JP2012038459A - Mass spectroscope - Google Patents

Abstract

PROBLEM TO BE SOLVED: To compress and store a mass spectrometric imaging image of high resolution and high mass resolution without damaging information thereof.SOLUTION: The same living tissues have similar colors on an optical microscopic image of a sample. Then, an area division discrimination processing part 23 executes cluster analysis with the color of a color optical microscopic image as a target, and divides a measurement range into a plurality of small areas corresponding to the living tissues. An image compression/decompression part 25 sets such a block to be completed within a divided small area, and executes image compression using a DCT in a block unit to a mass spectrometric imaging image. Since a change in ionic strength is small in the same living tissues, a high frequency component after conversion by the DCT is small, and data loss can be suppressed even though a data amount is reduced.

Description

  The present invention relates to a mass spectrometer, and more particularly to an imaging mass spectrometer capable of acquiring a mass spectrometry imaging image showing a signal intensity distribution of a specific mass-to-charge ratio (m / z) in a two-dimensional region on a sample.

  Mass spectrometry imaging is a technique for examining the distribution of substances having a specific mass-to-charge ratio by performing mass analysis in each of a plurality of minute regions within a two-dimensional region of a sample such as a biological tissue section. It is expected to be useful for marker search and investigation of the causes of various diseases and disorders. A mass spectrometer for performing mass spectrometry imaging is generally called an imaging mass spectrometer. It is also called a microscopic mass spectrometer because it usually performs microscopic observation of an arbitrary range on a sample, determines a region to be analyzed based on the microscopic observation image, and executes imaging mass spectrometry of the region. In this specification, it will be called an imaging mass spectrometer. For example, Patent Documents 1 and 2 and Non-Patent Documents 1 and 2 disclose configurations and analysis examples of conventional general imaging mass spectrometers.

  In the imaging mass spectrometer, mass spectrometry data is acquired at each of a large number of measurement points (micro areas) in a two-dimensional area on the sample. In the imaging mass spectrometers disclosed in Non-Patent Documents 1 and 2, a time-of-flight mass analyzer is used to separate sample-derived ions according to the mass-to-charge ratio. Time-of-flight spectrum data showing temporal changes in ion intensity at each measurement point is obtained, and a mass spectrum is created by converting the time of flight into a mass-to-charge ratio. In an imaging mass spectrometer, the interval between measurement points on a sample affects the spatial resolution, and the number of measurement points increases as the spatial resolution is increased in order to obtain a fine image. When the number of measurement points is large, the total amount of time-of-flight spectrum data in the two-dimensional region to be measured becomes enormous.

  For example, consider a case where a time-of-flight spectrum signal in a time range of about 20 [ms] is sampled at a sampling frequency of 1 [GHz] and each sample is converted to a digital signal with a bit length of 16 [bit]. In this time-of-flight spectrum, the number of samples per measurement point is about 20000, and since one sample is 2-byte data, the data amount per measurement point is about 40 [kB]. If the measurement points in the measurement area are two-dimensionally set in a 250 × 250 [pixel] grid, the number of measurement points is 62500, and the total data amount for the measurement area is about 2.32 [ GB] and huge. If the interval between measurement points is decreased to increase the spatial resolution and the number of measurement points is increased, or if the two-dimensional region to be measured is expanded, the total data amount will further increase. Further, in order to improve mass accuracy and mass resolution, it is necessary to increase the sampling frequency for the time-of-flight spectrum signal, but the total amount of data further increases. In other words, mass analysis imaging data with high resolution and high mass resolution has a larger data size.

  In general, in the field where imaging mass spectrometry is performed, it is necessary to store mass spectrometry imaging data acquired for each of a large number of samples, but the amount of mass spectrometry imaging data per sample is as described above. In order to store mass spectrometry imaging data, a storage device (typically a hard disk drive device) having a very large storage capacity is required. In addition, optical discs such as DVDs and Blu-ray discs are often used to back up data. However, if the data size is large as described above, the number of mass spectrometry imaging images that can be stored on one disc is quite limited. It is done. Therefore, it is necessary to manage a large amount of disks for data backup, which is very complicated and troublesome for the user.

