JP2015152480A - Method and device for observing formation of blood clot or blood clotting and its growth - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method and a device that make it possible to detect formation of blood clot or blood clotting over a wide range in a blood flow channel and observe its growth.SOLUTION: A method for observing formation of blood clot or blood clotting and its growth in a blood flow channel is provided in which a blood flow channel is continuously imaged at two wavelengths of a short-wavelength-side reference wavelength and a long-wavelength-side measurement wavelength, each having a wavelength of at least 600 nm or more, and a difference image in brightness between the image at the measurement wavelength and an image at the reference wavelength is given. A device for observing formation of blood clot or blood clotting and its growth in a blood flow channel is provided which includes: a camera that continuously images the blood flow channel; and image analysis means that, at two wavelengths of the short-wavelength-side reference wavelength and the long-wavelength-side measurement wavelength, each having a wavelength of at least 600 nm or more, gives a difference image in brightness between the image at the measurement wavelength and the image at the reference wavelength.

Description

  The present invention relates to a method and apparatus for observing the formation and growth of thrombus and blood clots, and in particular, to detect the formation of thrombus and blood clots over a wide range in a blood flow path and observe the growth. The present invention relates to a method and an apparatus thereof.

  Known diseases caused by blood clots formed in blood vessels include cerebral infarction and economy syndrome. Even in a device that guides blood outside the body, such as an oxygenator or a hemodialysis machine, if blood clots in the blood flow path inside the device, a thrombus is found when the blood is returned to the body. End up. Further, when blood coagulation grows, it may stay in the flow path and cause malfunction of the device. Therefore, there is a need for a method that enables external observation of the formation and growth of blood clots and blood clots.

  For example, in Patent Document 1, as a method for accurately and easily measuring a thrombus in blood flowing from the outside of a blood vessel without damaging the blood vessel, a laser beam having a wavelength of 600 nm to 1200 nm that is relatively easy to pass through the blood layer. Alternatively, a method of irradiating light emitting diode light as pulse light and measuring the amount of reflected light or transmitted light with respect to each pulse is disclosed. Here, the presence of a thrombus appears as a change in the amount of light because a non-normal composition such as a blood clot enters the optical path of the laser beam, resulting in a partial difference in hemoglobin density or reflectance. doing. On the other hand, changes such as hematocrit are also related to changes in hemoglobin density and give a change in light intensity, but the change is gradual and does not give a sudden change such as the presence or absence of a thrombus. It can be identified.

  Further, in Patent Document 2, blood guided outside the body like a hemodialysis apparatus is allowed to pass through a transparent tube, which is provided with a combination of optical monitoring means and ultrasonic monitoring means, and a solid substance such as a blood clot. Discloses a method of measuring or monitoring the air bubbles separately from the air bubbles. For the optical sensor of the optical monitoring means for detecting the blood clot, it is said that a light source having a wavelength region of about 805 nm that is extremely less absorbed by hemoglobin of red blood cells and is not affected by oxygen contained therein is optimal.

  By the way, as a method for measuring a planar distribution of a specific substance or the like over a wide range, a method using a spectral image has been proposed. For example, by using white light as a light source and analyzing an image captured by a CCD camera by dividing it into color gradations, it is possible to perform spectroscopic measurement for each pixel region in the plane.

  For example, Patent Document 3 discloses a method of visualizing blood distribution by obtaining a spectral image in a wavelength band within ± 50 nm including 430 nm from reflected light from a test surface of living skin. The amount of light in the wavelength band centered at 430 nm among the light reflected from the living tissue corresponds to the amount of oxygenated hemoglobin on the skin surface, so the reflected light in this wavelength band is imaged with a CCD camera. Thus, the oxygenated hemoglobin amount on the skin surface, that is, the blood volume distribution can be known. Here, the amount of light absorption increases at a site where the blood volume (oxygenated hemoglobin) is large, so that it is dark, and conversely the site where the volume is low is bright, and the distribution of blood volume can be known from these brightness distributions.

