Disclosure of Invention
The present specification provides an endoscope apparatus and method for measuring hemoglobin concentration, which obtains hemoglobin concentration information of shallow, middle and deep layers of biological tissue by utilizing different absorption characteristics of light with different wavelengths on hemoglobin and different penetration depths of the light in the biological tissue, so as to more accurately give out distribution of hemoglobin concentration, and simultaneously utilizes narrow-band light to combine illumination and synchronously obtain color images, thereby ensuring real-time observation of endoscopic images.
The present specification provides an endoscope apparatus for measuring hemoglobin concentration, comprising:
A light source unit that generates at least a narrow-band light combination 1 and a narrow-band light combination 2as illumination light;
An imaging unit that outputs a color image 1 and a color image 2 by imaging reflected light of a biological tissue under illumination of the narrowband light combination 1 and the narrowband light combination 2, respectively;
a processing unit for calculating and correcting a hemoglobin index pixel by pixel based on the color image 1 and the color image 2, and obtaining a hemoglobin concentration value in a biological tissue, specifically,
The processing part calculates hemoglobin indexes IHb1, IHb2 and IHb3 related to the contents of superficial, middle and deep hemoglobin of the tissue according to the color image 1 and the color image 2,
The processing part performs normalization correction on the hemoglobin index according to the hemoglobin light absorption coefficient at the corresponding wavelength to obtain IHb1', IHb2', IHb3',
The processing unit obtains a hemoglobin concentration value of the tissue from a relationship between the corrected hemoglobin indices IHb1', IHb2', IHb3' and the hemoglobin concentration.
Alternatively, the narrow-band light combination 1 includes a narrow-band light near the absorption peak of hemoglobin 415nm, a narrow-band light near the absorption peak of hemoglobin 540nm, and a narrow-band light near 650nm for background correction,
The center wavelength deviation of the narrow-band light is + -10 nm.
Optionally, the narrow-band light combination 2 includes a narrow-band light near 450nm for scatter correction and a narrow-band light near 590nm absorption peak of hemoglobin,
The center wavelength deviation of the narrow-band light is + -10 nm.
Optionally, the light source part comprises at least the narrow-band light sources in the narrow-band light combination 1 and the narrow-band light combination 2,
The full width at half maximum of each light source of the light source part is less than or equal to 40nm, the brightness of the light source can be adjusted,
The light source part is switched to emit the narrow-band light combination 1 and the narrow-band light combination 2 to illuminate the biological tissue.
Optionally, the photographing part is provided with a pixel array having sensitivity to illumination light of the light source part,
The imaging unit includes red, green and blue color filters, images the living tissue illuminated by the light from the light source unit, and generates a color image,
The photographing section is provided with a synchronous controller for synchronously recording the corresponding color image 1 and the corresponding color image 2 when the narrow-band light combination 1 and the narrow-band light combination 2 are illuminated.
Optionally, the processing part acquires red, green and blue components of corresponding pixels in the color image 1 and the color image 2, calculates the superficial, middle and deep hemoglobin indexes of the tissue pixel by pixel, specifically as follows,
Wherein Ib1 is a pixel blue component of the color image 1 obtained by shooting under the illumination of the narrow-band light combination 1,
Ig1 is a pixel green component of the color image 1 photographed under illumination of the narrow-band light combination 1,
Ir1 is the pixel red component of the color image 1 taken under illumination of the narrowband light combination 1,
Ib2 is the pixel blue component of the color image 2 captured under illumination of the narrowband light combination 2,
Irg2 is the sum of the pixel green component and the red component of the color image 2 obtained by photographing under illumination of the narrow-band light combination 2.
Optionally, the processing part uses IHb3 as a reference to normalize and correct the hemoglobin index as follows,
IHb3‘=IHb3
Wherein ε 1 is the integral value of the absorbance coefficient of hemoglobin of narrowband light around 415nm,
Epsilon 2 is the integral of the absorption coefficient of hemoglobin for narrowband light around 540nm,
Epsilon 3 is the integral of the absorption coefficient of hemoglobin for narrowband light around 590 nm.
Optionally, the processing unit includes a processor and a memory storing an executable program and a data table, wherein the executable program, when executed, causes the processor to execute the processing method in any one of the above-described apparatuses.
