CN116350182A - Circular scanning photosensitizer fluorescence quantitative detection system and working method thereof - Google Patents
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Abstract
环扫光敏剂荧光定量检测系统及其工作方法,能够解决管腔内光敏剂浓度分布的定量检测,引导管腔内病变的精准治疗,进一步提高光动力疗法的安全性和有效性。包括:内窥环扫检测模块(3),用于病灶可视化和管腔内的诊断与治疗;多模态信号检测模块(16),用于采集荧光信号、405nm激发光的反射信号和组织的OCT信号;信号处理与控制模块(15),用于处理多模态信号检测模块采集到的荧光信号、405nm激光的反射信号和组织的OCT信号,以及控制内窥环扫检测模块内各器件、405nm激光器(11)、扫频OCT(12)、第一雪崩光电二极管(13)、第二雪崩光电二极管(14)的运转。
The ring-scan photosensitizer fluorescence quantitative detection system and its working method can solve the quantitative detection of the concentration distribution of the photosensitizer in the lumen, guide the precise treatment of the lesions in the lumen, and further improve the safety and effectiveness of photodynamic therapy. Including: endoscopic ring scan detection module (3), used for lesion visualization and intraluminal diagnosis and treatment; multi-modal signal detection module (16), used for collecting fluorescence signals, reflection signals of 405nm excitation light and tissue OCT signal; signal processing and control module (15), for processing the fluorescent signal that multimodal signal detection module collects, the reflected signal of 405nm laser and the OCT signal of tissue, and each device in the control endoscopic ring scanning detection module, Operation of 405nm laser (11), frequency-swept OCT (12), first avalanche photodiode (13), and second avalanche photodiode (14).
Description
技术领域technical field
本发明涉及光电检测的技术领域,尤其涉及一种环扫光敏剂荧光定量检测系统,以及这种环扫光敏剂荧光定量检测系统的工作方法。The invention relates to the technical field of photoelectric detection, in particular to a ring-scan photosensitizer fluorescence quantitative detection system and a working method of the ring-sweep photosensitizer fluorescence quantitative detection system.
背景技术Background technique
光动力疗法是一种治疗恶性肿瘤及癌前病变的新型微创疗法,具有选择性高、创伤性小等优势。近年来,光动力疗法在宫颈上皮内瘤病变、食道癌等腔内病变中展现了良好的应用前景。其治疗过程主要包括:通过静脉注射或局部涂敷给予患者光敏剂,光敏剂可选择性地富集于病灶组织;一段时间后,采用特定波长激光照射病灶,潴留于病灶处的光敏剂被激发产生具有细胞毒性的单线态氧,进而杀伤肿瘤细胞。光敏剂作为光动力疗法的三要素之一,其在体浓度分布直接影响光动力疗效。因此,实现光敏剂浓度在体定量检测是开展个性化光动力精准治疗的前提。Photodynamic therapy is a new type of minimally invasive therapy for the treatment of malignant tumors and precancerous lesions, which has the advantages of high selectivity and less trauma. In recent years, photodynamic therapy has shown good application prospects in intraluminal lesions such as cervical intraepithelial neoplasia and esophageal cancer. The treatment process mainly includes: administering a photosensitizer to the patient through intravenous injection or local application, and the photosensitizer can be selectively enriched in the lesion tissue; Generates cytotoxic singlet oxygen, which in turn kills tumor cells. Photosensitizer is one of the three elements of photodynamic therapy, and its concentration distribution in the body directly affects photodynamic efficacy. Therefore, in vivo quantitative detection of photosensitizer concentration is a prerequisite for personalized photodynamic precision therapy.
光敏剂浓度的定量检测通常基于激光诱导荧光光谱检测技术,通过建立光敏剂浓度与荧光强度的定量关系曲线,实现光敏剂浓度的在体定量检测。光敏剂荧光在组织体中的激发以及发射传输均会受到组织光学特性的影响,因此,精确获取组织光学特性参数和荧光强度,建立荧光强度、组织光学特性和光敏剂浓度三者之间的定量关系模型,对于定量光敏剂浓度至关重要。Quantitative detection of photosensitizer concentration is usually based on laser-induced fluorescence spectroscopy detection technology. By establishing a quantitative relationship curve between photosensitizer concentration and fluorescence intensity, the in vivo quantitative detection of photosensitizer concentration is realized. The excitation and emission transmission of the photosensitizer fluorescence in the tissue will be affected by the optical properties of the tissue. Therefore, the precise acquisition of the tissue optical property parameters and fluorescence intensity, and the establishment of a quantitative relationship between the fluorescence intensity, tissue optical properties and the concentration of the photosensitizer Relational models are essential for quantifying photosensitizer concentrations.
