JPH07308312A - Apparatus for noninvasive hemanalysis and method therefor - Google Patents

Abstract

PURPOSE:To analyse the shape and/or the number of corpuscles from a photographed image and to analyze non-invasively a blood by providing an analysing means wherein a detecting region in a blood vessel is photographed by illumination and the photographed image is processed and the shape and/or the number of the blood are analyzed from the photographed image. CONSTITUTION:A light irradiating means consisting of a laser light source 22, an optical fiber 24 and a slit 60 is provided to illuminate a detecting region V of a blood vessel 12 in a living body 16. In addition, a photographing means constituted of a CCD 40 with an electronic shutter, a lens 38, a polarized filter 61 and a video system 44 is provided. In addition, to process the photographed image and to analyze the shape and/or the number of the corpuscles included in the detecting region V, an analyzing means provided with a means 48 for calculating the number of erythrocytes, a means 50 for calculating the mean vol. of erythrocytes, a means 52 for calculating the amt. of hemoglobin, a means 54A for calculating the amt. of hematocrit a means 54B for calculating the mean amt. of hemoglobin a means 56A for calculating the number of leucocytes, a means 56B for classifying the leucocytes and a means 57 for calculating the blood flow rate, is provided.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an apparatus and method for non-invasively analyzing blood, and more specifically, it optically measures blood flowing in a blood vessel of a living body to detect blood cell components necessary for blood test. The present invention relates to an apparatus for analyzing and a method thereof.

[0002]

2. Description of the Related Art Hematology such as blood cell count, hematocrit value, hemoglobin amount, red blood cell constant (average red blood cell volume: MCV, average hemoglobin amount: MCH, average hemoglobin concentration: MCHC) obtained by analyzing blood. The inspection items are
It is extremely important for diagnosis and treatment, and is one of the most frequently examined items in clinical examination.

These blood tests are carried out by collecting blood from a living body (collecting blood) and analyzing the sample with an analyzer. However, in addition to causing considerable pain to the living body at the time of this blood collection, the collected blood is analyzed after being transported to the laboratory in which the analyzer is installed, so a blood test can be performed in real time during diagnosis. Can not. Moreover, there is always a concern about accidental accidental injection of a blood sampling needle used for patients with infectious diseases such as hepatitis and AIDS.

Therefore, for many years, there has been a demand for the development of an apparatus capable of completely non-invasively performing a blood test without collecting blood from a living body. In addition, such a device
If you take it to the patient's bedside, it will be useful for understanding the condition in real time.

As a conventional technique related to such an apparatus, an observation site on the surface of a living body is irradiated with light and periodically video-imaged at a shutter speed of about one thousandth of a second, and from each of the obtained still images. A video microscope that identifies blood flow discontinuities and calculates blood flow velocity from the positions of blood flow discontinuities that move sequentially on each still image, or high-speed imaging of red blood cells in the conjunctival capillaries of the eye An analyzer including a video camera with a shutter is known (for example, Japanese Patent Laid-Open No. 4-16191).
5 and Japanese Patent Publication No. 1-502563.

[0006]

By the way, in a blood vessel in a living body, blood constantly flows from small and medium arteries and veins to fibrillation and capillaries, and its speed is 5 to 5 seconds per second.
It is several tens of mm. Now, set the blood flow velocity to 10 mm per second,
When red blood cells (8 to 10 microns in diameter) are imaged at a shutter speed of one thousandth of a second as in the above-mentioned conventional technique, the red blood cells move by the distance of the diameter in one thousandth of a second. A blur corresponding to the diameter occurs.

In blood vessels, erythrocytes are often adjacent to each other at intervals equal to or less than their diameter.
Most of the imaged red blood cells will overlap due to this image blur. Therefore, it is far from the conventional technique to quantitatively measure each blood test item by analyzing the morphology and number of blood cells from the captured image. On the other hand, in the analyzer disclosed in Japanese Patent Publication No. 1-502563, the conjunctival capillaries of the eyeball are photographed by a video camera. However, since the eyeball has a nature of slightly moving, the focus of the video camera is poor. Since the eyeball constantly moves relative to the imaged portion, it is difficult for the video camera to repeatedly capture the same area of the imaged portion. It is impossible to bring an object into close contact with the eyeball and mechanically stop the slight movement of the eyeball because there is a risk of damaging the eyeball. Further, Japanese Patent Publication No. 1-502563 discloses that RBC number, HCT, MCV and MCHC are measured, but no specific procedure is described.

The present invention has been made in consideration of such circumstances, and it is possible to accurately image a blood cell moving in a blood vessel of a living body and analyze the morphology and / or number of the blood cell from the captured image. A non-invasive device capable of analyzing blood and a method therefor are provided.

[0009]

SUMMARY OF THE INVENTION The present invention is directed to a light irradiation means for illuminating a detection area inside a blood vessel included in a part of a living body, an imaging means for imaging the illuminated detection area, and an imaging means. And a part of the living body relative to each other, a stabilizing means for stabilizing the focus of the image pickup means with respect to the detection area, and an image picked up by the image pickup means to be processed in the detection area. Morphology of blood cells contained in and /
Alternatively, the light irradiation means or the image pickup means is configured to form one image in the time of light irradiation or image pickup of 1/10000 to 1 billionth of a second. A non-invasive blood analyzer is provided.

This analyzer is characterized by non-invasively analyzing blood of a living body, and the living body is preferably a mammal including a human.

In the light irradiating means for illuminating a detection area in a blood vessel included in a part of a living body, the part of the living body has a skin which is not easily damaged by a contact object, and a portion having a blood vessel under the skin, For example, lips, fingers, ear lobes,
Parts that are easily damaged by external light or contact objects,
For example, the eyeball is excluded. Further, the detection area in the blood vessel means a predetermined area in the blood vessel that exists in the living body as it is. That is, in the present invention, this predetermined region is referred to as a detection region, and this region is a region having a volume capable of individually distinguishing blood cells existing in blood vessels. This region may be a region divided into two cross sections perpendicular or oblique to the blood flow direction of the blood vessel. Specifically, the division width of the detection region is preferably about 10 to 20 microns. On the other hand, the thickness of the target blood vessel is not particularly limited, but in order to obtain a result with good reproducibility, it is preferable to be a fibrillation vein. The blood cell information obtained from the venous veins can be converted into information on thick blood vessels (middle aortic veins).

