A method of distinguishing particle populations, a particle analysis device, and a storage medium
By obtaining a particle characteristic distribution histogram in blood cell analysis, determining the left and right boundaries, and setting reference lines to generate a flipped histogram, the problem of inaccurate particle population differentiation in existing technologies is solved, achieving higher accuracy and stability.
Patent Information
- Application Number
- CN202011626345.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2020-12-31
- Publication Date
- 2025-10-10
- Estimated Expiration
- 2040-12-31
AI Technical Summary
Existing blood cell analysis methods lack stability and accuracy in distinguishing particle populations, especially when using electrical impedance to measure red blood cells and platelets, which makes it difficult to effectively distinguish different particle populations.
By obtaining the particle characteristic distribution histogram, the left and right boundaries are determined, and the particle intersection area is determined based on these boundaries. A reference line is set in the intersection area to generate a flipped histogram. Finally, the boundary line of the particle community is determined based on the flipped histogram to achieve accurate distinction.
The accuracy of particle population differentiation is improved, and it is applicable to different blood samples with a certain degree of stability, especially when dealing with abnormal or low-concentration samples, it can still maintain high accuracy.
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Figure CN114689469B_ABST
Abstract
Description
Technical Field
[0001] The present application relates to the field of blood analysis, and in particular to a method for distinguishing particle colonies, a particle analysis device, and a storage medium. Background Art
[0002] Blood cell analysis is one of the most widely used examination items in clinical medicine. Currently, fully automatic blood cell analyzers are widely used both at home and abroad to automatically test anticoagulated whole blood, providing parameters such as white blood cell count (WBC), red blood cell count (RBC), platelet count (PLT), mean corpuscular volume (MCV), mean platelet volume (MPV), etc. These parameters will help clinicians and test personnel correctly analyze the test results and provide evidence for clinical diagnosis.
[0003] Currently, most blood cell analyses for platelet analysis use the electrical impedance method. When using the electrical impedance method to measure red blood cells and platelets, the cell size is generally used as the basis for dividing various cells. The pulse voltage corresponding to each cell is mapped to the cell volume, and this correspondence is converted into a histogram. By finding the lowest point in the intersection area of different volume communities in the histogram as the dividing line, different particle communities can be distinguished. However, this method may lack certain stability. Summary of the Invention
[0004] In order to solve the above problems, the present application provides a method for distinguishing particle colonies, a particle analysis device, and a storage medium, which can stably and accurately distinguish different particle colonies.
[0005] To solve the above technical problems, a technical solution adopted in the present application is: providing a method for distinguishing particle communities, the method comprising: obtaining a particle characteristic distribution histogram; wherein the first direction coordinate of the particle characteristic distribution histogram is a channel representing the particle characteristics, and the second direction coordinate of the particle characteristic distribution histogram is the number of particles; determining a left boundary in the particle characteristic distribution histogram, and determining a right boundary based on the maximum number of particles within a preset channel range to the right of the left boundary, and determining a particle intersection area based on the left boundary and the right boundary; determining a reference line located within the intersection area; wherein the reference line is parallel to the first direction; generating a corresponding flipped histogram based on the particle characteristic distribution histogram and the reference line; determining a dividing line of the particle community based on the flipped histogram to distinguish the particle community.
[0006] Determining the left boundary in the particle characteristic distribution histogram includes: determining a first preset channel range in the particle characteristic distribution histogram; and determining a left boundary corresponding to the maximum number of particles within the first preset channel range.
[0007] The first preset channel range is the estimated channel distribution range of the target particles.
[0008] Among them, within the preset channel range to the right of the left boundary, the right boundary is determined based on the maximum number of particles, including: within the second preset channel range to the right of the left boundary, determining the minimum number of particles; within the third preset channel range to the right of the channel corresponding to the minimum number of particles, determining the right boundary corresponding to the maximum number of particles.
[0009] Among them, the number of particles corresponding to the reference line is not less than the minimum number of particles.
[0010] The method of generating a corresponding flipped histogram according to the particle characteristic distribution histogram and the reference line includes: subtracting the height of the particle characteristic distribution histogram from the height of the reference line to obtain the corresponding flipped histogram.
[0011] The height of the particle characteristic distribution histogram is subtracted from the height of the reference line to obtain the corresponding flipped histogram, including: for outside the particle intersection area, determining the height of the flipped histogram to be 0; and for within the particle intersection area, determining the height of the flipped histogram to be the height value obtained by subtracting the height of the particle characteristic distribution histogram from the height of the reference line.
[0012] According to the flip histogram, the boundary line of the particle population is determined to distinguish the particle population, including: using the following formula to calculate the boundary line: Among them, M k is the boundary of the particle community, i is the channel value in the flipped histogram, f(i) is the value of the flipped histogram in the i-th channel, g(·) is the processing function, and satisfies: g(x)≥g(y)≥0.
[0013] To solve the above technical problems, another technical solution adopted in this application is: to provide a particle analysis device, which includes a processor and a memory, and the memory stores a computer program. When the computer program is executed by the processor, it is used to implement the above method of distinguishing particle colonies.
[0014] To solve the above technical problems, another technical solution adopted in this application is: providing a computer-readable storage medium for storing a computer program, which, when executed by a processor, is used to implement the above method for distinguishing particle colonies.
