WO2018110005A1 - Procédé de détermination d'une ligne de délimitation de classification dans un nuage de points concernant des cellules sanguines et dispositif d'analyse de sang comprenant une unité de traitement pour mettre en œuvre le procédé - Google Patents

Procédé de détermination d'une ligne de délimitation de classification dans un nuage de points concernant des cellules sanguines et dispositif d'analyse de sang comprenant une unité de traitement pour mettre en œuvre le procédé Download PDF

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WO2018110005A1
WO2018110005A1 PCT/JP2017/032821 JP2017032821W WO2018110005A1 WO 2018110005 A1 WO2018110005 A1 WO 2018110005A1 JP 2017032821 W JP2017032821 W JP 2017032821W WO 2018110005 A1 WO2018110005 A1 WO 2018110005A1
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boundary line
determination
scattergram
determination index
initial
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PCT/JP2017/032821
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English (en)
Japanese (ja)
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正志 西森
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株式会社堀場製作所
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/10—Investigating individual particles
    • G01N15/14—Optical investigation techniques, e.g. flow cytometry
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/483—Physical analysis of biological material
    • G01N33/487—Physical analysis of biological material of liquid biological material
    • G01N33/49—Blood

Definitions

  • the present invention relates generally to analysis of blood cells, and in particular, a method for determining a boundary line that distinguishes two or more different types of blood cells in a scattergram showing the distribution of blood cells, and to perform the method
  • the present invention relates to a blood analyzer having the processing section.
  • Blood cells such as red blood cells, platelets, and white blood cells change in various ways reflecting the state of the living body. For this reason, the frequency distribution regarding the number, form, ratio, etc. of various blood cells is an important measurement item in diagnosis for medical treatment.
  • the white blood cell classification display method using a scattergram such as the LMNE matrix can measure up to 5 white blood cells using various techniques such as staining, impedance, and optical techniques, and visually capture the classification results. Is an important technique for determining various diseases (eg, leukemia, malignant lymphoma, multiple myeloma, etc.) that reflect different blood cell counts, ratios, etc. Patent Document 1).
  • various diseases eg, leukemia, malignant lymphoma, multiple myeloma, etc.
  • the LMNE matrix is composed of four types of leukocytes stained using cell staining techniques such as fat staining and peroxidase staining, that is, lymphocytes (L: Lymphocyte), monocytes (M: Monocyte), and neutrophils (N: Neutrophil), a kind of scattergram for eosinophils (E).
  • FIG. 5 is a diagram showing a typical display example of the LMNE matrix, in which the volume and absorbance of each blood cell in the sample in which the four types of blood cells are mixed are measured, and the measurement for each obtained blood cell is performed.
  • Data is a graph plotted on an XY plane composed of an X axis (horizontal axis corresponding to volume) and a Y axis (vertical axis corresponding to absorbance). Even if the sample is a mixture of the above four types of blood cells, when the data pair (volume, absorbance) of each blood cell is plotted as an LMNE matrix, the plotted dots are clearly four types of blood cells as shown in FIG. Divided into four groups corresponding to. Therefore, various diseases can be determined from the distribution of each group.
  • Patent Documents 2 to 5 Several devices and methods for automatically setting the position of the classification boundary line in blood cell analysis have been proposed (for example, Patent Documents 2 to 5). However, automatic setting of the classification boundary line according to the prior art has not been sufficient in terms of accuracy.
  • JP 2000-329685 A Japanese Patent Laid-Open No. Sho 62-134559 JP-A-2-304361 JP-A-2-304363 JP-A-4-332847
  • the present invention has been made in view of the above-described problems in the prior art, and determines a boundary line that distinguishes two or more different types of blood cells in a scattergram showing the distribution state of blood cells with excellent accuracy. It is an object to provide a blood analyzer having a method for performing the method and a processing unit for performing the method.
  • the present inventor has conducted intensive studies to solve the above-mentioned problems.
  • the initial boundary line empirically determined is translated and displaced (that is, the initial boundary line is not rotated). It has been found that by moving the boundary line parallel to the X axis and / or parallel to the Y axis, it is possible to search for a boundary line that can accurately distinguish two or more different types of blood cells of interest.
  • the present inventor further selects a boundary line in which the number of dots existing in the entire region or in the vicinity of a specific portion of the initial boundary line and the moved boundary line is small in the search as a target boundary line candidate. Found that can be given as.
  • the present inventor has further studied based on such findings and has completed the present invention.
  • a blood analyzer which includes a boundary line determination unit that determines a boundary line that separates two or more different types of blood cells in a scattergram relating to blood cells
  • the boundary line determination unit Scattergram S 0 is created based on the measurement data of the blood cells, and, the initial boundary line B 0 predetermined for distinguishing two or more different types of blood cells of interest in the scattergram S 0
  • Initial setting part to accept, A set of displacement amounts ( ⁇ x i , ⁇ y i ) in the X-axis direction and Y-axis direction (i indicates a serial number of the translational displacement pattern) for translationally displacing the initial boundary line B 0 in one or more patterns.
  • Displacement amount set setting section to be set, Using a predefined method for determining a reliability determination index as a target boundary line, the determination index I 0 regarding the initial boundary line B 0 and 1 received from the displacement set setting unit For each of the above displacement amounts ( ⁇ x i , ⁇ y i ), one or more boundary lines generated based on translational displacement of the initial boundary line B 0 by ⁇ x i in the X-axis direction and ⁇ y i in the Y-axis direction.
  • a determination index determination unit that determines a determination index I i for B i , and Based on the determination index I 0 determined by the determination index determination unit and the one or more determination indexes I i , the initial boundary line B 0 and the one or more boundary lines B i as the target boundary line candidates
  • the blood analyzer including a boundary line candidate specifying unit that specifies at least one of the above.
  • the determination index determination unit is a dot counting unit, and the dot counting unit is the number Num of dots in the counting region R 0 defined as the whole or a part of a specific neighborhood region of the initial boundary line B 0.
