JP6184014B2 - Biological tissue diagnostic device - Google Patents

Description

  The present invention relates to a biological tissue diagnostic apparatus, and more particularly to a diagnostic apparatus that determines reversibility (Viability / viability) of brain tissue that has become in a low oxygen or low blood flow state.

  Among the organs of the whole body, the brain that consumes a large amount of oxygen reacts sensitively to oxygen deficiency, and if ischemia or hypoxia continues, it causes a decline in function and progresses from loss of function to destruction of brain cells. It leads to the danger of life.

  The following non-patent document 1 (hereinafter referred to as “Kawauchi”) relates to a technique for optically monitoring the viability of brain tissue under hypoxia. In this document, Kawauchi uses red to near infrared light. By irradiating the rat brain and measuring the time variation of the scattered light intensity, it is possible to determine the reversibility and irreversibility of the brain tissue due to hypoxia and depolarization of the brain.

  FIG. 1 shows an example of the temporal change in scattered light intensity from the brain of a rat inhaled with 100% nitrogen under spontaneous breathing, with the horizontal axis representing time and the vertical axis representing scattered light intensity. According to Kawauchi's report, depolarization occurs during the period A in FIG. 1, that is, when the intensity of scattered light rises after weakening. When depolarization occurs in the brain and a certain time has elapsed, recovery of brain function cannot be obtained even when blood flow (supply of oxygen) is resumed.

"Research on optical monitoring of brain tissue viability" by Atsuko Kawauchi, Laser Research Vol. 40, No. 4, (pp. 236-240) April 2012, The Laser Society of Japan

  By the way, Kawauchi's method diagnoses the state of the brain from temporal fluctuations in the scattered light intensity, and in order to make a diagnosis, the brain tissue is depolarized from a normal state due to lack of oxygen (in this state, functional recovery is no longer difficult). It is necessary to measure continuously until the occurrence of

  For this reason, unlike animal experiments in the laboratory, for example, when diagnosing the state of the brain of a patient who has been transported due to cerebral infarction, the state at any point in time is immediately (following time). It is not possible to make a diagnosis with Kawauchi's method. In addition, it is difficult to remove the measurement system from the diagnosis target and then attach it again because the measurement conditions are not the same, and diagnosis is also possible when the target tissue is already not normal due to insufficient oxygen or low blood flow. I can't do it.

  Therefore, it is desired to provide a technique capable of diagnosing the state of a living tissue without performing continuous measurement. An object of the present invention is to meet such a demand.

  In order to solve the above problems and achieve the object, a living tissue diagnostic apparatus according to the present invention irradiates a living tissue with laser light, receives light diffusely reflected by the living tissue, and distributes the intensity of this light. A diagnostic apparatus for determining the reversibility of the biological tissue based on a region setting unit for setting a determination region for performing determination in the biological tissue, and a laser light irradiation unit for irradiating the determination region with laser light A scattered light receiving unit that receives the scattered light of the laser light diffusely reflected by the living tissue, and a scattered light intensity distribution detecting unit that detects the intensity distribution of the scattered light received by the scattered light receiving unit in the determination region And a distribution degree calculation unit for calculating a degree of spread of the intensity distribution from the intensity distribution in the determination region detected by the scattered light intensity distribution detection unit, and the degree of spread calculated by the distribution degree calculation unit. Reversibility of the living tissue in the determination area and a determining reversibility determining unit that it has lost or reduced when the magnitude or more defined fit.

  When a living tissue is irradiated with laser light, which is coherent light, the irradiated laser light is diffusely reflected by the living tissue, and the diffusely reflected scattered light is superimposed (reflected light having different phases reflected at each location). ) Overlap, light and dark, that is, a speckle pattern due to a difference in light intensity occurs. This speckle pattern differs depending on the optical characteristics of the object. If it is a solid, the speckle pattern has a basic intensity of “0” for the weakest (dark) intensity and “1” for the strongest (bright) intensity. In this case, values from 0 (dark) to 1 (bright) are distributed.

  On the other hand, when blood is flowing in a living tissue, the speckle pattern shows temporal fluctuations without being fixed by the scattered light from red blood cells, which are the main components that scatter light (the fluctuation speed varies). A time average value of the light intensity of a certain range in the captured image (a small area obtained by finely dividing the determination area / for example, each pixel of a CCD camera that performs imaging), that is, The average value of the received light intensity during a certain period of time (for example, several tenths of a second to several seconds / for example, the charge accumulation time in a CCD pixel (photodiode)) takes a value between 0 and 1. As shown in FIG. 2, the speckle pattern intensity distribution D1 has a normal distribution centered on a certain value.