[0015] The beneficial effects of the embodiments of the present application are as follows: Different from the prior art, the method for distinguishing particle colonies provided by the present application determines the left and right boundaries in the obtained particle characteristic distribution histogram, and determines the particle intersection area based on the left and right boundaries, and determines the reference line located in the intersection area, further generates a corresponding flipped histogram based on the particle characteristic distribution histogram and the reference line, and finally determines the boundary line of the particle colony based on the flipped histogram to achieve the distinction of the particle colony. In this way, on the one hand, the accuracy of distinguishing particle colonies can be improved by determining the boundary line of the particle colony using the flipped histogram; on the other hand, by first determining the particle intersection area and then determining the reference line, it can be applied to different blood samples, has a certain stability, and can further improve the accuracy of distinguishing particle colonies. BRIEF DESCRIPTION OF THE DRAWINGS
[0016] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present application. For those skilled in the art, other drawings can be obtained based on these drawings without inventive efforts. Among them:
[0017] Figure 1 This is a flow chart of a first embodiment of a method for distinguishing particle colonies provided by the present application;
[0018] Figure 2 is a schematic diagram of the voltage pulse when the particle passes through the micropore;
[0019] Figure 3 This is a diagram of the distribution of platelets and red blood cells;
[0020] Figure 4 1 is a flow chart of a second embodiment of the method for distinguishing particle colonies provided by the present application;
[0021] Figure 5 yes Figure 4 Specific process diagram of S42;
[0022] Figure 6 is a particle characteristic distribution histogram provided by this application;
[0023] Figure 7 yes Figure 6 The corresponding flipped histogram;
[0024] Figure 8 1 is a flow chart of a third embodiment of the method for distinguishing particle colonies provided by the present application;
[0025] Figure 91 is a flow chart of a fourth embodiment of the method for distinguishing particle colonies provided by the present application;
[0026] Figure 10 It is a schematic diagram of the preset channel range;
[0027] Figure 11 is another particle characteristic distribution histogram provided by this application;
[0028] Figure 12 yes Figure 11 The corresponding flipped histogram;
[0029] Figure 13 It is a structural schematic diagram of an embodiment of a particle analysis device provided by the present application;
[0030] Figure 14 It is a structural diagram of an embodiment of a computer-readable storage medium provided by this application. DETAILED DESCRIPTION
[0031] The technical solutions in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. It will be understood that the specific embodiments described herein are only used to explain the present application, rather than to limit the present application. It should also be noted that, for ease of description, only some, rather than all, structures related to the present application are shown in the drawings. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.
[0032] References herein to "embodiments" mean that a particular feature, structure, or characteristic described in connection with the embodiments may be included in at least one embodiment of the present application. The appearance of this phrase in various places in the specification does not necessarily refer to the same embodiment, nor does it constitute an independent or alternative embodiment that is mutually exclusive of other embodiments. It is understood, both explicitly and implicitly, by those skilled in the art that the embodiments described herein may be combined with other embodiments.
[0033] See Figure 1 , Figure 1 : is a flow chart of the first embodiment of the method for distinguishing particle colonies provided by the present application. The method of this embodiment specifically includes:
[0034] S11: Obtaining a particle characteristic distribution histogram.
[0035] In this embodiment, the particle characteristic distribution histogram is obtained by statistically measuring a blood sample solution using a blood cell analyzer (particle analyzer). Generally, a blood cell analyzer includes a containing tank, a micropore, a power component, and an analysis circuit. When using the blood cell analyzer to analyze blood cells, a certain amount of the blood sample to be tested is added to a certain amount of diluent having particle morphology and conductive properties. The resulting mixed solution is then sucked into the micropore channel under the action of the power component. When each particle passes through the micropore, since the particle replaces an equal volume of electrolyte solution and has weaker conductive properties, the passage of the particle increases the equivalent impedance of the micropore, such as Figure 2 As shown in the figure, under the action of the power component, the change in voltage is proportional to the change in impedance, so when the particle passes through the micropore O, a pulse voltage will be generated accordingly. The height of this voltage pulse reflects the characteristics of the particle.
[0036] Furthermore, the analysis circuit will count all the particles in the mixed solution into the corresponding channels of the particle characteristic distribution histogram according to the characteristics of the particles, that is, the particles corresponding to the voltage of the same height will be counted into the same channel, thereby accumulating a channel in which the particle characteristics are represented by the first direction (horizontal axis direction) and the number of particles is represented by the second direction (vertical axis direction). Among them, since the volume of platelets and red blood cells is significantly different, in this embodiment, the particle characteristic is the volume of the particles.
[0037] by Figure 3 The example of the particle characteristic distribution histogram is briefly explained as shown in the figure. Figure 3 This is a distribution diagram of platelets and red blood cells. The curve in the figure can be called a volume / particle number curve, which is used to represent the volume distribution of different particles. Under normal circumstances, the volume of red blood cells is larger and the volume of platelets is smaller. The number of red blood cells is larger and the number of platelets is smaller. The number of platelets in a normal person is 1 / 20 of the number of red blood cells. The red blood cells are mainly distributed in 40 femtoliters to 130 femtoliters, and the platelets are mainly distributed in 2 femtoliters to 25 femtoliters. Therefore, it can be clearly seen that the figure is divided into two different communities of platelets and red blood cells. The platelet community is distributed in the lower volume range, and the red blood cell community is distributed in the higher volume range.
[0038] It can be seen that the mixed solution passing through the micropores primarily consists of three types of particles: white blood cells, red blood cells, and platelets. Any cell passing through the micropores generates a pulse. Therefore, the pulses can only reveal the distribution and number of all cells in the blood sample being tested, but cannot distinguish between cell types. Furthermore, white blood cells are larger in size and far fewer in number than red blood cells and platelets. Therefore, the impact of white blood cells can be ignored when distinguishing between different particle populations.
[0039] S12: Determine a particle intersection region in the particle characteristic distribution histogram.
[0040] The particle intersection area refers to the intersection of the platelet colony and the red blood cell colony. Figure 3 For example, it usually refers to the trough part between the platelet population and the red blood cell population. The specific intersection area needs to be determined or adjusted according to the actual situation. For example, when the trough feature is not obvious, it is necessary to accurately define the particle intersection area through certain calculations or historical experience to improve the accuracy of subsequent dividing line calculations.
[0041] In this embodiment, the particle intersection region can be a channel distribution range representing a volume segment, corresponding to a portion of the volume / particle number curve. In other embodiments, the particle intersection region can also be square, such as a rectangle, with the length and width of the rectangle parallel to the first direction or the second direction, respectively, to define the particle intersection region in the histogram. The particle intersection region includes the actual boundary between the platelet population and the red blood cell population, enabling differentiation between platelets and red blood cells.
[0042] S13: Determine a reference line within the intersection area.
[0043] The reference line extends along the first direction, which means that the reference line and the horizontal coordinate axis have the same orientation at least in their respective extension directions. Specifically, they may be parallel to each other in the extension directions, or they may be non-parallel to each other but also not intersecting in the extension directions.