  • the boundary line candidate specifying unit uses the initial boundary line as a target boundary line candidate on the basis of the small value of the determination index I 0 determined by the dot counting unit and one or more determination index I i.
  • the blood analyzer according to [1] above, which specifies at least one of B 0 and one or more boundary lines B i .
  • the scattergram S 0 is composed of dots plotted on discrete coordinates
  • the boundary line determination unit further includes a recalculation control unit, The recalculation control unit After the process by the determination index determination unit and before the process by the boundary line candidate specifying unit, determine whether recalculation using an additional scattergram is necessary, When it is determined that the recalculation is necessary, the boundary line determination unit is controlled to perform a series of processes again by the initial setting unit, the displacement amount setting setting setting unit, and the determination index determination unit, thereby Re-determining the determination index I 0 and one or more determination indices I i , This process is repeated until it is determined that the recalculation is not necessary.
  • a different additional scattergram S 0 ′ is used for each recalculation, and the additional scattergram S 0 ′ is , And is generated by subtracting a predetermined number of dots at each position on the discrete coordinates of the scattergram S 0 ,
  • the determination index as a target boundary line candidate based on the determination index I 0 determined in the last process by the determination index determination unit and one or more determination indexes I i
  • At least one of the initial boundary line B 0 and the one or more boundary lines B i in the final processing by the determination unit is identified;
  • the blood analyzer according to any one of [1] to [4] above.
  • a method used to determine a boundary line that distinguishes two or more different types of blood cells in a scattergram relating to blood cells, Scattergram S 0 is created based on the measurement data of the blood cells, and, the initial boundary line B 0 predetermined for distinguishing two or more different types of blood cells of interest in the scattergram S 0
  • Initial setting process to accept, A set of displacement amounts ( ⁇ x i , ⁇ y i ) in the X-axis direction and Y-axis direction (i indicates a serial number of the translational displacement pattern) for translationally displacing the initial boundary line B 0 in one or more patterns.
  • Displacement set setting process to set, Using a predefined method for determining a reliability determination index as a target boundary line, the determination index I 0 related to the initial boundary line B 0 and 1 set in the displacement amount set setting step For each of the above displacement amounts ( ⁇ x i , ⁇ y i ), one or more boundary lines generated based on translational displacement of the initial boundary line B 0 by ⁇ x i in the X-axis direction and ⁇ y i in the Y-axis direction.
  • a determination index determination step for determining a determination index I i for B i , and Based on the determination index I 0 determined in the determination index determination step and the one or more determination indexes I i , the initial boundary line B 0 and the one or more boundary lines B i as the target boundary line candidates
  • the method including the boundary line candidate specifying step of specifying at least one of the above.
  • the determination index determination step is a dot counting step, and in the dot counting step, the number Num of dots in the counting region R 0 defined as the whole or a part of a specific neighborhood region of the initial boundary line B 0.
  • the scattergram S 0 is, has been constructed from the plotted dots on a discrete coordinates
  • the method further includes a recalculation control step, In the recalculation control step, After the determination index determination step and before the boundary line candidate identification step, determine whether recalculation using an additional scattergram is necessary, When it is determined that the recalculation is necessary, the procedure of the method is controlled so as to perform a series of processes by the initial setting step, the displacement amount set setting step, and the determination index determination step again, thereby Re-determining the determination index I 0 and one or more determination indices I i , The above process is repeated until it is determined that the recalculation is not necessary.
  • a different additional scattergram S 0 ′ is used for each recalculation, and the additional scattergram S 0 ′ is Generated by reducing the number of dots at each position on the discrete coordinates of the gram S 0 by a predetermined number;
  • the final determination index is determined as a target boundary line candidate. At least one of an initial boundary line B 0 and one or more boundary lines B i in the determining step is identified; The method according to any one of [7] to [10] above.
  • a method for determining a boundary line that distinguishes two or more different types of blood cells in a scattergram showing a distribution state of blood cells having excellent accuracy and a processing unit for performing the method.
  • a blood analysis device is provided.
  • FIG. 3 illustrates a typical LMNE matrix.
  • translational displacement of the initial boundary lines B 0, illustrates the boundary line B i formed on the basis thereof.
  • a counting region R 0 as defined with respect to the initial boundary line B 0, are defined with respect to the boundary line B i after movement is a diagram for explaining the count region R i corresponding to count region R 0.
  • the counting region R 0 (b) corresponding to the initial boundary line B 0 , the boundary line B i (c) after translation, and the boundary line B i It is a figure explaining counting area
  • FIG. 11A shows an example of the result of the LMNE calculation in the case of using the initial boundary line (Before ⁇ Data) and in the case of using the boundary line after movement according to the present invention (After Data) by the visual (standard) method. It is a figure shown with a result.
  • LYM% lymphocyte%
  • MON% monocyte%
  • NEU% neutrophil%
  • EOS% eosinophil%
  • BAS% basophil%.
  • FIG. 11B shows the scattergram (height: ⁇ 15) finally used for determining the boundary line.
  • the “scattergram relating to blood cells” in the present invention refers to measurement data obtained by measuring blood cells to be analyzed with respect to two measurement items that are X-axis and Y-axis values ( FIG. 6 is a graph in which measurement data for X-axis items and measurement data for Y-axis items) are plotted in correspondence with the XY plane of a scattergram.
  • the combination of the measurement item shown as one axis and the measurement item shown as the other axis is not particularly limited.
  • blood cell volume examples include blood cell absorbance (or light transmittance), (blood cell volume, blood cell fluorescence), (forward scattered light, blood cell fluorescence), (side scattered light, blood cell fluorescence), and the like.