In the light irradiating means of the present invention, as a light source,
A continuous light source such as a laser, a halogen lamp, or a tungsten lamp that continuously emits light, or a pulse laser (for example, Spectra-Physics, 7000 series) or a multi-strobe (for example, Sugawara Laboratory, DSX) An intermittent light source that emits light intermittently, such as a series), can be used. It is usually preferable to use an optical shutter in combination with the continuous light source as an intermittent light source. A known acousto-optic effect element (acounsto-optic modulator) or electro-optic effect element (electro-optic modulator) can be used as the optical shutter. The light irradiation (flash) time of these intermittent light sources is
It can be set to 1 / 10,000 second to 1 / 1,000 million second.

In addition to the above-mentioned light source, the light irradiating means optionally includes an optical fiber, various reflecting mirrors, polarizing elements, various lenses, prisms, slits, filters, etc.,
The light from the light source may be led to the detection region by a combination thereof. In particular, it is preferable that the light irradiation means includes a polarization means for illuminating the detection area with polarized light.

A general CCD image sensor for visible light, infrared light or ultraviolet light can be used for the image pickup means of the present invention, and in particular, an electronic device having a shutter speed of 1 / 10,000 second or more is used. CCD image pickup device having a shutter function, for example, XC-73 / CE or XC-75 / 75 manufactured by Sony Corporation
It is preferable to use a CE type (with a variable shutter having a maximum shutter speed of 1 / 500,000 seconds).

In addition to the above CCD image pickup device, the image pickup means optionally includes an optical fiber, various reflecting mirrors, a polarizing element, various lenses, prisms, slits, filters, an image intensifier, etc., and a combination thereof. The reflected light from the detection area may be introduced into the CCD image pickup device. Particularly, it is preferable that the image pickup means includes a polarizing means for removing unnecessary scattered light components from the detection area.

In the present invention, the light irradiation means or the image pickup means is configured to form one image in the time of light irradiation or image pickup of 1 / 10,000 second to 1 / 1.0 billion second. For example, since red blood cells moving at a speed of 10 mm in a blood vessel move by 1 micron in 1 / 10,000 second, the image blur of the red blood cells imaged by the configuration of the present invention is 10% of the diameter (10 micron) of the red blood cells. Become.

It has been experimentally confirmed that with such an image blur, it is possible to analyze the morphology of blood cells in blood vessels and count the number of blood cells. Furthermore, this is 1 / 100,000
If one image is formed in a second time, the image blur is 1/10 (1%), and if it is formed in a one-millionth second, the image blur is 1/100 (0.1%). ), The accuracy of analysis of blood cell morphology and number improves as the formation time of one image decreases.

However, the shorter the time for forming one image, the smaller the amount of light received by the image pickup means. Therefore, it is necessary to increase the light amount of the light irradiation means and the light receiving sensitivity of the image pickup means.
Therefore, it is preferable that the formation time of one image is from 1 / 10,000 second to 1 billionth of a second, and preferably from 1 / 50,000 second to 20th.
More preferably, it is 1 / 10,000 second.

In order to form one image in the time of light irradiation or imaging of 1 / 10,000 second to 1 billionth second,
It is possible to combine a light emitting means having an intermittent light source and an image pickup means having a CCD image pickup element, or a light emitting means having a continuous light source and an image pickup means having a CCD image pickup element with an electronic shutter. preferable.

Further, the light irradiation means and the image pickup means are arranged to pick up a plurality of images at predetermined time intervals so that the analysis means can analyze the morphology and / or number including the color tone of blood cells based on the plurality of images. It is preferably configured.

The image pickup means may further include recording means for recording the picked-up image, for example, an image memory or a video tape recorder.

Generally, the number of blood cells as a blood test item is
Since it is calculated as the number of blood cells existing per unit volume of blood, it is necessary to know the volume (volume) of the detection region for the calculation.

Therefore, the detection region in the blood vessel targeted by the present invention includes a three-dimensional volume region in which blood cells existing in the region can be individually optically distinguished, and the volume of the detection region is increased. The (volume) is calculated, for example, by the following method. (1) Calculated from the imaged image area, the imageable depth (focus depth) of the image pickup means, and the image pickup magnification. (2) The light irradiation means illuminates only a region of a predetermined volume in the blood vessel, and the illuminated region is imaged. (3) Measuring the inner diameter of the imaged blood vessel wall in the detection area,
Calculate the volume of the detection area.

In the method (2), the light irradiating means irradiates the slit light from the direction perpendicular or oblique to the blood flow direction of the blood vessel to illuminate the blood vessel so as to slice the light with the slit light, and slice the light with the slit light. The region may be captured by the image capturing means from the cross-sectional direction. Thereby, the dynamics of blood cells flowing in the blood vessel can be imaged from the blood flow direction of the blood vessel, and the volume of the detection region is calculated from the product of the area of the blood vessel cross section and the slit width.

Incidentally, in imaging such a cross section of a blood vessel,
It is preferable that the image pickup surface of the image pickup means is arranged so that the image pickup surface can be tilted. Thereby, it is possible to focus on the entire cross section (the tilt photographing is known as one of the photographing techniques, and the description thereof will be omitted).

Since the analyzing means of the present invention performs preprocessing of the image picked up by the image pickup means, various filters, γ
It is preferable to provide an analog and / or digital image processing means selectively having functions such as correction, interpolation, jitter correction, color tone conversion, color balance correction, white balance, and shading correction.

Further, the analyzing means calculates the hemoglobin amount (HGB) by calculating the number of red blood cells and / or white blood cells, the hematocrit calculating means for calculating the hematocrit value, and analyzing the reflected light intensity from the detection region. Hemoglobin amount calculating means, means for calculating mean red blood cell volume (MCV), mean hemoglobin amount (MCH) and mean hemoglobin concentration (MCHC) from blood cell morphology, means for analyzing and classifying blood cell morphology, and fibrillation or It is preferable to provide a means for converting blood cell information obtained from the capillaries into blood cell information corresponding to the middle and large arteries and veins.

The analyzing means may be constructed by using a digital signal processor (DSP), for example, TMS320C30 manufactured by Texa Instruments.