Further, the relationship of the corrected hemoglobin indices IHb1', IHb2', IHb3 'and hemoglobin concentrations in the present invention can be obtained by obtaining a color image 1 and a color image 2 based on the photographing section in the case of different known hemoglobin concentrations using a standard tissue sample capable of simulating the superficial, middle, and deep blood vessels, and calculating the corrected hemoglobin indices IHb1', IHb2', IHb3' of the standard tissue sample from the color image 1 and the color image 2 using the processing section, whereby a relationship numerical table or function of the corrected hemoglobin indices and the hemoglobin concentrations can be obtained.
Further, the standard tissue sample uses polymethyl methacrylate (PMMA) as a substrate, a cavity made of Polydimethylsiloxane (PDMS) material is embedded in the substrate to simulate blood vessels, and a film made of a PDMS material doped with titanium dioxide is covered on the substrate, wherein the film has three different thicknesses, and the film and the simulated blood vessels are combined to simulate deep, middle and shallow blood vessels respectively;
The simulated blood vessel, peristaltic pump and gas washing bottle are connected by plastic pipe to form circulation system, peristaltic pump is used to power blood circulation and control blood flow speed, pure blood and pure water in different proportions are added into gas washing bottle, and after mixing uniformly by circulation system, blood with different hemoglobin concentration is formed, in addition, oxygen or nitrogen can be introduced into gas inlet of gas washing bottle to change blood oxygen saturation.
A method of hemoglobin concentration measurement based on an endoscopic device, implemented with a device as claimed in any one of the preceding claims.
In the invention, the absorption characteristics and penetration depths of light with different wavelengths are comprehensively considered, the hemoglobin concentration information with different depths is acquired, and particularly, in order to more accurately measure, 650nm and 450nm narrow-band wave bands are introduced to reduce interference of tissue background reflection and scattering, 415nm, 540nm and 590nm narrow-band wave bands are combined to more comprehensively calculate the hemoglobin of shallow, medium and deep blood vessels, and simultaneously, a matched processing flow and a standard tissue sample for simulating the blood vessels are designed to accurately realize hemoglobin concentration measurement and greatly reduce experimental difficulty.
Detailed Description
Hereinafter, modes for carrying out the present invention will be described with reference to the drawings.
The endoscopic device according to the embodiment of the present invention described below is a device that quantitatively calculates the hemoglobin concentration of a subject biological tissue based on two color images captured under illumination of a narrowband light combination 1 and a narrowband light combination 2, and displays the concentration distribution result in an image manner. In the quantitative analysis of hemoglobin concentration using the device, the property that absorption characteristics of hemoglobin by light having different penetration depths in biological tissues correspond to changes in hemoglobin concentration is utilized.
Before explaining the endoscope apparatus according to the embodiment of the present invention, spectral characteristics of hemoglobin and penetration depths of light of different wavelengths will be described.
Fig. 1 shows absorption spectra of hemoglobin and penetration depth curves of light of different wavelengths. In addition, fig. 2 shows the penetration depth of light of different wavelengths into biological tissue of the layered structure. The solid line in fig. 1 shows the absorption spectrum 11 of hemoglobin in the range of 400-700nm, and the dashed line in fig. 1 shows the penetration depth 12 of light in the range of 400-700nm in biological tissue. Absorption spectrum 11 shows that hemoglobin has absorption peaks at about 415nm 13, about 540nm 14 and about 580nm 15, respectively, and changes in hemoglobin concentration can be reflected relatively sensitively. The light near 415nm is equivalent to the light near 400-440nm in 16P, the light near 540nm is equivalent to the light near 470-580nm in 16G, the light near 540nm is equivalent to the light near 540nm in 22s, the light near 540nm is moderate in depth, the light near 21s is equivalent to the light near 470-580nm in 22m, but when the light is overlapped in the vertical direction, the information of the two can interfere with each other, the light near 580nm in 15 is equivalent to the light near 540nm in light absorption coefficient, no more information can be provided, the light near 480-610nm in 16O is deviated from the light near 540nm in 15 absorption peak, but the corresponding hemoglobin absorption coefficient can reflect the change of the hemoglobin concentration, the light penetration depth is obviously larger, the light 22m of the middle layer 21m and the light 22d of the deep layer 21d can be detected, and the light 22s of the surface layer 21s cannot be reflected well due to the fact that the hemoglobin absorption coefficient is relatively smaller and the surface blood vessel is thinner. In addition, the scattering effect is obvious in biological tissues, and the light in the range of 440-470nm 16B is sensitive to scattering, so that the tissue scattering is normalized and corrected by using the light. In addition, the light of the range of 610-700nm 16R has weaker absorption to hemoglobin and deeper penetration depth, is less affected by tissue and blood vessel absorption, and is used for normalizing and correcting the illumination background light.
