CN109596525B - Real-time measuring method and instrument for detecting tissue activity - Google Patents
Real-time measuring method and instrument for detecting tissue activity Download PDFInfo
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Abstract
The invention relates to a real-time measuring method and an instrument for detecting tissue activity. The optical fiber bundle consisting of a plurality of optical fibers is arranged, the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, and the optical fibers are sequentially connected with a light source and a light detection element in a light source module at intervals along the circumference, so that a light source optical fiber group and a measurement optical fiber group are respectively formed; the electronic control module is arranged to control the video camera and the switch of the plurality of LED lamps in the light source module and the control light detector, the light reaction from the visible light to the infrared light under the skin is detected by each light source optical fiber group and each optical fiber in the measuring optical fiber group in a permutation and combination mode, a neural network is trained by using the data collected by detection, thus, each measurement corresponding to the light source with different wavelengths and intensities corresponds to a correct output value, the trained neural network can be used for realizing real-time measurement without slicing, and the purpose of nondestructive detection is achieved.
Description
Technical Field
The invention relates to a detection method for detecting activity indexes of biological tissues, in particular to a detection method for measuring blood oxygen and hemoglobin concentration and a micro-vessel imaging instrument.
Background
Physical and physiological information of the microvasculature, such as blood vessel density and blood flow velocity, oxygenation of microtubules, total hemoglobin concentration can be an indicator of biological tissue activity, and quantitative descriptions of all these parameters are helpful to medical professionals in making diagnostic, therapeutic, and clinical management decisions.
In general, biological tissue often mimics a mixed medium of scatterers and absorbers. The total hemoglobin concentration and blood oxygenation in tissue are measured by placing a light transmitting fiber and a light collecting fiber on the same surface of the tissue at a distance, and the light collecting fiber detects the intensity of light reflected back from the interior of the tissue to the exterior of the skin by scattering diffusion at several positions adjacent to several millimeters of the light transmitting fiber. Light of a certain wavelength of light is injected into the subcutaneous tissue, the light from the transmission fiber and entering the tissue can be dispersed or absorbed, some light will be reflected back, i.e. reflected, and collected by the light collection fiber, and the physical model of the light transmission process inside the biological tissue can be expressed by a diffusion model or a random walk process by monte carlo simulation. By comparing the reflection results with these absorbers of extract concentration, and the scattering coefficients, the total hemoglobin concentration and tissue blood oxygenation were calculated using a physical model calculation or a Monte Carlo simulated random walk process. However, since the calculation process is time-consuming, it is difficult to perform real-time measurement. Moreover, such instruments provide limited information and are expensive, and due to these limitations, medical personnel are reluctant to use such instruments in medical practice. Furthermore, in the current measurement methods, although the measurement method based on the physical model can theoretically perform the measurement of the total hemoglobin concentration and the tissue blood oxygenation, since the human tissue has a complex structure and is often asymmetric and non-uniform, a single measurement cannot obtain a result closer to the actual situation, and it is reasonable to measure from a plurality of observation positions and take the average value as the result. However, the measurement of multiple positions may change the position state of the target to be measured due to the movement of the probe of the instrument, which affects the accuracy of the detection result. In addition to the above problems, the existing tissue oximetry instruments do not provide microvascular imaging and microvascular system parameters, blood vessel density and blood flow rate.
In the visible light range, the longest wavelength that hemoglobin can absorb is green light, with a wavelength of 540 nm. Therefore, in the existing microcirculation imaging system, the green illumination light is a recommended light source for obtaining a clear blood vessel image and the minimum light scattering characteristic in the visible light range.
Blood vessels in the tissue are due to the passage of reflected light from the tissue surface which can obscure the blood vessel image from glare. There are several ways to eliminate glare or reflected light. One approach is to place the illumination light outside the imaging zone, the setup being designed such that the reflected light does not enter the optical path of the imaging directly, but rather the light undergoes multiple scattering inside the tissue, exiting the tissue for imaging. Another approach is the orthogonal polarization spectral imaging technique with two polarizers. The first polarizer is used for polarizing the illumination light, and the second polarizer is arranged on the imaging path. The direct reflected light inherits the polarization direction of the illumination light, which can be blocked by the second polarizer, and only the multiply scattered light enters the image sensor, such as a charge-coupled device and a complementary metal oxide semiconductor, to form an image. Some prior art microcirculation imaging systems that use the above techniques require a rigid probe of fixed length to image the tissue surface of the optical system for observation, while the image sensor is placed inside the device.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide a real-time measurement method and an instrument for detecting the tissue activity, which can provide microvascular imaging and microvascular system parameters, have more accurate detection results and stronger real-time performance and are nondestructive.