The non-invasive blood analyzer of the present invention irradiates the detection area in the blood vessel with the light emitted from the light irradiating means, and correctly captures the reflected light from the illuminated detection area (without image blurring). For this reason, it is desirable to provide a fixing means for relatively fixing at least a part of the living body and the image pickup means, and a stabilizing means for stabilizing the focus of the image pickup means with respect to the detection region. For such purposes, the device preferably comprises fixing means and stabilizing means either by itself or separately. The structure of such means is appropriately designed in accordance with the relationship between the analysis device and the detection region, and is determined according to the shape and size of the living body part where the detection region exists. For example, when the detection region is the capillaries of the lip, the means shown in FIG. 17 can be used. In addition, when the detection area is the capillaries of the finger, FIG.
1 can be used.

Further, according to another aspect of the present invention, the step of illuminating the detection area in the blood vessel, the step of imaging the illuminated detection area, the image captured by the image capturing means are processed, and Blood cell morphology and / or contained in the detection area
Or a step of analyzing the number, wherein the light irradiation step or the imaging step forms one image in the time of the light irradiation or the imaging of 1/10000 to 1/1 billion seconds. An invasive blood analysis method is provided.

[0031]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below in detail with reference to the embodiments shown in the drawings. This does not limit the present invention. Embodiment 1 FIG. 1 is a structural explanatory view showing the structure of Embodiment 1 of the present invention. As shown in FIG. 1, the light irradiation means for illuminating the detection region V of the blood vessel 12 existing inside the skin surface 16 of the living body includes a laser light source 22, an optical fiber 24 and a slit 6.
It consists of zero. The image pickup means for picking up an image of the illuminated detection area V is composed of a CCD 40 with an electronic shutter having a shutter speed of 1 / 100,000 second, a lens 38, a polarizing filter 61, and a video system 44.

Then, the CCD 40 provided in the image pickup means
An analysis unit that processes the image captured by the above and analyzes the morphology and / or number of blood cells contained in the detection region V is
Image processing circuit 46, red blood cell count calculating means 48, average red blood cell volume calculating means 50, hemoglobin amount calculating means 52, hematocrit value calculating means 54A, average hemoglobin amount calculating means 5
4B, average hemoglobin concentration calculation means 54C, white blood cell count calculation means 56A, white blood cell classification means 56B, and blood flow velocity calculation means 57.

Then, the CCD 40 forms one frame image every time the detection area V illuminated by the laser light is imaged at an imaging time (shutter speed) of 1 / 100,000 second. In this embodiment, as shown in FIG. 2, the light irradiation means forms a thin detection region V having a cross-sectional area S and a thickness T in a cross section in a cross section oblique to the blood flow direction 14 of the blood vessel 12. And the blood cells present in the region V are imaged. Note that in FIG. 1, the skin surface 16 and below are illustrated in an enlarged manner for convenience.

The light source 22 is housed in the analyzer body 20. In addition, the tip of the optical fiber 24, the slit 6
0, the CCD 40, the lens 38, and the polarization filter 61 are housed in the probe 58. The laser light emitted from the light source 22 is emitted from the tip of the optical fiber 24 and then the slit 6
It is regulated by 0 and becomes a thin strip-shaped light beam (slit light) having a thickness T and irradiates a living body. The transparent plate 66 made of plastic or glass is used to obtain a stable image by bringing the probe tip 59 into close contact with the skin surface 16.

When the light beam (slit light) crosses the blood vessel 12, only a specific area of the blood vessel is illuminated and the detection area V
Is formed. The reflected light from the region V is the polarization filter 6
The image received by the light receiving surface of the CCD 40 via the lens 1 and the lens 38 and captured is recorded in the video system 44 via the transmission path 42. Here, in order to image the reflected light from the region V from the direction of the sliced cross section 62, a tilt photographing method known as a photographing technique by a camera is applied. That is, the cross section 62, the lens 38, and the CCD
Since the image pickup surface of 40 is in a positional relation with respect to the optical axis so that tilting photographing can be performed, a focused image is taken on the entire cross section 62.

The cross-sectional area S is obtained by dividing the image area of the imaged cross-section by the square of the imaging magnification. Since the thickness T, that is, the thickness of the strip-shaped light beam is known from the slit width of the slit 60, the volume of the region V can be calculated.

Alternatively, the image of the taken cross section may be cut out in a window having a predetermined area, and the value obtained by dividing the window area by the square of the imaging magnification may be multiplied by the thickness T to obtain the volume of the region V.

Since the thickness T of the region V is formed to be thin, for example, about 10 microns, it is not likely that the blood cells are overlapped on the planar image picked up by the CCD, but even if they are overlapped, two blood cells will be formed. It is easy to identify blood cells one by one on the image by image processing unless the two completely overlap each other.

Although it is possible to calculate the number of blood cells from only one (one frame) image as described above, in this embodiment, in order to improve the accuracy of analysis, a dozen or several hundreds of blood cells can be calculated. The frame images are shot continuously. In other words, originally, it is necessary to obtain the blood cell distribution in a wide range in the blood vessel and calculate each index based on it, but instead of this, here, the blood cell is obtained from a plurality of images of the same detection area in the blood vessel continuously captured. The distribution is calculated and statistically reliable indices are calculated based on the distribution.

When an image intensifier with a high-speed gate is used as the image pickup means, a clear image can be obtained even when the light irradiation amount on the blood vessel is small, so that there is no fear of burns due to light irradiation on the living body. Also, the light source may be of low power.

As shown in FIG. 1, the optical system is integrally housed in one probe 58, so that the probe 58 is compact and easy to handle, and the probe tip 59 is pressed against the skin surface 16 through the transparent plate 66 for measurement. Is possible.

FIG. 17 is an explanatory view showing a state in which the probe 58 is attached to the attachment device and fixed to the subject to measure blood vessels in the lip portion, and 100a fixes the probe attachment device 100 to the forehead of the subject. A forehead fixing portion 100b is a jaw fixing portion for fixing the probe mounting apparatus 100 to the subject's jaw. As shown in the figure, when the probe mounting device is used to bring the probe 58 into close contact with the lip as a detection region via a stabilizing means, for example, a transparent plate 66, the tip of the probe 58 is moved by the frictional action of the transparent plate 66. Since the microscopic vibration between the tip of the probe 58 and the lip is suppressed by being fixed to the skin surface of the subject, the focus of the imaging system is stabilized and mechanical blurring of the detection area is prevented.

Further, if the light receiving system is provided with the polarization filter 61, unnecessary scattered light components can be removed, and an image with better contrast can be obtained. At this time, even if the irradiation system does not have a polarization filter, the contrast can be improved significantly by only the filter of the light receiving system. However, a polarization filter should be provided in the irradiation system, or a linearly polarized laser should be guided by a polarization maintaining fiber. Preference is given to using the method.

