Imaging mass spectrometry data processing device

Abstract

After the imaging mass spectrometry unit (1) collects mass spectrometry data for each of the many measurement points in the two-dimensional region on the sample, the user inputs the target compound whose two-dimensional distribution is to be observed from the input unit (3). The image display indication receiving unit (22) calculates the m / z range for data integration according to the precise m / z value and the allowable range of m / z for each target compound. The mass-to-charge ratio range overlap determination unit (23) determines whether the m / z ranges of multiple compounds overlap. If there is an overlap, the overlap determination result processing unit (24) prepares a list of compounds with overlapping m / z ranges and displays it on the screen of the display unit (4). This prompts the user to review the compound or the allowable value. In addition, it is also possible to prepare an MS imaging image of each compound in a state where the m / z range overlaps, list it, and display it, and at this time, the MS imaging image of the compound with overlapping m / z ranges is given a mark that can be distinguished from other images.

Description

Technical Field

[0001] The present invention relates to an imaging mass spectrometry data processing device that processes mass spectrometry data of each of many tiny areas in a two-dimensional area on a sample collected by an imaging mass spectrometry device, and produces and displays an image, for example, representing the two-dimensional intensity distribution of a specific substance. Background Art

[0002] An imaging mass spectrometer is a device that can measure the two-dimensional intensity distribution of ions with a specific mass-to-charge ratio m / z on the surface of a sample such as a biological tissue slice while observing the morphology of the surface through an optical microscope (see Patent Document 1, Non-Patent Document 1, etc.). By using an imaging mass spectrometer to observe mass spectrometry imaging images related to ions derived from compounds that characteristically appear in a specific disease such as cancer, it is possible to understand the spread of the disease, etc. Therefore, in recent years, the following research has been prevalent: using imaging mass spectrometers to analyze the dynamic analysis of drugs, the differences in compound distribution in various organs, or the differences in compound distribution between pathological sites and normal sites of cancer, etc.

[0003] In the imaging mass spectrometry device, mass spectrometry is performed over a specified mass-to-charge ratio range for each of the many micro-regions (measurement points) set in a two-dimensional region on the sample. However, the data obtained in one micro-region is profile spectrum data representing a continuous waveform in the mass-to-charge ratio direction. In the data processing unit in the imaging mass spectrometry device, specifically, in the computer for data processing, the profile spectrum data of each micro-region collected by measurement is stored in a storage device, and various data processing is performed using the data to calculate information related to the sample.

[0004] In a conventional general imaging mass spectrometry data processing device (hereinafter referred to as "data processing device"), when a user wants to observe a two-dimensional distribution image of a specific compound in a sample, the user specifies the mass-to-charge ratio value M of the compound and the permissible range of the mass-to-charge ratio (hereinafter referred to as "permissible range") ΔM, and then instructs the execution of image production processing. After receiving the instruction, the data processing device integrates the signal intensity value of the mass-to-charge ratio range of M±ΔM based on the specified mass-to-charge ratio value M and the permissible range ΔM for each micro-region based on the profile spectrum data of each micro-region stored in the storage device, thereby calculating the signal intensity value corresponding to each micro-region, and forming and displaying an image representing the two-dimensional distribution of the signal intensity value.

[0005] The precise mass values ​​(or theoretical mass values) of various compounds are also included in known and common databases, etc. Therefore, when specifying a compound, the user can actually specify the mass-to-charge ratio value M corresponding to the compound by using this information. In addition, although the compound is unknown depending on the situation, there is also a situation where you want to observe the two-dimensional intensity distribution under a certain mass-to-charge ratio known to be contained in the sample. In this case, by directly specifying the mass-to-charge ratio value and the allowable range, it is also possible to display a two-dimensional intensity distribution image under the mass-to-charge ratio.

[0006] Generally, in most cases, the user wants to merge the two-dimensional distributions of many various compounds contained in the sample for confirmation. Therefore, in the above-mentioned data processing device, it is possible to specify the mass-to-charge ratio value M and the allowable range ΔM of multiple compounds during image production processing. However, the mass-to-charge ratio value is not necessarily unique to the compound. For example, different compounds with the same composition formula cannot be distinguished from each other in principle. In addition, there are also many compounds with different composition formulas but extremely close molecular weights. When the user specifies multiple such compounds as the compounds for which the two-dimensional distribution image is to be observed, the mass-to-charge ratio range as M±ΔM related to the multiple compounds overlaps in whole or in part. Therefore, an image showing substantially the same two-dimensional intensity distribution is formed for each compound.