  Usually, data collected by an imaging mass spectrometer can be expressed as a set of monochromatic images of a two-dimensional distribution of ion intensity for each mass-to-charge ratio. Therefore, by applying a well-known data compression algorithm to the data constituting each image, the amount of mass spectrometry imaging data can be reduced. As a method for compressing still image data, there is a method using a well-known compression format such as JPEG (Joint Photographic Experts Group). However, when such a known still image compression method is simply applied to mass spectrometry imaging data, the original information may be greatly lost on the imaging image due to compression / decompression, and target information may not be obtained. For this reason, there is a problem that the existing image compression method is not suitable particularly for storing high resolution and high mass resolution imaging images.

International Publication No. WO20008 / 068847 Pamphlet JP 2009-25268 A

Ogawa, et al., “Development of Microscopic Mass Spectrometer”, Shimazu Review, Vol. 62, No. 3, Issue 4, March 31, 2006, p. 125-135 Harada and others, “Biological tissue analysis using a micro-mass spectrometer,” Shimadzu review, volume 64, No. 3, issue 4, April 24, 2008, p. 139-145

  The present invention has been made in view of the above-mentioned problems, and its main purpose is to compress the amount of data without losing as much information as possible in high-resolution, high-mass resolution mass spectrometry imaging images, and to reduce the data size. An object of the present invention is to provide an imaging mass spectrometer that can be reduced and efficiently stored.

  In the JPEG format described above, a single image composed of a large number of pixels is divided into rectangular blocks of 8 × 8 pixels, and a standard discrete cosine transform (DCT) is performed for each block. Is used to convert the spatial change in color intensity of each pixel in the block into information on the frequency and the intensity of the frequency component. Then, the amount of data is compressed by dropping high frequency component information by quantization and entropy coding for the converted data. However, if the above compression is applied to an image in which the color intensity is greatly different between adjacent pixels in the block, a sudden intensity change between the pixels cannot be expressed sufficiently. It will cause a serious loss of information.

  For example, when mass spectrometry imaging is performed on a sample such as a biological section, since the components included in the same biological tissue are almost the same, the shapes of the mass spectra at a plurality of measurement points belonging to the same biological tissue are very similar. For example, FIG. 3A is an optical microscopic image of a mouse brain section, and FIG. 3B is a mass spectrometry imaging image for a certain mass-to-charge ratio in the same region. In the figure, gray tissues (gray matter: a range surrounded by a thick line), white matter (granular layer), etc. in the nervous tissue appear, but FIG. 3 (b) As can be seen, the color intensities in the same living tissue are similar and change little. This tendency is particularly remarkable in data standardized by the total ion count method for each mass spectrum. Therefore, instead of setting the block to which the DCT is applied regardless of the content of the image, if the block is completed within the same biological tissue, in other words, the block should be set so as not to cross different biological tissues. For example, the loss of information due to the compression as described above should be reduced.

  Normally, when compressing a still image using JPEG, it is impossible to know in advance the magnitude of the change in color intensity in one block to which DCT is applied. On the other hand, in the case of mass spectrometry imaging data, it is possible to acquire an optical microscopic image corresponding to the measurement region as shown in FIG. The inventor of the present application pays attention to the fact that the same biological tissue has a similar color on the optical microscopic image itself or on the optical microscopic image after the sample is stained, and performs data processing on the optical microscopic image to perform processing within the same biological tissue. It was conceived that the measurement point located at the position is identified, and the result is used to appropriately set a block delimiter for applying the DCT on the mass spectrometry imaging image.