目前,荧光定量主要通过漫反射光谱、空间频域成像、多光谱成像等方法得到组织光学特性参数,将其用于校正原始荧光光谱,进而得到定量荧光光谱。然而,目前常用的荧光定量技术均为前向检测,难以用于获取环形管腔内的组织光学特性及荧光分布信息。因此,发展管腔内在体同步获取组织光学特性参数和荧光分布新技术,是实现管腔内光敏剂浓度定量的关键。At present, fluorescence quantification mainly obtains tissue optical characteristic parameters through methods such as diffuse reflectance spectroscopy, spatial frequency domain imaging, and multispectral imaging, and uses them to correct the original fluorescence spectrum to obtain quantitative fluorescence spectra. However, currently commonly used fluorescence quantitative techniques are forward detection, which is difficult to obtain tissue optical properties and fluorescence distribution information in the annular lumen. Therefore, it is the key to realize the quantification of the concentration of photosensitizers in the lumen to develop new techniques for synchronous acquisition of tissue optical characteristic parameters and fluorescence distribution in the luminal exosome.
因此,如何实现管腔内光敏剂浓度分布定量检测为本发明所要解决的具体问题。Therefore, how to realize the quantitative detection of the concentration distribution of the photosensitizer in the lumen is a specific problem to be solved by the present invention.
发明内容Contents of the invention
为克服现有技术的缺陷,本发明要解决的技术问题是提供了一种环扫光敏剂荧光定量检测系统,其能够解决管腔内光敏剂浓度分布的定量检测,引导管腔内病变的精准治疗,进一步提高光动力疗法的安全性和有效性。In order to overcome the defects of the prior art, the technical problem to be solved in the present invention is to provide a ring-scan photosensitizer fluorescence quantitative detection system, which can solve the quantitative detection of the concentration distribution of the photosensitizer in the lumen, and guide the accurate detection of the lesion in the lumen. treatment, to further improve the safety and effectiveness of photodynamic therapy.
本发明的技术方案是:这种环扫光敏剂荧光定量检测系统,其包括:The technical scheme of the present invention is: this ring scan photosensitizer fluorescence quantitative detection system, it comprises:
内窥环扫检测模块(3),包括:内窥式环扫微探头(1)和步进电机平移台(2),所述内窥环扫检测模块用于病灶可视化和管腔内的诊断与治疗;An endoscopic ring scan detection module (3), including: an endoscopic ring scan microprobe (1) and a stepping motor translation platform (2), the endoscopic ring scan detection module is used for lesion visualization and intraluminal diagnosis and treatment;
多模态信号检测模块(16),包括:双包层光纤耦合器(4)、物镜(5)、反射镜(6)、二向色镜(7)、波分复用器(8)、中性密度滤光片(9)、带通滤光片(10)、405nm激光器(11)、扫频OCT(12)、第一雪崩光电二极管(13)、第二雪崩光电二极管(14),所述多模态信号检测模块用于采集荧光信号、405nm激发光的反射信号和组织的OCT信号;A multi-mode signal detection module (16), comprising: a double-clad fiber coupler (4), an objective lens (5), a mirror (6), a dichroic mirror (7), a wavelength division multiplexer (8), Neutral density filter (9), bandpass filter (10), 405nm laser (11), frequency-swept OCT (12), first avalanche photodiode (13), second avalanche photodiode (14), The multimodal signal detection module is used to collect fluorescence signals, reflection signals of 405nm excitation light and OCT signals of tissues;
信号处理与控制模块(15),用于处理多模态信号检测模块采集到的荧光信号、405nm激光的反射信号和组织的OCT信号,以及控制内窥环扫检测模块内各器件、405nm激光器(11)、扫频OCT(12)、第一雪崩光电二极管(13)、第二雪崩光电二极管(14)的运转;内窥式环扫微探头伸入至管腔内,微型相机实现管腔内的病灶成像引导,步进电机控制探头移动以精准定位病灶,球囊撑开以固定探头;扫频OCT和405nm激光器发出扫频激光和405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,并照射至病灶(29);扫频激光照射至病灶后产生OCT信号,405nm激光照射至病灶后,病灶处的光敏剂被激发出荧光,OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器;OCT信号经波分复用器返回至扫频OCT进行检测,并传输至信号处理与控制模块进行处理;405nm激光的反射信号和荧光信号经二向色镜分光后,405nm激光的反射信号经反射镜反射、中性密度滤光片滤光后到达第一雪崩光电二极管,并传输至信号处理与控制模块进行处理;荧光信号经带通滤光片滤光后到达第二雪崩光电二极管,并传输至信号处理与控制模块进行处理;控制微型马达旋转,对管腔病灶进行环形扫描以获取病灶的完整信息,进而完成组织三维重构、组织光学特性参数提取和光敏剂浓度定量。The signal processing and control module (15) is used to process the fluorescent signal collected by the multimodal signal detection module, the reflected signal of the 405nm laser and the OCT signal of the tissue, and control each device in the endoscopic ring scan detection module, the 405nm laser ( 11), the operation of frequency-sweeping OCT (12), the first avalanche photodiode (13), and the second avalanche photodiode (14); The lesion imaging guidance, the stepping motor controls the movement of the probe to accurately locate the lesion, and the balloon is stretched to fix the probe; the frequency-sweeping OCT and 405nm laser emit frequency-sweeping laser and 405nm laser, which are combined by a wavelength division multiplexer and double-clad The optical fiber coupler transmits to the endoscopic ring-scanning microprobe and irradiates the lesion (29); after the frequency-sweeping laser irradiates the lesion, an OCT signal is generated; Signal, fluorescence signal and reflection signal of 405nm laser return to the double-clad fiber coupler through the original optical path; OCT signal returns to frequency-sweeping OCT for detection through the wavelength division multiplexer, and is transmitted to the signal processing and control module for processing; 405nm After the reflection signal and fluorescence signal of the laser are split by the dichroic mirror, the reflection signal of the 405nm laser is reflected by the mirror and filtered by the neutral density filter, then reaches the first avalanche photodiode, and is transmitted to the signal processing and control module for further processing. processing; the fluorescent signal is filtered by a band-pass filter and reaches the second avalanche photodiode, and is transmitted to the signal processing and control module for processing; the rotation of the micro-motor is controlled, and the luminal lesion is circularly scanned to obtain the complete information of the lesion. Then complete three-dimensional reconstruction of tissue, extraction of tissue optical characteristic parameters and quantification of photosensitizer concentration.