[0007] In this case, when the user does not accurately grasp the mass-to-charge ratio of the specified compound, there is a concern that the user may mistakenly judge that the spatial distributions of the multiple compounds are very close, even though one of the multiple compounds is actually not present in the sample. On the contrary, there is also a concern that the user may mistakenly judge that the spatial distribution is that of one compound and the other compounds are not present, even though the multiple specified compounds are present in the sample with close spatial distributions.

[0008] Prior art literature

[0009] Patent Literature

[0010] Patent Document 1: International Publication No. 2017 / 183086

[0011] Non-patent literature

[0012] Non-Patent Document 1: "iMScopeTRIO Imaging Quality Microscope", [Online], [retrieved on March 16, 2011], Shimadzu Corporation, Internet <URL: http: / / www.an.shimadzu.co.jp / bio / imscope / > Summary of the invention

[0013] Problem that the invention aims to solve

[0014] The present invention is completed to solve the above-mentioned problem, and its purpose is to provide an imaging mass spectrometry data processing device that enables the user to accurately grasp the distribution status of compounds or ions with a specific mass-to-charge ratio when the user wants to observe the two-dimensional distribution images of multiple compounds or the two-dimensional intensity distribution images at multiple mass-to-charge ratios.

[0015] Solutions for solving problems

[0016] The present invention, which is completed in order to solve the above-mentioned problems, is an imaging mass spectrometry data processing device, which processes mass spectrometry data obtained from a plurality of micro-regions in a two-dimensional region on a sample, and the imaging mass spectrometry data processing device comprises:

[0017] a) an input setting section for a user to specify a compound and / or a mass-to-charge ratio value for which a two-dimensional intensity distribution based on the mass spectrometry data is desired to be observed;

[0018] b) a determination unit that, when there are multiple mass-to-charge ratio values ​​corresponding to the compound specified by the user via the input setting unit and / or multiple mass-to-charge ratio values ​​specified by the user, determines, for each of the mass-to-charge ratio values, whether multiple mass-to-charge ratio ranges having a prescribed or specified allowable range overlap; and

[0019] c) an information providing unit which, when the determining unit determines that a plurality of mass-to-charge ratio ranges overlap, provides the user with at least information indicating that the mass-to-charge ratio ranges overlap in the case of the compound and / or mass-to-charge ratio value specified by the user.

[0020] The "mass spectrometry data" in the present invention includes not only simple mass spectrometry data without fragmentation operation on ions, but also mass spectrometry data obtained by MS with n being 2 or more. n Analysis of the obtained MS n The mass spectrometry data is generally profile spectrum data showing a continuous waveform, but is not limited thereto and may also be data showing a mass spectrum having a mountain-shaped peak formed by histogramming using, for example, centroid processing and then assigning a predetermined peak width to each column.

[0021] When the compound for which the two-dimensional intensity distribution is to be observed has been determined, the user specifies the compound using the input setting unit. The method for specifying the compound is not particularly limited, and the compound name can be directly input, or the compound as the target can be selected from a pre-prepared compound list, or a plurality of compounds recorded in the pre-prepared compound list itself can be collectively specified. In addition, the mass-to-charge ratio value itself can be specified instead of the specified compound. In this case, the compound to be observed may also be unknown.

[0022] When there are multiple mass-to-charge ratio values ​​corresponding to the compound specified by the user via the input setting unit and / or when there are multiple mass-to-charge ratio values ​​specified by the user, the determination unit determines whether multiple mass-to-charge ratio ranges having a prescribed or specified tolerance overlap for each of the mass-to-charge ratio values.

[0023] The allowable range can also be specified at the same time when specifying a compound or mass-to-charge ratio value by inputting a setting unit. Alternatively, the allowable range can also be a predetermined value, or the allowable range can be calculated for each mass-to-charge ratio value (that is, according to the size of the mass-to-charge ratio value) according to a predetermined calculation formula or algorithm. The above-mentioned mass-to-charge ratio range is a window used when calculating the signal intensity value under the specified compound or mass-to-charge ratio value according to mass spectrum data. In other words, the area of ​​the peak waveform of the mass spectrum cut out by a mass-to-charge ratio range or the integral value of the data is the signal intensity value under the mass-to-charge ratio value in the mass-to-charge ratio range. Therefore, overlapping a part of the mass-to-charge ratio range corresponding to, for example, two different compounds refers to the same part of the peak waveform of the mass spectrum being repeatedly reflected in the signal intensity value of each compound.

