CN116584880A - Integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality - Google Patents

Abstract

The invention provides an endoscopic probe integrated with photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality includes a housing, a spectrum module, an ultrasound module and multiple channels, one end of the housing is provided with the spectrum module, and the other end is provided with a There are a plurality of channels extending to the inside, with recessed sides and equipped with the ultrasonic module; some of the channels are respectively connected to the spectrum module and the ultrasonic module, and some of the channels extend to the The recess on the side of the casing, and the first optical fiber, the second optical fiber or the biopsy needle are arranged inside it. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality provided by the present invention solves the problem.

Description

Integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality

technical field

The invention relates to the field of endoscopic probes, in particular to an endoscopic probe integrated with photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality.

Background technique

Cancers of the digestive system are a major public health problem worldwide. Cancers of the stomach, colon, rectum, liver, pancreas, and esophagus are highly prevalent and among the leading causes of cancer-related death in both men and women in both developed and developing countries. Traditional surgery, radiotherapy, and chemotherapy are important methods for the treatment of gastrointestinal tumors. However, after traditional treatment, patients may have problems such as treatment failure, cancer recurrence, and poor postoperative quality of life. Therefore, new treatment techniques are urgently needed in clinical practice to make up for the deficiencies of traditional treatment techniques.

As a locally targeted and minimally invasive therapy for tumor treatment that has emerged in recent years, photodynamic therapy can provide patients with a gentle, function-preserving, safe, repeatable and effective treatment option due to its safety, high efficiency and precision. Photodynamic therapy is to irradiate the tissue with laser light of a specific wavelength, so that the photosensitizer absorbed by the tissue is excited, and the photosensitizer in the excited state transfers energy to the molecular oxygen in the surrounding tissue to generate active oxygen (a considerable part of which is very active) Singlet oxygen), the latter reacts with adjacent biomacromolecules to produce cytotoxicity, thereby killing tumor cells.

Although photodynamic therapy has demonstrated good therapeutic effects on digestive tract malignant tumors in basic and clinical research, there are still major deficiencies in its practical application. Good tumor accumulation of photosensitizer, high tumor oxygen partial pressure and sufficient intensity of light are the three essential elements for successful photodynamic therapy. However, in clinical applications, doctors usually determine the time required for tumor accumulation after photosensitizer injection based on experience, and then use optical or endoscopic ultrasound to locate the tumor, and then insert an optical fiber for irradiation treatment. The lack of monitoring of the above three elements leads to therapeutic effects. of uncertainty. In addition, due to the relatively thin wall of the digestive tract, in the absence of monitoring and feedback control, photodynamic therapy may cause tissue necrosis throughout the thickness of the intestinal wall at the treatment site. Finally, due to the inability to obtain treatment parameters in real time, it is also difficult to establish a dose-effect relationship model in photodynamic therapy, which restricts the development of photodynamic therapy regulation theory.

However, current gastrointestinal endoscopy is mostly based on ultrasound and wide-field optical imaging, neither of which can effectively monitor the key parameters in the photodynamics mentioned above. Among them, the wide-field optical endoscope is a commonly used digestive tract endoscopy device in clinical practice. It can perform high-definition real-time imaging on the surface of the digestive tract, so as to quickly locate lesions according to the optical image features, but the detection results lack depth information and are difficult to detect. Molecular functional imaging of photosensitizers and oxygen content was not possible. Ultrasound imaging utilizes the difference in ultrasound reflectance between tumor tissue and normal tissue, which can obtain complete structural information of the tumor and its surrounding tissue, but it also does not have the ability of molecular functional imaging. Other conventional medical imaging methods, such as positron emission tomography, computed tomography, and magnetic resonance imaging, are also very deficient in imaging photosensitizers and oxygen content. At present, there are only a few methods that use wide-field fluorescence imaging to measure the content of photosensitizers on the tissue surface during photodynamic therapy. The determination of oxygen content in tissues generally uses single-point measurement methods such as polarographic oxygen electrodes, but such methods cannot obtain accurate oxygen distribution in the whole tissue.