本发明将内窥式环扫微探头伸入至管腔内,微型相机实现管腔内的病灶成像引导,步进电机控制探头移动,到达管腔底部后,球囊撑开以固定探头;扫频OCT和405nm激光器发出扫频激光和405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,并照射至病灶;扫频激光照射至病灶后产生OCT信号,405nm激光照射至病灶后,病灶处的光敏剂被激发出荧光,OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器,并分别传输至信号处理与控制模块;控制微型马达旋转,对管腔病灶进行环形扫描以获取病灶的完整信息,信号处理与控制模块对OCT信号、荧光信号以及405nm激光进行处理,进而完成组织三维重构、组织光学特性参数获取和光敏剂浓度定量;管腔内光敏剂浓度分布的定量检测,引导管腔内病变的精准治疗,进一步提高光动力疗法的安全性和有效性。In the present invention, the endoscopic ring-scanning micro-probe is inserted into the lumen, the micro-camera realizes the lesion imaging guide in the lumen, the stepping motor controls the movement of the probe, and after reaching the bottom of the lumen, the balloon stretches to fix the probe; Frequency OCT and 405nm lasers emit frequency-sweeping laser and 405nm laser, which are combined by wavelength division multiplexer and double-clad fiber coupler to transmit to endoscopic ring-scanning microprobe and irradiate to the lesion; after the frequency-sweeping laser is irradiated to the lesion OCT signal is generated, after the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce, and the OCT signal, the fluorescence signal, and the reflected signal of the 405nm laser return to the double-clad fiber coupler through the original optical path, and are respectively transmitted to the signal processing and control module; control the rotation of the micro-motor, scan the luminal lesion circularly to obtain the complete information of the lesion, the signal processing and control module processes the OCT signal, fluorescence signal and 405nm laser, and then completes the three-dimensional reconstruction of the tissue and the optical characteristics of the tissue Acquisition of parameters and quantification of photosensitizer concentration; quantitative detection of photosensitizer concentration distribution in the lumen guides precise treatment of intraluminal lesions and further improves the safety and effectiveness of photodynamic therapy.
还提供了一种环扫光敏剂荧光定量检测系统的工作方法,其包括以下步骤:Also provided is a working method of a ring-scan photosensitizer fluorescence quantitative detection system, which includes the following steps:
(1)通过局部涂敷或静脉注射给予患者光敏剂;(1) Administer photosensitizers to patients by local application or intravenous injection;
(2)内窥式环扫微探头伸入至管腔内,通过微型相机进行病灶可视化引导并精准定位病灶,探头到达病灶后球囊被撑开;(2) The endoscopic ring-scanning micro-probe is inserted into the lumen, and the lesion is visualized and guided by the micro-camera to accurately locate the lesion. After the probe reaches the lesion, the balloon is stretched;
(3)扫频OCT发出扫频激光,405nm激光器发出405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,并对病灶环扫照射,扫频激光照射至病灶后产生OCT信号,405nm激光照射病灶后,病灶处的光敏剂被激发出荧光;(3) Frequency-sweeping OCT emits a frequency-sweeping laser, and a 405nm laser emits a 405nm laser, which is combined by a wavelength division multiplexer and a double-clad fiber coupler and transmitted to the endoscopic ring-scanning microprobe, and irradiates the lesion in a ring-sweeping manner. OCT signals are generated after the high-frequency laser is irradiated to the lesion, and after the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce;
(4)OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器;OCT信号经波分复用器返回至扫频OCT进行检测,并传输至信号处理与控制模块进行处理;405nm激光的反射信号和荧光信号经二向色镜分光后,405nm激光的反射信号经反射镜反射、中性密度滤光片滤光后到达第一雪崩光电二极管,并传输至信号处理与控制模块进行处理;荧光信号经带通滤光片滤光后到达第二雪崩光电二极管,并传输至信号处理与控制模块进行处理;(4) OCT signal, fluorescence signal and the reflected signal of 405nm laser return to the double-clad fiber coupler through the original optical path; the OCT signal returns to the frequency-sweeping OCT for detection through the wavelength division multiplexer, and is transmitted to the signal processing and control module Processing; after the reflection signal and fluorescence signal of the 405nm laser are split by the dichroic mirror, the reflection signal of the 405nm laser is reflected by the mirror, filtered by the neutral density filter, and then reaches the first avalanche photodiode, and is transmitted to the signal processing Processing with the control module; the fluorescent signal reaches the second avalanche photodiode after being filtered by the band-pass filter, and is transmitted to the signal processing and control module for processing;
