|关键词||光学分子影像 微创手术 内窥镜 近红外荧光成像 手术导航 肺癌|
|英文摘要|| In recent years, optical molecular imaging is a new developing technology in optical imaging field. It is based on molecular probe technology to mark the lesions or important tissues and optical imaging technology to collect fluorescence signals. As an imaging method to objectively evaluate diseased tissues, optical molecular imaging provides surgeons with information for identifying suspected lesions. It enables surgeons to perform more accurate, objective and effective judgment during surgery. Optical molecular imaging provides new ways for non-invasive imaging in vivo.|
In the minimally invasive surgery, how to perform accurate tumor localization and tumor boundary identification is a clinically challenging problem. With the popularity of television-assisted thoracoscopic surgery, the manual palpation of the lesion area is limited, so that surgeons rely mainly on visual inspection. However, as the main imaging method during surgery, white-light endoscopic imaging lacks contrast between tumor and normal tissues, so that minimally invasive surgery needs a highly sensitive intraoperative imaging technique. Compared to traditional white-light observations, optical molecular imaging provides a powerful real-time imaging tool for the identification of micro tumors, which has the potential to improve surgical outcomes.
This research focuses on the study of multi-channel imaging method and prototype system construction based on intraoperative optical molecular imaging. It aims to solve practical application problems in minimally invasive surgery for lung cancer with in-depth studies of theory and algorithms, as well as a design of intraoperative minimally invasive imaging prototype system. The main work and innovations of the thesis are summarized as follows:
1. An intraoperative minimally invasive imaging method based on optical molecular imaging is proposed, namely multi-channel real-time optical imaging method, which effectively improves the sensitivity of intraoperative imaging. In order to solve the key scientific problems of lacking multi-channel real-time imaging technique for the minimally invasive surgery navigation, we studies the fusion imaging methods of intraoperative fluorescence molecular imaging and conventional white-light endoscopic imaging. The multi-channel imaging are realized by combining wavelet transform algorithm and adaptive threshold algorithm. Furthermore, we also studies the optimization of fluorescence molecular imaging. We not only ensure real-time fusion of multi-channel optical dynamic imaging (up to 20 fps), but also improve imaging sensitivity (indocyanine green (ICG) can be detected at a concentration of 0.01 μM). After comparison of the literature, the minimal detection concentration of ICG was about 10 times higher than that of the published imaging method.
2. An intraoperative minimally invasive imaging device based on optical molecular imaging was constructed. By designing multi-channel optical paths and optimizing various optical components, the signal-to-noise ratio of imaging devices was effectively improved. In order to solve the key technical issues of developing high signal-to-noise ratio and lightweight imaging equipment for minimally invasive surgery, we design a multi-channel optical path integrating optical excitation, white-light optical detection, and near-infrared fluorescence detection. Furthermore, optimization and retrofitting of imaging elements, spectroscopic elements, filter elements and other optical elements are implemented. As a result, we not only ensure the lightweight design of the handheld optical imaging device (only 23*11*4 cm3) and weight (1.15 kg only), but also improve the signal-to-noise ratio of the optical imaging system (for a concentration of 0.01 μM ICG, the signal-to-noise ratio ≥ 5 dB). A variety of imaging phantom experiments and animal experiments have confirmed that the device has improved imaging sensitivity by two orders of magnitude compared to commercial imaging device from the Karl Storz (a leading international endoscopic manufacturer).
3. Clinical transformation experiments based on minimally invasive imaging methods and imaging devices were designed to accurately navigate the minimally invasive lung cancer surgery. In order to solve the key clinical problems of multiple pulmonary nodules detection and segment boundaries identification, we design clinical trials of lung cancer nodule detection and segmentectomy based on intraoperative optical molecular imaging navigation technology. This program is registered in American clinical trial database (registration number: NCT02611245). This study enrolled 36 patients, the detection sensitivity of pulmonary nodules with optical molecular imaging was 88.7% and the positive predictive rate was 92.6%. In addition, the application of optical molecular imaging method led to the detection of 9 additional nodules which were missed using traditional detection methods (1mm computed tomography scan and white-light thoracoscopic exploration) in 7 patients (19.4%).
This study focuses on the intraoperative minimally invasive imaging method, device, and clinical applications based on optical molecular imaging method. A multi-channel real-time optical imaging method was proposed, which was published in the Journal of Biomedical Optics; An optical molecular imaging equipment was constructed, which was awarded one national invention patent, applied for one American invention patent, and won the gold medal at the 43rd International Exhibition of Inventions of Geneva; A clinical transformation experiments based on optical molecular imaging was designed to accurately navigate the minimally invasive lung cancer surgery in the People's Hospital of Peking University and achieved remarkable clinical results, which was published in the European Journal of Cardio-Thoracic Surgery. In addition, I was invited to give an oral report at WMIC and SPIE Photonics West. These research results have demonstrated the innovation of my research work during the Ph.D. period and the potential for clinical transformation of optical molecular imaging methods and device.
|毛亚敏. 光学分子影像术中微创成像技术研究和临床应用[D]. 北京. 中国科学院研究生院,2018.|