Photoacoustic imaging uses nanosecond pulsed light as the excitation source, and performs imaging by detecting ultrasonic signals excited by tissue-specific light absorption, thus breaking through the limit of high-resolution optical imaging depth and combining the high-level tissue imaging capabilities of pure optical imaging. Specificity and high penetration depth for ultrasound imaging. The researchers proposed a photoacoustic lifetime imaging technology based on the triplet difference of the photosensitizer to eliminate the strong background signal interference from blood, etc., and realized the specific dynamic imaging of the photosensitizer and tissue oxygen, and through the triplet lifetime of the photosensitizer The distribution of tissue oxygen partial pressure can be obtained by imaging, which makes it possible for clinical monitoring of photodynamic therapy by photoacoustic lifetime imaging.

Due to the relatively insufficient penetration depth of light in the human body, photoacoustic imaging needs to be combined with endoscopic technology to detect tumors in the digestive tract. The current mainstream photoacoustic endoscopic imaging generally adopts a laser/ultrasonic coaxial structure. This type of photoacoustic endoscope has a relatively simple and compact structure, a small probe size, and a single high-performance ultrasonic transducer for high-quality imaging. . However, such systems are mostly based on tens of kilohertz high-repetition single-wavelength lasers, but the pulse energy is usually less than 0.3 millijoules, which cannot well reflect the high penetration advantages of photoacoustic imaging. Photoacoustic endoscopic probes based on small medical ultrasound arrays are usually modified by adding optical fiber bundles on both sides of such probes. However, the existing photoacoustic endoscopes are usually large in size (typical diameter is about 2.5 cm), and are usually limited to a few studies such as human or large animal rectal endoscopy and prostate cancer detection.

Contents of the invention

In order to solve the problem that the existing photoacoustic imaging equipment cannot reflect the high penetration advantage of photoacoustic imaging or has a large volume, the present invention provides an integrated photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality. spy head.

An integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality, including a housing, a spectrum module, an ultrasound module and multiple channels, one end of the housing is provided with the spectrum module, and the other end is There are a plurality of channels extending to the inside, the sides are recessed, and the ultrasonic module is provided; some of the channels are respectively connected to the spectrum module and the ultrasonic module, and some of the channels extend to the The recess on the side of the shell, and the first optical fiber, the second optical fiber or the biopsy needle are arranged inside.

In a preferred embodiment of the integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality provided by the present invention, the housing is in the shape of a bullet, and one end is a tip and is equipped with the spectral module, The other end is a plane and is provided with the passage. The diameter of the housing is 12.7mm, the length is 25mm, and the size of the spectrum module is 2mm*2mm*0.5mm.

In a preferred embodiment of the integrated endoscopic probe for gastrointestinal tumor photodynamic diagnosis and treatment based on optical multimodality provided by the present invention, the side of the housing is provided with an arc-shaped depression, and along the arc of the depression, The shaped inner wall is provided with the ultrasonic module.

The ultrasonic module is an ultrasonic array with 96 array units, a center frequency of 10 MHz, and an ultrasonic array radius of 10 mm.

In a preferred embodiment of the optical multimodal photodynamic diagnosis and treatment integrated endoscopic probe for digestive tract tumors provided by the present invention, it includes five channels, two of which are respectively connected to the spectrum module and the ultrasonic module, the other three channels extend to the recesses on the side of the housing, two of which respectively extend to both sides of the ultrasonic module, and are respectively provided with the first optical fiber inside, and the other One respectively extends above the ultrasound module and is provided with the second optical fiber or the biopsy needle inside.

The first optical fiber is an angle-cut optical fiber, and the second optical fiber is an optical coherence tomography optical fiber or an optical focusing photoacoustic endoscopic optical fiber.

In a preferred embodiment of the integrated endoscopic probe for gastrointestinal tumor photodynamic diagnosis and treatment based on optical multimodality provided by the present invention, the first optical fiber transmits the laser light and makes it reflected at the top of the optical fiber, and the sideways The ultrasonic module emits ultrasound to irradiate the target body; the ultrasonic module receives photoacoustic signals.

The spectrum module integrates a micro-spectrometer composed of a free-form metasurface for spectrum recovery and real-time spectral imaging. The second optical fiber transmits the laser light, which is reflected at the top of the optical fiber, and illuminates the target body laterally; the second optical fiber is incorporated into an optical coherence tomography system, or incorporated into a light-focusing photoacoustic endoscopy system.