In FIG. 1 and FIG. 2, the detection volume region V is formed in a sliced shape in a cross section oblique to the blood flow direction 14 of the blood vessel 12, but as shown in FIG. The region V may be formed in a thin slice columnar shape having a diameter W and a thickness T in a cross section perpendicular to the blood flow direction 14. Also in this case, when the tilt imaging is performed as in FIG. 1, an image of a cross section perpendicular to the blood flow direction of the blood vessel is captured. The diameter W is determined by the blood vessel diameter, and the thickness T is determined by the beam width of the irradiation system. When it approximates a perfect circle of an image of a sliced cross section of a blood vessel, the cross sectional area is simply calculated from the diameter W. When the cross-sectional shape is out of the perfect circle, the cross-sectional area S may be obtained as in the case of FIG.

In both cases of FIG. 2 and FIG. 3, the entire area V may not fit in the image pickup screen. That is, FIG.
As shown in, the case where only a part of the area V'in the area V is displayed in the entire imaging screen. In that case,
The entire image captured on the entire screen can be considered as an enlarged image of the detection area V (V ′ is considered V again).

In this way, the dynamics of blood cells flowing in the blood vessel can be imaged from the blood flow direction of the blood vessel.

In FIG. 1, the video system 44 is CC
A video tape recorder (VTR) for recording the image picked up at D40 is provided. The recorded image is processed by the image processing circuit 46, and then the red blood cell count calculating means 48,
Average red blood cell volume calculation means 50, hemoglobin amount calculation means 52, hematocrit value calculation means 54A, average hemoglobin amount calculation means 54B, average hemoglobin concentration calculation means 54C, white blood cell count calculation means 56A, white blood cell classification means 56B and blood flow velocity calculation means 57. Then, the morphology and / or number including the color tone of the blood cells are analyzed and each value of the blood test item is calculated.

Further, the image processing circuit 46 selectively has various filters, γ correction, interpolation, jitter correction, color tone conversion, color balance correction, white balance, shading correction and the like to perform image preprocessing. .

Next, the red blood cell count calculating means 48 will be described. The means 48 counts the number of red blood cells in the image of the region V to obtain the number of red blood cells in a unit volume (RBC).
Is calculated. The procedure is as shown in the flowchart of FIG. That is, the image of the region V is read frame by frame from the video system 44 as shown in FIG. 8 (step S11), and the read image is cut out in a window of a predetermined size as shown in FIG. 9 (step S1).
2) The red blood cells in the window are recognized and the red blood cell count a in the window is calculated (step S13). Repeat this operation only a predetermined number of frames F, calculated in each case resulting calculated cumulative n number of red blood cells a (step S14, S15), the average erythrocyte count per unit volume _{N o = k o · n /} F Yes (step 16). Here, k _o is a conversion coefficient for calculating the number of red blood cells per unit volume, which is obtained from the window size, the imaging magnification, and the thickness T of the region V. Then, if necessary, by multiplying the correction factor k ₁ to N _o obtained is converted into fibrillation vein (capillaries) the number of red blood cells which correspond from data such as Chuo arteriovenous (RBC) (step S1
7). A known method is used for the image recognition processing of red blood cells in step S3 (for example, Akihide Hashizume et al., "Automatic red blood cell identification algorithm and its evaluation", Medical Electronics and Biotechnology, Vol. 28, No. 1 (March 1990). (See month))
It is also possible to perform subtraction processing between two consecutive captured images in which red blood cells have moved about 0.1 micron (time difference of 1 / 100,000 second with a blood flow of 10 mm per second), and only the edge of moving red blood cells It is also possible to perform red blood cell recognition at higher speed from the two-dimensional difference image in which is extracted and emphasized.

Next, the mean red blood cell volume calculating means 50 will be described. This means 50 calculates the area of each red blood cell from the image, calculates the volume value by multiplying the average value by a predetermined coefficient, and calculates the average red blood cell volume (MCV). The procedure is as shown in the flowchart of FIG. That is, an image is read frame by frame from the video system 44 (step S21), the read image is cut out in a window of a predetermined size (step S22), the red blood cells in the window are recognized, and the diameter d _{i of} each red blood cell is obtained, The average value b is calculated (step S23). This operation is repeated for a predetermined number of frames F to obtain a cumulative total v of the average values b obtained each time (steps S24 and S25), and this cumulative v is divided by the number of frames F to calculate the average diameter v _a. (Step S26), a function f for converting the diameter into the volume
The volume V _o is obtained using (the function obtained experimentally) (step S27). Then, the obtained V _o is _multiplied by the correction coefficient α ₁ to obtain the average erythrocyte volume (MCV) corresponding to the middle and large arteries and veins from the data of venous veins and capillaries (step S18).

Next, the hemoglobin amount calculating means 52 will be described. In this means, the total hemoglobin amount (HGB) per unit volume is calculated from the intensity of incident light on the region V and the intensity of reflected light from the region V according to the following principle. When the incident light intensity is Io (λ) and the reflected light intensity I (λ), I (λ) = Io (λ) · α (λ) × exp ((ε
₁ (λ) Hgb0 ₂ + ε ₂ (λ) Hgb)) (1)

Here, α (λ): scattering term (with wavelength dependence) ε ₁ (λ): absorption coefficient of oxygenated Hgb (with wavelength dependence) ε ₂ (λ): deoxygenated Hgb Absorption coefficient (with wavelength dependence) HgbO ₂ : concentration of oxygenated Hgb Hgb: concentration of deoxygenated Hgb λ: wavelength, and total hemoglobin amount HGB per unit volume is calculated by HGB = HgbO ₂ + Hgb .

Since the scattering term of the equation (1) can be regarded as a constant approximately by selecting an appropriate wavelength λ, if this is set to α ₀ , the equation (1) becomes log (I (λ) / Io). (Λ)) = (ε ₁ (λ) HbO ₂
+ Ε ₂ (λ) Hg + logα ₀ .