(5)信号处理与控制模块控制微型马达旋转,每旋转一个小角度,重复步骤(3)、(4)以获取单点病灶信息,微型马达旋转一圈而获得环形上每一点的扫描信息,步进电机控制光纤的直线移动,完成管腔内全部病灶位置的扫描;(5) The signal processing and control module controls the rotation of the micro-motor, and repeats steps (3) and (4) to obtain single-point lesion information every time a small angle is rotated, and the micro-motor rotates once to obtain the scanning information of each point on the ring, The stepping motor controls the linear movement of the optical fiber to complete the scanning of all lesions in the lumen;
(6)信号处理与控制模块对OCT信号、荧光信号及405nm激光的反射信号进行处理,OCT信号用于组织三维重构和组织光学特性参数提取,并结合荧光信号和激光反射信号完成荧光强度的校正;(6) The signal processing and control module processes the OCT signal, the fluorescence signal and the reflection signal of the 405nm laser. The OCT signal is used for the three-dimensional reconstruction of the tissue and the extraction of the optical characteristic parameters of the tissue, and combines the fluorescence signal and the laser reflection signal to complete the measurement of the fluorescence intensity. Correction;
(7)构建不同散射和吸收的组织光学仿体,建立荧光强度和光敏剂浓度的定量关系曲线,定量管腔内光敏剂浓度。(7) Construct optical phantoms of tissues with different scattering and absorption, establish a quantitative relationship curve between fluorescence intensity and photosensitizer concentration, and quantify the concentration of photosensitizer in the lumen.
附图说明Description of drawings
图1示出了根据本发明的环扫光敏剂荧光定量检测系统的结构示意图。Fig. 1 shows a schematic structural diagram of the fluorescence quantitative detection system for ring-scanning photosensitizers according to the present invention.
图2示出了根据本发明的环扫光敏剂荧光定量检测系统的环扫内窥微探头示意图。Fig. 2 shows a schematic diagram of a ring-scan endoscopic microprobe of the ring-scan photosensitizer fluorescence quantitative detection system according to the present invention.
图3示出了根据本发明的环扫光敏剂荧光定量检测系统的工作方法的食道粘膜实施例的示意图。Fig. 3 shows a schematic diagram of an embodiment of the esophageal mucosa according to the working method of the circular scanning photosensitizer fluorescence quantitative detection system of the present invention.
图4示出了根据本发明的环扫光敏剂荧光定量检测系统的工作方法的宫颈黏膜实施例的示意图。Fig. 4 shows a schematic diagram of an embodiment of the cervical mucous membrane of the working method of the ring-scan photosensitizer fluorescence quantitative detection system according to the present invention.
具体实施方式Detailed ways
为了使本技术领域的人员更好地理解本发明方案,下面将结合本发明实施例中的附图,对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分的实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都应当属于本发明保护的范围。In order to enable those skilled in the art to better understand the solutions of the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are only It is an embodiment of a part of the present invention, but not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts shall fall within the protection scope of the present invention.
需要说明的是,本发明的说明书和权利要求书及上述附图中的术语“包括”以及任何变形,意图在于覆盖不排他的包含,例如,包含了一系列步骤或单元的过程、方法、装置、产品或设备不必限于清楚地列出的那些步骤或单元,而是可包括没有清楚地列出的或对于这些过程、方法、产品或设备固有的其他步骤或单元。It should be noted that the terms "comprising" and any variations in the description and claims of the present invention and the above drawings are intended to cover non-exclusive inclusion, for example, processes, methods, and devices that include a series of steps or units The process, method, product or device are not necessarily limited to those steps or units explicitly listed, but may include other steps or units not explicitly listed or inherent to the process, method, product or device.