JP 2002-345787 A JP 2013-534160 A JP-A-8-327531

  A scanning method with a sensor probe in a narrow blood flow path cannot detect thrombus remaining in a certain place, thrombus or blood clot formation in a wide blood flow path, and observe its growth . Therefore, the use of the above-described spectral image capable of measuring the planar distribution over a wide range is considered.

  The present invention has been made in view of the above situation, and the object of the present invention is to detect the formation of thrombus and blood coagulation over a wide range in the blood channel and observe its growth. It is an object of the present invention to provide a method and an apparatus thereof.

  The method according to the present invention is a method for observing the formation and growth of thrombus and blood coagulation in the blood flow path, and is at least 600 nm, which is a reference wavelength on the short wavelength side and a measurement wavelength on the long wavelength side. The blood channel is continuously imaged at one wavelength, and a difference image of the luminance of the image at the measurement wavelength with respect to the image at the reference wavelength is given.

  According to this invention, formation of a thrombus or blood coagulation can be detected over a wide range in the imaged blood flow path, and the growth can be observed by a differential image.

  In the above-described invention, the image may be given by transmitted light, and an image showing an increase in the luminance value may be given. Alternatively, the image may be given by reflected light, and an image showing a decrease in the luminance value may be given. According to this invention, the formation of a thrombus or blood clot can be detected over a wide range in the imaged blood flow path, and its growth can be observed with a clearer differential image.

  In the above-described invention, the reference wavelength and the measurement wavelength may be given across 670 nm. According to this invention, blood coagulation increases the light transmittance of a wavelength of 670 nm or more, so that the formation of a thrombus or blood coagulation is detected over a wide range in the imaged blood flow path, and the growth thereof is clearer. It can be observed with a simple difference image.

  The apparatus according to the present invention is an apparatus for observing the formation and growth of thrombus and blood coagulation in the blood flow path, and a camera that continuously images the blood flow path and at least 600 nm and shorter. Image analysis means for providing a difference image of the luminance of the image at the measurement wavelength with respect to the image at the reference wavelength at two wavelengths, a reference wavelength on the wavelength side and a measurement wavelength on the long wavelength side, To do.

  According to this invention, it is possible to detect the formation of thrombus and blood coagulation over a wide range in the imaged blood flow path and observe the growth with a differential image.

  The above-described invention may further include a light source that provides each of the reference wavelength and the measurement wavelength. Alternatively, in the above-described invention, a white light source may be provided, and the image analysis unit may further include a spectroscopic unit that separates each of the reference wavelength and the measurement wavelength. According to this invention, the formation of a thrombus or blood clot can be detected over a wide range in the imaged blood flow path, and its growth can be observed with a clearer differential image.

  In the above-described invention, the camera may pick up an image with transmitted light from the light source, and the image analysis means may give an image showing an increase in the luminance value. Or in the above-mentioned invention, the said camera may image with the reflected light from the said light source, and the said image analysis means may give the image which shows the fall of the said luminance value. According to this invention, the formation of a thrombus or blood clot can be detected over a wide range in the imaged blood flow path, and its growth can be observed with a clearer differential image.

  In the above-described invention, the reference wavelength and the measurement wavelength may be given across 670 nm. According to this invention, blood coagulation increases the light transmittance of a wavelength of 670 nm or more, so that the formation of a thrombus or blood coagulation is detected over a wide range in the imaged blood flow path, and the growth thereof is clearer. It can be observed with a simple difference image.

It is a photograph of the verification test apparatus using the observation method according to the present invention. It is the cross section and top view which show the principal part of the apparatus of FIG. It is the photograph obtained with the apparatus of FIG. It is a graph of the time-dependent change of transmitted light imaging. It is the photograph obtained with the apparatus of FIG. It is a graph which shows the spectrum change of each point in FIG. It is a graph which shows a spectrum change. It is a difference image using the observation method by this invention. It is a photograph which shows a mode that the apparatus after observation was decomposed | disassembled. It is a difference image using the observation method by this invention.