In order to achieve the above object, the present invention discloses a real-time measurement method for detecting tissue viability, which is characterized by comprising the following steps: (1) firstly, establishing a physical model for simulating different concentrations of hemoglobin and tissue blood oxygenation;
(2) the collected data were measured as follows: a plurality of optical fibers are used, the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, the optical fibers are sequentially connected with a light source and a light detection element at intervals along the circumference, so that a light source optical fiber group and a measurement optical fiber group are respectively formed, the light source is a plurality of light-emitting secondary tube groups with fixed wavelengths, and the wavelengths are from visible light to infrared light; during measurement, a probe is contacted with the epidermis of a tissue to be measured, a certain optical fiber is selected as a light source input end, a light emitting diode with a certain wavelength in a light source group is turned on, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, then the light source is switched to a light emitting diode with another wavelength, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, all the light emitting diodes with different wavelengths in the light source group are sequentially turned on, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, then the next light source optical fiber in the light source optical fiber group is used as light source input, and all the steps are repeated until all the light source optical fibers in the light source optical fiber group are used;
(3) training a neural network by using the data collected in the step (2), wherein the number of nodes of an input layer of the neural network is the number of the measuring optical fibers in the measuring optical fiber group plus 2 and is used for inputting the light intensity of each measuring optical fiber and the wavelength and the light intensity of the used light source, and the number of nodes of an output layer of the neural network is consistent with the number of different simulated concentration grades; thus, each measurement using a light source of different wavelength and intensity corresponds to a correct output value, and real-time measurements can be made using a trained neural network.
Another object of the present invention is to provide an apparatus for carrying out the above method.
In order to achieve the above object, the present invention also discloses a real-time measurement device for detecting tissue viability, which is characterized by comprising:
a probe; the far end in the probe is provided with an optical tube with a replaceable lens and a video camera, the optical tube is internally provided with an amplifying and focusing lens group consisting of a plurality of lenses, the optical tube is arranged in front of the video camera, and a cable of the video camera is connected with the electronic control module;
and (3) optical fiber bundle: the optical fiber measuring probe consists of a plurality of optical fibers, wherein the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, and the optical fibers are sequentially connected with a light source and a light detection element in a light source module at intervals along the circumference so as to respectively form a light source optical fiber group and a measuring optical fiber group;
the light source module is provided with a plurality of LED lamps to form the light source, and the light wave wavelengths of the LED lamps comprise wavelengths from visible light to infrared rays;
the optical detector is provided with the optical detection element for detecting the light intensity of the light wave signals from visible light to infrared light wavelength;
the display module is used for displaying the collected original data, the collected images and the calculation result of the electronic control module;
the input layer node number of the neural network is the number of the measuring optical fibers in the measuring optical fiber group plus 2 and is used for inputting the light intensity of each measuring optical fiber and the wavelength and the light intensity of the used light source, and the output layer node number of the neural network is consistent with the number of the simulated different concentration levels;
and the electronic control module controls the video camera and the plurality of LED lamps in the light source module to be switched on and off and controls the light detector to detect, and reads and processes detection data.
As a further configuration of the present invention, the electronic control module includes a storage unit, a data processing unit and a detection control unit, the detection control unit controls the operations of the switches and the photodetectors of the plurality of LED lamps in the light source module, and the data processing unit receives a user instruction and data of the photodetectors, stores the user instruction and the data in the storage unit, and outputs the user instruction and the data to the display module after being processed by an internal program.
As a still further configuration of the present invention, the electronic control module further includes a light calibration module, the light calibration module is configured to calibrate the consistency of the photoelectric conversion responses of the measurement optical fiber sets illuminated by the same light source, and the outputs of the measurement optical fiber sets are recorded by the same optical detector.
As a further configuration of the present invention, the optical tube is cylindrical, and the light source fiber set and the measurement fiber set are circumferentially distributed in a tube wall of the optical tube.
As a further arrangement of the invention, the optical fiber bundle comprises optical fibers of various diameters.