[0024] Therefore, if it is determined that there is overlap in a plurality of mass-to-charge ratio ranges, the information providing unit at least provides information that enables the user to recognize that there is overlap in the mass-to-charge ratio ranges in the case of the compound or mass-to-charge ratio value specified by the user before making an image according to the specified conditions or at the time point when the made image is displayed on the screen of the display unit. The method of providing the information at this time can adopt various methods.

[0025] As a first aspect of the present invention, the information providing unit can provide the warning in a manner that can be recognized by a user.

[0026] That is, when a plurality of mass-to-charge ratio ranges overlap, the user's attention may be drawn to the warning display or warning sound.

[0027] Furthermore, as a second aspect of the present invention, the information providing unit can list compounds and / or mass-to-charge ratio values ​​having overlapping mass-to-charge ratio ranges and display the lists on the screen of the display unit.

[0028] Thus, the user can visually confirm on the display screen which mass-to-charge ratio range of a compound or which mass-to-charge ratio range corresponds to which mass-to-charge ratio that overlaps.

[0029] In addition, as a third aspect of the present invention, there is further provided an image generating unit for generating an image representing a two-dimensional intensity distribution using the mass spectrometry data for each of the plurality of mass-to-charge ratio ranges specified by a user via the input setting unit.

[0030] When displaying the image information created by the image creating unit on the screen of the display unit, the information providing unit can display images corresponding to compounds and / or mass-to-charge ratio values ​​having overlapping mass-to-charge ratio ranges so as to be visually distinguishable from other images.

[0031] In the third mode, even when there is overlap in multiple mass-to-charge ratio ranges, the image production unit uses the mass spectrometry data to produce images representing the two-dimensional intensity distribution for each mass-to-charge ratio range. In the case of a portion of the mass-to-charge ratio range corresponding to, for example, two different compounds overlapping, when a portion of the peak waveform of the mass spectrum exists in the overlapping range, the waveform portion is reflected to the signal intensity values ​​of both of the above-mentioned two compounds. Therefore, even if one of the two compounds does not exist at all, a false signal intensity value for the compound appears. Therefore, when the information providing unit displays the image information produced by the image production unit on the display screen, the image corresponding to the compound with overlapping mass-to-charge ratio ranges, for example, is displayed in a manner that can be visually identified with the image corresponding to other compounds.

[0032] Specifically, for example, a plurality of images corresponding to compounds with overlapping mass-to-charge ratio ranges can be given a specific mark, or the display color of the frame surrounding the plurality of images corresponding to compounds with overlapping mass-to-charge ratio ranges can be made different from the other images. In addition, only the plurality of images corresponding to compounds with overlapping mass-to-charge ratio ranges can be automatically collected and displayed in a specified display area within the display screen. In short, as long as the two-dimensional distribution image of the compound, that is, the mass spectrometry imaging image, is displayed on the display screen in a manner that can be easily visually recognized by the user when viewing it, it can be used.

[0033] Furthermore, as described above, when there is overlap in mass-to-charge ratio ranges, not only may the user be notified of relevant information, but an image may be created in which the influence of the overlap is reduced or an image may be created assuming the overlap exists.

[0034] That is, as another embodiment of the present invention, the following structure is preferred: it also includes a mass-to-charge ratio range changing unit, and when the determination unit determines that a plurality of mass-to-charge ratio ranges overlap, the mass-to-charge ratio range changing unit changes at least one of the overlapping plurality of mass-to-charge ratio ranges so that the overlap disappears.

[0035] In this structure, the mass-to-charge ratio range changing unit reduces the mass-to-charge ratio range, for example, by changing the permissible amplitude of a part of the mass-to-charge ratio ranges in the overlapping multiple mass-to-charge ratio ranges, thereby eliminating the overlap of the mass-to-charge ratio ranges. Thus, in the case where the lower hem of the peaks corresponding to two adjacent compounds on the mass spectrum overlap, the peaks can be segmented in the same way as the vertical segmentation to calculate the respective signal intensity values. Thus, although not completely, the influence of the overlap of multiple mass-to-charge ratio ranges can be reduced to improve the accuracy of the signal intensity value.