  The present inventor examined whether the formation and growth of thrombus and blood coagulation in the blood flow path could be observed by using a CCD camera as a light detector. In other words, if blood clots can be detected from images continuously captured by a camera, blood clots formed by blood coagulation reaction and blood clots flying from the outside to the shooting location can be detected in a wide imaging range. Can be imaged.

  The invention is roughly as follows.

  First, at least two light sources (LED or laser) having different wavelengths in the wavelength range of 600 to 750 nm and multi-wavelength imaging using a CCD camera, or a white light source such as a halogen lamp including a similar wavelength band Using a hyperspectral camera (CCD + spectrometer), a blood-filled device (in some cases, a blood vessel or the like) is photographed to obtain an image at each wavelength.

  When the blood coagulates, the light transmittance with a wavelength of 670 nm or more increases. Therefore, when image images (spectral images) at different wavelengths are compared, a change occurs in an image image of 670 nm or more (in the case of transmitted light imaging, the luminance value of the image increases, and in the case of reflected light imaging, the reverse is the case). To lower). In the comparison of the spectral images, a portion having an increased luminance value of a wavelength of 670 nm or more is determined as a thrombus, and the region is extracted by image processing. Note that this method extracts a region from a change in spectral shape regardless of the luminance value of the image, so even if the luminance value of the image is low due to weak light source or attenuation of light by blood, etc. Therefore, it is possible to perform imaging with less noise and less noise.

  In addition to the above, a ratio of luminance values of an image with a wavelength of 670 nm or less (reference wavelength image) and an image with a wavelength of 670 nm or more (measurement wavelength image) is taken, and a region that is judged to be a thrombus is extracted by setting a threshold value. Good. Although imaging accuracy is inferior, it is simple and low cost.

  Further, by using hyperspectral imaging (a system based on a combination of a CCD and a spectrophotometer), a continuous spectrum image can be acquired, and the accuracy of extraction of thrombus and the like can be improved. On the other hand, a lower cost imaging system can image a thrombus if it can acquire at least an image of 670 nm or less and two images (difference images) of a wavelength of 670 nm or more.

  The demonstration experiment is described below.

  Bovine whole blood is circulated through a device 5 including a blood circulation path 2 as shown in FIG. Here, the activated clotting time (ACT) of blood was adjusted to 150 seconds. Further, a continuous circulation blood pump 7 was driven at a rotational speed of 2780 rpm, 1 L / min, 121 mmHg to circulate blood. When the pump flow rate is 0.8 L / min or less due to thrombus formation, heparin is injected into the 3000 unit circuit and the experiment is terminated. Although details will be described later, the blood pump 7 was then washed with physiological saline, and the thrombus in the pump 7 was photographed and compared with an HSI imaging image (see FIG. 10).

  Referring also to FIG. 2, a ring light guide 9 is attached to the upper surface of the blood pump 7, the light from the halogen lamp 8 is guided to the ring light guide 9 by an optical fiber, and light is irradiated from the upper surface of the blood pump 7 (left hand in FIG. 2). did. Further, light from the halogen lamp 8 was guided by an optical fiber from the lower surface of the blood pump 7 at an angle of 45 ° and irradiated toward the lower surface of the blood pump 7. Each of the transmitted light passing through the blood pump 7 and the reflected light on the lower surface of the blood pump 7 was photographed with a hyperspectral imaging (HSI) camera 3 at a shutter speed of 1 msec. The image was spectrally divided by CCD imaging to obtain a spectral image having a wavelength of 600 to 750 nm (resolution 2 nm).