如图1所示,这种环扫光敏剂荧光定量检测系统,其包括:As shown in Figure 1, this ring scan photosensitizer fluorescence quantitative detection system includes:
内窥环扫检测模块3,包括:内窥式环扫微探头1和步进电机平移台2,所述内窥环扫检测模块用于病灶可视化和管腔内的诊断与治疗;The endoscopic ring
多模态信号检测模块16,包括:双包层光纤耦合器4、物镜5、反射镜6、二向色镜7、波分复用器8、中性密度滤光片9、带通滤光片10、405nm激光器11、扫频OCT12、第一雪崩光电二极管13、第二雪崩光电二极管14,所述多模态信号检测模块用于采集荧光信号、405nm激发光的反射信号和组织的OCT信号;The multi-mode
信号处理与控制模块15,用于处理多模态信号检测模块采集到的荧光信号、405nm激光的反射信号和组织的OCT信号,以及控制内窥环扫检测模块内各器件、405nm激光器11、扫频OCT12、第一雪崩光电二极管13、第二雪崩光电二极管14的运转;The signal processing and
内窥式环扫微探头伸入至管腔内,微型相机实现管腔内的病灶成像引导,步进电机控制探头移动以精准定位病灶,球囊撑开以固定探头;扫频OCT和405nm激光器发出扫频激光和405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,并照射至病灶29;扫频激光照射至病灶后产生OCT信号,405nm激光照射至病灶后,病灶处的光敏剂被激发出荧光,OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器;OCT信号经波分复用器返回至扫频OCT进行检测,并传输至信号处理与控制模块进行处理;405nm激光的反射信号和荧光信号经二向色镜分光后,405nm激光的反射信号经反射镜反射、中性密度滤光片滤光后到达第一雪崩光电二极管,并传输至信号处理与控制模块进行处理;荧光信号经带通滤光片滤光后到达第二雪崩光电二极管,并传输至信号处理与控制模块进行处理;控制微型马达旋转,对管腔病灶进行环形扫描以获取病灶的完整信息,进而完成组织三维重构、组织光学特性参数提取和光敏剂浓度定量。The endoscopic ring-scanning micro-probe extends into the lumen, the micro-camera realizes the imaging guidance of the lesion in the lumen, the stepping motor controls the movement of the probe to accurately locate the lesion, and the balloon is stretched to fix the probe; frequency-sweeping OCT and 405nm laser The frequency-sweeping laser and 405nm laser are emitted, which are combined by a wavelength division multiplexer and double-clad fiber coupler to transmit to the endoscopic ring-scanning microprobe, and irradiated to the lesion29; the frequency-sweeping laser is irradiated to the lesion to generate OCT signals, After the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce, and the OCT signal, the fluorescence signal, and the reflection signal of the 405nm laser return to the double-clad fiber coupler through the original optical path; the OCT signal returns to the Sweep frequency OCT for detection, and transmit to signal processing and control module for processing; 405nm laser reflection signal and fluorescence signal are split by dichroic mirror, 405nm laser reflection signal is reflected by mirror and filtered by neutral density filter The light reaches the first avalanche photodiode and is transmitted to the signal processing and control module for processing; the fluorescent signal is filtered by a bandpass filter and then reaches the second avalanche photodiode, and is transmitted to the signal processing and control module for processing; The micro-motor rotates and scans the luminal lesion circularly to obtain the complete information of the lesion, and then completes the three-dimensional reconstruction of the tissue, the extraction of the optical characteristic parameters of the tissue, and the quantification of the concentration of the photosensitizer.
本发明将内窥式环扫微探头伸入至管腔内,微型相机实现管腔内的病灶成像引导,步进电机控制探头移动,到达管腔底部后,球囊撑开以固定探头;扫频OCT和405nm激光器发出扫频激光和405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,并照射至病灶;扫频激光照射至病灶后产生OCT信号,405nm激光照射至病灶后,病灶处的光敏剂被激发出荧光,OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器,并分别传输至信号处理与控制模块;控制微型马达旋转,对管腔病灶进行环形扫描以获取病灶的完整信息,信号处理与控制模块对OCT信号、荧光信号以及405nm激光进行处理,进而完成组织三维重构、组织光学特性参数获取和光敏剂浓度定量;管腔内光敏剂浓度分布的定量检测,引导管腔内病变的精准治疗,进一步提高光动力疗法的安全性和有效性。In the present invention, the endoscopic ring-scanning micro-probe is inserted into the lumen, the micro-camera realizes the lesion imaging guide in the lumen, the stepping motor controls the movement of the probe, and after reaching the bottom of the lumen, the balloon stretches to fix the probe; Frequency OCT and 405nm lasers emit frequency-sweeping laser and 405nm laser, which are combined by wavelength division multiplexer and double-clad fiber coupler to transmit to endoscopic ring-scanning microprobe and irradiate to the lesion; after the frequency-sweeping laser is irradiated to the lesion OCT signal is generated, after the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce, and the OCT signal, the fluorescence signal, and the reflected signal of the 405nm laser return to the double-clad fiber coupler through the original optical path, and are respectively transmitted to the signal processing and control module; control the rotation of the micro-motor, scan the luminal lesion circularly to obtain the complete information of the lesion, the signal processing and control module processes the OCT signal, fluorescence signal and 405nm laser, and then completes the three-dimensional reconstruction of the tissue and the optical characteristics of the tissue Acquisition of parameters and quantification of photosensitizer concentration; quantitative detection of photosensitizer concentration distribution in the lumen guides precise treatment of intraluminal lesions and further improves the safety and effectiveness of photodynamic therapy.
优选地,所述内窥式环扫微探头包括:微型相机供电线17、微型马达供电线18、曲面反射镜19、UV固化胶20、金属防护罩21、转矩线圈22、双包层光纤23、球囊24、自聚焦透镜25、微型马达26、微型相机27、透明套管28;该探头通过微型相机进行病灶的可视化成像引导,并实现管腔中病灶的环形扫描检测。Preferably, the endoscopic ring scan microprobe includes: micro camera
优选地,所述内窥式环扫微探头根据管腔大小定制球囊尺寸,球囊直径分别为:1.0cm、1.5cm、2.0cm、2.5cm、3.0cm,以适应不同管腔如宫颈管、食道的大小,保证管腔被均匀撑开以减少褶皱。Preferably, the endoscopic ring scanning microprobe customizes the size of the balloon according to the size of the lumen. , The size of the esophagus, to ensure that the lumen is evenly stretched to reduce folds.