  • blood cells to be displayed as a scattergram include, for example, red blood cells (pre-erythroblasts, basophil erythroblasts, polychromatic erythroblasts, positive erythroblasts, reticulocytes, and reticulocytes, which are pre-maturation stages of erythrocytes. , Including those with abnormal morphologies), platelets (including those with abnormal morphologies such as large platelets, giant platelets), leukocytes (neutrophils, eosinophils, basophils, lymphocytes, monocytes, atypical lymphocytes) Spheres, abnormal lymphocytes, large lymphocytes, immature cells, etc.).
  • lymphocytes, monocytes, neutrophils and eosinophils displayed on the LMNE matrix are important blood cells in diagnosing infections and blood diseases.
  • the combination of two or more different types of blood cells whose boundary line should be determined according to the present invention is not particularly limited, and may be any two or more different types of blood cells that can be displayed on the same scattergram.
  • the combination comprises two or more different types of blood cells that are located in areas close to each other on the scattergram.
  • the combination may be composed of, for example, two or more cell types belonging to leukocytes, specifically, neutrophils, eosinophils, basophils, lymphocytes, monocytes, atypical lymphocytes, abnormalities It may be composed of two or more types of cells selected from lymphocytes, large lymphocytes, and immature cells.
  • Preferred combinations include, for example, combinations of (lymphocytes, monocytes, neutrophils).
  • Measurement of the measurement items as described above can be performed in the same manner as a conventionally known blood analyzer.
  • a set (set) of measurement data (measurement data for the X-axis item, measurement data for the Y-axis item) obtained for the blood cells to be analyzed is left as it is by an electrical and optical measurement device. Since this is a set of output numerical values, conversion processing corresponding to the scales of the X-axis and Y-axis is usually performed so that the target scattergram can be plotted on the XY plane.
  • dot means a dot plotted at an arbitrary coordinate on the scattergram and indicating that a blood cell corresponding to the coordinate is detected in the measurement data.
  • Each dot in the scattergram can be expressed by using two parameters (X coordinate value, Y coordinate value).
  • the scattergram may be composed of dots plotted on discrete coordinates (hereinafter, such a scattergram is also referred to as a discrete scattergram).
  • the discrete coordinates refer to a coordinate system in which the X coordinate value and the Y coordinate value are composed only of discrete numerical values (for example, integers).
  • the discrete scattergram can be created by a process (for example, rounding down after the decimal point) that converts the X coordinate value and the Y coordinate value based on the measurement data into a discrete numerical value.
  • the discrete scattergram can be used, for example, for display of the scattergram on a display device, in which a specific coordinate (a combination of X coordinate value and Y coordinate value) and a specific pixel correspond to each other. is doing.
  • the present invention can be implemented assuming that a plurality of dots are plotted on one coordinate.
  • One or more additional scattergrams can be created from one discrete scattergram.
  • the additional scattergram may be generated by reducing the number of dots at each position on the discrete coordinates of the discrete scattergram by a predetermined number.
  • an additional scattergram S 1 obtained by subtracting the number of dots by 1 from all the coordinates with respect to the discrete scattergram S 0 formed by plotting 0 to F max dots at each coordinate.
  • An additional scattergram S 2 in which the number of dots is reduced by 2 at all coordinates,...,
  • An additional scattergram S Fmax-1 in which the number of dots is reduced by (F max ⁇ 1) at all coordinates, and so on.
  • a series (S 1 , S 2 ,..., S Fmax-1 ) consisting of (F max ⁇ 1) additional scattergrams can be generated.
  • the number of dots at a certain coordinate is zero, it means that there is no dot.
  • the number to be reduced is larger than the number of dots at a certain coordinate, the number of dots at that coordinate may be zero. Needless to say.
  • the additional scattergram generated in this way can be used to additionally search for a target boundary line candidate by recalculation.
  • the “boundary line” refers to a line that can demarcate the boundary between two or more types of blood cells to be classified in the scattergram.
  • N A type that is an object of division (N A 2 or more integers.)
  • Regions in the scattergram blood cells generally present in may be divided into N A number of compartments ( That is, each coordinate in the region may determine whether included in one any of the N a number of compartments).
  • the boundary line may be one that does not divide an area in a scattergram that is considered to have no blood cells that are subject to classification.
  • the boundary line may be formed from a single straight line or curve having no branch, or may be formed from a line having a branch (straight line and / or curve) (in the latter case, the boundary line is It can also be thought of as being formed from two or more lines connected to each other).
  • the boundary line is usually formed from one line or two or more lines connected to each other, but may be formed from two or more lines not connected to each other as appropriate.
  • the “initial boundary line B 0 ” refers to a boundary line that serves as a reference (that is, a start position) for searching for a target boundary line.
  • the initial boundary line B 0 is, for example, a boundary line that is empirically known to be able to roughly classify two or more different types of blood cells of interest in a scattergram created based on measurement data from a normal specimen. There may be.
  • the initial boundary line B 0 is determined by determining the validity of the result of measuring a large number (for example, several hundreds) of samples on the tentatively determined fraction line and correlating with the visual (standard method) case. It may be a thing.
  • the boundary line B i generated based on translational displacement of the initial boundary line B 0 by ⁇ x i in the X-axis direction and ⁇ y i in the Y-axis direction is a line B 0 ′ after translational displacement by ⁇ x i in the X-axis direction and ⁇ y i in the Y-axis direction as defined above (FIG. 6A).
  • FIG. 6B when the moved line B 0 ′ does not fit in the scattergram, only the portion of the line B 0 ′ that fits in the scattergram is defined as the boundary line B i. It is good.
  • FIG. 6B when the moved line B 0 ′ does not fit in the scattergram, only the portion of the line B 0 ′ that fits in the scattergram is defined as the boundary line B i. It is good.
  • FIG. 6B when the moved line B 0 ′ does not fit in the scattergram, only the portion of the line B 0 ′ that fits in the scattergram is defined as the boundary line
  • the region U 3 the line B 0 which moves the initial boundary lines B 0 between the two regions U 1 and U 2 to be subjected to classification 'is not subject to classification when entering the may be a boundary line B i those omitted part that has entered the area U 3 of the line B 0 '.