Compared with the prior art, the integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality provided by the present invention is greatly reduced in size compared with traditional endoscopic probes. Ultrasound imaging and photoacoustic imaging can be realized, and high-speed imaging of photosensitizer concentration and tissue oxygen partial pressure can be provided. It has the function of measuring parameters related to tissue layering, microvascular morphology and blood flow velocity, and has the ability of real-time imaging of a wide range of spectra in the lumen of the digestive tract. It can guide tumor localization, tissue biopsy in deep tissue, and precise projection of photodynamic therapy light, so as to realize cross-scale and cross-modal complete characterization of digestive tract tumor photodynamic therapy.

Description of drawings

Figure 1 is a schematic structural diagram of an integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality;

Fig. 2 is a front view of an integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality;

Fig. 3 is a diagram of the simulation reconstruction results of point targets at different positions by the arc-shaped ultrasonic array;

Fig. 4 is a graph of the lateral resolution of the curved ultrasonic array at different depths.

Detailed ways

The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some, not all, embodiments of the present invention.

Please refer to Fig. 1 and Fig. 2 at the same time, which are respectively a structural schematic diagram and a front view of an endoscopic probe integrated with photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality provided by the present invention.

The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality includes a housing 1, a spectrum module 2, an ultrasound module 3 and five channels.

The shell 1 is bullet-shaped, with a diameter of 12.7 mm and a length of 25 mm. One end of the shell 1 is a tip and is provided with a spectrum module 2, and the size of the spectrum module 2 is 2mm*2mm*0.5mm. The side of the housing 1 is provided with an arc-shaped depression, and an ultrasonic module 3 is arranged along the arc-shaped inner wall of the depression. The other end of the shell 1 is a plane and is provided with a channel.

Two of the channels are respectively connected to the spectrum module 2 and the ultrasound module 3 to provide power supply and data transmission functions. The other three channels extend to the depression on the side of the housing 1, two of the three extend to both sides of the ultrasonic module 3 respectively, and the first optical fiber 4 is respectively arranged inside, and the other extends to the top of the ultrasonic module 3, and inside it A second optical fiber 5 is provided.

The first optical fiber 4 is an angle-cut optical fiber. Multimode angle-cut fiber optics in both channels are used to deliver the laser light into the lumen of the alimentary canal. The multi-mode angle-cut optical fiber protrudes from the two channels located on both sides of the ultrasonic module 3, and the laser light is directly reflected at the top of the optical fiber to irradiate the lesion sideways.

Please refer to Fig. 3 and Fig. 4 at the same time. In the integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality provided by the present invention, the ultrasonic module 3 is used for ultrasonic imaging and photoacoustic imaging. Figures of simulation reconstruction results of the array for point targets at different positions; and lateral resolution curves at different depths. It can be seen from the figure that the resolution of the array in this area is in the range of 150 μm-300 μm, which is high resolution.

The ultrasonic module 3 is an ultrasonic array with 96 array units, a center frequency of 10 MHz, and a radius of the ultrasonic array of 10 mm. When performing ultrasonic imaging, the ultrasonic array first emits ultrasonic waves, the ultrasonic waves are reflected by the target, and then received by the ultrasonic array, and finally the image is reconstructed through the ultrasonic reconstruction algorithm.

To perform photoacoustic imaging, the first optical fiber 4 is used to irradiate laser light onto the target object, and then the ultrasound array is used to receive the generated ultrasound, and finally the image is reconstructed through the photoacoustic reconstruction algorithm. Ultrasound imaging can detect the morphological structure of tissues, and real-time monitoring of parameters such as blood oxygen and physiological functions in deep tissues can be performed through multi-wavelength photoacoustic imaging technology. High-specificity photoacoustic lifetime imaging can provide high-speed imaging of photosensitizer concentration and tissue oxygen partial pressure.

The second optical fiber 5 is an optical coherence tomography optical fiber, which is incorporated into an optical coherence tomography system. The optical coherence tomography system is mainly composed of a pulsed laser, an ultrasonic excitation device, an optical fiber device and an ultrasonic motor micro-probe. Optical coherence tomography has the function of measuring parameters related to tissue layering, microvascular morphology and blood flow velocity.