  On the other hand, when the living tissue is in an oxygen-deficient state such as an ischemic state, the fluctuation is reduced due to a decrease in blood flow and a change in cell shape due to depolarization, and the speckle pattern is fixed as shown in FIG. A broad intensity distribution D2. That is, when the oxygen deficiency is reached, the degree of spread of the scattered light intensity distribution increases (for example, the full widths at half maximum W1 and W2 satisfy W1> W2). Furthermore, when a laser beam is irradiated onto an object that does not move at all, the light intensity and the speckle pattern are constant and do not change, for example, a flat intensity distribution D3 as shown in FIG.

  Depolarization is a phenomenon in which ions inside and outside the cell membrane violently flow in and out, causing a sudden change in extracellular DC potential, causing changes in the shape of cells and organelles, and irreversible neuronal cell death if sustained for a long time. Connected.

  The present invention utilizes the phenomenon that the intensity distribution of the scattered light changes as described above. The intensity distribution of the speckle pattern is measured, and the reversibility of the living tissue is determined depending on the extent of the intensity distribution. Determine. As a result, it is possible to immediately determine the state of the biological tissue at an arbitrary time point without performing continuous measurement over time as in the river.

  Specifically, first, a region of the living tissue (determination region) to be determined is set by the region setting unit. Next, the living tissue including the determination region is irradiated with laser light by the laser beam irradiation unit, and the light diffusely reflected by the living tissue is received by the scattered light receiving unit. The scattered light intensity distribution detector detects the intensity distribution in the determination region from the received scattered light. Using the detected intensity distribution, the distribution degree calculation unit calculates the degree of spread of the intensity distribution. When the calculated spread degree is equal to or larger than a predetermined size, the reversibility determination unit determines that the reversibility of the living tissue in the determination region has been lost or decreased.

  In a typical embodiment of the present invention, the scattered light receiving unit is an image sensor (for example, a CCD image sensor), and the intensity distribution of the scattered light is a distribution of received light intensity of each pixel (pixel) of the image sensor. It is frequency distribution (distribution of the number of pixels) regarding received light intensity.

  As the laser light, it is preferable to use red to near-infrared laser light, that is, laser light having a wavelength of 600 nm to 900 nm. This is because the absorption by living tissue and blood (red blood cells) is small in the wavelength region. More preferably, laser light having a wavelength of about 800 nm is used. This is because in this wavelength region, the absorption coefficients of oxygenated and deoxygenated red blood cells are almost equal and are not easily affected by the degree of oxygenation of blood.

  Further, in the biological tissue diagnostic apparatus of the present invention, the polarization set in the polarization direction perpendicular to the polarization direction of the laser light in order to prevent or reduce the laser light reflected on the surface of the biological tissue from being taken into the scattered light receiving unit. It is preferable to further provide a plate. This is because the light reflected from the surface of the living tissue is blocked to make a more accurate determination.

  Furthermore, in one aspect of the present invention, the region setting unit can set a plurality of regions as determination regions, and for each of the plurality of determination regions, the scattered light intensity distribution detection unit detects the intensity distribution, and the distribution degree The calculation unit calculates the extent of spread, and the reversibility determination unit performs the determination.

  Moreover, in the said aspect, the image display part which displays a biological tissue and a determination area | region is further provided, and this image display part is the said determination, when it is not determined by the reversibility determination part that the reversibility was lost or reduced. While it is displayed with the first color applied to the area, when it is determined that the reversibility has been lost or decreased, the second color different from the first color is applied to the determination area for display. I can do it.

  According to such an aspect, it is possible to determine at a glance which part of the living tissue can be recovered and which part cannot be recovered.

  The biological tissue referred to in the present invention is typically the brain, but is not limited to this, and includes various organs and organs other than the brain. This is because organs other than the brain and living tissues such as organs are composed of cells that perform life activity by blood flow and oxygen like the brain tissue, and it is considered possible to apply the present invention similarly to the brain. . Further, the living tissue to which the present invention is applied may be related to either animals or humans.

  According to the biological tissue diagnostic apparatus according to the present invention, it is possible to immediately determine the reversibility of biological tissue without performing continuous measurement.

  Other objects, features, and advantages of the present invention will become apparent from the following description of embodiments of the present invention described with reference to the drawings. It should be noted that the present invention is not limited to the following embodiments, and it will be apparent to those skilled in the art that various modifications can be made within the scope of the claims.