[0044] In some embodiments, the reference line can be parallel to the first direction, and the distance between the reference line and the first direction represents the reference flip height RefH (ReferenceHeight, reference size height) of the reference line. In this embodiment, the setting of the specific position of the reference line is related to the histogram particle intersection area, specifically to the height of the volume / particle number curve in the particle intersection area. The existence of the reference line is equivalent to setting a reference standard value for the curve of the particle intersection area, which can set the number of particles in all channels in the intersection area to a reasonable standard, so that the dividing line can be subsequently calculated and determined based on the number of particles under this standard.
[0045] In other embodiments, the reference line may be a curve. In this case, the reference line is not parallel to the first direction, and the specific position of the reference line varies with the volume channel value in the first direction and / or with the particle count value in the second direction. The curved reference line obtained in this manner can adapt to the volume / particle count curves in different particle characteristic distribution histograms, thereby ensuring stable generation of subsequent flipped histograms when the volume / particle count curves in the intersection region do not change significantly. In this and subsequent embodiments, the reference line is preferably a straight line and is arranged parallel to the first direction.
[0046] S14: Generate a corresponding flipped histogram according to the particle characteristic distribution histogram and the reference line.
[0047] Among them, the flipped histogram is a histogram formed by flipping the particle characteristic distribution histogram according to the reference line. In other embodiments, it is also called an equivalent negative histogram. In each volume channel of the particle intersection area, there is the same or different height difference (distance) between all reference lines and the corresponding volume / particle number curve. The height difference between different channels is the height value of the corresponding channel of the flipped histogram, thereby generating a flipped histogram corresponding to the particle intersection area. The particle community represented in the flipped histogram is the flipped particle community.
[0048] S15: Determine the boundary line of the particle population according to the flipped histogram to distinguish the particle population.
[0049] Among them, the boundary line of the particle population refers to the target straight line that can be used to distinguish different particle populations. When the calculated boundary line is accurate enough, the left side of the boundary line of the particle characteristic distribution histogram should be the platelet population, and the right side of the boundary line should be the red blood cell population.
[0050] It can be seen that in the particle characteristic distribution histogram obtained by converting normal blood samples, the dividing line should theoretically be the lowest point of the volume / particle number curve in the particle intersection area. However, when it is necessary to distinguish the particle communities of abnormal blood samples with lower concentrations, the lowest point in the particle intersection area may not be the actual lowest point. In this case, the accuracy of distinguishing particle communities cannot be guaranteed.
[0051] Therefore, in this embodiment, by converting the particle intersection area of platelets and red blood cells into a flipped histogram, it is equivalent to converting the goal of finding the lowest point in the particle intersection area into finding the highest point in the flipped histogram, and then calculating the maximum statistic of the flipped particle community in the flipped histogram according to a preset formula. The maximum statistic represents the value of the volume channel, that is, the lowest point in the corresponding particle intersection area. Finally, the channel where the dividing line between platelets and red blood cells in the corresponding particle characteristic distribution histogram is located can be determined, thereby accurately distinguishing the platelet community from the red blood cell community.
[0052] Furthermore, the method for determining the dividing line in this embodiment can be applied to different blood samples (including normal, abnormal or low-concentration samples). When determining the intersection area, the particle intersection area can be adaptively determined based on the actual situation of the trough in the particle characteristic distribution histogram; and then when determining the reference line, the reference line can be adaptively determined based on the actual situation of the volume / particle number curve in the particle intersection area. This approach can further improve the calculation accuracy of the dividing line, thereby further improving the accuracy of distinguishing particle populations.
[0053] Unlike existing techniques, the method for distinguishing particle populations provided in this embodiment determines the particle intersection region and a reference line within the obtained particle characteristic distribution histogram. A corresponding flipped histogram is then generated based on the particle characteristic distribution histogram and the reference line. Ultimately, the boundary between particle populations is determined based on the flipped histogram to achieve particle population differentiation. This approach not only improves the accuracy of distinguishing particle populations by using the flipped histogram to determine the boundary between particle populations, but also allows for the method to be applied to different blood samples, providing a certain degree of stability and further improving the accuracy of distinguishing particle populations.
[0054] See Figure 4 , Figure 4 : is a flow chart of a second embodiment of the method for distinguishing particle colonies provided by the present application. The method of this embodiment specifically includes:
[0055] S41: Obtaining a particle characteristic distribution histogram.
[0056] The first direction coordinate of the particle characteristic distribution histogram is the channel representing the particle characteristic, and the second direction coordinate of the particle characteristic distribution histogram is the number of particles. In this embodiment, the particle characteristic is the volume of the particle.
[0057] S42: Determine the left boundary in the particle characteristic distribution histogram.
[0058] Among them, the left boundary corresponds to a certain volume channel; optionally, the left boundary can be preset based on historical experience. For example, after obtaining the analysis statistical information of multiple historical blood samples, the analyzer operator combines the historical particle characteristic distribution histogram to analyze and predict the volume channel corresponding to the maximum number of platelet particles, the volume channel corresponding to the maximum number of red blood cell particles, and the volume channel where the dividing line between platelets and red blood cells is located, etc., included in the information, so as to obtain a preset value of the left boundary, and pre-input the preset value into the instrument to obtain the left boundary of this particle characteristic distribution histogram.
[0059] Optionally, S42 can be Figure 5 The method steps shown are implemented, specifically including:
[0060] S421: Determine a preset channel range in the particle characteristic distribution histogram.
[0061] The preset channel range refers to the channel distribution range of platelet colony volume. This can also be based on the analyzer operator's experience. By observing historical particle characteristic distribution histograms or combining historical analysis statistics, the operator can pre-set a channel range based on their experience and input it into the instrument to obtain the preset channel range for the current particle characteristic distribution histogram. This approach can effectively improve the accuracy of the preset channel range when the histogram curve changes are not obvious.
[0062] In some embodiments, the left boundary may be determined by the following method in S422:
[0063] S422: Determine the corresponding left boundary according to the channel corresponding to the maximum number of particles in the preset channel range.
[0064] The maximum number of particles is represented by the maximum height point in the second direction within the preset channel range of the particle characteristic distribution histogram, and the left boundary is the volume channel position corresponding to the maximum height point.