That is, in order to solve the above problems, the present invention performs mass analysis for each of a plurality of minute regions set in a predetermined two-dimensional region on a sample, and based on the results, mass analysis imaging images are obtained. In the mass spectrometer to be created,
a) an imaging means for acquiring an optical microscopic image of the two-dimensional region on the sample;
b) area dividing means for dividing the sample surface in the two-dimensional area into a plurality of small areas corresponding to characteristic structures based on the optical microscopic image obtained by the imaging means;
c) Means for compressing data of a mass spectrometry imaging image composed of ion intensity signals of a specific mass-to-charge ratio collected for each minute area in the two-dimensional area, wherein the small image divided by the area dividing means Compression means for performing compression processing in units of blocks completed in the area;
It is characterized by having.

  In the mass spectrometer according to the present invention, the “sample” is typically a sample derived from a living body, and in this case, the “characteristic structure” is “biological tissue”.

  As one aspect of the mass spectrometer according to the present invention, preferably, the region dividing unit performs cluster analysis on the color of each pixel on a color optical microscopic image, and performs a sample surface in the two-dimensional region. It may be configured to be divided into a plurality of small regions showing similar colors.

  Note that the optical microscopic image to be processed by the region dividing means may be a color optical microscopic image of the sample itself when the color of each characteristic structure on the sample appears relatively clearly, but otherwise A color optical microscopic image picked up after performing an appropriate staining process on the sample may be used.

  In particular, when the sample is a sample derived from a living body, the same living tissue shows a similar color on the optical microscopic image, and the color difference between different living tissues is relatively clear. Therefore, a plurality of living tissues can be identified fairly accurately by clustering each pixel using color similarity on an optical microscopic image. Since the same biological tissue contains almost the same components and the content ratio is close, a region corresponding to the same biological tissue on the mass spectrometry imaging image for a specific mass-to-charge ratio (the small region divided by the region dividing means) The change in ionic strength in () is small. Therefore, by performing compression processing in units of blocks set to be completed within this area, it is possible to reduce information loss due to compression / decompression.

  Moreover, as one aspect of the mass spectrometer according to the present invention, the compression means uses a plurality of minute regions included in each small region divided by the region dividing means as one or a plurality of blocks, and the ion intensity in units of blocks. The two-dimensional distribution may be compressed using discrete cosine transform (DCT).

  As described above, in the JPEG format, the entire image to be processed is divided into a plurality of blocks of a fixed size and DCT is applied in units of blocks. In this case, one block may straddle a plurality of small areas. . On the other hand, in the above configuration, the block size is variable, and DCT is applied to each block set to fit within one small region. The size of the block can be arbitrarily determined. For example, if the area of the small area is large, one small area may be divided into a plurality of blocks, and if the area of the small area is small, the entire small area Should be one block.

  The data obtained by DCT includes the frequency component of the ion intensity change in the block and information on the strength of the frequency component. As described above, generally, the change width of the signal intensity of ions with respect to the same mass-to-charge ratio is small in the same living tissue, and therefore the data after DCT has many low frequency components and few high frequency components. Therefore, even if high frequency component information is removed, information loss can be reduced.

  In addition, according to examination of this inventor, especially in the mass spectrum data normalized by the total ion count method, it was confirmed that the change of the ion intensity in the same biological tissue is small. Therefore, in the mass spectrometer according to the present invention, the compression means is a signal value obtained by normalizing the ion intensity signal of the mass-to-charge ratio collected for each minute region in the two-dimensional region by the total ion count of each mass spectrum. It is preferable to adopt a configuration in which data compression is performed on a mass spectrometry imaging image using the.

  Further, in the mass spectrometer according to the present invention, after all the mass analysis for the two-dimensional region on the sample is completed, the compression processing by the compression means can be performed batchwise on the mass spectrometry imaging data collected thereby. . However, in that case, it is necessary to temporarily store all uncompressed mass spectrometry imaging data collected for one sample in a storage device. On the other hand, before performing mass analysis on a two-dimensional region on a sample, if it is known how to divide the region in the two-dimensional region, that is, the block to be compressed is determined. If so, it is possible to sequentially execute mass analysis on a plurality of minute regions in an order convenient for the compression process.

  Therefore, as one aspect of the mass spectrometer according to the present invention, a plurality of micro regions are configured to perform mass analysis on the micro regions included in the small regions for each small region based on the region division information by the region dividing unit. And a measurement order determining means for determining the order of analysis in the method, and after the order is determined by the measurement order determining means, mass analysis is performed on the two-dimensional region to collect data constituting a mass spectrometry imaging image. Good.

  According to this configuration, since compression processing can be performed on data that has already been collected while performing mass spectrometry, all uncompressed mass spectrometry imaging data collected on one sample can be temporarily stored. Storage of data equivalent to a buffer that adjusts the input / output speed of data and transfers data between data collection by mass spectrometry and compression processing. You just have to keep it.

  According to the mass spectrometer of the present invention, it is possible to compress the mass spectrometry imaging data much more than the original data size while suppressing the loss of the original information accompanying the data compression as much as possible. This makes it possible to efficiently store a plurality of high-definition mass spectrometry imaging images for a wide area on the sample in a storage device or a recording medium. Moreover, since appropriate block division at the time of such compression is automatically performed by cluster analysis or the like with respect to an optical microscopic image, there is no burden on the user.

The block diagram of the principal part of the imaging mass spectrometer by 1st Example of this invention. The control flowchart in the imaging mass spectrometer by 1st Example. The figure which shows an example of the optical microscopic image of a mouse | mouth brain slice, and the mass spectrometry imaging image with respect to a certain mass to charge ratio in the same area | region. The conceptual diagram which shows the simple example of the area | region division in the imaging mass spectrometer by 1st Example. The block diagram of the principal part of the imaging mass spectrometer by 2nd Example of this invention. The control flowchart in the imaging mass spectrometer by 2nd Example.

[First embodiment]
Hereinafter, an imaging mass spectrometer which is an embodiment (first embodiment) of a mass spectrometer according to the present invention will be described with reference to FIGS. 1, 2, and 4. FIG. 1 is a configuration diagram of a main part of the imaging mass spectrometer according to the present embodiment.

  Inside the non-vacuum chamber 1 having airtightness, a sample stage 2 for loading a sample plate 3 on which a sample 4 is placed is disposed. On the other hand, an ion transport optical system 8, a mass analyzer 9, an ion detector 10 and the like are disposed in a vacuum chamber 7 which is provided in connection with the non-vacuum chamber 1 and is evacuated by a vacuum pump (not shown). ing. As the ion transport optical system 8, for example, an electrostatic electromagnetic lens, a multipolar high-frequency ion guide, or a combination thereof is used. In this example, the mass analyzer 9 is a reflectron type time-of-flight mass analyzer, but the mass analyzer is not limited to this, and includes a quadrupole mass filter, an ion trap, a magnetic sector type analyzer, etc. Various types are available.

  Outside the non-vacuum chamber 1 and the vacuum chamber 7, a laser irradiation unit 11, a laser focusing optical system 12, a CCD camera 13, an observation optical system 14, and the like are arranged. The sample stage 2 is provided with a drive mechanism (not shown) including a stepping motor and the like in order to drive the sample stage 2 with high accuracy in two axial directions x and y orthogonal to each other. It is driven by the drive unit 15.

  The laser beam for ionization emitted from the laser irradiation unit 11 under the control of the analysis control unit 21 included in the control / processing unit 20 is focused by the laser focusing optical system 12 and provided on the side surface of the non-vacuum chamber 1. The sample 4 is irradiated through the irradiation window 5. The irradiation diameter of the laser beam on the sample 4 at this time is a very small diameter of, for example, 1 μm to several tens of μm. As described above, when the sample stage 2 is moved in the xy plane by the driving mechanism, the laser light irradiation position on the sample 4, that is, the minute region on which the mass analysis is performed moves on the sample 4. As a result, the position where the mass analysis is performed on the sample 4 is two-dimensionally scanned, and mass analysis is performed on each minute region (measurement point) obtained by finely dividing a two-dimensional region of an arbitrary shape into a grid. Is done.

  The CCD camera 13 images a predetermined range on the sample plate 3 through the observation window 6 and the observation optical system 14 provided on the side surface of the non-vacuum chamber 1. Image data photographed by the CCD camera 13 is sent to the control / processing unit 20 and stored in the optical image storage unit 22 as necessary. In addition, the control / processing unit 20 includes a region division determination processing unit 23, a mass spectrometry imaging data temporary storage unit 24, an image compression / decompression unit 25, a data storage unit 26, a spectrum processing unit 27, a display processing unit 28, and the like. Also connected to the control / processing unit 20 are an operation unit 30 for an analyzer (operator) to perform operations and instructions, and a display unit 31 for displaying an optical microscopic image, a mass spectrometry imaging image, and the like of the sample 4. ing.

  It should be noted that at least a part of the functions of the control / processing unit 20 can be realized by executing dedicated software installed in the personal computer on the computer. In this case, each unit included in the control / processing unit 20 is a functional block realized by software.

  FIG. 2 is a flowchart showing an example of a control operation when performing mass spectrometry imaging in the imaging mass spectrometer of the present embodiment. A typical operation will be described with reference to FIG.

  When the sample plate 3 on which the sample 4 to be analyzed is placed is placed on the sample stage 2 and the analyst performs a predetermined operation from the operation unit 30, the control / processing unit 20 captures the sample imaged by the CCD camera 13. 4 is displayed on the screen of the display unit 31 (step S1). The analyst designates a two-dimensional region in which mass spectrometry imaging is performed on the display screen using the operation unit (for example, mouse) 30. Thereby, the measurement range which performs mass spectrometry is determined (step S2). Further, since an optical microscopic image in which the position is accurately associated with the measurement range is obtained, this is stored in the optical image storage unit 22.

  Subsequently, under the control of the analysis control unit 21, mass analysis is sequentially performed on all measurement points included in the measurement range determined as described above (step S3). For example, when a certain measurement point on the sample 4 is moved to the laser irradiation position by the stage driving unit 15, the laser beam is irradiated for a short time as described above, and various ions are emitted from the sample 4. The ions are introduced into the vacuum chamber 7, sent to the mass analyzer 9 through the ion transport optical system 8, and separated by the mass analyzer 9 according to the mass to charge ratio. When the ions separated in time reach the detector 10, the detector 10 outputs a detection signal corresponding to the amount of incident ions, and this detection signal is input to the spectrum processing unit 27. The spectrum processing unit 27 digitizes the detection signal and executes predetermined data processing. Specifically, a time-of-flight spectrum is created from the detection signal at the measurement point, and the time spectrum is converted into a mass-to-charge ratio to create a mass spectrum. Furthermore, normalization is performed by total ion count for each spectrum. The mass spectrometry imaging data thus obtained is stored in the mass spectrometry imaging data temporary storage unit 24. Each time the next measurement point comes to the laser irradiation position by moving the sample stage 2 within the measurement range on the sample 4, the mass spectrum data is obtained as described above, and the mass analysis imaging data thereby is temporarily stored. Stored in the unit 24. Thus, mass spectrometry imaging data for all measurement points included in the measurement range is collected (step S4).

Data compression is performed on the data stored in the mass spectrometry imaging data temporary storage unit 24 as described above in the following procedure.
When the compression processing is instructed, the region division determination processing unit 23 reads the optical microscopic image to be processed from the optical image storage unit 22, and divides the range on the image for each living tissue (step S5). Specifically, the region division determination processing unit 23 performs a well-known cluster analysis on the color information of each pixel (or a group of pixels in which a certain number of adjacent pixels are grouped) in the optical microscopic image, and obtains similar colors. Grouping (clustering) is performed so that pixels or pixel groups having the same value belong to the same group. Various algorithms are known for cluster analysis, and any algorithm can be used as long as clustering using color information as a parameter can be performed. However, a method of determining the number of groups to be divided in advance and performing grouping so as to be the number is not appropriate here. This is because in such a method, if the specified number of divisions is not appropriate, living tissues having colors that are not very similar may enter the same group. Therefore, it is preferable to employ an algorithm that can automatically determine the optimal number of divisions in the process of cluster analysis.

  As an index for determining the optimum number of divisions in the cluster analysis, for example, there are statistics such as pseudo F statistic (Pseudo F statistic) and beer F value (Beale's F statistic). To simplify these statistics, we can think of them as the ratio of the variation of the average value in the cluster between the clusters to the variation of each element in the cluster, and these statistics show maximum values at the optimal number of divisions. . Therefore, while performing clustering by cluster analysis, that is, each pixel is divided into a plurality of groups having similar colors, and the similarities of the groups are compared and treated as new groups. The number of groups is sequentially reduced while repeating the above process. Each time the number of groups changes in the process, the above statistic is obtained, a division number whose statistic shows a maximum value is found, and a result corresponding to the division number is obtained. This makes it possible to accurately divide the optical microscopic image of the sample into small regions corresponding to each living tissue without depending on human subjectivity or judgment, and without any operation or work by the analyst.

  A simple example is shown in FIG. By performing area discrimination processing on the optical microscopic image shown in FIG. 4A, the area is divided into three areas A, B, and C as shown in FIG. 4B. Each region is a range indicated by oblique lines in FIG. 4B, and pixels (or measurement points) included in this range belong to the same group. In this case, the number of divisions is three.

  When the clustering for the optical microscopic image is completed, the area division determination processing unit 23 obtains the result, that is, the division position information (for example, coordinate information indicating the division position with the reference position of the image as zero coordinates) as an image compression / expansion unit 25 (step S6). The image compression / decompression unit 25 reads mass analysis imaging data corresponding to the optical microscope image from the mass analysis imaging data temporary storage unit 24, and based on the data, an image of a two-dimensional distribution of ion intensity for each mass to charge ratio (mass analysis). Imaging image). At this time, only a mass spectrometry imaging image at a specific mass-to-charge ratio specified in advance may be created, or peak picking is automatically performed on the mass spectrum to correspond to the mass-to-charge ratio at which the peak is detected. A mass spectrometry imaging image may be created.

  If one or more mass spectrometry imaging images are obtained, data compression processing is performed for each image (step S7). First, based on the division position information received from the area division discrimination processing unit 23, a DCT target block is determined. A block is completed within at least one area, and one whole area may be one block, or a plurality of blocks may exist in one area. In general, for the convenience of processing, it is desirable to align the number of pixels included in one block as much as possible. In addition, it is necessary to know the block delimiters when decompressing data, and therefore information indicating the block delimiters must be added to the compressed image data, so that the information indicating the block delimiters can be reduced as much as possible. desirable.

  Once the block division is determined, signal intensity data on the target mass-to-charge ratio at each measurement point included in the block is collected in units of blocks, and the spatial intensity distribution is obtained by DCT to determine the frequency of the intensity change and the intensity change. Convert to frequency component strength information. Then, after the conversion, the strength of each frequency component is compared, and the frequency component having a relatively low strength is deleted. This reduces the amount of data. The intensity and frequency information of the frequency component after data deletion obtained in units of blocks are used as information for the mass spectrometry imaging image. Such processing is performed on the mass spectrometry imaging images of all mass to charge ratios to reduce the total amount of data. The data thus reduced is stored in the data storage unit 26 together with compression / decompression parameters, for example, information indicating the above-described block division.

  As described above, mass spectrometry imaging data can be compressed for each living tissue composed of substantially the same components (molecules). Since compression by DCT across different living tissues is not performed, a high compression rate can be realized while suppressing missing of information accompanying compression as much as possible. Thereby, a large number of imaging images can be stored in a storage device having the same storage capacity.

  When a mass spectroscopic imaging image based on compressed data stored in the data storage unit 26 is to be viewed, when the analyst performs a predetermined operation on the operation unit 30, the image compression / decompression unit 25 reads the specified sample or Data corresponding to the mass-to-charge ratio is read out, and the decompression process opposite to that at the time of compression is executed for each block using the block delimiter information, and the signal intensity at each measurement point is obtained. The expanded image is used to reconstruct an imaging image that is a two-dimensional distribution of ion intensity at a specified mass-to-charge ratio, and this image is displayed on the screen of the display unit 31 through the display processing unit. As described above, since information loss during compression is small, a high-definition imaging image can be drawn.

  In the above embodiment, imaging mass spectrometry is performed on the sample, and all the spectral data acquired at each measurement point is temporarily stored in the mass spectrometry imaging data temporary storage unit 24, and then compression processing is performed. Therefore, it is necessary to prepare a storage memory that can store all data acquired for one sample. This is because the compression processing is executed in batches, and if the compression processing can be executed sequentially during the measurement, the storage capacity of the temporary storage unit 24 can be small. The following second embodiment performs such processing.

[Second Embodiment]
FIG. 5 is a configuration diagram of a main part of the imaging mass spectrometer according to the second embodiment, and FIG. 6 is a control flowchart in the imaging mass spectrometer of the second embodiment. As shown in FIG. 5, the basic configuration is the same as that of the apparatus of the first embodiment, but a measurement order determining unit 29 that receives the division position information obtained by the region division determination processing unit 23 and determines the measurement order. Is provided in association with the analysis control unit 21.

A typical operation of the apparatus of the second embodiment will be described with reference to FIG.
When the analyst performs a predetermined operation with the operation unit 30, the CCD camera 13 takes an optical microscopic image of a predetermined range on the sample 4 under the control of the control / processing unit 20 (step S1). This image is displayed on the screen of the display unit 31 through the display processing unit, and the analyst designates a two-dimensional region on which to perform imaging mass spectrometry as a measurement range on the screen (step S2). This is the same as in the first embodiment. Thereafter, the optical microscopic image corresponding to the designated measurement range is stored in the optical image storage unit 22, and the region division determination processing unit 23 immediately divides the region for each biological tissue as described above with respect to the optical microscopic image. The process which performs is performed (step S5). That is, in the second embodiment, prior to the collection of the mass spectrometry imaging data, the region division based on the optical microscopic image corresponding to the measurement range on the sample 4 is executed.

  When the division position information is obtained by the area division determination processing unit 23 (step S6), the division position information is sent to the measurement order determination unit 29 together with the image compression / decompression unit 25. In the imaging mass spectrometer of the first embodiment, the measurement order for a large number of measurement points included in the measurement range is determined regardless of the pattern of the sample surface, the color distribution, and the like. For example, mass analysis is sequentially performed on each measurement point in a raster scan form from one end of the measurement range. On the other hand, in the apparatus of the second embodiment, the measurement order determining unit 29 adaptively, that is, according to the state of division, so as to execute mass spectrometry for each of a plurality of small regions given by the division position information. The measurement order is determined (step S10). For example, when the measurement range is divided into three regions A, B, and C as shown in FIG. 4B, first, mass spectrometry is performed on only the measurement points belonging to the region A in order. If the measurement for all measurement points in A is completed, then mass spectrometry is performed in order for only the measurement points belonging to region B, and the measurement for all measurement points in region B is completed. Finally, the measurement order is determined so that mass spectrometry is executed in order for only the measurement points belonging to the region C. And the analysis control part 21 performs mass spectrometry with respect to each measurement point according to the order determined by the measurement order determination part 29 (step S3).

  If mass spectrometry imaging data for the divided area is obtained, it is determined Yes in step S11, and the image compression / decompression unit 25 executes the compression process as described above (step S7). That is, for example, if mass spectrometry imaging data for a measurement point belonging to the region A is obtained, the mass spectrometry imaging data for the measurement point belonging to the region A is collected while collecting the mass spectrometry imaging data for the measurement point belonging to the region B. Perform data compression. As described above, a block that straddles the region A and the region B is not set at the time of data compression. Therefore, parallel processing of such data compression processing and collection of mass spectrometry imaging data is possible. Then, when the processing of all the regions within the measurement range (regions A, B, and C in the example of FIG. 4) is finally finished (Yes in step S12), the processing is finished. As a result, similarly to the first embodiment, the compressed data is stored in the data storage unit 26 together with the compression / decompression parameters.

  The above-described embodiment is an example of the present invention, and it is a matter of course that changes, modifications, and additions within the scope of the present invention are included in the scope of the claims of the present application.

DESCRIPTION OF SYMBOLS 1 ... Non-vacuum chamber 2 ... Sample stage 3 ... Sample plate 4 ... Sample 5 ... Irradiation window 6 ... Observation window 7 ... Vacuum chamber 8 ... Ion transport optical system 9 ... Mass analyzer 10 ... Ion detector 11 ... Laser irradiation Section 12 ... Laser focusing optical system 13 ... CCD camera 14 ... Observation optical system 15 ... Stage drive section 20 ... Control / processing section 21 ... Analysis control section 22 ... Optical image storage section 23 ... Area division discrimination processing section 24 ... Mass Analytical imaging data temporary storage unit 25 ... image compression / decompression unit 26 ... data storage unit 27 ... spectrum processing unit 28 ... display processing unit 29 ... measurement order determining unit 30 ... operation unit 31 ... display unit

Claims (5)

In a mass spectrometer that performs mass analysis for each of a plurality of minute regions set within a predetermined two-dimensional region on a sample and creates a mass spectrometry imaging image based on the result,
a) an imaging means for acquiring an optical microscopic image of the two-dimensional region on the sample;
b) area dividing means for dividing the sample surface in the two-dimensional area into a plurality of small areas corresponding to characteristic structures based on the optical microscopic image obtained by the imaging means;
c) Means for compressing data of a mass spectrometry imaging image composed of ion intensity signals of a specific mass-to-charge ratio collected for each minute area in the two-dimensional area, wherein the small image divided by the area dividing means Compression means for performing compression processing in units of blocks completed in the area;
A mass spectrometer comprising: The mass spectrometer according to claim 1,
The region dividing means performs cluster analysis on the color of each pixel on a color optical microscopic image, and divides the sample surface in the two-dimensional region into a plurality of small regions showing similar colors. Characteristic mass spectrometer. The mass spectrometer according to claim 1 or 2,
The compressing means applies a discrete cosine transform to a two-dimensional distribution of ion intensity in units of blocks, each of which includes a plurality of minute areas included in each small area divided by the area dividing means. A mass spectrometer characterized by performing compression. The mass spectrometer according to claim 3,
The compression means compresses data of a mass spectrometry imaging image using a signal value obtained by normalizing an ion intensity signal of a mass-to-charge ratio collected for each minute region in the two-dimensional region with a total ion count of each mass spectrum. A mass spectrometer characterized by that. The mass spectrometer according to any one of claims 1 to 4,
Measurement order determining means for determining the order of analysis in a plurality of micro regions so as to perform mass analysis on the micro regions included in the small regions for each small region based on the region division information by the region dividing unit. Prepared,
A mass spectrometer that collects data constituting a mass spectrometry imaging image by executing mass analysis on the two-dimensional region after the order is determined by the measurement order determination unit.