FIG. 1 is a diagram showing an example of a temporal change in scattered light intensity from the brain of a rat inhaled with 100% nitrogen under spontaneous breathing. FIG. 2 is a diagram showing an intensity distribution of scattered light (diffuse reflected light) when a living tissue is irradiated with laser light. FIG. 3 is a block diagram showing a biological tissue diagnostic apparatus according to an embodiment of the present invention. FIG. 4 is a diagram showing the time change of the average scattered light intensity from the brain of a rat inhaled with 100% nitrogen under spontaneous breathing. FIG. 5 shows the normalized full width at half maximum (full width at half maximum normalized by the mean value of scattered light intensity) regarding the intensity distribution of scattered light from the brain of a rat inhaled with 100% nitrogen under spontaneous breathing as in FIG. It is a diagram which shows the time change of.

  As shown in FIG. 3, the biological tissue diagnostic apparatus 11 according to an embodiment of the present invention determines the reversibility of brain tissue, and irradiates the brain 10 to be diagnosed with laser light and captures the reflected light. And an apparatus main body 31 that obtains an intensity distribution (histogram) of reflected light from the captured image data, calculates the extent of the spread, and determines the reversibility of the living tissue 10. FIG. 3 is a functional block diagram functionally grasping the apparatus according to the present embodiment, and each part (each block) of the apparatus may be appropriately realized by hardware or computer software.

  The imaging unit 21 includes a laser light irradiation unit 22 that emits laser light and a CCD camera 23 that receives the reflected light.

  On the other hand, the apparatus main body 31 is composed of a computer including a display unit (display) 33 and an input device (keyboard / mouse, etc.), an image display control unit 32 for controlling image display on the display unit 33, and reversibility determination. A ROI setting unit 34 that enables a region to be set (determination region / hereinafter referred to as “ROI” (Region of Interest)) to be set on an image displayed on the display unit 33; The scattered light intensity distribution detection unit 35 that obtains the intensity distribution of the scattered light in the ROI set through the setting unit 34 from the image data acquired by the CCD camera 23, and the scattered light obtained by the scattered light intensity distribution detection unit 35 The distribution degree calculation unit 36 that calculates the degree of distribution (expansion degree) from the intensity distribution, and compares the degree of spread calculated by the distribution degree calculation unit 36 with a preset threshold value An abnormal state in the case of more than the threshold value and a reversible determination unit 37 determines (reversibility reduced or lost the) and Te.

  In diagnosis, an ROI (determination region) is set by surrounding a desired range by an operation of the mouse on the image of the brain 10 photographed by the CCD camera 23 and displayed on the screen of the display 33 by the image display control unit 32. The brain tissue 10 including the ROI is irradiated with laser light by the laser light irradiation unit 22 and scattered light diffusely reflected by the brain tissue 10 is received by the CCD camera 23. Note that the ROI setting unit 34 can set a plurality of ROIs. For example, it is possible to select a plurality of suspicious affected parts and simultaneously determine each of these parts.

  The image signal from the CCD camera 23 is taken into the image display control unit 32, and the image display control unit 32 extracts the light intensity signal of each pixel in the set ROI from the image signal and extracts the signal in the ROI. The light intensity data of each pixel is output to the scattered light intensity distribution detector 35. The scattered light intensity distribution detection unit 35 calculates a time average value of the received light intensity of each pixel from the light intensity data of each pixel included in the data, and obtains an intensity distribution regarding each pixel in each ROI.

  These intensity distribution data are output to the distribution degree calculation unit 36. The distribution degree calculation unit 36 calculates the degree of spread from the intensity distribution. In this embodiment, the degree of spread is a normalized half-width N.FWHM (= FWHM) which is a value obtained by normalizing (dividing) the half-value full width FWHM of scattered light intensity by the average value Rm of scattered light intensity in the ROI. / Rm) and the distribution degree calculation unit 36 calculates the normalized full width at half maximum N.FWHM and outputs it to the reversibility determination unit 37. Note that the degree of spread is not particularly limited as long as it indicates how much the intensity distribution of scattered light varies, and therefore, an indicator such as a standard deviation may be used.

  The reversibility determination unit 37 compares the N.FWHM provided from the distribution degree calculation unit 36 with a threshold value stored in advance, and when N.FWHM is less than the threshold value, the normal state is detected. When FWHM is equal to or greater than the threshold, it is determined that the state is abnormal, and the determination results are output to the image display control unit 32.