[0065] In some other embodiments, the left boundary may be determined by the method of S423:
[0066] S423: Determine the corresponding left boundary according to any channel within the preset particle number range to the right of the maximum particle number in the preset channel range.
[0067] The preset particle number range refers to a range of particle numbers starting at the maximum particle number and ending at 80% of the maximum particle number, with the range ending to the right of the starting point. If multiple range endings of the same size appear, the closest point is selected. Therefore, the portion between the starting point and the end point constitutes the preset particle number range. The left boundary should be any channel between the channel corresponding to the range starting point (maximum value) and the channel corresponding to the range end point (80% of the maximum value). For example, if the maximum particle number in the preset channel range is 10 units, corresponding to channel 15, and 80% of the maximum particle number is 8 units, corresponding to channel 20, then the left boundary is any channel between 15 and 20. The specific choice can be made based on actual conditions, such as determining the most stable one through variance calculation. The 80% setting can also be adjusted based on actual conditions, such as 85%, 90%, or 95%, etc. No further restrictions are imposed here.
[0068] S43: Determine the right boundary in the particle characteristic distribution histogram.
[0069] The right boundary corresponds to a certain volume channel; optionally, the right boundary can also be preset based on historical experience, for example, by setting it in the manner described above, which will not be elaborated here.
[0070] Optionally, S43 may also be implemented by the following step: determining the right boundary at a preset channel interval on the right side of the left boundary.
[0071] The preset channel interval is represented as a channel interval range, and the preset channel interval is positively correlated with the total number of particles within the preset channel range, i.e., the number of channels at the right boundary = the number of channels at the left boundary + the number of channels within the preset channel interval. Specifically, since the preset channel range represents the channel distribution range of the platelet colony volume, the number of platelet particles within the preset channel range is constant. As the number of platelet particles within the preset channel range increases, the channel interval range corresponding to the preset channel interval increases, and the distance between the right and left boundaries increases. Therefore, the channel position of the right boundary can be determined based on the difference between the left boundary and the preset channel interval.
[0072] S44: Determine a particle intersection region based on the left boundary and the right boundary.
[0073] like Figure 6 As shown, Figure 6 A particle characteristic distribution histogram provided for this application shows that the particle intersection region is a channel distribution range representing the intersection between platelets and red blood cells. The dashed line A near the left is the left boundary A, and the dashed line B near the right is the right boundary B. Both dashed lines A and B are parallel to the second direction. The particle intersection region determined in this way can be within a more reasonable channel range, excluding channels that clearly do not fall within the boundary from the particle intersection region. Alternatively, when the trough characteristics of the curve are not obvious, the intersection region can be accurately defined using the above method, thereby improving the accuracy of subsequent boundary calculations.
[0074] S45: Determine a reference line within the intersection area.
[0075] Continue reading Figure 6 The horizontal dotted line C in the figure is the reference line C, and its height represents the reference flip height RefH. The reference line C is parallel to the first direction. In some embodiments, the number of particles corresponding to the reference line C is not lower than the number of particles corresponding to the right boundary B. That is to say, the height of the example reference line C in the figure needs to be greater than the height of the channel corresponding to the right boundary B, and since the height of the channel corresponding to the right boundary B is usually also greater than the height of the channel corresponding to the left boundary A, the height of the reference line C should be greater than the corresponding heights of all channels in the particle intersection area.
[0076] In other embodiments, the number of particles corresponding to reference line C is no less than the number of particles corresponding to any channel within a preset particle number range to the left of right boundary B. The preset particle number range, similar to the above, refers to a particle number interval starting with the number of particles in the channel corresponding to right boundary B and ending at 80% of the number of particles in the channel corresponding to right boundary B, with the end point located to the left of the starting point. In other words, the height of reference line C needs to be greater than multiple heights within the corresponding channels from the starting point to the end point. Furthermore, the multiple heights can be specifically determined based on actual conditions, and the setting of 80% can also be adjusted based on actual conditions, for example, to 85%, 90%, 95%, etc.
[0077] S46: Subtract the height of the particle characteristic distribution histogram from the height of the reference line to obtain a corresponding flipped histogram.
[0078] Among them, for particles outside the intersection area, the height of the flipped histogram is determined to be 0. For particles within the intersection area, the height of the flipped histogram is determined to be the height of the reference line, and the height value obtained by subtracting the height of the particle characteristic histogram distribution diagram is the height difference between the reference line C and the corresponding volume / particle number curve.
[0079] In this embodiment, the flipped histogram mainly corresponds to the particle intersection area. The height of the particle characteristic distribution histogram is the height corresponding to multiple volume channels in the particle intersection area. In each volume channel of the particle intersection area, there is the same or different height difference between the reference line C and the corresponding volume / particle number curve. The height difference between different channels is the height value of the corresponding channel in the flipped histogram. Therefore, the height of the reference line minus the height of the particle characteristic histogram can be obtained to obtain the corresponding flipped histogram. The flipped histogram is specifically as follows: Figure 7 As shown in FIG, the particle community represented in the flipped histogram is the flipped particle community.
[0080] S47: Determine a boundary line of the particle community according to the flipped histogram to distinguish the particle community.
[0081] Optionally, the boundary of the particle cluster can be calculated using the following formula:
[0082]
[0083] Among them, M k is the boundary line of the particle population, that is, the boundary line between the platelet and red blood cell populations, corresponding to a certain volume channel; i is the channel value in the flipped histogram, corresponding to the volume size of the particle, g(i) is the value of the flipped histogram in the i-th channel, and g(·) is the processing function that satisfies: g(x)≥g(y)≥0.
[0084] In this embodiment, by converting the particle intersection area of platelets and red blood cells into a flipped histogram, it is equivalent to converting the goal of finding the lowest point in the particle intersection area into finding the highest point in the flipped histogram. The above formula can be used to characterize the highest point of the flipped histogram from a statistical perspective, that is, the lowest point in the corresponding particle intersection area. Finally, the channel where the dividing line between platelets and red blood cells in the corresponding particle characteristic distribution histogram is located can be determined, thereby accurately distinguishing the platelet population from the red blood cell population.