The optical fiber bundle consisting of a plurality of optical fibers is arranged, the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, and the optical fibers are sequentially connected with a light source and a light detection element in a light source module at intervals along the circumference, so that a light source optical fiber group and a measurement optical fiber group are respectively formed; the electronic control module is arranged to control the video camera and the switch of the plurality of LED lamps in the light source module and the control light detector, the light reaction from the visible light to the infrared light under the skin is detected by each light source optical fiber group and each optical fiber in the measuring optical fiber group in a permutation and combination mode, a neural network is trained by using the data collected by detection, thus, each measurement corresponding to the light source with different wavelengths and intensities corresponds to a correct output value, the trained neural network can be used for realizing real-time measurement without slicing, and the purpose of nondestructive detection is achieved.
The invention will be described in further detail with reference to the following drawings and specific embodiments.
Drawings
FIG. 1 is a schematic diagram of the light transmission process in tissue;
FIG. 2 is a schematic illustration of the major absorption in biological tissue in the visible infrared wavelength range including deoxyhemoglobin and water;
FIG. 3 is a block diagram illustrating the structure of a real-time measuring device according to an embodiment of the present invention;
FIG. 4 is a block diagram illustrating the structure of an embodiment of a flexible probe according to the present invention;
FIG. 5 is a block diagram illustrating the structure of an exemplary embodiment of an electronic control module according to the present invention;
FIG. 6 is a schematic structural diagram of an embodiment of a cap according to the present invention;
FIG. 7 is a schematic view of a partial internal structure of an exemplary probe of the present invention;
FIG. 8 is a schematic end view of an embodiment of a probe of the present invention;
FIG. 9 is a schematic structural diagram of an embodiment of an internal fiber bundle of a probe according to the present invention;
FIG. 10 is a second schematic structural diagram of an embodiment of an internal fiber bundle of a probe according to the present invention.
Detailed Description
In order to provide microvascular imaging and microvascular system parameters, and to achieve more accurate and real-time detection results, the general real-time measurement method for detecting tissue viability comprises the following steps: (1) firstly, establishing a physical model for simulating different concentrations of hemoglobin and tissue blood oxygenation; as a specific example, the model of the present invention is prepared as follows: using cells containing whole human erythrocytesTissue model, StO2The verified volume fraction is about 0.8%, the THC verified volume fraction is about 0.6-2.4%. Blood from two volunteers was collected in tubes containing heparin sodium, mixed with approximately equal volume of phosphate buffer solution for centrifugation, and finally centrifuged red blood cells were added to approximately 1% diluted Liposyn II solution in PBS and kept at a constant temperature and homogeneity of 37 ℃;
(2) using microelectrodes pO2Standard method of electrode and the following method for measuring StO of model solution collected during yeast deoxygenation2And pO2Data: a plurality of optical fibers are used, the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, the optical fibers are sequentially connected with a light source and a light detection element at intervals along the circumference, so that a light source optical fiber group and a measurement optical fiber group are respectively formed, the light source is a plurality of light-emitting secondary tube groups with fixed wavelengths, and the wavelengths are from visible light to infrared light; during measurement, as shown in fig. 1, a probe is contacted with the epidermis of a tissue to be measured, a certain optical fiber is selected as a light source input end, a light emitting diode with a certain wavelength in a light source group is turned on, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, then a light source is switched to a light emitting diode with another wavelength, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, all the light emitting diodes with different wavelengths in the light source group are sequentially turned on, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, then the next light source optical fiber in the light source optical fiber group is used as light source input, and all the steps are repeated until all the light source optical fibers in the light source optical fiber group are used;
in-use microelectrode pO2Standard methods for electrodes are performed by first bubbling air into the saline solution for 15 to 20 minutes and in 0% oxygen (pO)2= 0 mmHg) in an oxygen-free solution, bubbling air (pO) with air2= 159 mmHg) pre-calibration pO in air saturated water2The electrode added sodium sulfite to distilled water.
(3) Training a neural network by using the data collected in the step (2), wherein the number of nodes of an input layer of the neural network is the number of the measuring optical fibers in the measuring optical fiber group plus 2, the nodes are used for inputting the light intensity of each measuring optical fiber and the wavelength and the light intensity of the used light source, and the number of nodes of an output layer of the neural network is consistent with the number of different simulated concentration grades; thus, each measurement using light sources of different wavelengths and intensities corresponds to a correct output value, and real-time measurements can be made using a trained neural network, which may be a three-layer neural network having an input layer, a hidden layer, and an output layer.
The measuring device for implementing the real-time measuring method for detecting the tissue activity comprises a probe 1, an optical fiber bundle, a light source module 8, a light detector 9, a display module 10 and an electronic control module 11. As shown in fig. 7 and 8, the probe 1 is a tubular member, preferably a round tube, the inner distal end of which is provided with an optical tube 2 with replaceable lens and a video camera 4, the optical tube 2 is provided with a magnifying and focusing lens group 3 composed of a plurality of lenses to facilitate clear imaging, the optical tube 2 is arranged in front of the video camera 4, the video camera 4 can be black and white or colored, and the cable of the video camera 4 is connected with the electronic control module 11.