  • an additional line for example, a point P 4 in FIG. 6C and a point P 4 in FIG. 6C
  • a line supplemented with a line connecting the point P 4 ′ may be used as the boundary line B i .
  • a set of displacement amounts ( ⁇ x i , ⁇ y i ) indicates the movement amounts ( ⁇ x i and ⁇ y i, respectively) in the X-axis direction and the Y-axis direction for translationally displacing the initial boundary line B 0.
  • the set of displacement amounts can be defined as, for example, a rectangular range, but is not limited to this.
  • a set of displacements is defined as a rectangular range for a discrete scattergram, displacement is performed using a minimum displacement ⁇ x min and a maximum displacement ⁇ x max in the X-axis direction, and a minimum displacement ⁇ y min and a maximum displacement ⁇ y max in the Y-axis direction.
  • the magnitudes of the displacement ⁇ x i in the X-axis direction and the displacement ⁇ y i in the Y-axis direction are not particularly limited, and may be appropriately determined in consideration of various factors such as the initial boundary line and the distribution of blood cells to be processed. it can.
  • the displacement ⁇ x i in the X-axis direction and the displacement ⁇ y i in the Y-axis direction may be a positive value, a negative value, or 0, and the negative displacement is a negative direction of the X-axis or the Y-axis. Means moving to.
  • the determination index of reliability as a target boundary line can be used to determine how reliable a given boundary line is as a target boundary line
  • the determination index may be a numerical value, for example.
  • a pre-defined method for determining a reliability determination index as a target boundary line can determine the above determination index for a given boundary line.
  • the determination index is given as the number of dots. Details of a preferred embodiment for determining the number of dots for a given boundary will be described below.
  • the “neighboring region” may be, for example, a set of coordinates whose distance from at least one point included in the entire initial boundary line B 0 or a specific portion is within a predetermined threshold.
  • the counting region R 0 may be a one-dimensional region (ie, a set of points on a line), a two-dimensional region (ie, a region surrounded by a certain closed line), or a combination thereof.
  • the counting region R0 may be composed of one section, or may be composed of two or more divided sections.
  • the “counting region R i corresponding to the counting region R 0 ” defined with respect to the boundary line B i generally means that all points in the counting region R 0 are ⁇ x i in the X-axis direction. Further, it refers to a region R 0 ′ composed of a set of points obtained by translational displacement by ⁇ y i in the Y-axis direction.
  • An example of the counting area R i corresponding to the counting area R 0 shown in FIG. 7A is shown in FIG. In the example of FIG.
  • the counting area R i is obtained from a set of points obtained by translating all the points in the counting area R 0 by ⁇ x i in the X-axis direction and ⁇ y i in the Y-axis direction. This is the same as the region R 0 ′. However, as described above with respect to the boundary line B i , it may not be appropriate to set the area R 0 ′ after movement as the counting area R i (for example, the area R 0 ′ does not fit in the scattergram). The region R 0 ′ enters a region that is not considered, or the region R 0 ′ needs to be partially supplemented). In that case, in accordance with the above description of the border line B i, 'be omitted partial area of the region R 0' region R 0 compensate for additional areas can take processing such as appropriate, it Thus, the counting area R i can be appropriately defined.
  • the blood analysis device of the present invention performs measurement and analysis on a predetermined analysis item for a given blood sample, and generates a scattergram indicating the analysis result. It is preferable to have also.
  • the blood analysis data processing unit may be a conventional blood analysis data processing unit capable of measuring and analyzing a blood sample to generate a scattergram.
  • FIG. 1 is a block diagram showing an example of the configuration of the boundary line determination unit in the blood analyzer of the present invention.
  • the boundary line determination unit 10 is a functional unit for determining a boundary line that separates two or more different types of blood cells in a scattergram relating to blood cells, and includes an initial setting unit 11 and The displacement amount set setting unit 12, the determination index determination unit 13, and the boundary line candidate specifying unit 14 are configured.
  • the initial setting unit 11 is a scattergram S 0 created based on blood cell measurement data, and a predetermined initial value for classifying two or more different types of blood cells as targets in the scattergram S 0 . accept the boundary line B 0.
  • the displacement amount set setting unit 12 includes displacement amounts ( ⁇ x i , ⁇ y i ) (i is a serial number of a translational displacement pattern) for translationally displacing the initial boundary line B 0 in one or more patterns. Set).
  • the determination index determination unit 13 uses a predetermined method for determining a reliability determination index as a target boundary line, and uses the determination index I 0 regarding the initial boundary line B 0 and the displacement amount set setting. 1 is generated based on translational displacement of the initial boundary line B 0 by ⁇ x i in the X-axis direction and ⁇ y i in the Y-axis direction for each of one or more displacement amounts ( ⁇ x i , ⁇ y i ) received from the unit.
  • the boundary line candidate specifying unit 14 determines the initial boundary line B 0 and one or more boundaries as candidate boundary lines based on the determination index I 0 determined by the determination index determination unit and the one or more determination indexes I i. At least one of the lines B i is identified.
  • the determination index determining unit 13 is functionally connected to the initial setting unit 11, the displacement amount setting setting unit 12, and the boundary line candidate specifying unit 14. based on the the scattergram S 0 and an initial boundary line B 0 accepted, a set amount of displacement of the displacement amount set setting section 12 has set, an initial determination indicator for border B 0 I 0 and the boundary line B i Are determined, and these determination indexes are transferred to the boundary line candidate specifying unit 14.
  • the displacement amount set setting unit 12 may set a displacement amount independently of the initial setting unit 11, or the scattergram S 0 and the initial boundary line B received by the initial setting unit 11. A set of displacement amounts may be set using 0 or the result of a predetermined calculation using these. Therefore, in the block diagram of FIG. 1, the initial setting unit 11 and the displacement amount set setting unit 12 are connected by a broken line.