The spectrum module 2 at the front end of the probe performs high-definition optical and hyperspectral imaging. Hyperspectral imaging is a method based on computational spectroscopy, which uses free-form metasurfaces for spectral sensing, and can integrate micro-spectrometers composed of free-form metasurfaces on a large scale within a limited area, and then accelerate algorithms through deep neural networks to achieve high Precision spectral recovery and real-time spectral imaging. Hyperspectral imaging has the capability of real-time imaging of a wide range of spectra in the lumen of the digestive tract.

Together with ultrasound imaging, these modalities can guide tumor localization in deep tissue, tissue biopsy, and precise delivery of photodynamic therapy light. Since the probe will also integrate high-definition wide-field optics, hyperspectral and other modes, and realize the integration with multi-modal endoscopic probes such as optical coherence tomography/optical focusing photoacoustic endoscopy through surgical instrument channels, so as to realize the Cross-scale and cross-modal complete characterization of photodynamic therapy for gastrointestinal tumors.

Together with ultrasound imaging, these modalities can guide tumor localization in deep tissue, tissue biopsy, and precise delivery of photodynamic therapy light. Since the probe will also integrate high-definition wide-field optics, hyperspectral and other modes, and realize the integration with multi-modal endoscopic probes such as optical coherence tomography/optical focusing photoacoustic endoscopy through surgical instrument channels, so as to realize the Cross-scale and cross-modal complete characterization of photodynamic therapy for gastrointestinal tumors.

The above descriptions are only examples of the present invention, and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the content of the description of the present invention, or directly or indirectly used in other related technical fields, shall be The same reasoning is included within the scope of patent protection of the present invention.

Claims (10)

1. An integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality, characterized in that: it includes a housing, a spectrum module, an ultrasound module and a plurality of channels, and one end of the housing is provided with the Spectrum module, the other end is provided with a plurality of channels extending to the inside, the side is recessed, and is provided with the ultrasonic module; some of the channels are respectively connected to the spectral module and the ultrasonic module, and the other part is The channel extends to the recess on the side of the housing, and the first optical fiber, and the second optical fiber or the biopsy needle are arranged inside it. 2. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 1, characterized in that: the shell is bullet-shaped, one end is a tip and the spectrum module is provided, The other end is a plane and is provided with the passage. 3. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 2, characterized in that: the diameter of the housing is 12.7 mm, the length is 25 mm, and the spectrum module The size is 2mm*2mm*0.5mm. 4. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 2, characterized in that: the side of the housing is provided with an arc-shaped depression, and along the arc of the depression The shaped inner wall is provided with the ultrasonic module. 5. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 4, characterized in that: the ultrasonic module is an ultrasonic array, the number of array units is 96, and the center frequency is 10MHz , the ultrasonic array radius is 10mm. 6. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 2, characterized in that it includes five channels, two of which are respectively connected to the spectrum module and the ultrasonic module, the other three channels extend to the recesses on the side of the housing, two of which respectively extend to both sides of the ultrasonic module, and are respectively provided with the first optical fiber inside, and the other One respectively extends above the ultrasound module and is provided with the second optical fiber or the biopsy needle inside. 7. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 6, characterized in that: the first optical fiber is an angle-cut optical fiber, and the second optical fiber is an optical coherent layer Analysis optical fiber or optical focusing photoacoustic endoscopic optical fiber. 8. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claims 1 to 6, characterized in that: the first optical fiber transmits the laser light, and makes it be held at the top of the optical fiber Reflecting and irradiating the target body sideways, the ultrasound module emits ultrasound to irradiate the target body; the ultrasound module receives photoacoustic signals. 9. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 8, characterized in that: the spectrum module integrates a micro-spectrometer composed of a free-form metasurface for spectrum recovery and real-time spectral imaging. 10. The integrated endoscopic probe for photodynamic diagnosis and treatment of digestive tract tumors based on optical multimodality according to claim 9, characterized in that: the second optical fiber transmits the laser light and makes it reflected at the top of the optical fiber, and the sideways Irradiating to the target body; the second optical fiber is incorporated into an optical coherence tomography system, or into a light-focusing photoacoustic endoscopy system.