优选地,所述内窥式环扫微探头采用曲面反射镜,用于消除色差和像散。Preferably, the endoscopic ring-scanning microprobe adopts a curved mirror to eliminate chromatic aberration and astigmatism.
优选地,所述信号处理与控制模块同步采集组织微结构、组织光学特性和光敏剂荧光。Preferably, the signal processing and control module collect tissue microstructure, tissue optical properties and photosensitizer fluorescence synchronously.
优选地,所述第一雪崩光电二极管采集405nm激光的反射信号,第二雪崩光电二极管采集病灶处光敏剂被405nm激光激发后的荧光信号,以进行光敏剂荧光定量检测。Preferably, the first avalanche photodiode collects the reflection signal of the 405nm laser, and the second avalanche photodiode collects the fluorescence signal of the photosensitizer at the lesion after being excited by the 405nm laser, so as to perform quantitative fluorescence detection of the photosensitizer.
还提供了一种环扫光敏剂荧光定量检测系统的工作方法,其包括以下步骤:Also provided is a working method of a ring-scan photosensitizer fluorescence quantitative detection system, which includes the following steps:
(1)通过局部涂敷或静脉注射给予患者光敏剂;(1) Administer photosensitizers to patients by local application or intravenous injection;
(2)内窥式环扫微探头伸入至管腔内,通过微型相机进行病灶可视化引导并精准定位病灶,探头到达病灶后球囊被撑开;(2) The endoscopic ring-scanning micro-probe is inserted into the lumen, and the lesion is visualized and guided by the micro-camera to accurately locate the lesion. After the probe reaches the lesion, the balloon is stretched;
(3)扫频OCT发出扫频激光,405nm激光器发出405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,并对病灶环扫照射,扫频激光照射至病灶后产生OCT信号,405nm激光照射病灶后,病灶处的光敏剂被激发出荧光;(3) Frequency-sweeping OCT emits a frequency-sweeping laser, and a 405nm laser emits a 405nm laser, which is combined by a wavelength division multiplexer and a double-clad fiber coupler and transmitted to the endoscopic ring-scanning microprobe, and irradiates the lesion in a ring-sweeping manner. OCT signals are generated after the high-frequency laser is irradiated to the lesion, and after the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce;
(4)OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器;OCT信号经波分复用器返回至扫频OCT进行检测,并传输至信号处理与控制模块进行处理;405nm激光的反射信号和荧光信号经二向色镜分光后,405nm激光的反射信号经反射镜反射、中性密度滤光片滤光后到达第一雪崩光电二极管,并传输至信号处理与控制模块进行处理;荧光信号经带通滤光片滤光后到达第二雪崩光电二极管,并传输至信号处理与控制模块进行处理;(4) OCT signal, fluorescence signal and the reflected signal of 405nm laser return to the double-clad fiber coupler through the original optical path; the OCT signal returns to the frequency-sweeping OCT for detection through the wavelength division multiplexer, and is transmitted to the signal processing and control module Processing; after the reflection signal and fluorescence signal of the 405nm laser are split by the dichroic mirror, the reflection signal of the 405nm laser is reflected by the mirror, filtered by the neutral density filter, and then reaches the first avalanche photodiode, and is transmitted to the signal processing Processing with the control module; the fluorescent signal reaches the second avalanche photodiode after being filtered by the band-pass filter, and is transmitted to the signal processing and control module for processing;
(5)信号处理与控制模块控制微型马达旋转,每旋转一个小角度,重复步骤(3)、(4)以获取单点病灶信息,微型马达旋转一圈而获得环形上每一点的扫描信息,步进电机控制光纤的直线移动,完成管腔内全部病灶位置的扫描;(5) The signal processing and control module controls the rotation of the micro-motor, and repeats steps (3) and (4) to obtain single-point lesion information every time a small angle is rotated, and the micro-motor rotates once to obtain the scanning information of each point on the ring, The stepping motor controls the linear movement of the optical fiber to complete the scanning of all lesions in the lumen;
(6)信号处理与控制模块对OCT信号、荧光信号及405nm激光的反射信号进行处理,OCT信号用于组织三维重构和组织光学特性参数提取,并结合荧光信号和激光反射信号完成荧光强度的校正;(6) The signal processing and control module processes the OCT signal, the fluorescence signal and the reflection signal of the 405nm laser. The OCT signal is used for the three-dimensional reconstruction of the tissue and the extraction of the optical characteristic parameters of the tissue, and combines the fluorescence signal and the laser reflection signal to complete the measurement of the fluorescence intensity. Correction;
(7)构建不同散射和吸收的组织光学仿体,建立荧光强度和光敏剂浓度的定量关系曲线,定量管腔内光敏剂浓度。(7) Construct optical phantoms of tissues with different scattering and absorption, establish a quantitative relationship curve between fluorescence intensity and photosensitizer concentration, and quantify the concentration of photosensitizer in the lumen.