  • each unit constituting the boundary line determination unit (the above-described initial setting unit, displacement amount setting unit, determination index determination unit, boundary line candidate specifying unit, recalculation control unit described later, blood cell calculation unit, etc.)
  • an electronic circuit, an electric circuit, and an independent processing device may be combined, it is a preferred embodiment that each of these units is configured by a program executed by the computer using a computer.
  • the example at the time of comprising the said boundary line determination part using a computer is given, and the preferable aspect of each part which comprises a boundary line determination part is demonstrated.
  • the configuration of each unit described below can be implemented partially or entirely in combination with an electronic circuit, an electric circuit, an independent processing device, and the like instead of a computer.
  • Initial setting unit 11 receives the scattergram S 0 and an initial border B 0.
  • receiving the scattergram S 0 it is performed by accepting a scattergram generated by the data processing unit for blood analysis blood analysis device of the present invention via an electrical or electronic communications.
  • reception of the scattergram S 0, for example, may be performed by reading the scattergram stored in a storage device such as a hard disk.
  • the initial boundary line B 0 can be received, for example, by storing a parameter related to the initial boundary line empirically determined in advance in a storage device such as a hard disk and reading it out.
  • the initial setting unit 11 may be configured to accept other classification boundary lines that are not targets of position determination according to the present invention, in addition to the initial boundary lines used for position determination by translational displacement.
  • the displacement amount set setting unit 12 includes displacement amounts ( ⁇ x i , ⁇ y i ) (i is a serial number of a translational displacement pattern) for translationally displacing the initial boundary line B 0 in one or more patterns. Set).
  • the displacement amount set setting unit 12 can be performed, for example, by reading a set of predefined displacement amounts ( ⁇ x i , ⁇ y i ) stored in a storage device such as a hard disk.
  • the displacement amount set setting unit 12 may be configured to receive an input regarding a set of displacement amounts ( ⁇ x i , ⁇ y i ) from the user.
  • the displacement amount set setting unit 12 is configured to set a set of displacement amounts ( ⁇ x i , ⁇ y i ) based on the scattergram S 0 and / or the initial boundary line B 0 received by the initial setting unit 11. It may be. For example, the displacement set setting unit 12 determines the abundance ratio of each type of blood cell based on the scattergram S 0 , the initial boundary line B 0 , and / or other classification boundary lines received by the initial setting unit 11.
  • a blood cell calculation unit (not shown; for example, an LMNE calculation unit that calculates the abundance ratio of at least lymphocytes, monocytes, neutrophils, and eosinophils in the LMNE matrix), or
  • the set of displacement ( ⁇ x i , ⁇ y i ) may be set using the calculated existence ratio of one or more kinds of blood cells, which may be functionally connected to the blood cell calculation unit. It may be configured. Specifically, for example, as shown in the examples described later, in the determination of the boundary line between lymphocytes, monocytes, and neutrophils in the LMNE matrix, for example, displacement based on the presence ratio of neutrophils A set of quantities ( ⁇ x i , ⁇ y i ) may be set.
  • the determination index determination unit 13 is based on the scattergram S 0 and the initial boundary line B 0 received by the initial setting unit 11 and the set of displacement amounts ( ⁇ x i , ⁇ y i ) set by the displacement amount set setting unit 12. determining a judgment index I i for determination index I 0 and the boundary line B i of the initial boundary line B 0.
  • the determination index is given as the number of dots, and the number of dots is determined by a dot counter described below. Therefore, preferably, the determination index determination unit 13 is a dot counting unit 13 ′.
  • the dot counting unit 13 ′ counts the number of dots Num (R 0 ) in the above-described counting region R 0 and sets the number Num (R 0 ) as a determination index I 0 .
  • the dot counting unit counts the number Num (R i ) of dots in the one or more counting regions R i described above, and uses the number Num (R i ) as a determination index I i .
  • the order of these count processes is not particularly limited.
  • the boundary line candidate specifying unit 14 Based on the determination index I 0 determined by the determination index determination unit 13 and one or more determination indexes I i , the boundary line candidate specifying unit 14 sets initial boundary lines B 0 and one or more target boundary lines as candidates. At least one of the boundary lines B i is specified.
  • the boundary line candidate specifying unit 14 may determine one target boundary line based on the specified one or more boundary line candidates, or presents the specified one or more boundary line candidates to the user.
  • the user may be configured to determine a target boundary line based on the candidate.
  • the identified boundary line candidate or boundary line can be output to the user through an output device such as a display device.
  • the boundary line determination unit 10 calculates a blood cell calculation that calculates the presence ratio of each type of blood cell based on the scattergram S 0 , the identified boundary line candidate or boundary line, and / or other classification boundary line. May include a unit (not shown; for example, the above-described LMNE calculation unit), or may be functionally connected to the blood cell calculation unit.
  • the boundary line candidate specifying unit 14 determines the determination index I 0 determined by the dot counting unit 13 ′ and the values of one or more determination indexes I i (that is, the number Num (R 0 ) and a small number of one or more Num (R i )) as a reference, at least one of the initial boundary line B 0 and one or more boundary lines B i as a target boundary line candidate May be specified.
  • the boundary line candidate specifying unit 14 determines a boundary line to which the determination index I 0 and one or more determination indices I i give a minimum value as a target boundary line.
  • the boundary line candidate specifying unit 14 may be configured to select one boundary line according to a predefined criterion when there are two or more such boundary lines. Examples of the reference include selecting a boundary line having the smallest displacement distance (that is, (( ⁇ x i ) 2 + ( ⁇ y i ) 2 ) 1/2 ) from the initial boundary line B 0 .
  • FIG. 2 is a flowchart showing an example of the boundary line determination method of the present invention.
  • the embodiment shown in the flowchart of FIG. 2 can be executed using the boundary line determination unit 10 of the embodiment shown in the block diagram of FIG. Therefore, all the embodiments described above with respect to the boundary line determination unit 10 can be applied to the boundary line determination method of the embodiment shown in the flowchart of FIG.