The optical fiber bundle is composed of a plurality of optical fibers 5, the front ends of the optical fibers 5 form a circle with a diameter of several millimeters and are distributed on the periphery of the probe 1, in this embodiment, as shown in fig. 9 and 10, the optical fibers 5 are uniformly distributed in the tube wall of the optical tube 2 in the probe 1 along the circumference, and the optical fibers 5 are sequentially connected with the light source and the light detection element in the light source module 8 at intervals along the circumference, so as to respectively form a light source optical fiber group 7 and a measurement optical fiber group 6. In order to balance the throughput of the illuminating light and the receiving light, the fiber bundle preferably comprises optical fibers of various diameters, preferably between 0.2 and 1.5mm, and by using the cooperation of source fibers and measuring fibers of different diameters, the diameters of the respective fibers should be selected such that the emitting and receiving optical paths can provide sufficient light intensity required for measurement and can be balanced so as not to have too weak light intensity to signal-to-noise ratio or too strong light intensity to saturate the receiving.
The light source module 8 is used for adjusting light intensity and wavelength; the photo detector 9 is used for photoelectric conversion, and the display module 10 is used for outputting a detection result and system conditions.
The light source module 8 is provided with a plurality of LED lamps to form the light source, and the light wave wavelengths of the plurality of LED lamps comprise discrete wavelengths from visible light to infrared rays; or a single LED containing wavelengths from visible light to infrared light, and an optical filter, the wavelengths of which are measured data of microcirculation imaging and tissue oxyhemoglobin concentration, as shown in fig. 2, the longest wavelength that hemoglobin can absorb in the visible light range is the green light wavelength which is 540nm, so that in the existing microcirculation imaging system, the green illumination light is the recommended light source for obtaining a clear blood vessel image and the minimum light scattering property in the visible light range.
The photo detector 9 is provided with the photo detection element for detecting the light intensity of the light wave signal from the visible light to the infrared light wavelength, and the photo detection element can specifically select a photoelectric tube or a photodiode array sensitive to the detection of the corresponding wavelength, and can also select a spectrometer sensitive to the wavelength from the visible light to the infrared light wavelength.
The display module 10 is used for displaying the collected original data, images and calculation results of the electronic control module 11; the display module 10 includes a display screen and a display control unit, and provides a hardware interface between the device and a user. The display screen may be any of the existing display devices, such as a black/white or color liquid crystal display, or a black/white or color touch liquid crystal display, and serves as a panel for providing user input data or instructions.
As shown in fig. 5, the electronic control module 11 includes a storage unit, a data processing unit and a detection control unit, the data processing unit and the detection control unit are integrated into an information processing system including a microprocessor and peripheral components with data processing capability, and control the operations of the switches of the plurality of LED lamps and the light detectors 9 in the video camera 4 and the light source module 8 according to an internally set program, and simultaneously receive and read data sent back by the light detectors 9, perform data processing according to a predetermined algorithm, store the data in the storage unit, and output the data to the display module 10 for display and output after being processed by the internal program.
The electronic control module 11 preferably further comprises a light calibration module for calibrating the consistency of the photoelectric conversion reaction of the measuring fiber set 6 illuminated by the same light source, the output of the measuring fiber set 6 being recorded by the same light detector 9. The accuracy of measurement can be further improved by arranging the light calibration module.
As shown in fig. 3, for convenience of installation and use, the real-time tissue activity measuring device is preferably provided with a housing 12, the housing 12 has a rectangular or trapezoidal main body, the main body is hollow to form a cavity, the light source module 8, the optical detector 9, the optical calibration module, the display module 10 and the electronic control module 11 are disposed in the cavity inside the main body, the display screen in the display module 10 is disposed on the rear end face of the main body, the probe 1 is disposed on the front end face of the main body, the optical tube 2 of the probe 1 may be rigid or flexible, as shown in fig. 4, they share the same internal structure, only the material of the cylindrical optical tube 2 is different, and the lower portion of the main body is provided with a handle portion 13 to make the whole body in a handheld structure, so as to facilitate use.