[0036] However, when the composition formulas of the multiple compounds to be observed are the same, the mass-to-charge ratio ranges of the multiple compounds completely overlap, and when the mass-to-charge ratio values ​​of two compounds are extremely close, the difference between the mass-to-charge ratio ranges of the multiple compounds may be below the limit of the device performance. In such a case, it is essentially impossible to eliminate the overlap of the overlapping mass-to-charge ratio ranges.

[0037] Therefore, as another embodiment of the present invention, the following structure is preferred: it is equipped with an image production unit, which, when the determination unit determines that a plurality of mass-to-charge ratio ranges overlap, merges the overlapping plurality of mass-to-charge ratio ranges, virtually treats the plurality of compounds and / or mass-to-charge ratio values ​​corresponding to the plurality of mass-to-charge ratio ranges as one component, and uses the mass spectrometry analysis data to produce an image representing the two-dimensional intensity distribution.

[0038] According to this structure, although the two-dimensional intensity distribution of each of the plurality of compounds virtually used as one component is unknown, at least it is possible to avoid making erroneous judgments such as judging that a compound that does not exist is present or judging that a compound that exists is absent. In addition, the two-dimensional intensity distribution of a virtual component can be imaged with high precision.

[0039] Effects of the Invention

[0040] According to the present invention, when a user wants to observe mass spectrometry imaging images in multiple compounds, the user can accurately grasp, for example, whether the displayed mass spectrometry imaging image may not be derived from one compound, that is, whether the displayed mass spectrometry imaging image may be mixed with two-dimensional intensity information of other compounds, or whether the displayed mass spectrometry imaging image is likely to be derived purely from the target compound, etc. Thus, the user can accurately grasp the distribution of the target compound or ions with a specific mass-to-charge ratio. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 It is a schematic structural diagram of an embodiment of an imaging mass spectrometry device including the imaging mass spectrometry data processing device involved in the present invention.

[0042] Figure 2It is an explanatory diagram of the MS imaging image creation operation in the imaging mass spectrometer of this embodiment.

[0043] Figure 3 This is a schematic diagram showing the relationship between mass-to-charge ratio ranges when calculating signal intensity values ​​of a plurality of compounds close to each other on the m / z axis.

[0044] Figure 4 This is a diagram showing an example of a list displaying a plurality of compounds having overlapping mass-to-charge ratio ranges.

[0045] Figure 5 This is a diagram showing an example of a display screen that displays MS imaging images of a plurality of compounds having overlapping mass-to-charge ratio ranges.

[0046] Figure 6 This is a schematic diagram for explaining the operation when the mass-to-charge ratio range corresponding to a plurality of compounds close to each other on the m / z axis is changed.

[0047] Figure 7 This is a schematic diagram for explaining the operation when mass-to-charge ratio ranges corresponding to a plurality of compounds close to each other on the m / z axis are combined. DETAILED DESCRIPTION

[0048] Hereinafter, an embodiment of an imaging mass spectrometry device including an imaging mass spectrometry data processing device according to the present invention will be described with reference to the accompanying drawings.

[0049] Figure 1 is a schematic structural diagram of an imaging mass spectrometry device according to this embodiment, Figure 2 It is an explanatory diagram of the MS imaging image creation operation in the imaging mass spectrometer of this embodiment.

[0050] The imaging mass spectrometry device of this embodiment includes: an imaging mass spectrometry unit 1 for measuring a sample, a data processing unit 2, and an input unit 3 and a display unit 4 as a user interface. In addition, although not described here, the imaging mass spectrometry device also includes an optical microscope camera unit for capturing an optical microscope image of the sample.

[0051] The imaging mass spectrometry unit 1 includes, for example, a matrix-assisted laser desorption ionization ion trap time-of-flight mass spectrometry device, such as Figure 2 As shown in (a), mass spectrometry is performed on a plurality of measurement points (micro areas) 102 in a two-dimensional measurement area 101 on a sample 100 such as a biological tissue slice, and mass spectrometry data is acquired for each measurement point. Here, the mass spectrometry data is mass spectrometry data covering a predetermined mass-to-charge ratio range, but it may also be MS data for a specific precursor ion. n Spectral data.