  • the initial setting step S1 accepts scattergram S 0 and an initial border B 0.
  • the initial setting step S1 can be executed using the initial setting unit 11 described above.
  • a set of displacement amounts ( ⁇ x i , ⁇ y i ) (i indicates a serial number of the translational displacement pattern) is set.
  • the displacement amount set setting step S2 can be executed using the displacement amount set setting unit 12 described above. If you do not use the scattergram S 0 and an initial boundary line B 0 received in process S1 for setting the set amount of displacement, the order of performing step S1 and the step S2 are not limited.
  • the determination index determination step S3 based on the set of the scattergram S 0 and the initial boundary line B 0 received in the initial setting step S1 and the displacement amounts ( ⁇ x i , ⁇ y i ) set in the displacement amount set setting step S2. determining a judgment index I i for determination index I 0 and the boundary line B i of the initial boundary line B 0.
  • the determination index determination step S3 can be executed using the determination index determination unit 13 described above.
  • the determination index determination step S3 is a dot counting step S3 ′.
  • the dot counting step S3 ′ the number of dots Num (R 0 ) in the counting region R 0 described above is counted, the number Num (R 0 ) is set as the determination index I 0, and one or more counting regions described above are used. the number of dots in the R i Num of (R i) counting respectively, the number of the coefficients Num of (R i) and determination index I i.
  • the dot counting step S3 ′ can be executed using the dot counting unit 13 ′ described above.
  • the boundary line candidate specifying step S4 based on the determination index I 0 and the one or more determination indices I i determined in the determination index determination step S3, the initial boundary line B 0 and one or more of the initial boundary lines B 1 as the target boundary line candidates are used. At least one of the boundary lines B i is specified.
  • the boundary line candidate specifying step S4 can be executed using the boundary line candidate specifying unit 14 described above.
  • the boundary line candidate specifying step S4 is a value of the determination index I 0 determined in the dot counting step S3 ′ and one or more determination indexes I i (that is, the number Num (R 0 ) and a small number of one or more Num (R i )) as a reference, at least one of the initial boundary line B 0 and one or more boundary lines B i as a target boundary line candidate May be specified.
  • the boundary line determination method of the embodiment shown in the flowchart of FIG. 2 includes various steps using other parts (for example, a blood cell calculation part) described above with respect to the boundary line determination part 10 of the embodiment shown in the block diagram of FIG. Further, it may be included.
  • FIG. 3 is a block diagram showing another example of the configuration of the boundary line determination unit in the blood analyzer of the present invention.
  • the boundary line determination unit 100 includes an initial setting unit 111, a displacement amount set setting unit 112, a determination index determination unit 113, a boundary line candidate specification unit 114, and a recalculation control unit 115.
  • the determination index determination unit 113 is a dot counting unit 113 '.
  • the configurations of the initial setting unit 111, the displacement amount set setting unit 112, the determination index determination unit 113, and the dot counting unit 113 ′, the functional relevance between them, and additional functional units that may accompany them are shown in FIG.
  • a remarkable feature of the boundary line determination unit 100 of the present embodiment compared with the boundary line determination unit 10 of the embodiment shown in the block diagram of FIG. 1 is the presence of the recalculation control unit 115.
  • the recalculation control unit 115 needs to recalculate a series of processes by the initial setting unit 111, the displacement amount set setting unit 112, and the determination index determination unit 113 based on the determination index determination result by the determination index determination unit 113.
  • the boundary line determination unit 100 is controlled to perform the recalculation, thereby causing the determination index I 0 and one or more determination indices I i to be determined again.
  • the recalculation control unit 115 repeats this process until it is determined that the recalculation is not necessary.
  • the recalculation control unit 115 can determine whether or not recalculation is necessary, for example, based on the determination index I 0 determined by the determination index determination unit 113 and one or more determination indexes I i . Therefore, the recalculation control unit 115 may be configured to check whether these determination indexes satisfy the set determination criterion. For example, when the determination index is given as a numerical value, the recalculation control unit 115 may determine whether or not recalculation is necessary by comparing a set threshold with these determination indexes.
  • the determination as to whether recalculation is necessary is performed by determining the determination index I 0 and the value of one or more determination indexes I i (that is, the number Num (R 0 ) and 1 The above number Num (R i )) may be compared with a predetermined threshold value Thr.
  • the threshold value Thr may be a value set in advance by the user in accordance with, for example, the distribution of blood cells to be processed and various analysis parameters.
  • recalculation is necessary when all of the determination indexes I 0 and one or more determination indexes I i are greater than the threshold value Thr, while the re-calculation is performed when at least one of the determination indexes is equal to or less than the threshold value Thr. It can be determined that no operation is necessary. Further, as an additional or alternative determination criterion regarding the necessity of recalculation, an upper limit (for example, once) of the number of recalculations is set in advance, and the recalculation is performed when the number of recalculations exceeds the upper limit. May not be performed.
  • the recalculation control unit 115 determines that the recalculation is necessary, the recalculation control unit 115 performs a series of processes by the initial setting unit 111, the displacement amount set setting unit 112, and the determination index determination unit 113 again. 100 is controlled. Each recalculation, the initial setting unit 111 receives a different additional scattergram S 0 ', which is generated based on the scattergram S 0. On the other hand, in the recalculation process, the initial boundary line received by the initial setting unit 111 and the displacement amount set by the displacement amount set setting unit 112 are the same as those used by the functional units in the previous processing. It may be different or different (therefore, the number of displacements used may be different between recalculations).
  • a specimen that needs to be recalculated may be an abnormal specimen, and accordingly, a displacement amount set in a narrower range than the displacement amount set set for the initial processing by the displacement amount set setting unit 112 is set. May be used.
  • the determination index determination method used by the determination index determination unit 113 or the dot count method used by the dot counting unit 113 ′ is the same as those used in the previous processing by these functional units.
