Whenever I talk to others about my work, I always say “a glimpse of the leopard through the tube can reveal a part of it” (Part 2)

Produced by: Science Popularization China

Author: Xue Yadi, Ran Yue (Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences)

Producer: China Science Expo

Editor's note: In order to unveil the mystery of scientific work, the China Science Popularization Frontier Science Project launched a series of articles called "Me and My Research", inviting scientists to write articles themselves, share their scientific research experiences, and create a scientific world. Let us follow the explorers at the forefront of science and technology and embark on a journey full of passion, challenges, and surprises.

In the world of minimally invasive surgery, the medical endoscope is the undisputed star. With its small size, it can easily shuttle through our complex body structure, providing doctors with an unprecedented field of vision, making surgery more precise and greatly reducing the pain of patients.

Have you ever wondered how doctors examined internal organs before the invention of endoscopes? How did endoscopes help doctors see the target clearly and even accurately guide surgery in a narrow and lightless body?

To this end, we have specially planned a series on medical endoscopes, which is divided into two parts to take you to understand the past and present of medical endoscopes and explore the scientific principles and amazing achievements behind them. This is the second part of the series.

Our team has been engaged in the field of high-resolution real-time in vivo fluorescence imaging of biological tissues for a long time. The work carried out includes medical optical endoscopic imaging, such as laser confocal microendoscopic imaging, fluorescence laparoscopic imaging, laser speckle blood flow imaging, computational phase contrast endoscopic imaging, structured light illumination super-resolution microscopy (SIM) imaging, etc. The confocal fluorescence microscopy imager has been approved for medical device registration.

Narrow-band imaging: allowing doctors to see more clearly

Narrow Band Imaging (NBI) is an endoscopic technology that allows doctors to "see more clearly".

Traditional endoscopes use white light for illumination, which can see the surface of organs, but it is often easy to overlook small lesions in the early stage. Narrow-band imaging uses blue and green light of specific wavelengths to specifically illuminate the surface of blood vessels and mucosa, making small lesions "visible", which is particularly suitable for early cancer screening.

Simply put, NBI is like adding a filter to the doctor's "vision", highlighting the details of the diseased area, similar to making hidden clues clearly visible under a "magnifying glass".

This technology is particularly suitable for examinations of the digestive and respiratory tracts, allowing doctors to detect abnormalities earlier and make more accurate diagnoses. Narrow-band imaging adds a "perspective" effect to the observation power of the endoscope, greatly improving the accuracy of detection and the success rate of early diagnosis.

Micro-ducts with different degrees of lesions under NBI

(Image source: Reference 1)

Fluorescence endoscopy: illuminating hidden lesions

Fluorescent endoscopes inject fluorescent substances to make the diseased area "glow" under specific light, providing doctors with precise navigation.

Similar to the effect of night vision goggles in movies, fluorescent endoscopes allow doctors to see lesions that cannot be displayed under normal optics. Especially in cancer surgery, fluorescence-guided surgery becomes a "beacon" for tumor removal.

Fluorescent endoscopes are more often used for surgical navigation and precise positioning of lesions. By injecting or applying fluorescent dyes, specific tissues can emit fluorescence under specific light, especially tumors and lesion areas, which become more conspicuous during surgery. In this way, doctors can accurately identify and remove lesion tissues during surgery to avoid accidental injury to healthy tissues.

Fluorescence imaging of tumors

(Image source: Reference 2)

Fluorescent endoscopes are similar to "high-precision maps" for doctors, providing clear navigation in complex surgical environments, helping doctors ensure the thoroughness and safety of surgery and reduce the risk of recurrence. This technology is mainly used for real-time guidance in cancer surgery and has become a beacon for tumor removal.

Endoscopic Ultrasound: Listen and Describe

Endoscopic Ultrasound (EUS) can be said to be a perfect combination of endoscopy and ultrasound technology. It is not only a pair of "eyes", but also can listen and detect structures deep inside the body like "ears".

Traditional endoscopes can only see the surface of organs, but ultrasound endoscopes are like "radars" in the hands of doctors. They emit high-frequency sound waves to penetrate the surface of tissues and capture images at deeper levels. When sound waves encounter tissues of different densities, they reflect back different signals, forming detailed images, allowing doctors to not only observe the surface, but also "see through" adjacent organs or tumors.

Ultrasound endoscopy is most commonly used to diagnose digestive tract diseases, such as lesions in the stomach, pancreas, duodenum, etc. During operation, it "detects" the digestive tract wall or surrounding organs through an ultrasound probe, like an imaging instrument that passes through the "barrier" to help doctors identify deep lesions.

Endoscopic ultrasound helps to accurately diagnose digestive tract diseases

(Photo source: Xinhuanet)

What’s more interesting is that EUS can also be used in conjunction with fine needle aspiration biopsy to directly obtain deep tissue samples for further pathological analysis. The magic of this technology is that it can not only “see” but also “hear” changes in the body, expanding the imaging depth of traditional endoscopes and enabling doctors to see lesions in deep tissues.

Ultrasound endoscopy is like a "periscope" in modern medicine, allowing doctors to explore the hidden corners of the body more deeply and ensure that no lesions can escape detection.

Confocal laser endomicroscopy: a "microscopic explorer" that reveals the mysteries of cells

Confocal Laser Endomicroscopy (CLE) is a groundbreaking endoscopic technology that combines confocal microscopy and endoscopy to provide real-time tissue imaging at the microscopic level.

This technology not only allows doctors to observe the details of the organ surface, but also to observe the cytological morphology of tissues to help diagnose diseases. It is like a doctor can carry a microscope to "explore" the patient's body, directly observe the changes in tissues and cells, and achieve real-time imaging at the cellular level.

The core of confocal laser endoscopy lies in the two parts of "confocal" and "imaging probe". The basic idea is to use a small hole to eliminate scattered light from non-focal planes and non-focal points[3], so that only the light signal from the focal point is retained, thus forming a high-resolution image.

The laser in CLE is introduced into the human body through the optical fiber of the endoscope. The light emitted by the light source accurately illuminates the tissue at the conjugate point, and the excited fluorescence is accurately focused at the pinhole to form a point image. This pinhole is the key to CLE's cellular-level observation capability. It is conjugate with the illumination point light source, so stray light outside the focus is filtered out.

CLE also often requires the assistance of fluorescent agents. Doctors will inject fluorescent agents, such as sodium fluorescein, before the operation. These fluorescent agents can combine with certain cell structures in the tissue to show the vascular structure, intracellular spaces, etc. of the tissue being tested.

Left: Intestinal metaplasia under ordinary endoscopy

Middle: Intestinal metaplasia under confocal endoscopy

Right: Intestinal metaplasia under histological examination

(Image source: Reference 4)

In traditional diagnosis, doctors usually need to remove a small piece of tissue through biopsy for pathological analysis. The biopsy process is not only traumatic, but may also take longer, and the sampling results may also be inaccurate.

However, CLE performs real-time imaging of the luminal surface and is a non-invasive "optical biopsy" method that can perform cellular-level detection without removing tissue, enabling early diagnosis and treatment of tissue lesions. This means that patients will suffer less trauma during the examination and will be able to obtain diagnostic results more quickly, thereby reducing the time and uncertainty of diagnosis and treatment.

At present, the clinical application of CLE is relatively mature, such as imaging of the intestines and stomach. In the future, as the clinical application areas expand, it will play a greater role.

Capsule endoscopy: Swallowing a reconnaissance satellite

Imagine that you only need to swallow a capsule, which is like a miniature "reconnaissance satellite" that enters your digestive tract and begins its own exploration. This is the magic of capsule endoscopy.

In the past, doctors could only "forcibly penetrate" the body through a long endoscope tube, which was not only uncomfortable but also easy to miss key lesions. Today, capsule endoscopy completely liberates this experience. It can freely travel through the gastrointestinal tract of the human body, like a loyal explorer, taking pictures while walking, and transmitting high-definition images to the receiver worn outside the patient's body through the built-in wireless transmitter.

Left: Image of the digestive tract under capsule endoscopy Right: Actual size of capsule endoscopy

(Image source: Wikipedia)

This receiver acts like a data collection station, recording the entire digestive tract exploration process, allowing doctors to analyze the images in detail later and see every corner of the digestive tract. Even more amazing is that capsule endoscopy can fully examine areas that are difficult to reach with traditional endoscopes, especially the complex and tortuous small intestine[5].