[0052] The data processing unit 2 receives the mass spectrum data at each measurement point collected by the imaging mass spectrometry analysis unit 1 and performs prescribed processing. The data processing unit 2 includes a data collection unit 20, a data storage unit 21, an image display designation receiving unit 22, a mass-to-charge ratio range overlap determination unit 23, an overlap determination result processing unit 24, a mass-to-charge ratio range change processing unit 25, an imaging image production unit 26, a display processing unit 27 and other functional blocks.

[0053] Generally, the entity of the data processing unit 2 is a personal computer (or a workstation with higher performance), and the functions of the above-mentioned blocks are realized by running the dedicated software installed on the computer. In this case, the input unit 3 is a pointing device such as a keyboard or a mouse, and the display unit 4 is a display monitor.

[0054] In the imaging mass spectrometry apparatus of this embodiment, the user (operator) places the sample 100 at a predetermined measurement position of the imaging mass spectrometry unit 1. When a predetermined operation is performed through the input unit 3, the optical microscope camera unit (not shown) captures the surface of the sample 100 and displays the image on the screen of the display unit 4. The user specifies the desired measurement area 101 on the image using the input unit 3, and then instructs the start of measurement. Then, the imaging mass spectrometry unit 1 performs a measurement on the sample 100. Figure 2 The mass spectrometry analysis is performed on each of the many measurement points 102 in the measurement area 101 as shown in (a) to obtain mass spectrum data covering a predetermined mass-to-charge ratio range. At this time, the data acquisition unit 20 performs the so-called profile acquisition to collect Figure 2 The data storage unit 21 stores a waveform continuous in the mass-to-charge ratio direction over a predetermined mass-to-charge ratio range as shown in (b), i.e., profile spectrum data. Of course, the data storage unit 21 stores a data string obtained by digitizing samples, and the samples are obtained by sampling the continuous profile waveform at a predetermined sampling interval (an interval sufficiently small compared to the peak width of the waveform).

[0055] After the measurement of the target sample 100 is completed, the user specifies the compound (hereinafter referred to as the "target compound") in the sample 100 for which the two-dimensional intensity distribution is desired to be confirmed through the input unit 3. The target compound can be specified by, for example, directly inputting the compound name, selecting the compound from a pre-prepared compound list, etc. In addition, when specifying multiple target compounds, the target compounds can be specified one by one by the above method, or it is also possible to list multiple target compounds in advance, and by selecting the list, multiple target compounds recorded in the list can be collectively specified.

[0056] In addition, it is also possible to specify the mass-to-charge ratio value (hereinafter referred to as "target mass-to-charge ratio value") itself instead of specifying the target compound. It is preferred that, for example, the user can specify by selecting a peak of an appropriate mass-to-charge ratio from a peak list, which is prepared by performing peak detection on a mass spectrum obtained in the sample. Of course, the user can also directly input the mass-to-charge ratio value. In addition, when specifying a target mass-to-charge ratio value, the compound corresponding to the mass-to-charge ratio may also be unknown.

[0057] In addition, when the user specifies the target compound or target mass-to-charge ratio as the confirmation object of the two-dimensional intensity distribution, the user also specifies the allowable range ΔM when calculating the signal intensity value. However, it is also possible that when specifying multiple target compounds or target mass-to-charge ratio values, the allowable range may not be specified for each target compound or each target mass-to-charge ratio value. For example, the allowable range may be common to all target compounds or target mass-to-charge ratio values. In addition, it is also possible not to specify the allowable range with the numerical value of the unit of mass-to-charge ratio such as "Da" or "u", but to specify the allowable range with the ratio relative to the mass-to-charge ratio value that becomes the center, such as "ppm". Of course, it is also possible to specify methods other than this. It is important to determine some allowable ranges for each target compound or each target mass-to-charge ratio.

[0058] When a target compound is specified, the image display instruction receiving unit 22 refers to a pre-stored compound database, etc. to obtain a precise mass-to-charge ratio value (usually a theoretical value of the mass-to-charge ratio) corresponding to the specified compound. Therefore, regardless of whether the target compound or the target mass-to-charge ratio value is specified, information on the central mass-to-charge ratio value M and the allowable width ΔM is obtained for each target compound or each target mass-to-charge ratio value.

[0059] The mass-to-charge ratio range overlap determination unit 23 calculates the mass-to-charge ratio range [M-ΔM to M+ΔM] for integrating the signal intensity value for each target compound or each target mass-to-charge ratio value based on the mass-to-charge ratio value M and the allowable width ΔM. Then, it is checked whether there is any overlap between the mass-to-charge ratio ranges of all the specified target compounds and the mass-to-charge ratio range of the target mass-to-charge ratio value.