Claims (6)
1. A real-time measurement method for detecting tissue viability, comprising the steps of: (1) firstly, establishing a physical model for simulating different concentrations of hemoglobin and tissue blood oxygenation;
(2) the collected data were measured as follows: a plurality of optical fibers are used, the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, the optical fibers are sequentially connected with a light source and a light detection element at intervals along the circumference, so that a light source optical fiber group and a measurement optical fiber group are respectively formed, the light source is a plurality of light-emitting secondary tube groups with fixed wavelengths, and the wavelengths are from visible light to infrared light; during measurement, a probe is contacted with the epidermis of a tissue to be measured, a certain optical fiber is selected as a light source input end, a light emitting diode with a certain wavelength in a light source group is turned on, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, then the light source is switched to a light emitting diode with another wavelength, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, all the light emitting diodes with different wavelengths in the light source group are sequentially turned on, the light intensity of all the measuring optical fibers in the measuring optical fiber group is read and recorded, then the next light source optical fiber in the light source optical fiber group is used as light source input, and all the steps are repeated until all the light source optical fibers in the light source optical fiber group are used;
(3) and (3) training a neural network by using the data collected in the step (2), wherein the number of nodes of an input layer of the neural network is the number of the measuring optical fibers in the measuring optical fiber group plus 2, the nodes are used for inputting the light intensity of each measuring optical fiber and the wavelength and the light intensity of the used light source, and the number of the nodes of an output layer of the neural network is consistent with the number of the simulated different concentration grades.
2. A real-time measurement device for detecting tissue viability, comprising:
a probe; the far end in the probe is provided with an optical tube with a replaceable lens and a video camera, the optical tube is internally provided with an amplifying and focusing lens group consisting of a plurality of lenses, the optical tube is arranged in front of the video camera, and a cable of the video camera is connected with the electronic control module;
and (3) optical fiber bundle: the optical fiber measuring probe consists of a plurality of optical fibers, wherein the front ends of the optical fibers form a circle with the diameter of several millimeters and are distributed on the periphery of the probe, and the optical fibers are sequentially connected with a light source and a light detection element in a light source module at intervals along the circumference so as to respectively form a light source optical fiber group and a measuring optical fiber group;
the light source module is provided with a plurality of LED lamps to form the light source, and the light wave wavelengths of the LED lamps comprise wavelengths from visible light to infrared rays;
the optical detector is provided with the optical detection element for detecting the light intensity of the light wave signals from visible light to infrared light wavelength;
the display module is used for displaying the collected original data, the collected images and the calculation result of the electronic control module;
the input layer node number of the neural network is the number of the measuring optical fibers in the measuring optical fiber group plus 2 and is used for inputting the light intensity of each measuring optical fiber and the wavelength and the light intensity of the used light source, and the output layer node number of the neural network is consistent with the number of the simulated different concentration levels;
the electronic control module controls the video camera and the light source module to switch on and off the plurality of LED lamps and controls the light detector to detect, reads and processes detection data, and the control mode of the electronic control module is as follows: selecting a certain optical fiber as a light source input end, turning on a light emitting diode with a certain wavelength in a light source group, reading and recording light intensities of all measuring optical fibers in the measuring optical fiber group, switching a light source to a light emitting diode with another wavelength, reading and recording light intensities of all measuring optical fibers in the measuring optical fiber group, sequentially turning on all light emitting diodes with different wavelengths in the light source group, reading and recording light intensities of all measuring optical fibers in the measuring optical fiber group, then taking the next light source optical fiber in the light source optical fiber group as light source input, and repeating all the steps until all light source optical fibers in the light source optical fiber group are used.
3. The real-time measurement device for detecting tissue viability of claim 2, wherein: the electronic control module comprises a storage unit, a data processing unit and a detection control unit, wherein the detection control unit controls the on-off of a plurality of LED lamps in the light source module and the work of the light detectors, and the data processing unit receives user instructions and data of the light detectors, stores the user instructions and the data in the storage unit, and outputs the user instructions and the data to the display module after being processed by an internal program.
4. The real-time measurement device for detecting tissue viability of claim 3, wherein: the electronic control module further comprises a light calibration module, the light calibration module is used for calibrating the photoelectric conversion reaction consistency of the measurement optical fiber group illuminated by the same light source, and the output of the measurement optical fiber group is recorded by the same light detector.
5. The real-time measurement device for detecting tissue viability of claim 2, wherein: the optical tube is cylindrical, and the light source optical fiber group and the measuring optical fiber group are circumferentially distributed in the tube wall of the optical tube.
6. The real-time measurement device for detecting tissue viability of claim 5, wherein: the optical fiber bundle includes optical fibers of various diameters.
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