  FIG. 3 shows transmitted light imaging (FSI: Forward Scattering Image) at the start of the experiment (t = 0 min), (b) after 96 minutes (t = 96 min), and (c) after 98 minutes (t = 98 min). ) And reflected light imaging (BSI: Backward Scattering Image). Here, the image is taken at a wavelength of 700 nm. According to this, in transmitted light imaging, flicker occurred at t = 96 min, and the transmitted light intensity increased clearly at t = 98 min. On the other hand, in the reflected light imaging, the vicinity of the center of the blood pump 7 was blurred.

  FIG. 4 shows changes with time in transmitted light imaging. That is, the change of the average luminance value of the transmitted light imaging of FIG. 3 is shown. According to this, the luminance value increases over t = 96 min.

  FIG. 5 shows hyperspectral imaging. Here, the wavelength is 600 nm to 750 nm, the wavelength interval is 2 nm, and the bandwidth is 2.6 nm. (A) is at the start of the experiment, and (b) is after a predetermined time. Before and after the passage of time, the ratio of the light intensity of the long wavelength (changed to red in the color image) increased.

  FIG. 6 shows spectral changes in the regions ROI1, ROI2, and ROI3 shown in FIG. According to this, the center of gravity of the spectrum is shifted to the long wavelength side. As an index representing such shift, τ was defined as a wavelength equal to the luminance value at a wavelength of 750 nm.

FIG. 7 shows (a) the spectral change S1 of the transmitted light imaging at the start of the experiment, and (b) the spectral change S2 of the transmitted light imaging after the lapse of a predetermined time, and the oxygenated hemoglobin in the ROI 1 of FIG. Absorption spectrum S3 was shown. From the absorption spectrum of hemoglobin, the wavelength τ _Hb representing the absorption equivalent to the wavelength of 750 nm is 634 nm. The stronger the absorption, the more light is absorbed and the lower the received light intensity. Therefore, the transmitted light intensity shows a tendency that the absorption spectrum is inverted.

Further, in blood, τ _Blood = 645 nm, which is a value different from τ _Hb , because the blood has scattering and the spectrum is distorted. Since the scattering of blood becomes lower as the wavelength becomes longer, the longer wavelength becomes easier to transmit. That is, a relationship of τ _Hb <τ _Blood is obtained. When blood coagulates, the light transmittance at a wavelength of 680 nm or more is improved. This is because fibrin is formed and the scattering property of fibrin is low in the region of 680 nm or more, and the center of gravity of the spectrum is further shifted to a long wavelength. Conceivable. From this, thrombus imaging is possible by extracting the region where the center of gravity shift of this spectrum occurred.

  FIG. 8A shows a shift region (difference image) for reflected light imaging at the start of the experiment of FIG. The entire inside of the blood pump 7 is shown in black, indicating that the wavelength having the same luminance value as the wavelength of 750 nm is common. On the other hand, FIG. 8B shows a shift region (difference image) for reflected light imaging after the elapse of a predetermined time in FIG. 5B. The change region where τ has changed corresponds to the thrombus formation portion in the blood pump 7. The white solid line region L1 is a region where a thrombus was clearly confirmed, and the white dotted line region L2 is a region where a thin film-like thrombus was confirmed.

  It should be noted that a change in τ is also observed outside the region where thrombus is confirmed. However, although there is a possibility that thrombus or blood coagulation has occurred in such a region, since the inside of the blood pump 7 is filled with blood, it is difficult to confirm this from the outside. Therefore, the blood pump was washed with physiological saline to confirm the remaining thrombus. (However, a weakly adhered thrombus may be washed away with physiological saline.)

  FIG. 9 shows the result after the inside of the blood pump was washed with physiological saline. That is, (a) hyperspectral imaging, (b) a macroscopic image taken with a normal digital camera, (c) a thrombus attached to the pump impeller after pump disassembly, and (d) a removed thrombus. It can be confirmed that hyperspectral imaging gives observation of thrombus.