[0060] For example, Figure 3 (a) is an example in which the mass-to-charge ratio range of compound A [Ma-ΔM to Ma+ΔM] and the mass-to-charge ratio range of compound B [Mb-ΔM to Mb+ΔM] adjacent to each other on the mass-to-charge ratio axis do not overlap. Figure 3(b) is an example of a case where the mass-to-charge ratio range [Ma-ΔM to Ma+ΔM] of compound A and the mass-to-charge ratio range [Mb-ΔM to Mb+ΔM] of compound B, which are adjacent on the mass-to-charge ratio axis, overlap, and the partially overlapped portion is shown by hatching in the figure. The mass-to-charge ratio range overlap determination unit 23 determines whether there is overlap for all mass-to-charge ratio ranges. Of course, depending on the situation, there is also a situation where the mass-to-charge ratio ranges of more than three compounds overlap.

[0061] In the case where there is no overlap of mass-to-charge ratio ranges, the imaging image generating unit 26 that has received the notification of the result extracts data included in the mass-to-charge ratio range of the target compound or the target mass-to-charge ratio value from the profile spectrum data of each measurement point 102 and reads it from the data storage unit 21, and integrates the data included in the mass-to-charge ratio range to obtain a signal intensity value (refer to Figure 3 (c)). Thus, the signal intensity values ​​of the plurality of measurement points 102 included in the measurement region 101 are obtained for each target compound or each target mass-to-charge ratio value, and the signal intensity values ​​are arranged two-dimensionally according to the positions of the measurement points, and display colors are assigned to the signal intensity values ​​according to a predetermined color scale, thereby producing Figure 2 The display processing unit 27 displays the mass spectrometry imaging image 200 created for each target compound or each target mass-to-charge ratio on the screen of the display unit 4 in the form of a list, for example.

[0062] On the other hand, when at least one set of the plurality of mass-to-charge ratio ranges overlaps, the overlap determination result processing unit 24 that has received notification of the result simultaneously executes any one or more of the following processes. In addition, it is preferable that the user can set in advance which process to execute.

[0063] <Process 1> Warning about overlapping mass-to-charge ratio ranges

[0064] The overlap determination result processing unit 24 displays a warning indicating that there is an overlap in the mass-to-charge ratio ranges on the screen of the display unit 4. Alternatively, a warning sound or the like may be issued at the same time.

[0065] <Processing 2> List display of compounds with overlapping mass-to-charge ratio ranges, etc.

[0066] The overlap determination result processing unit 24 creates a list of target compounds or target mass-to-charge ratio values ​​having overlapping mass-to-charge ratio ranges, and displays the list on the screen of the display unit 4 . Figure 4 The mass-to-charge ratio of compounds A and B is as follows Figure 3 An example of a list in the case of overlapping as shown in (b) of FIG. 1. The user can immediately confirm, for example, which compound has an overlapping mass-to-charge ratio range from which compound based on the displayed list.

[0067] In addition, in the case of the above-mentioned process 1 and process 2, a warning display or a list display may be performed, and a mass spectrometry imaging image may be produced for each target compound or each mass-to-charge ratio value as described above while maintaining the mass-to-charge ratio range in an overlapping state. Alternatively, a mass spectrometry imaging image may be produced for each target compound or each mass-to-charge ratio value as described above after the mass-to-charge ratio range is automatically changed as described later. Alternatively, after the warning display or the list display is performed, the user's instruction may be waited for, that is, if there is an instruction from the user to produce an image, the mass spectrometry imaging image may be produced instead of being produced immediately.

[0068] <Process 3> Explicit display of overlapping compounds etc. on mass spectrometry imaging image display

[0069] After receiving the instruction from the overlap determination result processing unit 24, the imaging image production unit 26 produces a mass spectrometry imaging image for each target compound or each mass-to-charge ratio value as described above, while keeping the mass-to-charge ratio range in which a part of the overlap exists unchanged. The display processing unit 27 displays the mass spectrometry imaging image produced for each target compound or each target mass-to-charge ratio value on the screen of the display unit 4 in the form of a list, for example. At this time, the overlap determination result processing unit 24 gives the mass spectrometry imaging image corresponding to the target compound or target mass-to-charge ratio value overlapping with the mass-to-charge ratio range a mark that can be distinguished from other mass spectrometry imaging images (that is, mass-to-charge ratio ranges that do not overlap) on the display.