[0085] Expanding the above formula reveals that the essence of the formula is actually a weighted summation of the volume sizes corresponding to all channels, and the weight of each channel is determined by the number of particles at the current channel in the flipped histogram. For example, the weight ai of the i-th channel is determined by the value of the height of the i-th channel in the flipped histogram processed by the function g(·) and the sum of the heights of all channels in the flipped histogram processed by the function g(·). Since the function g(·) satisfies g(x)≥g(y)≥0, Therefore, the larger the channel height in the flip histogram, the larger the corresponding weight ai, that is, channel i in M k Therefore, the M calculated in this way k It should be close to the actual highest point in the flip histogram, so that the boundary of the particle population can be accurately determined and used to distinguish platelets from red blood cells.
[0086] Moreover, in this embodiment, since the number of particles corresponding to the reference line in the particle characteristic distribution histogram is not lower than the number of particles corresponding to the right boundary, or not lower than the number of particles corresponding to any channel within the preset particle number range to the left of the right boundary, this makes the method of this embodiment have a certain adaptability and can be adapted to different blood samples, especially when abnormal blood samples with lower concentrations appear, a better solution can be obtained.
[0087] For example, when the upper limit of platelet volume and the lower limit of red blood cell volume of the sample are quite close, the selection and determination of the particle intersection area and the reference line will become particularly important. If the intersection area is too large or too small, it may lead to a large error in calculating the dividing line, resulting in poor results in distinguishing particle populations. The method of this embodiment can use some rules to reasonably avoid such errors and improve the accuracy of the dividing line.
[0088] And for the determination of the reference line, if the reference line height is set too low, the difference between the reference line height and the height of each channel is not much, so that the number of each channel of the flip particle colony in the flip histogram is small. Since the basis for calculating the dividing line according to the above-mentioned preset formula is related to weight and weight ratio, when the height difference is not big, it may cause the weight corresponding to each channel of the flip particle colony calculated to have an error, or even an error in the weight ratio, thereby obtaining a dividing line with poor accuracy. The method of the present embodiment sets the reference line height to be not less than the corresponding height of the right boundary, which can increase the height difference between the reference line and each channel, thereby reducing the problem of low accuracy of the dividing line caused by the weight error. Therefore, by determining the rationality of the particle intersection area, and further reasonably setting the reference line on the basis of the particle intersection area, the accuracy of the dividing line calculation can be improved together.
[0089] It should be noted that this embodiment does not limit the upper limit of the height of the reference line. In some embodiments, the specific setting of the reference line may not be limited to the above two cases. Under the premise of ensuring the calculation accuracy, the height of the reference line can even be much larger than the height corresponding to the right boundary. For example, the height of the reference line is N times the height corresponding to the right boundary, where the value of N can be set according to the upper and lower limits of the volume of different particle communities, or can also be set according to the highest and lowest points of the corresponding channels in the particle intersection area, so that the reference line obtained according to a reasonable setting method can adapt to various blood samples, have a certain stability, and accurately calculate the dividing line based on the preset formula.
[0090] See Figure 8 , Figure 8 : is a flow chart of a third embodiment of the method for distinguishing particle colonies provided by the present application. The method of this embodiment specifically includes:
[0091] S81: Obtaining a particle characteristic distribution histogram.
[0092] The first coordinate of the particle characteristic distribution histogram is the channel representing the particle characteristic, and the second coordinate of the particle characteristic distribution histogram is the number of particles. In this embodiment, since the volume of platelets and red blood cells is significantly different, the particle characteristic is the volume of the particle.
[0093] The particle characteristic distribution histogram is obtained by statistically measuring the blood sample solution using a blood cell analyzer. The specific principle has been introduced in the above embodiments and will not be elaborated on here.
[0094] S82: Determine a left boundary in the particle characteristic distribution histogram, determine a right boundary based on the maximum number of particles within a preset channel range to the right of the left boundary, and determine a particle intersection area based on the left boundary and the right boundary.
[0095] The particle intersection region refers to the part where the platelet colony and the red blood cell colony meet, and usually refers to the trough part between the platelet colony and the red blood cell colony. The specific intersection region needs to be determined or adjusted according to the actual situation. For example, when the trough feature is not obvious, the particle intersection region needs to be accurately limited through certain calculation or historical experience to improve the accuracy of subsequent boundary line calculation.
[0096] In this embodiment, the left boundary corresponds to a certain volume channel. The left boundary can be determined according to the number of specific particles in a certain volume range. For example, in the volume channel of the platelet colony, the channel with the maximum number of particles is taken as the left boundary corresponding channel, or in the volume range of the platelet colony, the channel adjacent to the right side of the channel with the maximum number of particles is taken as the left boundary corresponding channel. This is not limited, and can be set according to the actual situation.
[0097] The preset channel range refers to the estimated distribution range of the target particles. In this embodiment, it can be the distribution range of the platelet colony. Usually, it is preset based on the experience of the analyzer operator. A maximum particle number is determined in the preset channel range, which is the right boundary. The particle intersection region is determined based on the left boundary and the right boundary. The particle intersection region represents a special channel distribution range, which corresponds to a part of the volume / particle number curve and includes the actual boundary line between the platelet colony and the red blood cell colony, and can distinguish platelets and red blood cells.
[0098] S83: Determine the reference line located in the intersection region.
[0099] The reference line is parallel to the first direction, and the distance between the reference line and the first direction represents the reference flip height RefH (Reference Height) of the reference line. In this embodiment, the specific position of the reference line is related to the histogram particle intersection region, and specifically related to the height of the volume / particle number curve in the particle intersection region. The existence of the reference line is equivalent to setting a reference standard value for the curve of the particle intersection region, which can set the particle number of all channels in the intersection region to a reasonable standard, so that the boundary line can be calculated and determined based on the particle number under the standard in the subsequent process.
[0100] S84: Generate a corresponding flip histogram according to the particle characteristic distribution histogram and the reference line.
[0101] Among them, the flipped histogram is a histogram formed by flipping the particle characteristic distribution histogram according to the reference line. In other embodiments, it is also called an equivalent negative histogram. In each volume channel of the particle intersection area, there is the same or different height difference (distance) between all reference lines and the corresponding volume / particle number curve. The height difference between different channels is the height value of the corresponding channel of the flipped histogram, thereby generating a flipped histogram corresponding to the particle intersection area. The particle community represented in the flipped histogram is the flipped particle community.
[0102] S85: Determine a boundary line of the particle population according to the flipped histogram to distinguish the particle population.
[0103] In this embodiment, by converting the particle intersection area of platelets and red blood cells into a flipped histogram, it is equivalent to converting the goal of finding the lowest point in the particle intersection area into finding the highest point in the flipped histogram, and then calculating the maximum statistic of the flipped particle community in the flipped histogram according to a preset formula. The maximum statistic represents the value of the volume channel, that is, the lowest point in the corresponding particle intersection area. Finally, the channel where the dividing line between platelets and red blood cells in the corresponding particle characteristic distribution histogram is located can be determined, thereby accurately distinguishing the platelet community from the red blood cell community.
[0104] Furthermore, the method for determining the dividing line in this embodiment can be applied to different blood samples (including normal, abnormal or low-concentration samples). When determining the intersection area, the particle intersection area can be adaptively determined based on the actual situation of the trough in the particle characteristic distribution histogram; and then when determining the reference line, the reference line can be adaptively determined based on the actual situation of the volume / particle number curve in the particle intersection area. This approach can further improve the calculation accuracy of the dividing line, thereby further improving the accuracy of distinguishing particle populations.
[0105] Different from the existing technology, the method for distinguishing particle colonies provided in this embodiment determines the left and right boundaries in the obtained particle characteristic distribution histogram, and determines the particle intersection area based on the left and right boundaries, as well as a reference line located within the intersection area. A corresponding flipped histogram is further generated based on the particle characteristic distribution histogram and the reference line. Finally, the boundary line of the particle colony is determined based on the flipped histogram to achieve particle colony differentiation. In this way, on the one hand, using the flipped histogram to determine the boundary line of the particle colony can improve the accuracy of distinguishing particle colonies. On the other hand, by first determining the particle intersection area and then determining the reference line, it can be applied to different blood samples, has a certain degree of stability, and can further improve the accuracy of distinguishing particle colonies.
[0106] See Figure 9 , Figure 9 : is a flow chart of a fourth embodiment of a method for distinguishing particle colonies provided by the present application. The method of this embodiment specifically includes:
[0107] S91: Obtain a particle characteristic distribution histogram.
[0108] The first direction coordinate of the particle characteristic distribution histogram is the channel representing the particle characteristic, and the second direction coordinate of the particle characteristic distribution histogram is the number of particles. In this embodiment, the particle characteristic is the volume of the particle.
[0109] S92: Determine a first preset channel range in the particle characteristic distribution histogram.
[0110] Among them, the first preset channel range is a part of the estimated channel distribution range of the target particles, which can specifically be the channel distribution range of the platelet community in this embodiment. The first preset channel range is used to determine the left boundary of the intersection area, and can be preset based on historical experience. For example, after obtaining the analysis statistical information of multiple historical blood samples, the analyzer operator analyzes the historical particle characteristic distribution histogram to obtain different multiple historical left boundary information. The first preset channel range can be further determined based on this part of the historical left boundary information, and the operator inputs the value into the instrument for use in this or subsequent particle characteristic histograms.
[0111] S93: Determine a left boundary corresponding to the maximum number of particles within the first preset channel range.
[0112] See Figure 10 , Figure 10 This is a schematic diagram of the preset channel range. As shown in the figure, the range indicated by X1 is the first preset channel range. As can be clearly seen from the figure, there is a maximum point, Max1, within the first preset channel range. This indicates that the volume channel corresponding to this point has the largest number of particles within X1, thus determining the left boundary channel. In other embodiments, the left boundary channel may also be the channel to the right of the channel corresponding to the maximum number of particles. This is not a limitation here and can be set according to actual circumstances.
[0113] Optionally, when there are multiple maximum particle counts within the first preset channel range, the particle counts of the Q adjacent left and right channels corresponding to the multiple maximum particle counts can be calculated to obtain the difference between the particle counts of the Q channels and the maximum particle count. The channel corresponding to the maximum particle count of the Q channels with the smallest difference is then selected as the left boundary channel. Q can be 5-10.
[0114] S94: Determine the minimum number of particles within a second preset channel range on the right side of the left boundary.
[0115] like Figure 10 As shown, the range represented by X2 is the second preset channel range, which is another part of the estimated channel distribution range of the target particles. It can be clearly seen from the figure that there is a minimum point Min in the second preset channel range, indicating that the number of particles in the volume channel corresponding to this point is the smallest in X2, so it can be determined that the channel corresponding to the minimum point min is the middle channel.
[0116] S95: Determine a right boundary corresponding to the maximum number of particles within a third preset channel range to the right of the channel corresponding to the minimum number of particles.
[0117] like Figure 10 As shown in the figure, the range represented by X3 is the third preset channel range. The third preset channel range indicates that the channel corresponding to the lowest point Min in X2 is the starting point of the range, and the channel to the right of the channel corresponding to Min is separated by a certain number of channels as the end point of the range, thereby forming the third preset channel range. It can be clearly seen from the figure that there is a highest point Max2 in the third preset channel range, indicating that the number of particles in the volume channel corresponding to this point is the largest in X3, which can be determined as the right boundary channel.
[0118] In other embodiments, the left boundary and the right boundary can also be determined based on any channel within the preset particle number range to the right or left of the highest point Max1 in X1, and any channel within the preset particle number range to the left or right of the highest point Max2 in X3. The specific method is similar to that of the aforementioned embodiment and will not be elaborated on here.
[0119] Optionally, X1, X2 and X3 may all be channel ranges preset based on historical experience, which can be used to accurately define the ranges of the left boundary and the right boundary, thereby adapting to different samples.
[0120] Optionally, the second preset channel range can be a fixed value, and its specific position needs to be determined by the first preset channel range, that is, the size of the second preset channel range can remain unchanged, while the size of the first preset channel range may change, and the specific setting needs to be made according to the actual situation; further, the third preset channel range can also be a fixed value, and its specific position changes according to the specific position of the lowest point Min in the second preset channel range. Therefore, the end point of the third preset channel range may be within the end point of the second preset channel range, or it may be outside the end point of the second preset channel range, or it may coincide with the end point of the second preset channel range. The intersection area determined in this way has a certain adaptability and can improve the accuracy of the calculation of subsequent dividing lines.
[0121] S96: Determine a particle intersection region based on the left boundary and the right boundary.
[0122] See 11, Figure 11 Another particle characteristic distribution histogram provided for this application shows that the particle intersection area is a channel distribution range used to represent the intersection between platelets and red blood cells. The dotted line D near the left is the left boundary D, and the dotted line E near the right is the right boundary E. Both dotted lines D and E are parallel to the second direction, wherein the number of particles in the channel corresponding to the right boundary E is greater than the number of particles in the channel corresponding to the left boundary D. The particle intersection area determined in this way can be within a more reasonable channel range, and some channels that clearly do not belong to the dividing line can be excluded from the particle intersection area. Or, when the trough characteristics of the curve are not obvious, the intersection area can be accurately defined in the above manner, thereby improving the accuracy of subsequent dividing line calculations.
[0123] S97: Determine a reference line within the intersection area.
[0124] Continue reading Figure 11 The horizontal dotted line F in the figure is the reference line F, and its height represents the reference flip height RefH. The reference line F is parallel to the first direction. In this embodiment, the number of particles corresponding to the reference line F is not less than the minimum number of particles, that is, not less than the number of particles corresponding to the middle channel, that is, the height corresponding to the reference line F needs to be greater than the lowest point Min( Figure 11 (not shown) corresponds to the height.
[0125] In a specific embodiment, the number of particles corresponding to the reference line may be equal to:
[0126] 0.3*MIN(m1, m2)+0.7*m3, where m1 is the number of particles corresponding to the left boundary, m2 is the number of particles corresponding to the right boundary, m3 is the minimum number of particles, and MIN(m1, m2) is the smaller value between m1 and m2. The number of particles corresponding to the reference line calculated in this way can then be used to determine the height position of the reference line. The reference line determined in this way comprehensively refers to the actual particle conditions at the left boundary, right boundary, and middle channel, so that the determined reference line can be at a relatively reasonable height to adapt to different blood samples and have a certain degree of stability. In other embodiments, the setting of the reference line can be adjusted according to actual conditions, which will not be detailed here.
[0127] S98: Subtract the height of the particle characteristic distribution histogram from the height of the reference line to obtain a corresponding flipped histogram.
[0128] Among them, for particles outside the intersection area, the height of the flipped histogram is determined to be 0. For particles within the intersection area, the height of the flipped histogram is determined to be the height of the reference line, and the height value obtained by subtracting the height of the particle characteristic distribution histogram is the height difference between the reference line F and the corresponding volume / particle number curve.
[0129] In this embodiment, the flipped histogram mainly corresponds to the particle intersection area. The height of the particle characteristic distribution histogram is the height corresponding to multiple volume channels in the particle intersection area. In each volume channel of the particle intersection area, there is the same or different height difference between the reference line F and the corresponding volume / particle number curve. The height difference between different channels is the height value of the corresponding channel in the flipped histogram. Therefore, the height of the reference line minus the height of the particle characteristic histogram can be obtained to obtain the corresponding flipped histogram. The flipped histogram is specifically as follows: Figure 12 As shown in FIG, the particle community represented in the flipped histogram is the flipped particle community.
[0130] S99: Determine the boundary of the particle population based on the flipped histogram to distinguish the particle population.
[0131] Alternatively, the boundary of a particle cluster can be calculated using the following formula:
[0132]
[0133] Among them, M k is the boundary line of the particle population, that is, the boundary line between the platelet and red blood cell populations, corresponding to a certain volume channel; i is the channel value in the flipped histogram, corresponding to the volume size of the particle, f(i) is the value of the flipped histogram in the i-th channel, g(·) is the processing function, and satisfies: g(x)≥g(y)≥0.
[0134] The principle of the above formula has been described in the aforementioned embodiment. It can be seen that the formula can accurately determine the boundary line of the particle community and be used to distinguish platelets from red blood cells. The rest of the formula will not be elaborated here and should be understood by those skilled in the art.
[0135] Moreover, in this embodiment, since the number of particles corresponding to the reference line in the particle characteristic distribution histogram is not lower than the number of particles corresponding to the middle channel, this makes the method of this embodiment have a certain adaptability and can be adapted to different blood samples, especially when abnormal blood samples with lower concentrations appear, a better solution can be obtained.
[0136] For example, when the upper limit of platelet volume and the lower limit of red blood cell volume of the sample are quite close, the selection and determination of the particle intersection area and the reference line will become particularly important. If the intersection area is too large or too small, it may lead to a large error in calculating the dividing line, resulting in poor results in distinguishing particle populations. The method of this embodiment can use some rules to reasonably avoid such errors and improve the accuracy of the dividing line.
[0137] As for determining the reference line, if the reference line height is set too low, it will eventually lead to poor accuracy of the dividing line calculated by the preset formula in the flipped histogram. The method of this embodiment sets the reference line height to be no less than the number of particles corresponding to the middle channel, and can even be much larger than the middle channel, the left boundary channel or the right boundary channel, thereby improving the accuracy. The details have been introduced in the previous embodiment and will not be repeated here.
[0138] It should be noted that this embodiment does not limit the upper limit of the height of the reference line. In some embodiments, the specific setting of the reference line may not be limited to the above situation. Under the premise of ensuring the calculation accuracy, the height of the reference line can be, for example, N times the height corresponding to the middle channel, where the value of N can be set according to the upper and lower limits of the volume of different particle communities, or can also be set according to the highest and lowest points of the corresponding channels in the particle intersection area, so that the reference line obtained according to a reasonable setting method can adapt to various blood samples, have a certain stability, and accurately calculate the dividing line based on the preset formula.
[0139] See Figure 13 , Figure 13 1 is a schematic structural diagram of an embodiment of a particle analysis device provided by the present application. The particle analysis device 130 of this embodiment includes a processor 131 and a memory 132. The processor 131 is coupled to the memory 132. The memory 132 is used to store a computer program executed by the processor 131. The processor 131 is used to execute the computer program to implement the following method steps:
[0140] A particle characteristic distribution histogram is obtained; wherein the first direction coordinate of the particle characteristic distribution histogram is a channel representing the particle characteristic, and the second direction coordinate of the particle characteristic distribution histogram is the particle number; a left boundary is determined in the particle characteristic distribution histogram, and a right boundary is determined based on the maximum particle number within a preset channel range to the right of the left boundary, and a particle intersection area is determined based on the left boundary and the right boundary; a reference line located within the intersection area is determined; wherein the reference line is parallel to the first direction; a corresponding flipped histogram is generated based on the particle characteristic distribution histogram and the reference line; and a boundary line of a particle population is determined based on the flipped histogram to distinguish the particle populations.