  FIG. 10 shows simple thrombus imaging using two-wavelength images. When blood coagulates, scattering of light with a wavelength of 680 nm or more is suppressed. In particular, since it has the greatest influence on the scattering of light in the vicinity of a wavelength of 710 to 720 nm, it was considered to image a thrombus from images of two wavelengths of wavelengths 680 nm and 720 nm. In the imaging shown in FIG. 7, the hyperspectral imaging camera 3 is used in order to use the shift of the center of gravity of the spectrum. Here, observation is possible if there are two light sources, for example, an LED and a laser, and a normal CCD camera. It is.

Let T be the intensity ratio of two images at wavelengths of 680 nm and 720 nm.
T = (luminance value at wavelength 720 nm) / (luminance value at wavelength 680 nm)
And The difference image is an image obtained by taking an image with wavelengths of 680 nm and 720 nm and a luminance value ratio T = (720 nm / 680 nm) between the two, and binarizing T ≧ 1 with white and T <1 with black. It can be confirmed that observation of thrombus is still given.

  According to the above method, it is possible to image when and where a thrombus has been formed or in the growth process of the thrombus in an artificial cardiopulmonary circuit, a hemodialysis circuit, or the like. Here, since it is not necessary to fix the sensor and normal camera photography is possible, detection is possible anywhere as long as it is not surrounded by an object that does not transmit light. Furthermore, thrombus detection in blood vessels and living tissues can be performed if the principle is not deep. Moreover, application to a blood vessel endoscope or the like is also possible. Since the thrombus growth can be imaged at the moment of thrombus formation, it can be used when developing cardiovascular devices such as artificial hearts, artificial lungs, artificial blood vessels, and stents, and it can also be used as a method for evaluating blood compatibility. Is possible. Furthermore, in clinical settings, blood coagulation can be evaluated using cardiopulmonary bypass or hemodialysis, which is effective in preventing thrombosis.

  As mentioned above, although the Example by this invention and the modification based on this were demonstrated, this invention is not necessarily limited to this, A person skilled in the art will deviate from the main point of this invention, or the attached claim. Various alternative embodiments and modifications could be found without doing so.

2 Blood circuit 5 Device 7 Circulating blood pump 8 Halogen lamp 9 Ring light guide

Claims (10)

A method of observing the formation and growth of thrombus and blood clots in the blood flow path,
The blood channel is continuously imaged at two wavelengths of a reference wavelength on the short wavelength side and a measurement wavelength on the long wavelength side that is at least 600 nm or more, and an image at the measurement wavelength with respect to the image at the reference wavelength is captured. A method for observing the formation and growth of thrombus and blood coagulation, characterized by providing a difference image of brightness.   The method of claim 1, wherein the image is provided by transmitted light and provides an image showing the increase in the luminance value.   The method of claim 1, wherein the image is provided by reflected light to provide an image that shows a decrease in the luminance value.   The method according to claim 1, wherein the reference wavelength and the measurement wavelength are provided across 670 nm. A device for observing the growth and formation of thrombus and blood clots in the blood flow path,
A camera that continuously images the blood flow path;
Image analysis means for providing a difference image of the luminance of the image at the measurement wavelength with respect to the image at the reference wavelength at two wavelengths of a reference wavelength on the short wavelength side and a measurement wavelength on the long wavelength side that is at least 600 nm or more A device for observing the growth of thrombus and blood clot formation, characterized by comprising:   6. The apparatus of claim 5, further comprising a light source that provides each of the reference wavelength and the measurement wavelength.   6. The apparatus according to claim 5, further comprising a white light source, and the image analysis means further includes a spectroscopic means for separating each of the reference wavelength and the measurement wavelength.   The apparatus according to claim 6 or 7, wherein the camera captures an image using transmitted light from the light source, and the image analysis unit provides an image indicating an increase in the luminance value.   The apparatus according to claim 6 or 7, wherein the camera captures an image with reflected light from the light source, and the image analysis unit provides an image indicating a decrease in the luminance value. 10. The apparatus according to claim 5, wherein the reference wavelength and the measurement wavelength are provided with 670 nm interposed therebetween.

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