[0070] Figure 5 It is shown as Figure 3 FIG. 4 is an example of a mass spectrometry imaging image list in the case where the mass-to-charge ratio ranges of compounds A and B overlap as shown in (b). In this example, thumbnail images of mass spectrometry imaging images of multiple target compounds specified by the user are arranged in an image list screen 400. Among them, the mass spectrometry imaging images of compounds A and B with overlapping mass-to-charge ratio ranges are surrounded by a frame 401 of the same display color. Thus, the user can recognize at a glance the mass spectrometry imaging images of the target compounds or target mass-to-charge ratio values ​​with overlapping mass-to-charge ratio ranges. Of course, it is possible not to use Figure 5 The frame 401 shown in the figure is shown in the figure using a mark or symbol of any shape such as an arrow. In addition, the image can be appropriately rearranged so that the mass spectrometry imaging images of the target compound or target mass-to-charge ratio value with overlapping mass-to-charge ratio ranges converge within the same frame for display. In short, as long as the mass spectrometry imaging images of the target compound or target mass-to-charge ratio value with overlapping mass-to-charge ratio ranges are displayed in a manner that can be easily distinguished from other images.

[0071] When a mass spectrometry imaging image is produced in a state where the mass-to-charge ratio ranges of compounds A and B overlap as described above, the signal intensity value of the overlapping portion of the mass spectrometry imaging image of compound A and the mass spectrometry imaging image of compound B is repeatedly reflected in both. In fact, the signal intensity value of the overlapping portion is the signal intensity value of one of compounds A and B or is a value that should be allocated to both compounds A and B in an appropriate proportion, so the accuracy of the two-dimensional intensity distribution of the mass spectrometry imaging image is reduced anyway. Therefore, in order to produce a more accurate mass spectrometry imaging image, it is necessary for the user to change the allowable amplitude, for example, by manual operation so that the overlap of the mass-to-charge ratio range disappears. However, in the case where you want to observe the mass spectrometry imaging images of many compounds at one time, the number of compounds with overlapping mass-to-charge ratio ranges also increases, and it is troublesome to eliminate the overlap of the mass-to-charge ratio ranges one by one for them by manual operation.

[0072] Therefore, in the device of this embodiment, when the user performs a predetermined operation via the input unit 3, the mass-to-charge ratio range change processing unit 25 automatically changes the mass-to-charge ratio range to eliminate the overlap of the mass-to-charge ratio ranges. Figure 6 is a schematic diagram for explaining the operation when the mass-to-charge ratio range corresponding to a plurality of compounds close to each other on the m / z axis is changed. Figure 7 This is a schematic diagram for explaining the operation when mass-to-charge ratio ranges corresponding to a plurality of compounds close to each other on the m / z axis are combined.

[0073] When the mass-to-charge ratio range change processing unit 25 is instructed to perform processing to eliminate the overlap of the mass-to-charge ratio ranges of the two compounds A and B, it first calculates the width of the overlap. Then, it determines whether the width of the overlap is greater than a specified value smaller than the allowable width ΔM. If the width of the overlap is less than the specified value, then Figure 7 As shown in the figure, the overlapping part is divided and distributed to both sides to reduce the allowable width. Figure 7 In the example of (b), the mass-to-charge ratio range is changed by reducing the allowable widths on both sides of the overlapping portion by α.

[0074] Ideally, the peak shape of the profile spectrum is also a Gaussian distribution shape, so it is bilaterally symmetrical. Therefore, the allowable range of each target compound can also be set to ΔM-α. In addition, when the allowable ranges on both sides of the overlapping part are different, it is preferred to change the allocation to both sides according to the ratio of the allowable ranges.

[0075] In this way, after changing the mass-to-charge ratio range in such a way that the overlap disappears, the data included in the mass-to-charge ratio range is integrated at each measurement point as described above, thereby obtaining the signal intensity value and producing a mass spectrometry imaging image. In this way, a mass spectrometry imaging image with a higher accuracy and with the influence of the overlap of the mass-to-charge ratio range reduced can be obtained.