By the way, I (λ) / Io (λ) is a value obtained by measurement. ε ₁ (λ) and ε ₂ (λ) are constants with respect to the selected wavelength, and the unknown quantity is HgbO ₂ ,
Since there are three, H and α ₀ , (a) HgbO ₂ and Hgb can be obtained by measuring I (λ) / Io (λ) for three appropriate wavelengths. (B) If α ₀ can be assumed to be constant regardless of the living body, HgbO ₂ and Hgb can be obtained by measuring α ₂ in advance by experimentally determining for two wavelengths (in practice, even if α ₀ is constant, there is a problem. Not). (C) Furthermore, the absorbance is oxygenated and deoxygenated Hg.
If the same wavelength (for example, 525 nm) is selected for b, ε ₁
Since (λ) = ε ₂ (λ), the total hemoglobin amount per unit volume can be obtained by the wavelength. In the field of blood analysis, the total amount of hemoglobin per unit volume is simply referred to as (total) hemoglobin (amount), which will be referred to below.

Based on the above principle, the hemoglobin amount calculating means 52 calculates the total hemoglobin amount (HGB) by any one of the three procedures shown in the flow charts of FIGS. 12 to 14.

First, the procedure shown in FIG. 12 is characterized in that the reflected light intensity I (λ) is obtained from the sum of the image intensities. That is, the image is read frame by frame from the video system 44 and GB is calculated, which is performed by any one of the three procedures shown in the flowcharts of FIGS.

First, the procedure shown in FIG. 12 is characterized in that the reflected light intensity I (λ) is obtained from the sum of the image intensities. That is, an image is read frame by frame from the video system 44 (step S31), the read image is cut out in a window of a predetermined size (step S32), the red blood cells in the window are recognized, and the intensity s of the red blood cell image is obtained (step S32). Step S33). Then, the intensity b of the background of the image is obtained (step S34).

The above operation is repeated for a predetermined number of frames F, and the respective sums S and B of the intensities s and b obtained each time are obtained (steps S35 and S36). Then, the intensity I is calculated by the function g that obtains the intensity I (λ) from the difference between S and B.
(Λ) is calculated (step S37). The function g is obtained experimentally. Next, assuming that Io (λ) is known, the total hemoglobin amount and HGB are obtained from the equation (1) (step 38).

Next, the procedure shown in FIG. 13 is characterized in that the reflected light intensity I (λ) is obtained from the average concentration of red blood cells. That is, an image is read frame by frame from the video system 44 (step S41), the read image is cut out in a window of a predetermined size (step 42), red blood cells in the window are recognized, and the average scatter of one red blood cell image is detected. The light intensity c is obtained (step S43), the above operation is repeated for a predetermined number of frames F, and the cumulative total C of the intensity c obtained each time is obtained (steps S44, 45).
The average scattered light intensity Ca of one red blood cell is calculated (step S46). Then, using a function (experimentally obtained) for obtaining I (λ) from the average intensity Ca and the red blood cell count RBC, I (λ) is obtained (step S47), and Io (λ) is known, and The total hemoglobin amount HGB is calculated from the equation 1) (step S48).

The above two procedures (FIGS. 12 and 13)
Both may be carried out and the one having the smaller difference between the frames may be adopted. When the light source 2 emits light of two wavelengths, the procedure of FIG. 12 or the procedure of FIG. 13 is performed for each wavelength, and the hemoglobin amount is calculated based on the equation (1). In this case, The amount of oxygenated hemoglobin and the amount of deoxygenated hemoglobin can be obtained respectively.

Next, in the procedure shown in FIG.
It is characterized in that the amount of hemoglobin is obtained from the color tone of the image when irradiating with light having a wavelength or white or broadband spectrum. That is, an image is read out one frame at a time from the video system 44, the read-out image is cut out in a window of a predetermined size, red blood cells in the window are recognized, and R (red), G (green) of the red blood cell image,
Each component r, g, b of B (blue) is extracted (step S
51, S52, S53).

The above operation is repeated for a predetermined number of frames F, and the cumulative sum R, R of each of the components r, g, b obtained each time,
G and B are calculated (steps S54 and S55). Then, the average primary color components Ra, Ga, and Ba are obtained (step S56), and the total hemoglobin amount HGB is calculated using the function f obtained experimentally in advance (step S57).

Next, the hematocrit value calculating means 54A will be described. This means calculates the hematocrit value HCT by calculating the following equation. HCT = α ₂ × (MCV) × (RBC) where MCV is the average red blood cell volume calculation means 50, and RB
C is a value obtained by the red blood cell count calculating means 48,
α ₂ is a correction coefficient for converting from fibrillation to medium and large arteries.

Next, the average hemoglobin amount calculating means 54B will be described. This means calculates the average hemoglobin amount MCH by calculating the following equation. MCH = (HGB) / (RBC) Here, HBC is calculated by the hemoglobin amount calculating means 52.
RBC is a value obtained by the red blood cell count calculating means 48.

Next, the mean hemoglobin concentration calculating means 54c will be described. This means 54c calculates the average hemoglobin concentration MCHC by calculating the following formula: MHCH = (HGB) / (HCT) where HGB is the hemoglobin amount calculation means 52.
HCT is a value obtained by the hematocrit value calculating means 54A.

Next, the white blood cell count calculating means 56A will be described. The means 56A recognizes white blood cells in the image of the region V and counts the number of white blood cells to calculate the number of white blood cells in a unit volume. The procedure is based on red blood cell count (RB
Although the description is omitted because it is the same as the calculation procedure of C) (FIG. 10), the number of frames F needs to be increased because white blood cells are smaller (about one thousandth) than red blood cells.

Next, the white blood cell classification means 56B will be described. In this means 56B, white blood cells are classified into lymphocytes, monocytes, neutrophils, eosinophils, basophils, etc. based on their morphological characteristics. The procedure is as shown in the flowchart of FIG. That is, an image is read frame by frame from the video system 44 (step S61), the read image is cut out in a window of a predetermined size (step S62), and white blood cells in the window are recognized based on the scattered light intensity and color tone (step). S63). Then, the characteristic parameters (size, shape, nucleus size, nucleus shape, etc.) of individual white blood cells are obtained (step S64), and classification is performed according to the obtained characteristic parameters (step S65). The above operation is repeated for the predetermined number of frames F to calculate each classification ratio (step S65).

Next, the blood flow velocity calculation means 57 will be described. As shown in FIGS. 2, 3, and 4, the means 57 is adapted to obtain a cross-sectional image of a blood vessel, so that blood flow is performed by the principle shown in FIG. 16 (zero-cross method extended to space). The speed is calculated. That is, when a particle passes in the direction of arrow M through a detection region V partitioned by parallel planes A and B having a distance T as shown in FIG. 16A, it is observed from the direction of arrow N. To do. As shown in FIG. 7B, 10 particles are observed at time t, and after time Δt, particles (1) and (9) close to the plane A escape from the region V, and at time t When the particles (11) that are close to the plane B on the outside enter the region V, the newly appearing particles within the time Δt with respect to the region V are as shown in (b) of FIG. 16 and (c) of FIG. If the difference is taken, it becomes clear as shown in FIG. Therefore,
If the distribution density of particles is constant, the frequency of appearance and disappearance of particles in the region V is proportional to the velocity of particles. That is,
The higher the speed, the higher the number of haunts, and the lower the number.