[0141] See Figure 14 , Figure 14 1 is a schematic diagram of the structure of an embodiment of a computer-readable storage medium provided by the present application. The computer-readable storage medium 140 of this embodiment is used to store a computer program 141. When the computer program 141 is executed by a processor, it is used to implement the following method steps:
[0142] A particle characteristic distribution histogram is obtained; wherein the first direction coordinate of the particle characteristic distribution histogram is a channel representing the particle characteristic, and the second direction coordinate of the particle characteristic distribution histogram is the particle number; a left boundary is determined in the particle characteristic distribution histogram, and a right boundary is determined based on the maximum particle number within a preset channel range to the right of the left boundary, and a particle intersection area is determined based on the left boundary and the right boundary; a reference line located within the intersection area is determined; wherein the reference line is parallel to the first direction; a corresponding flipped histogram is generated based on the particle characteristic distribution histogram and the reference line; and a boundary line of a particle population is determined based on the flipped histogram to distinguish the particle populations.
[0143] It should be noted that the method steps executed by the computer program 141 of this embodiment are based on the above method embodiments, and their implementation principles and steps are similar. Therefore, when the computer program 141 is executed by the processor, it can also implement other method steps in any of the above embodiments, which will not be repeated here.
[0144] When the embodiments of the present application are implemented in the form of software functional units and sold or used as independent products, they can be stored in a computer-readable storage medium. Based on this understanding, the technical solution of the present application is essentially or the part that contributes to the prior art or all or part of the technical solution can be embodied in the form of a software product, and the computer software product is stored in a storage medium, including a number of instructions for enabling a computer device (which can be a personal computer, a server, or a network device, etc.) or a processor to execute all or part of the steps of the method described in each embodiment of the present application. The aforementioned storage medium includes various media that can store program codes, such as a USB flash drive, a mobile hard disk, a read-only memory (ROM), a random access memory (RAM), a magnetic disk or an optical disk.
[0145] The above description is only an implementation method of the present application and does not limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made according to the contents of the description and drawings of this application, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present application.
Claims
1. A method for distinguishing particle populations, characterized in that: The method comprises: Obtaining a particle characteristic distribution histogram; wherein the first direction coordinate of the particle characteristic distribution histogram is a channel representing a particle characteristic, the second direction coordinate of the particle characteristic distribution histogram is the number of particles; the particle characteristic is the volume of the particle; each channel includes a plurality of particles corresponding to voltages of the same height; Determining a left boundary in the particle characteristic distribution histogram, and determining a right boundary based on a maximum number of particles within a preset channel range to the right of the left boundary, and determining a particle intersection area based on the left boundary and the right boundary; wherein the left boundary and the right boundary respectively correspond to different volume channels, and the preset channel range refers to an estimated channel distribution range of the target particles; Determining a reference line located within the intersection area; wherein the reference line extends along the first direction; generating a corresponding flipped histogram according to the particle characteristic distribution histogram and the reference line; According to the flipped histogram, the boundary line of the particle population is determined to distinguish the particle population.
2. The method according to claim 1, characterized in that Determining the left boundary in the particle characteristic distribution histogram includes: Determining a first preset channel range in the particle characteristic distribution histogram; Within the first preset channel range, a left boundary corresponding to the maximum number of particles is determined.
3. The method according to claim 2, characterized in that The first preset channel range is the estimated channel distribution range of the target particles.
4. The method according to claim 1, wherein Determining the right boundary based on the maximum number of particles within the preset channel range to the right of the left boundary includes: Determining a minimum number of particles within a second preset channel range to the right of the left boundary; Within a third preset channel range on the right side of the channel corresponding to the minimum value of the particle quantity, a right boundary corresponding to the maximum value of the particle quantity is determined.
5. The method according to claim 4, characterized in that The number of particles corresponding to the reference line is not less than the minimum number of particles.
6. The method according to claim 5, characterized in that The number of particles corresponding to the reference line is equal to: 0.3*MIN(m1,m2)+0.7*m3; Among them, m1 is the number of particles corresponding to the left boundary, m2 is the number of particles corresponding to the right boundary, m3 is the minimum number of particles, and MIN(m1, m2) is the smaller value between m1 and m2.
7. The method according to claim 1, characterized in that Generating a corresponding flip histogram according to the particle characteristic distribution histogram and the reference line includes: The height of the particle characteristic distribution histogram is subtracted from the height of the reference line to obtain a corresponding flipped histogram.
8. The method according to claim 7, characterized in that Subtracting the height of the particle characteristic distribution histogram from the height of the reference line to obtain a corresponding flipped histogram includes: For regions outside the particle intersection region, determining the height of the flipped histogram to be 0; and Within the particle intersection region, the height of the flipped histogram is determined to be the height of the reference line minus the height of the particle characteristic distribution histogram.
9. The method according to claim 1, characterized in that Determining the boundary of the particle population according to the flipped histogram to distinguish the particle population includes: The dividing line is calculated using the following formula: Among them, M k is the boundary of the particle community, i is the channel value in the flipped histogram, f(i) is the value of the flipped histogram in the i-th channel, g(·) is the processing function, and satisfies: g(x)≥g(y)≥0.
10. A particle analysis device, characterized in that: The method comprises a processor and a memory, wherein the memory is used to store a computer program, and when the computer program is executed by the processor, it is used to implement the method for distinguishing particle colonies according to any one of claims 1 to 9.
11. A computer-readable storage medium, characterized in that Used to store a computer program, which, when executed by a processor, is used to implement the method for distinguishing particle colonies according to any one of claims 1 to 9.
Citation Information
Patent Citations
Method for recognizing erythrocyte chips
CN101464245A
Method for classifying particles and device for detecting particles
CN101762448A