  The image display control unit 32 performs display based on the determination result by the reversibility determination unit 37 for each of a plurality of set ROIs (determination regions) via the display unit 33. Specifically, a specific color (for example, red) is applied to the ROI in the normal state, and a specific color (for example, blue) different from the normal state is applied to the ROI in the abnormal state, and displayed on the screen of the display unit 33. . In addition, instead of two colors in this way (two levels of normal and abnormal states), color display of three colors (for example, three levels of normal, abnormal and intermediate states) according to the numerical value of N.FWHM It is also possible to perform stepwise display beyond that.

  In addition, the image display control unit 32 causes the display unit 33 to display an image of a speckle pattern and a graph indicating the intensity distribution of scattered light (the scattered light intensity distribution detection unit 35 transmits the intensity distribution data to the image display control unit 32. Or display on the screen according to the intensity of the scattered light according to the intensity and display corresponding to the image of the living tissue 10. I can do it.

  FIG. 4 shows the results of continuous measurement of the temporal change of scattered light intensity (light reception intensity) from the brain of a rat inhaled with 100% nitrogen under spontaneous breathing using the diagnostic device 11 according to this embodiment. FIG. In the measurement, since the time was 0 second, 100% nitrogen was inhaled to damage the brain. From this measurement result, it is considered that depolarization occurs in the vicinity of 150 to 200 seconds. In Kawauchi, it is reported that the survival rate of rats after the increase of scattered light intensity (after about 250 seconds) is 0%, and the survival rate before that is 10 to 40%. Therefore, if the state of the brain tissue is 250 seconds or less, it is considered possible to survive by applying an appropriate treatment.

  Furthermore, FIG. 5 shows the normalized full width at half maximum (full width at half maximum normalized by the average value of scattered light intensity) N.FWHM regarding the intensity distribution of scattered light from the brain of a rat inhaled with 100% nitrogen under spontaneous breathing. It is a diagram which shows a change, and shows the result measured using the diagnostic apparatus 11 of this embodiment similarly to the said FIG.

  In FIG. 5, a rapid rise in N.FWHM is observed from about 220 seconds. After about 250 seconds, N.FWHM shows about twice the value before nitrogen inhalation. This spread of N. FWHM is thought to reflect a decrease in blood flow and a decrease in viability in brain cells. Thus, the reversibility of the brain tissue can be determined from the extent of the scattered light intensity distribution.

DESCRIPTION OF SYMBOLS 10 Living tissue 11 Living tissue diagnostic apparatus 21 Image pick-up part 22 Laser beam irradiation part 23 CCD camera 31 Apparatus main body part 32 Image display control part 33 Display part (display)
34 ROI setting unit 35 Scattered light intensity distribution detection unit 36 Distribution degree calculation unit 37 Reversibility determination unit

Claims (6)

A diagnostic apparatus that irradiates a living tissue with laser light, receives light diffusely reflected by the living tissue, and determines reversibility of the living tissue based on an intensity distribution of the light,
An area setting unit for setting a determination area for performing determination in the living tissue;
A laser beam irradiation unit that irradiates a laser beam to the determination region;
A scattered light receiving unit that receives the scattered light of the laser light diffusely reflected by the biological tissue;
A scattered light intensity distribution detector that detects an intensity distribution of the scattered light received by the scattered light receiver in the determination region;
A distribution degree calculation unit that calculates a degree of spread of the intensity distribution from the intensity distribution in the determination region detected by the scattered light intensity distribution detection unit;
A reversibility determination unit that determines that the reversibility of the biological tissue in the determination region has been lost or decreased when the spread degree calculated by the distribution degree calculation unit is greater than or equal to a predetermined size. A biological tissue diagnostic apparatus characterized by the above. The biological tissue diagnostic apparatus according to claim 1, wherein the laser light irradiated by the laser light irradiation unit has a wavelength of 600 nm to 900 nm. The biological tissue diagnostic apparatus according to claim 1, further comprising a polarizing plate that prevents or reduces laser light reflected by the surface of the biological tissue from being taken into the scattered light receiving unit. The biological tissue diagnostic apparatus according to any one of claims 1 to 3, wherein the biological tissue is a brain. The region setting unit can set a plurality of regions as the determination region,
The scattered light intensity distribution detection unit detects the intensity distribution for each of the plurality of determination regions, the distribution degree calculation unit calculates the spread degree, and the reversibility determination unit performs determination. The biological tissue diagnostic apparatus according to any one of 4. An image display unit for displaying the living tissue and the determination region;
If the reversibility determination unit does not determine that the reversibility has been lost or reduced, the image display unit displays the determination area with a first color, while the reversibility is lost or reduced. The biological tissue diagnostic apparatus according to any one of claims 1 to 5, wherein when the determination is made, the determination region is displayed with a second color different from the first color.

Images