Therefore, the average number of particles observed is Na,
Assuming that the average of the number of particles appearing in the difference between the images observed at time t and t + Δt is Aa, only Aa / 2 will leave the region V at Δt time. Since the time required for all Na particles to move by the distance T is 2Δt · Na / Aa, the average velocity Xa of the particles is Xa = T · Aa / (2Δt · Na) (2) Given in. Here, Δt is a preset value, and T is known.

Using this principle, the means 57 reads the image from the video system 44, obtains Na and Aa for the imaged red blood cells, and calculates the blood flow velocity by the equation (2).

The various blood cell information (calculated values) thus obtained are all multiplied by the correction coefficient obtained experimentally to obtain the blood adopted in the middle and large arteries and veins which have been clinically used conventionally. It can be converted into information.

Embodiment 2 FIG. 5 is a structural explanatory view showing an essential part of Embodiment 2 of the present invention. As shown in FIG. 6, the light irradiation means makes the blood flow direction 14 parallel to the blood vessel 12. , A width W, a length L, and a thickness T are formed into a thin detection region V, and the number of blood cells present in the region V is counted. Also in FIG. 5, the skin surface 16 and below are drawn in an enlarged scale for convenience. In FIG. 5, the blood flow direction of the blood vessel 12 is perpendicular to the paper surface. The analyzer main body 20 is similar to that shown in FIG.

The light emitted from the light source 22 in the analyzer body 20 illuminates the diffuser 26 via the optical fiber 24. The light is diffused by the diffuser 26 and illuminates the plate 28 uniformly. The plate 28 substantially becomes a surface light emitter, and the lenses 30, 32, the dichroic mirror 3 are formed.
The real image 3 of the plate 28 is passed through the optical system formed by 4.
6 are formed across the blood vessel 12. In addition, plate 2
8 is a light diffusing plate, for example, a frost type diffusing plate manufactured by Sigma Optical Material Co., Ltd.

The thickness of the real image 36 of the plate 28 is T. The area where the real image 36 of the plate 28 and the blood vessel 12 intersect is the detection area V.

In order to secure the contrast between the brightness of the real image 36 and the brightness other than that of the real image 36, at least the irradiation optical path from the skin surface 16 to the real image 36 may be sharply narrowed.

The width W of the region V is equal to the diameter of the blood vessel in the case of FIGS. The length of the area V in FIG. 5 in the plane of the drawing is L (see FIG. 6). The length L is determined by the degree of stop of the light irradiation system.

The reflected light from the area V is received by the CCD 40a via the dichroic mirror 34 and the lens 38a. By analyzing the image captured by the CCD 40a, as shown in FIG.
As in the case of FIG. 2, the value of each item of the blood test is obtained from the morphology and / or number of blood cells in the image of the region V.

In FIGS. 5 and 6, the real image 3 of the plate is shown.
6 illustrates the case where the blood vessel 12 intersects with the blood vessel 12, but when the blood vessel diameter is large, the real image 36 of the plate 28 may be formed completely inside the blood vessel 12 as shown in FIG. 7.
In this case, the real image 36 of the plate itself becomes the detection area V.

In the case of FIG. 6 and the case of FIG.
The enlargement magnification of the imaging system may be too high to fit the entire detection volume region V within the imaging screen. In that case, the entire image captured in the entire imaging screen may be considered as an enlarged image of the detection area V again. In that case, the width W and the length L of the region V
The actual size of is calculated by dividing the width and height of the screen by the magnification of the image pickup system. The thickness T of the region V is the plate 2
The thickness of the real image 36 of 8 is unchanged.

In the embodiment shown in FIG. 5, the plate 2
By forming the real image 36 of No. 8 in the living body, the detection area V
In addition to that, by irradiating the living body with laser light from different directions through a focusing lens and a scanning means so that both focus at a certain depth in the living body (confocal),
The same region V as in FIG. 5 can be formed.

In any case, since light is irradiated only to a certain depth in the living body, the influence of scattered light from other portions of the living body, for example, a portion deeper than the position where the blood vessel to be measured is present is extremely large. Little.

Embodiment 3 FIG. 18 is a structural explanatory view showing Embodiment 3 of the present invention. The configuration of FIG. 18 is obtained by substituting the hematocrit value calculating means 54A and the average red blood cell volume calculating means 50 of the configuration of FIG. 1 with a hematocrit value calculating means 100 and an average red blood cell volume calculating means 101, respectively, and the rest is the configuration of FIG. Is equivalent to

First, the hematocrit value calculating means 100 in this embodiment will be described. The hematocrit value calculating means 100 calculates the hematocrit value (HCT) from the ratio of the area occupied by the red blood cell image within a certain region in the image captured by the video system 44 and processed by the image processing circuit 46. The procedure is as shown in the flowchart of FIG. That is, the image of the region V is read frame by frame from the video system 44 as shown in FIG. 8 (step S71), and the read image is cut out in a window of a predetermined size (step S7).
2) The image in the window is binarized only at the red blood cell portion with an appropriate threshold value (step S73), and the area ratio AR (%) occupied by the red blood cell image is obtained (step S7).
4). This operation is repeated for a predetermined number of frames F (step S76), and the cumulative value h of AR obtained each time is calculated.
Is calculated and divided by F to calculate the average bar h (step S
77), H is calculated using a function f (calculated theoretically and experimentally) that corrects the overlap of red blood cells (step S7).
8). By multiplying H obtained in this way by the correction coefficient α,
The hematocrit value HCT corresponding to the middle and large arteries and veins is obtained from the data of the venules and capillaries (step S7).
9).

Next, the mean red blood cell volume calculating means 101 will be described. This means calculates the following formula to calculate the mean red blood cell volume (MCV). MCV = (HCT) / (RBC) Here, HCT is a value obtained by the hematocrit value calculating means 100, and RBC is a value obtained by the red blood cell count calculating means 48.