From the above analysis, embodiments of the present invention select five narrowband lights for illumination, and combine color image sensors with color filters, using a combination illumination format for real-time measurement of hemoglobin concentration.
Fig. 3 shows the relative wavelength positions of the light source spectra of the narrowband light combination 1 and the narrowband light combination 2 with respect to the hemoglobin absorption spectrum and the penetration depth curve. Fig. 4A and 4B show the relative wavelength positions of the light source spectra of the narrow-band light combinations 1 and 2 and the transmission spectrum of the optical filter of the imaging unit image sensor, respectively.
As an example of the present invention, the narrowband light combination 1 is composed of narrowband light 31, narrowband light 32, and narrowband light 33, and the narrowband light combination 2 is composed of narrowband light 34 and narrowband light 35, the full width at half maximum of which is 40nm or less. The imaging unit image sensor includes a blue filter 41, a green filter 42, and a red filter 43, and a wavelength region having a transmittance of 10% or more in each color filter is defined as each color region. I.e., as shown in fig. 4A or 4B, the blue region is 400-525nm, the green region is 470-610nm, and the red region is 590-700nm.
The center wavelength of the narrowband light 31 is 415nm, which is sensitive to the change of the concentration of the surface layer hemoglobin, the center wavelength of the narrowband light 32 is 540nm, which is sensitive to the change of the concentration of the surface layer hemoglobin, the center wavelength of the narrowband light 33 is 650nm, which has a low hemoglobin absorption coefficient, and which is used for the correction of the background light. The narrowband light 31, the narrowband light 32 and the narrowband light 33 are respectively positioned in a blue area, a green area and a red area, the color image 1 is obtained under the illumination of the narrowband light combination 1, and reflection signals of the narrowband light 31, the narrowband light 32 and the narrowband light 33 after the tissue are respectively obtained by blue, green and red channel values of the color image 1.
The narrowband light 34 has a center wavelength of 450nm, which is sensitive to tissue scattering, for tissue scattering correction, and the narrowband light 35 has a center wavelength of 590nm, which is sensitive to deep hemoglobin concentration changes. The narrow-band light 34 is positioned in a blue region, the narrow-band light 35 is positioned at the junction of a green region and a red region, the color image 2 is obtained under the illumination of the narrow-band light combination 2, the reflection signal of the narrow-band light 34 after passing through tissues is obtained by the blue channel value of the color image 2, and the reflection signal of the narrow-band light 35 after passing through the tissues is obtained by the sum of the values of the green channel and the red channel of the color image 2.
The narrow-band light is generated by the light source unit, and fig. 5 shows an example of the structure of the light source unit. The light source section is composed of a light source box 51 and a light source control section 52.
The light source box contains at least five narrow-band light sources of the above-mentioned narrow-band light combination 1 and narrow-band combination 2, and the narrow-band light sources can be lasers or LEDs. The narrow-band light sources 511, 512, 513, 514, 515 are arranged according to the structure shown in fig. 5, the beams are combined by the beam combining mirror 516, and are collimated by the collimating mirror 517 and finally emitted from a unified outlet for illumination, so that a plurality of narrow-band light sources can be simultaneously lightened for illumination in a narrow-band light combination mode. The above light source box structure is merely an example, and many more light source box structures are possible to satisfy the use requirement according to the expert knowledge.
The light source control unit 52 is connected to the narrow-band light sources 511, 512, 513, 514, 515, and changes the luminance of the narrow-band light sources or the on/off of the light sources by changing the driving current or voltage. The light source control unit 52 can control the light source box to illuminate with the narrow-band light combination 1 or the narrow-band light combination 2.
Under the illumination of the narrow-band light combination, a color image is acquired using the imaging unit, and fig. 6 shows an example of the configuration of the imaging unit. The image pickup section is composed of an image sensor 61 and an image control section 62.
The image sensor 61 is a color image sensor, and separates the 3 wavelength regions of the blue region, the green region, and the red region, and generates a blue channel value, a green channel value, and a red channel value independently. The image sensor 61 may be a CMOS or CCD image sensor that covers a bayer array filter including a blue filter 41, a green filter 42, and a red filter 43.
The image control unit 62 is used for adjusting parameters such as exposure time and gain of the image sensor, controlling image acquisition, and outputting color image data.
The light source control unit 52 and the image control unit 62 are to operate under synchronous conditions, and fig. 7 is a schematic diagram of synchronous control. The synchronization controller 71 controls the light source control unit 52 to illuminate with the narrow-band light combination 1 or the narrow-band light combination 2, and synchronously controls the image control unit 62 to acquire the color image 1 or the color image 2, and synchronously controls the color image input processing unit 72 to calculate the hemoglobin concentration.