优选地,使用OCT信号计算组织衰减系数时,所使用的具体计算方法为公式(1):Preferably, when using the OCT signal to calculate the tissue attenuation coefficient, the specific calculation method used is formula (1):
其中,i为A-line上的第i个像素,I[i]为第i个像素上的信号强度,Among them, i is the i-th pixel on the A-line, I[i] is the signal intensity on the i-th pixel,
Δ为像素大小,μ[i]表示待测组织在A-line上第i个像素的衰减系数。Δ is the pixel size, and μ[i] represents the attenuation coefficient of the i-th pixel of the tissue to be measured on the A-line.
优选地,在进行荧光强度的校正时,所使用的具体方法是:利用OCT信号计算得到组织衰减系数后,将采集到的原始荧光信号、405nm激光反射信号和组织衰减系数代入至公式(2)校正荧光强度:Preferably, when correcting the fluorescence intensity, the specific method used is: after the tissue attenuation coefficient is calculated using the OCT signal, the collected original fluorescence signal, 405nm laser reflection signal and tissue attenuation coefficient are substituted into the formula (2) Correct for fluorescence intensity:
其中,为校正后的荧光强度,/>为原始荧光信号,Rx(λ)为405nm激光的漫反射率,α为经验系数。in, is the corrected fluorescence intensity, /> is the original fluorescence signal, R x (λ) is the diffuse reflectance of the 405nm laser, and α is the empirical coefficient.
以下详细说明本发明的具体实施例。Specific embodiments of the present invention will be described in detail below.
实施例1:病灶组织为食道粘膜组织Example 1: The lesion tissue is esophageal mucosal tissue
如图3所示,本发明的工作过程为:As shown in Figure 3, the working process of the present invention is:
(1)将光敏剂预先通过静脉注射入体内;(1) Inject the photosensitizer into the body through intravenous injection in advance;
(2)内窥式环扫微探头伸入至食道管腔内,通过微型相机进行病灶可视化引导并精准定位食道病灶,探头到达病灶后球囊被撑开;(2) The endoscopic ring-scanning micro-probe is inserted into the lumen of the esophagus, and the micro-camera is used to guide the visualization of the lesion and accurately locate the esophageal lesion. After the probe reaches the lesion, the balloon is stretched;
(3)启动扫频OCT和405nm激光器,发出扫频激光和405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,照射至食道病灶,扫频激光照射至病灶后产生OCT信号,405nm激光照射病灶后,病灶处的光敏剂被激发出荧光;(3) Start the frequency-sweeping OCT and 405nm laser, and emit the frequency-sweeping laser and 405nm laser, which are combined by a wavelength division multiplexer and double-clad fiber coupler and transmitted to the endoscopic ring-scanning microprobe, irradiated to the esophageal lesion, and scanned. OCT signals are generated after the high-frequency laser is irradiated to the lesion, and after the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce;
(4)OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器;OCT信号经波分复用器返回至扫频OCT进行检测,并传输至信号处理与控制模块进行处理;405nm激光的反射信号和荧光信号经二向色镜分光后,405nm激光的反射信号经反射镜反射、中性密度滤光片滤光后到达第一雪崩光电二极管,并传输至信号处理与控制模块进行处理;荧光信号经带通滤光片滤光后到达第二雪崩光电二极管,并传输至信号处理与控制模块进行处理;(4) OCT signal, fluorescence signal and the reflected signal of 405nm laser return to the double-clad fiber coupler through the original optical path; the OCT signal returns to the frequency-sweeping OCT for detection through the wavelength division multiplexer, and is transmitted to the signal processing and control module Processing; after the reflection signal and fluorescence signal of the 405nm laser are split by the dichroic mirror, the reflection signal of the 405nm laser is reflected by the mirror, filtered by the neutral density filter, and then reaches the first avalanche photodiode, and is transmitted to the signal processing Processing with the control module; the fluorescent signal reaches the second avalanche photodiode after being filtered by the band-pass filter, and is transmitted to the signal processing and control module for processing;
(5)控制微型马达旋转,每旋转一个小角度,重复步骤(3)、(4)以获取单点病灶信息,微型马达旋转一圈而获得环形上每一点的扫描信息,步进电机控制光纤的直线移动,完成食道管腔内全部病灶位置的扫描;(5) Control the rotation of the micro-motor, and repeat steps (3) and (4) to obtain single-point lesion information every time a small angle is rotated. The micro-motor rotates one circle to obtain the scanning information of each point on the ring. Linear movement to complete the scanning of all lesions in the esophageal lumen;
(6)信号处理与控制模块对OCT信号、荧光信号及405nm激光的反射信号进行处理,OCT信号用于组织三维重构和组织光学特性参数提取,并结合荧光信号和激光反射信号完成荧光强度的校正;(6) The signal processing and control module processes the OCT signal, the fluorescence signal and the reflection signal of the 405nm laser. The OCT signal is used for the three-dimensional reconstruction of the tissue and the extraction of the optical characteristic parameters of the tissue, and combines the fluorescence signal and the laser reflection signal to complete the measurement of the fluorescence intensity. Correction;
(7)构建针对食道组织光学特性的不同散射和吸收的组织光学仿体,建立荧光强度和光敏剂浓度的定量关系曲线,定量食道管腔内光敏剂浓度。(7) Construct a tissue optical phantom for different scattering and absorption of esophageal tissue optical properties, establish a quantitative relationship curve between fluorescence intensity and photosensitizer concentration, and quantify the concentration of photosensitizer in the esophagus lumen.