  • the scattergram S 0 is a discrete scattergram
  • the additional scattergram S 0 ′ described above determines the number of dots at each position on the discrete coordinates of the discrete scattergram S 0. Is generated by subtracting the number of.
  • the additional scattergram S 0 ′ the series (S 1 , S 2 ,..., S Fmax-1 ) of the above-described (F max ⁇ 1) additional scattergrams is used. Any of them can be used.
  • an additional scattergram generation unit (not shown) for generating an additional scattergram based on the scattergram S 0 is provided in the boundary line determination unit 100, and the additional scattergram generation unit generates an additional scattergram when necessary. It may be generated.
  • the recalculation control unit 115 performs the scattergram S 1 in the first recalculation and the second recalculation in the second recalculation.
  • the scattergram S 2 may be configured so as to give additional scattergrams to the initial setting unit 111 sequentially from the smallest number.
  • an additional scattergram used for recalculation may be determined in accordance with a predetermined procedure from the additional scattergrams of the series (S 1 , S 2 ,..., S Fmax-1 ). This method is particularly useful in an embodiment in which an upper limit (for example, once) of the number of recalculations is set.
  • a provisional boundary line is determined based on a determination index determined before recalculation, and a predetermined condition is satisfied when the provisional boundary line is used.
  • a predetermined condition is satisfied when the provisional boundary line is used.
  • the determination index determination unit 113 is the dot counting unit 113 ′, when it is determined that recalculation is necessary, the determination index (that is, the number of dots) determined before the recalculation is minimized.
  • the boundary line is determined as a temporary boundary line, and the number of dots (in the order of scattergrams S 1 , S 2 ,..., S Fmax-1 using the temporary boundary line and the count area before recalculation ( (Determination index) is counted, and a scattergram in which the number is initially less than a predetermined threshold value can be determined.
  • the boundary line candidate specifying unit 114 uses the determination index determination unit 113 as a target boundary line candidate based on the determination index I 0 determined in the final process by the determination index determination unit 113 and one or more determination indexes I i. At least one of the initial boundary line B 0 and the one or more boundary lines B i in the last processing by 113 is specified.
  • the boundary line candidate specifying method by the boundary line candidate specifying unit 114 is based on the initial boundary line B 0 and one or more boundary lines B i and the corresponding determination index I 0 and one or more of the last processing in the determination index determination unit 113. Except for using the determination index I i , it may be the same as the specifying method by the boundary line candidate specifying unit 14 of the embodiment shown in FIG.
  • the boundary line determination unit 100 includes a blood cell calculation unit (not shown; for example, the above-described LMNE calculation unit) that calculates the existence ratio of each type of blood cell. Alternatively, it may be functionally connected to the blood cell calculation unit.
  • a blood cell calculation unit (not shown; for example, the above-described LMNE calculation unit) that calculates the existence ratio of each type of blood cell. Alternatively, it may be functionally connected to the blood cell calculation unit.
  • FIG. 4 is a flowchart showing another example of the boundary line determination method of the present invention.
  • the embodiment shown in the flowchart of FIG. 4 can be executed using the boundary line determination unit 100 of the embodiment shown in the block diagram of FIG. Therefore, all the embodiments described above with respect to the boundary line determination unit 100 can be applied to the boundary line determination method of the embodiment shown in the flowchart of FIG.
  • the initialization step S11 accepts a scattergram S 0 and an initial border B 0.
  • the initial setting step S11 can be executed using the initial setting unit 111 described above.
  • the initial setting step S11 may be the same as the initial setting step S1 described above with respect to the boundary line determination method shown in the flowchart of FIG.
  • a set of displacement amounts ( ⁇ x i , ⁇ y i ) (i indicates a serial number of the translational displacement pattern) is set.
  • the displacement amount set setting step S12 can be executed using the displacement amount set setting unit 112 described above.
  • the displacement amount set setting step S12 may be the same as the displacement amount set setting step S2 described above with respect to the boundary line determination method shown in the flowchart of FIG. If you do not use the scattergram S 0 and an initial boundary line B 0 accepted in step S11 for setting the set amount of displacement, the order of performing steps S11 and step S12, no matter.
  • decision index determination step S13 initialization step S11 scattergram S 0 and an initial boundary line B 0 accepted in, and the displacement amount set by the displacement amount set setting step S12 ( ⁇ x i, ⁇ y i) based on a set of, determining a judgment index I i for determination index I 0 and the boundary line B i of the initial boundary line B 0.
  • the determination index determination step S13 can be executed using the determination index determination unit 113 described above.
  • the determination index determination step S13 is a dot counting step S13 ′.
  • the dot counting step S13 ′ the number of dots Num (R 0 ) in the counting region R 0 described above is counted, the number Num (R 0 ) is set as the determination index I 0, and one or more counting regions described above are used. the number of dots in the R i Num of (R i) counting respectively, the number of the coefficients Num of (R i) and determination index I i.
  • the dot counting step S13 ′ can be performed using the dot counting unit 113 ′ described above.
  • the recalculation control step S15 (1) it is determined whether recalculation using an additional scattergram is necessary, and (2) when it is determined that recalculation is necessary, the initial setting step S11, displacement amount set setting step S12, and controls the procedure of the method to perform a series of processing by the determination indicator determining step S13 again, thereby re-determining said determination index I 0 and 1 or more determination index I i The process is repeated until it is determined that the recalculation is not necessary.
  • the recalculation control step S15 can be executed using the recalculation control unit 115 described above.
  • boundary line candidate specifying step S14 based on the final determination index determining step of determining index I 0 and 1 or more determined in S13 determination index I i, as a candidate for a boundary line of interest, the final determination index determination at least one of the initial boundary lines B 0 and 1 or more boundary lines B i is identified in step S13.
  • the boundary line candidate specifying step S14 can be executed using the above-described boundary line candidate specifying unit 114.
  • the boundary line determination method of the embodiment shown in the flowchart of FIG. 4 is the same as the boundary line determination unit 10 of the embodiment shown in the block diagram of FIG. 1 or the boundary line determination unit 100 of the embodiment shown in the block diagram of FIG.