Fig. 8 is a sequence diagram of narrow-band light combination illumination and simultaneous acquisition of color images. Image acquisition is divided into odd and even frames. The color image 1 is obtained by illumination with the combination of narrowband light 1 at odd frames, i.e. simultaneously illuminating 415nm narrowband light 31, 540nm narrowband light 32 and 650nm narrowband light 33. The color image 2 is obtained with illumination of the narrow-band light combination 2 at even frames, i.e. with simultaneous illumination of the 450nm narrow-band light 34 and the 590nm narrow-band light 35. The processing unit processes the obtained color images 1 and 2 of two adjacent frames to give a hemoglobin concentration result in real time.
The odd and even frames can also be illuminated with the same principle by using the narrowband light combination 2 and the narrowband combination 1, respectively.
The processing section calculates the hemoglobin concentration based on the obtained color image, and fig. 9 is a flowchart of the hemoglobin concentration calculation, including 5 processing steps.
The image acquisition 91 acquires the color image 1 and the color image 2 of the adjacent two frames.
Information extraction 92 extracts reflected signals of the narrowband light after passing through the tissue from the color image. Specifically, the reflected signal Ib1 of 415nm light, the reflected signal Ig1 of 540nm light, and the reflected signal Ir1 of 650nm light are extracted from the blue, green, and red channels of the color image 1, respectively, the reflected signal Ib2 of 450nm light is extracted from the blue channel of the color image 2, and the sum of the green and red channel values of the color image 2 yields the reflected signal Irg2 of 590nm light.
Hemoglobin index calculation 93, the superficial hemoglobin index IHb1, the middle hemoglobin index IHb2, and the deep hemoglobin index IHb3 are calculated according to the following formulas.
The hemoglobin index correction 94 normalizes and corrects the hemoglobin index based on the integral epsilon 1 of the absorbance of the narrowband light near 415nm, the integral epsilon 2 of the absorbance of the narrowband light near 540nm, and the integral epsilon 3 of the absorbance of the narrowband light near 590nm, keeping the deep hemoglobin index unchanged. IHb1', IHb2', IHb3' are corrected superficial, middle and deep haemoglobin indices respectively.
IHb3‘=IHb3
Hemoglobin concentration calculation 95, obtaining a hemoglobin concentration value of the tissue from a numerical table or function of the corrected hemoglobin indices IHb1', IHb2', IHb3' and the relationship of hemoglobin concentrations. The numerical table or function used is calibrated in advance based on the endoscopic device and the standard tissue sample. The function may take the form of an n-degree polynomial with respect to IHb1', IHb2', IHb3', but n suggests no more than 3.
Fig. 10 is a schematic diagram showing an example of the structure of the standard tissue sample. Polymethyl methacrylate (PMMA) is used as the substrate 101. A channel made of Polydimethylsiloxane (PDMS) material was buried in the substrate 101 to simulate the blood vessel 102, and the diameters of the blood vessels 102 were different. To simulate tissue scattering, films 103a, 103b and 103c of titania (TiO 2) doped PDMS material are coated on the substrate 101, the films 103a, 103b and 103c being of different thickness, and in combination with the vessel 102, simulate deep, medium and shallow vessels, respectively.
The vessel 102, peristaltic pump 105 and gas washing bottle 106 are connected by a plastic tubing 104 to form a circulatory system. Peristaltic pump 105 provides motive force to blood circulation, controlling blood flow rate. Pure blood and pure water with different proportions are added into the gas washing bottle 106, and are uniformly mixed through a circulation system to form blood with different hemoglobin concentrations, and oxygen or nitrogen is introduced into the gas inlet 106a of the gas washing bottle 106 to change the blood oxygen saturation degree of the blood. In the simulated body structure, because PMMA and PDMS are high light-transmitting materials, the thickness influence of the PMMA and PDMS can be ignored, the PDMS film doped with titanium dioxide has a scattering effect and is used for simulating mucosal tissues covered on blood vessels, the thickness of the PDMS film is different, which means that the depths of the blood vessels in the tissues are different, in actual manufacturing, the doping amount of the titanium dioxide in the PDMS film can be controlled to control the normalized scattering coefficient of the obtained film so as to enable the PDMS film to be close to the tissues to be simulated, the thickness of the covered film is controlled to be close to the depths of the blood vessels in the tissues to be simulated so as to simulate deep, middle and shallow blood vessels, for example, when an endoscope is commonly used in a digestive organ, when a standard tissue sample simulating the digestive organ is manufactured, the film with the mass ratio of the titanium dioxide and the PDMS film is 0.8% -1.0%, the normalized scattering coefficient of the PDMS film is close to the gastric mucosa tissues, the thickness of the PDMS film is 50-200 mu m, the PDMS film can be used for simulating the shallow blood vessels, the PDMS film is used for simulating the substrate, the PDMS film is used for simulating the blood vessels, and the thickness of the PDMS film is used for simulating the blood vessels, and the film is used for the simulation. The shallower blood vessel in the actual tissue is usually thinner, but the thickness of the blood vessel is not required to be considered in the simulation, because the calculated hemoglobin index counteracts the influence of different optical paths caused by different thicknesses of the blood vessel, the diameter of the shallow blood vessel can be 100-300 mu m, the diameter of the middle blood vessel can be 300 mu m-1 mm, and the diameter of the deep blood vessel can be 1-3 mm for the convenience of manufacturing.