In the hematocrit value calculating means 54A of the embodiment shown in FIG. 1, the mean red blood cell volume (MCV) and the red blood cell count (R
The hematocrit value HCT is calculated from BC). In this case, in order to obtain the MCV, it is necessary to recognize each red blood cell and analyze its shape, so that the calculation time becomes relatively long. However, in the hematocrit value calculating means 100 of the embodiment shown in FIG. 18, it is not necessary to individually recognize red blood cells, and the HCT can be obtained directly from the image, so the HCT calculation time is extremely shortened. When the calculation time is shortened, it is possible to analyze multiple screens, and the HCT calculation accuracy is improved.

Embodiment 4 FIG. 20 is a structural explanatory view showing Embodiment 4 of the present invention. The same elements as those in FIG. 1 have the same reference numerals. In FIG. 20, light emitted from the light source in the analyzer body 20 is transmitted through the optical fiber 24 to the probe 58.
It is guided inside and illuminates the diffuser 26. The light is diffused by the diffuser 26 and converted into parallel light by the collimator lens 30.

The central portion of the parallel light is shielded by the disc-shaped light shielding plate 67, and the peripheral portion of the parallel light is ring-shaped mirror 34a.
And is emitted from the probe tip 59 via 34b. The light emitted from the probe tip 59 illuminates the detection region V in the blood vessel 12 through the transparent plate 66 and the skin surface 16.
The reflected light from the area V is transmitted through the transparent plate 66 and the objective lens 3.
The light is received by the CCD 40a via 8b. CCD 40a
The image captured in (1) is analyzed by the analyzer body 20. The analyzer main body 20 has already been described in the first embodiment, and thus the description thereof is omitted here.

The feature of the fourth embodiment is that the detection area is illuminated by ultra-illumination, that is, dark field illumination, and the contrast of a captured image is improved. The dark-field illumination here means that the illumination light is detected from the outside of the objective lens 38b as shown in FIG.
It is a lighting system that irradiates the. That is, the illumination light illuminates the area V at angles ψ1 and ψ2 larger than the opening angle θ of the objective lens 38b with respect to the detection area V. Therefore, of the illumination light, the light reflected on the skin surface 16 is reflected to the outside of the objective lens 38b and does not reach the CCD 40a.
The contrast of the image captured by D40a is improved.

FIG. 21 is an explanatory view showing a state in which the probe 58 shown in FIG. 20 and a part of the subject (herein, the fingernail cage) are fixed relatively to each other, and the L-shaped support base 71 is the probe. It is attached to 58. The probe tip 59 includes a tube 59a extending from the probe 58 and a sliding tube 59b mounted on the tube 59a so as to be slidable in the directions of arrows a and b on the outer circumference of the tip. A transparent plate 66 is attached to the tip of the sliding cylinder 59b.
Is fixed. A sliding cylinder 59b is provided at the tip of the cylinder 59a.
Springs 72a and 72b for urging the arrow mark in the direction of arrow b are provided. The inner cylinder 73a contains the objective lens 38b and the ring mirror 34b, and is fixed to the probe 58 via the fine movement element 74. Here, the support base 71 is a cylinder 59.
A, the sliding cylinder 59a, the springs 72a and 72b and the transparent plate 66 constitute a fixing means, and the sliding cylinder 59b, the springs 72a and 72b and the transparent plate 66 also constitute a stabilizing means.

As shown in FIG. 21, the subject's finger 75 is placed on the support base 7 as shown in FIG.
1 and the transparent plate 66, the spring 72
The a and 72b press the transparent plate 66 against the nail shell of the finger 75 with an appropriate pressure. As a result, the detection region in the blood vessel of the nail fold is fixed in the visual field of the CCD 40a, and the detection region is prevented from blurring due to minute vibration of the finger 75.

The focus of the CCD 40a can be adjusted by moving the lens 38b in the optical axis direction (arrow a or b direction) by the fine movement element 74.
The fine movement element 74 is, for example, an element P-720 / P-721 (manufactured by Physik instrumente) using a piezo element.
An element using an ultrasonic motor or the like can be applied.

The transparent plate 66 is detachably attached to the probe tip 59 so that it can be replaced for each subject. The transparent plate 66 can be replaced in this manner for hygiene reasons (to protect the subject from infection of a disease, etc.). As the transparent plate 66, a glass plate, a flexible film made of resin, or the like can be used. Alternatively, the transparent plate 66 itself may not be replaced, and a replaceable film may be closely attached to the finger 75.

Further, in order to prevent irregular reflection on the skin surface 16 and obtain a clearer image, a liquid or gel-like optical medium 76 which is safe for the living body is provided between the skin surface 16 and the transparent plate 66 as shown in FIG. It is more preferable to interpose between the two.
Oil or cream can be used as the optical medium 76. In the present embodiment, the transparent plate 66 was brought into contact with the living body. However, if the central portion has a hole (light path) through which light can pass, blurring of the detection area can be prevented even with an opaque plate. It can be used.

[0094]

According to the present invention, a blood image of a predetermined volume of blood in a blood vessel can be taken non-invasively without collecting blood from a living body, and the unit volume can be obtained by analyzing the image. The number of blood cells per hit can be counted, and the hematocrit value, the amount of hemoglobin, and the red blood cell constant can also be calculated. Furthermore, the white blood cells can be classified because the image obtained is clear even though the image is taken from outside the body.

[Brief description of drawings]

FIG. 1 is a configuration explanatory view showing a first embodiment of the present invention.

FIG. 2 is an explanatory diagram showing an example of a detection area.

FIG. 3 is an explanatory diagram showing an example of a detection area.

FIG. 4 is an explanatory diagram showing an example of a detection area.

FIG. 5 is a structural explanatory view showing a main part of a second embodiment of the present invention.

FIG. 6 is an explanatory diagram showing an example of a detection area.

FIG. 7 is an explanatory diagram showing an example of a detection area.

FIG. 8 is an explanatory diagram showing a captured image.

FIG. 9 is an explanatory diagram showing a situation where an image is cut out in a window.

FIG. 10 is a flowchart showing a red blood cell count calculation procedure.

FIG. 11 is a flowchart showing an average red blood cell volume calculation procedure.

FIG. 12 is a flowchart showing a hemoglobin calculation procedure.

FIG. 13 is a flowchart showing a hemoglobin calculation procedure.

FIG. 14 is a flowchart showing a hemoglobin calculation procedure.

FIG. 15 is a flowchart showing a white blood cell classification procedure.

FIG. 16 is an explanatory diagram showing a blood flow velocity calculation principle.

