchi prior to OCT examination which is useful to increase the tolerance of patients, and reduce the possibility of OCT catheter touching the bronchial wall and lesions, so as to prevent cough stimulation from affecting the imaging effect and destroying the lesions.
The traditional method of respiratory endoscopy for distinguishing benign bronchial lesions from malignant ones is to identify with the naked eyes through the endoscopic images formed in the process of WLB or AFB. WLB has significantly increased the image resolution and improved the ability to distinguish the nature of bronchial lesions by using electronic bronchoscope instead of fiberoptic bronchoscope. However, it is still difficult for experienced bronchoscopic operators to identify subtle mucosal lesions [22, 23]. Fluorescence bronchoscopy has been proved to be highly sensitive in differentiating benign and malignant endobronchial lesions, but it has a high false positive rate due to bronchial mucosal inflammation and bleeding. Low specificity is another problem for fluorescence bronchoscopy [24, 25], which is further confirmed in our research results. Former studies [12, 13, 26] have confirmed that OCT could distinguish normal bronchial tissue from tumor lesions with the principle that the mucous layer and submucosa of bronchial wall thickened in different stages of cancer, however, no study had summarized and proposed the main OCT image features in distinguishing benign bronchial lesions from malignant ones. In our study, for the first time, we found that whether the mucosal layer is edematous and the normal structural layer is destroyed are the main OCT image features in distinguishing between benign and malignant bronchial lesions. The accuracy of the main OCT image features in distinguishing benign and malignant bronchial lesions was 94.1%, and the sensitivity and specificity were 97.1%, and 83.3%, respectively, both of which were significantly higher than those of AFB. Therefore, comparing to AFB, OCT has more clinical value in distinguishing benign and malignant bronchial lesions. It is worth noting that the histopathological results of malignant lesions were invasive cancer in our study, while OCT images of precancerous lesions and carcinoma in situ could also show the integrity of normal tissue structure which was reported in early studies. But there was a significant difference between benign and malignant bronchial lesions in OCT images in our findings. Therefore, the differentiation between bronchial benign lesions and bronchial precancerous lesions or carcinoma in situ still needs more research and further exploration.
OCT has been used to assist the diagnosis and treatment of lung cancer with the development of interventional diagnosis and treatment of respiratory diseases. Many studies [14, 15, 27] have preliminarily reported the accuracy of main OCT image features for distinguishing adenocarcinoma, squamous cell carcinoma and poorly differentiated lung cancer in vitro was more than 82.6%. However, whether the OCT image features of tissue specimens in vitro can reflect the actual condition still needs to be further confirmed, because tissue degeneration and internal blood flow changes will occur in the excised specimens, and the effects of cough, spontaneous breathing, heartbeat and secretions on the imaging results will not be truly reflected in the examination process. In our study, the clinical value of OCT in real-time diagnosis of lung cancer was evaluated for the first time, and the main OCT image features for predicting adenocarcinoma, squamous cell carcinoma and small cell lung cancer were proposed and verified. There are three main OCT image features with squamous cell carcinoma. The sensitivity of any image features in predicting squamous cell carcinoma was 100%, but the specificity was only about 31.2%. The specificity was 100% by combining three image features to predict squamous cell carcinoma, but the sensitivity was very low. However, the main image features (2) showed high clinical value with the accuracy of 95.6%, and the sensitivity and specificity were 96.2%, and 93.8%, respectively. The accuracy and specificity of the main OCT image features of squamous cell carcinoma which was proposed by previous studies in vitro were 82.6%, and 87% , respectively. Therefore, the main OCT image features (1), (2) or (3) can be used as the preliminary screening image for the diagnosis of squamous cell carcinoma, and the final image features should be the main OCT image features (2) or the combination of features (1), (2) and (3). It is recommended to choose the combination of each (1) and (2) as the main OCT image features in predicting adenocarcinoma and small cell lung cancer. The accuracy of the main OCT image features of adenocarcinoma was 94.3%, the sensitivity and specificity were 89.5%, and 100%, respectively, which were significantly higher than those in the previous studies in vitro (80.3%, 88.6%). The main OCT image features of small cell lung cancer were proposed by the study for the first time, and initially showed high accuracy, sensitivity and specificity. Therefore, compared with previous studies, the main OCT image features in the study can be used to predict the histological classification of lung cancer significantly. In addition, the sensitivity and specificity have been comparable to the results of studying esophageal and cardiovascular diseases for which the application of OCT is more mature [28–30], and the accuracy results by verification had significant statistical results (P༜0.05=. In addition, the study also found that the accuracy, sensitivity and specificity of OCT in predicting the pathological classification of lung cancer were higher than those of WLB, so the clinical value should be affirmed. While the OCT images cannot be compared with the histopathological images one by one, therefore, the analysis of OCT images is affected by subjective factors to a certain extent, and the related research data need to be confirmed by more studies. The latest study  reports that the OCT catheter is integrated into the 19G puncture needle which design is useful to highly match the location of OCT examination and aspiration tissue; and the OCT images are more matched with histopathological images which is expected to obtain more OCT image features with reality and reliability. But currently the product is tested using animals, we are looking forward to the relevant findings for clinical research after the product is put on the market.
To sum up, OCT is very useful to clinicians in differentiating benign and malignant bronchial lesions and for the histological classification of lung cancer, especially for patients who are unable to perform tissue biopsy or cannot obtain accurate histological pathological results after biopsy. Meanwhile, it can also provide real-time imaging of the lesions during bronchoscopy and guide the location of bronchoscopy biopsy to improve the positive rate of biopsy and the diagnosis rate of lung cancer. We can even choose direct operation after evaluating the lesion by OCT examination for patients who was diagnosed as lung cancer clinically and have the chance for operation, and there is no need for bronchoscopic biopsy so that the lung cancer metastasis caused by biopsy can be avoided. In addition, studies [32, 33] have suggested that OCT is also helpful in the treatment of lung cancer including auxiliary airway stent implantation, APC, cryosurgery and other interventional therapy, and to explore the relationship between OCT image features and gene mutations in patients with lung cancer who cannot be biopsied because of high risk of secondary biopsy after targeted drug resistance. However, the findings in the studies were still preliminary. It is expected that more research findings will form a sufficient basis to support its clinical application.
Although the findings of the study are quite encouraging, the accuracy, sensitivity and specificity are not sufficient to support OCT as a complete substitute for tissue biopsy. A study  reported that the histopathological results of specimens obtained by FNA were consistent with the pathological results of resection specimens, including 96.2% for adenocarcinoma and 84.7% for squamous cell carcinoma. There are differences between the accuracy of the main OCT image features of lung adenocarcinoma in our study and the above findings, which might due to some important factors that could affect the OCT process. For example, we mainly analyzed the OCT image features of the most common primary lung cancer, but the histological classifications of lung cancer diverses, and the OCT image features of some rare lung cancer and metastatic lung tumors still need to be further explored. It has been reported that only 32% of poorly differentiated cancers can be accurately classified by histopathological method [34–36]. With the rapid development of targeted therapy in the field of lung cancer treatment in recent years, it may be necessary to perform multiple tissue biopsies for gene detection to evaluate the targeted drug resistance of lung cancer and guide the next step of treatment [37–39]. This situation makes other non-invasive tissue biopsy techniques including OCT difficult to completely replace tissue biopsy in a short time. In addition, the resolution of OCT cannot fully reach the level of the microscope, and adjustable factors such as lens selection, focal length adjustment and high power lens field of view of the microscope cannot be achieved by OCT temporarily. Some factors affecting OCT imaging include spontaneous respiration, heartbeat, blood, airway secretions, calcification, fibrosis and so on, more advanced technologies need to be developed for data acquisition and automatic image processing, to improve the authenticity of airway images and standardize the clinical application of OCT images [40, 41].