By using the standard tissue sample, the corrected hemoglobin indexes corresponding to the simulated shallow, middle and deep blood vessels can be determined by adopting the same method of the invention to perform experiments under the condition of different known hemoglobin concentrations, so that a relation value table or function of the corrected hemoglobin indexes and the hemoglobin concentrations can be obtained. The adoption of the imitation body structure of the invention greatly reduces the experimental difficulty required to be carried out in order to obtain the relation value table or the function.
FIGS. 11A, 11B and 11C are graphs showing the distribution of hemoglobin concentration of the tissue measured under illumination of 415nm narrow band light 31, 540nm narrow band light 32 and 590nm narrow band light 35, respectively. FIG. 11D is a graph showing the concentration profile of hemoglobin obtained in accordance with the present invention. They are gray-scale images, wherein the gray-scale values correspond to the hemoglobin concentration, and in some embodiments of the present invention, pseudo-color images may be used for the gray-scale images, and different colors correspond to different hemoglobin concentrations. By comparing fig. 11A to 11D, it can be seen that:
Only the hemoglobin concentration is measured by using the 415nm narrow band light 31, and only the hemoglobin information of the shallow capillary 22s can be extracted.
The hemoglobin concentration can be measured only by using 540nm narrow band light 32, and hemoglobin information of the superficial thin blood vessel 22s and the middle blood vessel 22m can be extracted, but in the case of blood vessel lamination, the information of both interfere with each other.
The hemoglobin information of the middle layer blood vessel 22m and the deep layer crude blood vessel 22d can be extracted by measuring the hemoglobin concentration only with the 590nm narrow band light 35, the shallow layer blood vessel 22s is difficult to extract the shallow layer blood vessel information because of the thin and small absorption coefficient of the hemoglobin to the 590nm narrow band light 35, and the middle layer and the deep layer information are also interfered with each other in the case of blood vessel lamination.
The method of the invention can more accurately obtain the hemoglobin concentration of biological tissues.
The hemoglobin information of the shallow thin blood vessel 22s is directly obtained from the 415nm narrow-band light 31 signal, the hemoglobin information of the middle blood vessel 22m is obtained by subtracting the signal contribution of the shallow thin blood vessel 22s from the 540nm narrow-band light 32 signal, and the hemoglobin information of the deep thick blood vessel 22d is obtained by subtracting the signal contributions of the shallow thin blood vessel 22s and the middle blood vessel 22m from the 590nm narrow-band light 35 signal. Therefore, in the case of using the tissue reflection signals of the 415nm narrow-band light 31, the 540nm narrow-band light 32, and the 590nm narrow-band light 35 at the same time, the embodiment of the present invention can independently extract the hemoglobin information of the shallow thin blood vessel 22s, the middle blood vessel 22m, and the deep thick blood vessel 22d, and thus can more accurately express the hemoglobin concentration of the tissue. The above effect also enables a more accurate response to the real situation in a numerical table or function of the relationship between the corrected hemoglobin indices IHb1', IHb2', IHb3' and hemoglobin concentrations obtained from calibration of standard tissue samples.
In addition, the signals of the 630nm narrow-band light 33 and the 450nm narrow-band light 34 are used for respectively carrying out normalization treatment on tissue background reflection and tissue scattering, so that deviation of a hemoglobin concentration calculation result caused by tissue difference is reduced. Meanwhile, by adopting the mode of alternately illuminating the narrow-band light combination 1 and the narrow-band light combination 2, the rapid calculation and real-time display of the hemoglobin concentration distribution map can be realized.