For doctors, capsule endoscopy is like a pair of "eyes" that can scan seamlessly, and can even help detect early lesions such as Crohn's disease and gastrointestinal bleeding. For patients, this is a revolutionary progress. They no longer need to endure the pain of intubation, but only need to swallow a capsule, and the examination process is as easy as usual.

In the future, in what direction will endoscopes evolve?

The future endoscopic camera system will not only develop in the direction of high-definition, intelligent and minimally invasive, but will also focus more on breakthroughs in microcavity imaging technology. With the advancement of optics, microelectronics and imaging technology, endoscopic cameras will provide ultra-high-definition and even 8K real-time images, helping doctors to observe the lesion area more accurately in complex surgical scenarios. At the same time, 3D stereo imaging will become a standard configuration, greatly enhancing doctors' spatial perception, especially in minimally invasive surgeries such as laparoscopy, improving the accuracy and safety of operations.

Imaging of tiny natural cavities: Imaging of tiny cavities is an important direction in the development of endoscopic technology. It allows doctors to enter tiny channels that were difficult to reach with traditional endoscopes in the past, such as the bile duct, pancreatic duct, urinary tract, and blood vessels. In the past, the inspection and treatment of these areas often relied on invasive surgery or radiological imaging, but the precision and miniaturization of microcavity endoscope equipment allows doctors to directly observe and treat diseases in these cavities through extremely small channels. For example, early detection of bile duct cancer and pancreatic cancer can now be performed directly through microcavity imaging, which greatly improves the accuracy of diagnosis and the opportunity for early treatment.

AI technology: Artificial intelligence (AI) is also a core driving force for future endoscopic technology[6]. AI can analyze endoscopic images in real time, automatically identify diseased tissues, and provide diagnostic recommendations. With the assistance of AI, doctors can make diagnoses more quickly and reduce human errors. AI technology has shown great potential in certain areas, such as the automatic detection of colon polyps. In the future, its application will be expanded to more disease screening and precise analysis of tiny cavities.

3D imaging technology: In addition, microcavity imaging technology will be combined with high-definition and 3D imaging, allowing doctors to not only see delicate images in extremely narrow channels, but also accurately determine the location and extent of lesions through a three-dimensional perspective. This technological breakthrough has brought great possibilities for minimally invasive surgery. Doctors can monitor and operate in real time during the operation, reduce damage to surrounding healthy tissues, and greatly reduce surgical risks.

The advancement of medical devices has far-reaching significance for the diagnosis and treatment of modern medicine. Higher-definition and more intelligent endoscopes not only improve the ability to detect early lesions, but also promote the development of minimally invasive surgery, reducing patients' pain and postoperative recovery time.

In the future, as these technologies develop further, endoscopes will continue to be a "super tool" in the hands of doctors, helping them complete complex diagnostic and treatment tasks with unprecedented accuracy and efficiency.

References:

[1] Zhu Yanan, Wang Jun, Wang Juan, et al. Manifestations of early gastric cancer and intraepithelial neoplasia under magnifying endoscopic narrow-band imaging technology[J]. Chinese Journal of Endoscopy, 2024, 30(07): 56-62.

[2] Liu Sheng, Yin Xinmin, Liu Yi, et al. Safety and feasibility study of ICG fluorescence-guided laparoscopic anatomical right hepatectomy for the treatment of liver tumors[J]. Chinese Journal of Practical Surgery, 2019, 39(09): 944-948.

[3] Xu Baoteng. Research on key technologies of confocal microendoscopic image acquisition and processing based on fiber bundle[D]. University of Science and Technology of China, 2023.

[4] Yu Xiaoyun, Chen Jie, Zheng Liduan, et al. Diagnostic value of laser confocal endoscopy for chronic atrophic gastritis and intestinal metaplasia[J]. Journal of Clinical Digestive Diseases, 2013, 25(05): 280-282.

[5] Liao Zhuan, Li Zhaoshen. 20-year development and prospects of capsule endoscopy[J]. Chinese Journal of Practical Internal Medicine, 2022, 42(01): 1-7.

[6] Sun Jiawei, Chen Zhaoqing, Zhao Bin, et al. Application progress of deep learning in fiber optic imaging (invited) [J]. Laser & Optoelectronics Progress, 2024, 61(16): 70-85.