  • the processing step using the above-mentioned part may be included.
  • the present invention further provides a blood analysis method using the blood analyzer of the present invention.
  • the blood analysis method of the present invention uses a step of measuring and analyzing a predetermined analysis item for a given blood sample to generate a scattergram indicating the analysis result, and the boundary line determination method of the present invention. Determining a boundary line that separates two or more different types of blood cells of interest.
  • the blood analysis method of the present invention may further include a step of determining the abundance ratio of two or more different types of blood cells of interest after the determination of the boundary line.
  • the boundary lines that distinguish lymphocytes, monocytes, and neutrophils in the LMNE matrix were determined according to the present invention.
  • the X-axis used for the analysis was an electrical resistance (showing the blood cell volume), and the Y-axis used for the analysis was an LMNE matrix showing the absorbance.
  • Each of the X axis and Y axis had coordinates of 0 to 127.
  • information about the frequency of each dot is expressed using the height direction of the matrix (see Japanese Patent Application Laid-Open No. 2014-106161).
  • An example of the matrix used for the analysis is shown in FIG.
  • FIG. 8 shows an explanatory diagram of the boundary line of interest and its displacement.
  • the thick line in FIG. 8A is the initial boundary line B 0 to which attention is paid.
  • the initial boundary line B 0 is translated and displaced in the X-axis direction and / or the Y-axis direction.
  • FIG. 8C schematically shows the boundary line B i after translational displacement. Change border B i is shown in the drawing, but generally is obtained by translating the initial boundary lines B 0, is omitted is a portion in the initial boundary line B 0, and are supplemented, also compartment noise region Has been.
  • the number of dots in the counting area was calculated, and the boundary line corresponding to the counting area where the number of dots was minimized was recorded.
  • the boundary was determined.
  • the boundary line with the minimum number of dots is provisionally used, and the matrix height direction is lowered by ⁇ 1, so that the minimum number of dots is A matrix that was within 100 for the first time was used for re-search.
  • FIG. 9 schematically shows how the number of dots in the matrix decreases as the height direction of the matrix is lowered stepwise.
  • the search range was narrowed because of an abnormal specimen, and a rectangular range of x: 0 to 10 and y: 0 to 10 was set as the displacement amount set.
  • the boundary line finally obtained by the above procedure was set as the target boundary line, and LMNE calculation was further performed using the boundary line.
  • the overall procedure and the flowchart of the search function are shown in FIGS. 10A and 10B. As shown in FIG. 10B, when there are two or more movements giving the same number of dots in the search function, the boundary line that has the smallest movement from the initial boundary line is selected.
  • FIG. 11A shows an example of the result of the LMNE calculation in the case of using the initial boundary line (Before Data) and in the case of using the boundary line after movement according to the present invention (After Data) by the visual (standard) method. Shown with results.
  • FIG. 11B is a scattergram (height: ⁇ 15) finally used for determining the boundary line. It has been found that a more accurate boundary line can be determined by translating the boundary line according to the present invention.
  • a method for determining a boundary line that distinguishes two or more different types of blood cells in a scattergram showing a distribution state of blood cells having excellent accuracy and a processing unit for performing the method.
  • a blood analysis device is provided.

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Abstract

Grâce à la présente invention, un indice d'évaluation de fiabilité sous forme d'une ligne de délimitation souhaitée est déterminé pour chaque ligne de délimitation initiale définie à l'avance et une ou plusieurs lignes de délimitation obtenues en déplaçant par translation la ligne de délimitation initiale, et la ligne de délimitation souhaitée est déterminée sur la base de l'indice d'évaluation.
PCT/JP2017/032821 2016-12-15 2017-09-12 Procédé de détermination d'une ligne de délimitation de classification dans un nuage de points concernant des cellules sanguines et dispositif d'analyse de sang comprenant une unité de traitement pour mettre en œuvre le procédé WO2018110005A1 (fr)

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Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62134559A (ja) * 1985-12-07 1987-06-17 Japan Spectroscopic Co 血液細胞自動分析方法および装置
JPH0222537A (ja) * 1988-07-11 1990-01-25 Omron Tateisi Electron Co 細胞分折装置
JPH0534263A (ja) * 1991-07-26 1993-02-09 Omron Corp 細胞分析装置
JPH05149863A (ja) * 1991-11-27 1993-06-15 Toa Medical Electronics Co Ltd 粒子計数方法
JPH10260127A (ja) * 1997-03-17 1998-09-29 Toa Medical Electronics Co Ltd スキャッタグラムの表示方法
US20120036175A1 (en) * 2010-02-18 2012-02-09 Becton, Dickinson And Company Determining population boundaries using radial density histograms
JP2014106161A (ja) * 2012-11-28 2014-06-09 Horiba Ltd 血液細胞に関するスキャッターグラムの表示装置、表示方法、および、該表示装置を有する血液分析装置

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62134559A (ja) * 1985-12-07 1987-06-17 Japan Spectroscopic Co 血液細胞自動分析方法および装置
JPH0222537A (ja) * 1988-07-11 1990-01-25 Omron Tateisi Electron Co 細胞分折装置
JPH0534263A (ja) * 1991-07-26 1993-02-09 Omron Corp 細胞分析装置
JPH05149863A (ja) * 1991-11-27 1993-06-15 Toa Medical Electronics Co Ltd 粒子計数方法
JPH10260127A (ja) * 1997-03-17 1998-09-29 Toa Medical Electronics Co Ltd スキャッタグラムの表示方法
US20120036175A1 (en) * 2010-02-18 2012-02-09 Becton, Dickinson And Company Determining population boundaries using radial density histograms
JP2014106161A (ja) * 2012-11-28 2014-06-09 Horiba Ltd 血液細胞に関するスキャッターグラムの表示装置、表示方法、および、該表示装置を有する血液分析装置

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