实施例2:病灶组织为宫颈管内黏膜组织Example 2: The lesion tissue is mucosal tissue in the cervical canal
如图4所示,本发明的工作过程为:As shown in Figure 4, the working process of the present invention is:
(1)将光敏剂预先通过局部涂敷的方式在宫颈管位置敷药4小时;(1) Apply the photosensitizer to the cervical canal for 4 hours in advance by local application;
(2)内窥式环扫微探头伸入至宫颈管腔内,通过微型相机进行病灶可视化引导并精准定位宫颈管内病灶区域,探头到达病灶后球囊被撑开;(2) The endoscopic ring-scanning micro-probe is inserted into the cervical lumen, and the lesion is visualized and guided by the micro-camera to accurately locate the lesion area in the endocervical canal. After the probe reaches the lesion, the balloon is stretched;
(3)启动扫频OCT和405nm激光器,发出扫频激光和405nm激光,经波分复用器合束和双包层光纤耦合器传输至内窥式环扫微探头,照射宫颈病变黏膜处,扫频激光照射至病灶后产生OCT信号,405nm激光照射病灶后,病灶处的光敏剂被激发出荧光;(3) Start the frequency-sweeping OCT and 405nm laser, and emit the frequency-sweeping laser and 405nm laser, which are combined by a wavelength division multiplexer and double-clad fiber coupler and transmitted to the endoscopic ring-scanning microprobe to irradiate the cervical lesion mucosa, OCT signals are generated after the frequency-sweeping laser is irradiated to the lesion, and after the 405nm laser is irradiated to the lesion, the photosensitizer at the lesion is excited to fluoresce;
(4)OCT信号、荧光信号以及405nm激光的反射信号经原光路返回至双包层光纤耦合器;OCT信号经波分复用器返回至扫频OCT进行检测,并传输至信号处理与控制模块进行处理;405nm激光的反射信号和荧光信号经二向色镜分光后,405nm激光的反射信号经反射镜反射、中性密度滤光片滤光后到达第一雪崩光电二极管,并传输至信号处理与控制模块进行处理;荧光信号经带通滤光片滤光后到达第二雪崩光电二极管,并传输至信号处理与控制模块进行处理;(4) OCT signal, fluorescence signal and the reflected signal of 405nm laser return to the double-clad fiber coupler through the original optical path; the OCT signal returns to the frequency-sweeping OCT for detection through the wavelength division multiplexer, and is transmitted to the signal processing and control module Processing; after the reflection signal and fluorescence signal of the 405nm laser are split by the dichroic mirror, the reflection signal of the 405nm laser is reflected by the mirror, filtered by the neutral density filter, and then reaches the first avalanche photodiode, and is transmitted to the signal processing Processing with the control module; the fluorescent signal reaches the second avalanche photodiode after being filtered by the band-pass filter, and is transmitted to the signal processing and control module for processing;
(5)控制微型马达旋转,每旋转一个小角度,重复步骤(3)、(4)以获取单点病灶信息,微型马达旋转一圈而获得环形上每一点的扫描信息,步进电机控制光纤的直线移动,完成宫颈管内全部病灶位置的扫描;(5) Control the rotation of the micro-motor, and repeat steps (3) and (4) to obtain single-point lesion information every time a small angle is rotated. The micro-motor rotates one circle to obtain the scanning information of each point on the ring. Linear movement to complete the scanning of all lesions in the cervical canal;
(6)信号处理与控制模块对OCT信号、荧光信号及405nm激光的反射信号进行处理,OCT信号用于组织三维重构和组织光学特性参数提取,并结合荧光信号和激光反射信号完成荧光强度的校正;(6) The signal processing and control module processes the OCT signal, the fluorescence signal and the reflection signal of the 405nm laser. The OCT signal is used for the three-dimensional reconstruction of the tissue and the extraction of the optical characteristic parameters of the tissue, and combines the fluorescence signal and the laser reflection signal to complete the measurement of the fluorescence intensity. Correction;
(7)构建针对宫颈组织光学特性的不同散射和吸收的组织光学仿体,建立荧光强度和光敏剂浓度的定量关系曲线,定量宫颈管内光敏剂浓度。(7) Constructing tissue optical phantoms for different scattering and absorption of cervical tissue optical properties, establishing a quantitative relationship curve between fluorescence intensity and photosensitizer concentration, and quantifying the concentration of photosensitizer in the cervical canal.
以上所述,仅是本发明的较佳实施例,并非对本发明作任何形式上的限制,凡是依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰,均仍属本发明技术方案的保护范围。The above are only preferred embodiments of the present invention, and are not intended to limit the present invention in any form. Any simple modifications, equivalent changes and modifications made to the above embodiments according to the technical essence of the present invention are still within the scope of this invention. The protection scope of the technical solution of the invention.
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