[0076] On the other hand, when the overlap width of the mass-to-charge ratio range is greater than a specified value smaller than the allowable width ΔM, when the mass-to-charge ratio range is reduced in a manner to eliminate the overlap, the signal intensity value as the integration result becomes smaller and is disadvantageous in terms of sensitivity. In addition, as shown in (a) of Figure 8, in the case of a large overlap, separation is substantially impossible. In this case, as shown in (b) of Figure 8, the overlapping mass-to-charge ratios are merged and treated as the mass-to-charge ratio range of the mixture of compound A and compound B.

[0077] After the mass-to-charge ratio range is expanded by merging the mass-to-charge ratio range in this way, the data included in the mass-to-charge ratio range is integrated at each measurement point as described above, thereby obtaining the signal intensity value and making a mass spectrometry imaging image. Thus, a mass spectrometry imaging image representing the two-dimensional intensity distribution of the mixture of compound A and compound B can be obtained. In this case, although the two-dimensional intensity distribution of each of compound A and compound B is unknown, the two-dimensional intensity distribution of the mixture of the two compounds can be obtained with high accuracy.

[0078] In addition, the above-mentioned embodiment is an example of the present invention, and it is needless to say that changes, modifications, and additions appropriately made within the scope of the gist of the present invention are also included in the claims of the present application.

[0079] Description of Reference Numerals

[0080] 1: Imaging mass spectrometry analysis unit; 2: Data processing unit; 20: Data collection unit; 21: Data storage unit; 22: Image display instruction receiving unit; 23: Mass-to-charge ratio range overlap determination unit; 24: Overlap determination result processing unit; 25: Mass-to-charge ratio range change processing unit; 26: Imaging image production unit; 27: Display processing unit; 3: Input unit; 4: Display unit; 100: Sample; 101: Measurement area; 102: Measurement point; 200: Mass spectrometry imaging image; 400: Image list screen; 401: Frame.

Claims

1. An imaging mass spectrometry data processing device for processing mass spectrometry data obtained from a plurality of micro-regions in a two-dimensional region on a sample, wherein the imaging mass spectrometry data processing device is characterized by comprising: a) an input setting unit for a user to specify a compound or a mass-to-charge ratio value for which a two-dimensional intensity distribution based on the mass spectrometry data is desired to be observed; b) a determination unit that, when there are multiple mass-to-charge ratio values ​​corresponding to the compound specified by the user via the input setting unit and / or multiple mass-to-charge ratio values ​​specified by the user, determines, for each of the mass-to-charge ratio values, whether multiple mass-to-charge ratio ranges having a prescribed or specified allowable range overlap; and c) an information providing unit, which provides to the user at least information that is preset and recognizable by the user indicating that the mass-to-charge ratio ranges overlap in the case of the compound or mass-to-charge ratio value specified by the user, when the determining unit determines that at least one group of the plurality of mass-to-charge ratio ranges overlap. in, The imaging mass spectrometry data processing device further comprises: a mass-to-charge ratio range changing unit, which, when the determining unit determines that a plurality of mass-to-charge ratio ranges overlap, determines whether the width of the overlap is greater than or equal to a specified value that is smaller than the allowable width, and, when it is determined that the width of the overlap is smaller than the specified value, changes the allowable width of at least one of the plurality of overlapping mass-to-charge ratio ranges to reduce the at least one mass-to-charge ratio range so that the overlap disappears; After the at least one mass-to-charge ratio range is changed in such a way that the overlap disappears, the data included in the at least one mass-to-charge ratio range is integrated for each micro-region to obtain a signal intensity value and produce a mass spectrometry imaging image.

2. The imaging mass spectrometry data processing device according to claim 1, characterized in that: The information providing section sets the warning in a manner that can be recognized by a user.

3. The imaging mass spectrometry data processing device according to claim 1, characterized in that: The information providing unit lists compounds and / or mass-to-charge ratio values ​​having overlapping mass-to-charge ratio ranges and displays the lists on a screen of the display unit.

4. The imaging mass spectrometry data processing device according to claim 1, characterized in that: The apparatus further comprises an image generating unit for generating an image representing a two-dimensional intensity distribution using the mass spectrometry data for each of the plurality of mass-to-charge ratio ranges specified by a user via the input setting unit. When displaying the image information created by the image creating unit on the screen of the display unit, the information providing unit displays images corresponding to compounds and / or mass-to-charge ratio values ​​having overlapping mass-to-charge ratio ranges so as to be visually distinguishable from other images.

Images