FIG. 17 is an explanatory diagram showing a mounting example of the probe in the example.

FIG. 18 is a structural explanatory view showing a third embodiment of the present invention.

19 is a flow chart showing a hematocrit value calculation procedure of the embodiment shown in FIG.

FIG. 20 is a structural explanatory view showing Embodiment 4 of the present invention.

FIG. 21 is an explanatory diagram showing a modified example of the embodiment shown in FIG. 20.

22 is an explanatory diagram showing a main part of FIG. 21. FIG.

23 is a partially enlarged view of FIG. 20.

[Explanation of symbols]

 12 blood vessel 14 blood flow direction 16 skin surface 20 analyzer body 22 light source 24 optical fiber 38 lens 40 CCD 42 transmission line 44 video system 46 image processing circuit 48 red blood cell count calculating means 50 average red blood cell volume calculating means 52 hemoglobin amount calculating means 54A hematocrit Value calculating means 54B Average hemoglobin amount calculating means 54C Average hemoglobin concentration calculating means 56A White blood cell count calculating means 56B White blood cell classifying means 57 Blood flow velocity calculating means 58 Probe 60 Slit 61 Polarizing filter 66 Transparent plate

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Mitsuru Watanabe 72-1 Minatojima Nakamachi, Chuo-ku, Kobe Toa Medical Electronics Co., Ltd. (72) Kaoru Asano 7-2 Minatojima Nakamachi, Chuo-ku, Kobe No. 1 Toa Medical Electronics Co., Ltd. (72) Inventor Akio Suzuki 72-1 Minatojima Nakamachi, Chuo-ku, Kobe City No. 1 Toa Medical Electronics Co., Ltd. No. 2-1 Toa Medical Electronics Co., Ltd.

Claims (24)

[Claims] 1. A light irradiation unit that illuminates a detection region inside a blood vessel included in a part of a living body, an imaging unit that images the illuminated detection region, and an imaging unit and a part of the living body relative to each other. The fixing means for fixing, the stabilizing means for stabilizing the focus of the imaging means with respect to the detection area, and the image captured by the imaging means are processed to determine the morphology and / or number of blood cells contained in the detection area. The light irradiation means or the image pickup means is provided with an analyzing means for analyzing,
A non-invasive blood analyzer configured to form one image with a light irradiation or imaging time of seconds. 2. The non-invasive blood analyzer according to claim 1, wherein the stabilizing means includes a translucent member that comes into contact with a part of the living body, and the imaging means images the detection area through the translucent member. 3. The noninvasive blood analyzer according to claim 2, wherein the translucent member is a translucent plate or a flexible film. 4. The non-invasive blood analyzer according to claim 2, wherein the stabilizing means further comprises a liquid or gel optical medium interposed between the translucent member and a part of the living body. 5. The non-invasive blood analyzer according to claim 1, wherein the imaging means further comprises adjusting means for adjusting the focus on the detection region. 6. The image pickup means comprises an objective lens for condensing light from the detection area, and the light irradiation means illuminates the detection area at an angle larger than an opening angle of the objective lens with respect to the detection area. The non-invasive blood analyzer according to claim 1. 7. An imaging system, wherein the imaging means collects the reflected light from the detection region, and an imaging device for receiving the collected light.
The non-invasive blood analyzer according to claim 1, comprising image recording means for recording an image picked up by the image pickup device. 8. The non-invasive blood analyzer according to claim 1, wherein the detection region includes a volume region capable of individually optically distinguishing blood cells. 9. The non-invasive blood analyzer according to claim 1, wherein the detection region is a region partitioned by a cross section perpendicular or oblique to the blood flow direction of the blood vessel. 10. The non-invasive blood analyzer according to claim 1, wherein the imaging means is configured to collect and image in a direction non-parallel to the light irradiation direction of the light irradiation means. 11. The non-invasive blood analyzer according to claim 7, wherein the imaging surface of the detection region and the imaging surface of the imaging element are arranged so as to allow tilting imaging. 12. The non-invasive blood analyzer according to claim 1, wherein the light irradiation means and the imaging means are configured so that the detection region is imaged at predetermined time intervals. 13. The non-invasive blood analyzer according to claim 1, wherein the imaging means comprises a polarizing means for removing unnecessary scattered light components from the detection region. 14. The light irradiating means comprises a polarizing means for illuminating the detection area with polarized light.
The non-invasive blood analyzer described. 15. The non-invasive blood analyzer according to claim 1, wherein the analyzing means analyzes the number of red blood cells and / or white blood cells. 16. The noninvasive blood analyzer according to claim 1, wherein the analyzing means calculates a hematocrit value. 17. The non-invasive blood analyzer according to claim 1, wherein the analyzing means further comprises a light intensity analyzing means for analyzing the reflected light intensity, and the hemoglobin amount is calculated thereby. 18. The non-invasive blood analyzer according to claim 1, wherein the analyzing means calculates the average red blood cell volume from the morphology of red blood cells. 19. The non-invasive blood analyzer according to claim 1, wherein the analyzing means is configured to analyze and classify the morphology of blood cells. 20. The non-invasive blood analyzer according to claim 1, wherein the analyzing means converts blood cell information obtained from the venules or capillaries into blood cell information corresponding to the middle and large arteries and veins. 21. The non-invasive blood analyzer according to claim 1, wherein the analyzing means comprises means for calculating a hematocrit value from a ratio of an area occupied by a red blood cell image in a fixed region in the captured image. . 22. The analyzing means comprises means for calculating a hematocrit value and a red blood cell count, and then calculating an average red blood cell volume by dividing the calculated hematocrit value by the red blood cell count. Item 2. The non-invasive blood analyzer according to Item 1. 23. A step of relatively fixing the imaging means and a part of the living body, a step of illuminating a detection area in a blood vessel included in the part of the living body, and a focus of the imaging means with respect to the detection area. A stabilizing step; a step of capturing an image of the detection area by an image capturing means; a step of processing the image captured by the image capturing means to analyze the morphology and / or number of blood cells contained in the detection area, The non-invasive blood analysis method, wherein the light irradiation step or the imaging step forms one image in the time of the light irradiation or the imaging of 1 / 10,000 to 1 / 1.0 billion seconds. 24. A step of stabilizing the focus and a step of imaging the detection region respectively include a step of bringing a translucent member into contact with a part of the living body, and an image of the detection region via the translucent member. 24. The non-invasive blood analysis method according to claim 23, further comprising the step of: