JP2013061196A - Program, recording medium, and method for imaging receptor binding potential - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a BP (Binding Potential) imaging program capable of; presenting BP of abnormal regions even if both normal and abnormal regions are present in an ROI (Region of Interest); presenting BP for a brain under pathological conditions with damage to gray matter or white matter; accurately identifying anatomical regions on a PET brain image; and facilitating BP evaluation of the whole cerebral region.SOLUTION: A BP imaging program includes steps of; aligning an MRI brain image to a PET brain image; separating gray matter portions and white matter portions from the MRI brain image and applying noise removal processing; defining an ROI in a reference region of the MRI brain image and defining the same ROI on the PET brain image; defining an elliptical ROI on the PET brain image and inputting a time-radiation count value for each pixel therein; computing BP for each pixel in the elliptical ROI of the PET brain image by means of the reference region method using the PET brain image in the elliptical ROI and the time-radiation count values in the ROI in the reference region; and displaying BP in the gray matter portions and/or white matter portions.

Description

  The present invention relates to a receptor binding ability imaging program for imaging receptor binding ability from PET brain image data.

  In recent years, in the field of cranial nerves, studies have been conducted to evaluate neurotransmitter function using a radiopharmaceutical that selectively binds to a neuroreceptor. When performing this evaluation, not only imaging the distribution of radiopharmaceuticals in the brain by positron emission tomography (PET), but also the receptor binding ability (BP) etc. from the PET brain image Calculation of pharmacological indicators is also performed. BP can be expressed by the ratio between the radioactivity concentration of the drug specifically bound to the receptor and the concentration of the free drug in the tissue (see Non-Patent Document 1).

  Radiopharmaceuticals taken into the brain through the brain barrier include regions that are easily taken up (easy to stay) and regions that are hard to take up (hard to stay) according to the characteristics of the radiopharmaceutical. BP indicates the degree of ease of capturing, and the BP increases in a region where it is easily captured. Therefore, by checking the height of BP in each region corresponding to the radiopharmaceutical in a normal brain in advance, a BP height pattern can be obtained. When there are normal and abnormal regions in the brain, the radiopharmaceuticals taken into the brain remain in the normal region according to the above-mentioned BP height pattern, but not in the abnormal region. Since it flows out of the brain, BP becomes lower than usual. Therefore, by obtaining the BP, it becomes possible to find an abnormal region in the brain.

  Conventionally, when calculating a BP from a PET brain image, first, a region of interest (ROI) is set for the PET brain image, and the process of taking in and washing out a radiopharmaceutical over time is examined for the ROI. As a result, BP was calculated. More specifically, a time-radioactivity count value curve indicating a change between the measured time and the average value of the radioactivity count values of all pixels in the ROI is obtained, and data of the time-radioactivity count value curve is obtained. BP was calculated based on the above. That is, the behavior of the ROI (what kind of BP it will be) is represented by one value that is the average value of the radioactivity count values of all the pixels in the ROI.

  In the conventional BP calculation method described above, ROI is first set for the PET brain image, and the behavior of the ROI is represented by one value, which is the average value of the radioactivity count values of all pixels in the ROI. It was. For this reason, when a normal area and an abnormal area are mixed in the ROI, the normal radioactivity count value and the abnormal radioactivity count value are mixed, and is the BP of the normal area, There is a problem that it is unclear whether the BP is in an abnormal area.

  Depending on the pathology in the field of cranial nerves, gray matter may be damaged or white matter may be damaged. However, in the above-described conventional BP calculation method, ROI is first set for the PET brain image, and thus gray matter and white matter may be included in the ROI. Even in this case, since the behavior of the ROI is represented by one value, which is the average value of the radioactivity count values of all the pixels in the ROI, there is a problem that it is difficult to calculate an accurate BP according to the pathological condition. there were.

  PET brain images have a lower resolution than images obtained by X-ray tomography (CT), magnetic resonance imaging (MRI), and the like. For this reason, there is a problem that it is difficult to specify an anatomical region on a PET brain image.

  Conventionally, since the BP was only calculated as a numerical value for each set ROI, there was a problem that it was difficult to evaluate the BP in the entire region of the brain in a short time.

  Therefore, an object of the present invention is to solve the above problem, and even when a normal region and an abnormal region are mixed in the set ROI, a normal radioactivity count is obtained. To provide a receptor-binding ability imaging program or the like that can clearly indicate whether a BP is a normal region or an abnormal region without mixing the value with an abnormal radioactivity count value It is in.

  The second object of the present invention is to provide a receptor binding ability imaging program capable of showing an accurate BP for a pathological condition in which gray matter is damaged or a pathological condition in which white matter is damaged. Is to provide.

  The third object of the present invention is to accurately identify an anatomical region on a functional brain image such as a PET brain image or a single photon emission computed tomography (SPECT) brain image. It is to provide a receptor binding ability imaging program and the like.

  A fourth object of the present invention is to provide a receptor binding ability imaging program and the like that can easily evaluate BP in the entire brain region by instantaneously showing the BP in the entire brain region. There is.

  The receptor binding ability imaging program of the present invention is a receptor binding ability imaging program for imaging receptor binding ability from functional brain image data (preferably PET or SPECT brain image data). A functional brain image data input means for inputting functional brain image data of a subject imaged by using a predetermined radiopharmaceutical that selectively binds to a receptor, and morphological brain image data of the subject (preferably Is a morphological brain image data input means for inputting MRI or CT brain image data), and the functional brain image data and the morphology are based on the functional brain image data of the subject input by the functional brain image data input means. Alignment means for aligning with the subject's morphological brain image data input by the brain image data input means; Separating means for separating gray matter partial data and white matter partial data from the morphological brain image data of the subject, and the predetermined radiopharmaceutical is not present in the morphological brain image data aligned by the alignment means A region of interest setting means for setting a region of interest in a reference region that can be regarded as a region of interest, and setting the region of interest in the functional brain image data of the subject input by the functional brain image data input means, the functional brain image data input About the region of interest in the reference region of the functional brain image data set by the region-of-interest setting means, the region of interest having the predetermined shape set in the functional brain image data of the subject inputted by the means , Radioactivity count value input means for inputting time-radioactivity count value for each pixel, set by the predetermined shape region of interest setting means Of the radiopharmaceutical using the functional brain image data in the region of interest of a predetermined shape and the time-radioactivity count value in the region of interest in the reference region input by the radioactivity count value input means. A receptor binding ability calculating means for calculating a receptor binding ability for each pixel of the functional brain image data in the region of interest of the predetermined shape based on a reference region method which is a mathematical model representing the receptor binding, Based on the receptor binding capacity for each pixel calculated by the performance calculating means and the gray matter portion data and / or white matter portion data separated by the separating means, a receptor for gray matter portion and / or white matter portion data It is a receptor binding ability imaging program for functioning as a receptor binding ability display means for displaying binding ability in a predetermined display format.

  Here, in the receptor binding ability imaging program of the present invention, the reference region method may be an SRTM (Simplified Reference Tissue Model) method and / or a non-invasive Logan method.

  Here, the receptor binding ability imaging program of the present invention further comprises noise removal means for performing predetermined noise removal processing on the gray matter partial data and / or white matter partial data separated by the separation means, The body binding ability display means is a gray matter portion that is separated by the receptor binding ability for each pixel calculated by the receptor binding ability calculation means and separated by the separation means and subjected to predetermined noise removal processing by the noise removal means. Based on the data and / or white matter portion data, the receptor binding ability of the gray matter portion and / or the white matter portion can be displayed in a predetermined display format.

  Here, in the receptor binding ability imaging program of the present invention, the noise removing means performs noise expansion and fine line processing on the gray matter partial data and / or white matter partial data separated by the separating means, thereby generating noise. A removal process can be performed.

  Here, in the receptor binding ability imaging program of the present invention, a region of interest is set for the image data in which the receptor binding ability is displayed by the receptor binding ability display means, and a functional corresponding to the region of interest is provided. It further comprises other receptor binding capacity calculating means for inputting a time-radioactivity count value for the region of the brain image data and calculating an average receptor binding capacity in the region of interest based on the time-radioactivity count value. it can.

  Here, in the receptor binding ability imaging program of the present invention, the predetermined shape set by the predetermined shape region-of-interest setting means can be an ellipse.

  Here, in the receptor binding ability imaging program of the present invention, when the reference region method is the Logan-DVR method, the start point regarded as a regression line by the Logan-DVR method is changed from the initial value to the end value, Repeating means for repeating the processing of the receptor binding ability calculating means for each starting point, and starting point selection for displaying each receptor binding ability obtained by the repeating means in a predetermined format and selecting a specific starting point Means.

  The recording medium of the present invention is a computer-readable recording medium on which any receptor binding ability imaging program of the present invention is recorded.

  The receptor binding ability imaging method of the present invention is a receptor binding ability imaging method in which a computer executes imaging of receptor binding ability from functional brain image data, and selectively binds to a receptor. A functional brain image data input step for inputting functional brain image data of a subject imaged using a predetermined radiopharmaceutical, a morphological brain image data input step for inputting morphological brain image data of the subject, and the functional Using the functional brain image data of the subject input in the brain image data input step as a reference, the functional brain image data and the morphological brain image data of the subject input in the morphological brain image data input step are aligned. The gray matter portion data and the white matter portion data are separated from the morphological brain image data of the subject aligned in the alignment step to be performed and the alignment configuration step. A region of interest in a reference region in which the predetermined radiopharmaceutical can be regarded as non-existent with respect to the morphological brain image data aligned in the alignment step, and the region of interest in the functional brain A region-of-interest setting step set in the functional brain image data of the subject input in the image data input step, and a region of interest having a predetermined shape in the functional brain image data of the subject input in the functional brain image data input step A predetermined shape region-of-interest setting step for setting a region of interest, and a radioactivity count value for inputting a time-radioactivity count value for each pixel for the region of interest in the reference region of the functional brain image data set in the region-of-interest setting step Functional brain image data in a region of interest of a predetermined shape set in the input step; Based on the reference area method, which is a mathematical model representing the dynamics of the radiopharmaceutical, using the time-activity count value in the region of interest of the reference area input in the radioactivity count value input step, A receptor binding ability calculating step for calculating a receptor binding ability for each pixel of the functional brain image data in the region of interest of the shape, and a receptor binding ability for each pixel calculated by the receptor binding ability calculating step A receptor binding ability display step for displaying the gray matter portion and / or the receptor binding ability of the white matter portion in a predetermined display format based on the gray matter portion data and / or white matter portion data separated by the separation step; The functional brain image data input step and the morphological brain image data input step can be executed in reverse, and the predetermined shape region of interest setting step includes the function If it is after the functional brain image data input step, it can be executed before each preceding step.

  Here, in the receptor binding ability imaging method of the present invention, the reference region method may be an SRTM (Simplified Reference Tissue Model) method and / or a non-invasive Logan method.

  Here, in the receptor binding ability imaging method of the present invention, the gray matter portion data and / or the white matter portion data separated in the separation step after the separation step and before the receptor binding ability display step. A noise removal step for performing a predetermined noise removal process on the receptor binding ability display step, wherein the receptor binding ability display step is separated from the receptor binding ability for each pixel calculated in the receptor binding ability calculation step in the separation step. Based on the gray matter portion data and / or white matter portion data subjected to the predetermined noise removal processing in the noise removal step, the receptor binding ability of the gray matter portion and / or the white matter portion is displayed in a predetermined display format. be able to.

  Here, in the receptor binding ability imaging method of the present invention, the noise removing step performs expansion and fine line processing on the gray matter portion data and / or the white matter portion data separated in the separation step, thereby providing noise. A removal process can be performed.

  Here, in the receptor binding ability imaging method of the present invention, a region of interest is set for the image data in which the receptor binding ability is displayed in the receptor binding ability display step, and the functional corresponding to the region of interest is displayed. The method further includes another receptor binding capacity calculating step of inputting a time-radioactivity count value for the region of the brain image data and calculating an average receptor binding capacity in the region of interest based on the time-radioactivity count value. it can.

  Here, in the receptor binding ability imaging method of the present invention, the predetermined shape set in the predetermined shape region-of-interest setting step may be an ellipse.

  Here, in the receptor binding ability imaging method of the present invention, when the reference region method is the Logan-DVR method, before the receptor binding ability calculation step, the starting point considered as a regression line by the Logan-DVR method Is changed from the initial value to the end value, and the process of the receptor binding capacity calculation means is repeated for each starting point, and each receptor binding capacity obtained in the repetition step is displayed in a predetermined format. And a starting point selection step of selecting a specific starting point.

  According to the receptor binding ability imaging program or the like of the present invention, a morphological (anatomical) brain image such as an MRI brain image or a CT brain image and a functional brain image such as a PET brain image or a SPECT brain image are positioned. Together, both brain images have the same coordinates. Thus, after setting an anatomical region for a morphological (anatomical) brain image such as an MRI image rich in anatomical information, the anatomical region is converted into a functional brain image such as a PET brain image. It is set to. For this reason, there is an effect that an anatomical region can be accurately specified even on a functional brain image such as a PET brain image.

  A time-radioactivity count value is obtained for each pixel of a functional brain image such as a PET brain image, and a receptor binding ability is obtained for each pixel. For this reason, even if a normal region and an abnormal region are mixed in the set region of interest, a normal region is not mixed with a normal radioactivity count value and an abnormal radioactivity count value. There is an effect that it is possible to clearly indicate whether the BP is an BP of an abnormal region or a BP of an abnormal region. Since the obtained BP is displayed as an image, the BP in the entire area of the brain can be instantly shown, and the BP in the entire area of the brain can be easily evaluated in a short period of time. . The BP is obtained for each of the gray matter and the white matter. For this reason, there is an effect that an accurate BP corresponding to the pathological condition can be calculated even for a pathological condition in which the gray matter is damaged or a pathological condition in which the white matter is damaged.

1 is a diagram illustrating a BP imaging system 1 in which a BP imaging program or the like according to Embodiment 1 of the present invention is executed. FIG. It is a figure which illustrates PET brain image 40 based on PET brain image data inputted by PET brain image data input part 21. It is a figure which illustrates the MRI brain image 50 based on the MRI brain image data input by the MRI brain image data input part 22. FIG. It is a figure which illustrates the brain image 60 of the result as which the position alignment part 23 performed position alignment. It is a conceptual diagram for demonstrating mutual information content. It is a figure for demonstrating the average information content (entropy) of a medical brain image. It is a figure for demonstrating the histogram of a coupling | bonding event. It is a figure which shows the three-dimensional joint histogram 400 at the time of seeing the joint histogram 300 shown by FIG. 7 from viewpoint VP. It is a figure for demonstrating the method of calculating a mutual information amount from a two-dimensional joint histogram. It is a figure which shows the joint probability distribution p (A, B) of the reference image 270 (event A) and the floating image 260 (event B) calculated from the two-dimensional joint histogram G (A, B) (histogram 310). It is a figure which shows the example which isolate | separates gray matter part data 55 and white matter part data 56 from the test subject's MRI brain image data 50 by the segmentation part 24. FIG. It is a figure which illustrates the thin line and expansion process (closing operation) by the thin line and expansion process part 25. FIG. It is a figure which shows the screen 70 which illustrates the processing state by the thin line and expansion process part. It is a figure which shows the screen 80 which illustrates the processing condition of the reference ROI setting part. It is a figure which shows the screen 90 which illustrates the processing condition of the ellipse ROI setting part. It is a figure which shows the screen 100 which illustrates the processing condition of the radioactivity count value input part. It is a figure which shows the compartment model for demonstrating a SRTM method. It is a diagram showing a screen 120a~120d displayed by BP image display unit 30 when ^{the [11} C] PE2I was used as a radiopharmaceutical to the subject. It is a figure which shows the screens 130a-130d displayed by the BP image display part 30 in case a [< ¹⁸ > F] flumazenil is used with respect to a test subject as a radiopharmaceutical. It is a figure which shows the screen 140 displayed by the BP image display part 30. FIG. It is a flowchart in the Example 1 etc. of this invention which shows the flow of a process of the BP imaging program and method in which a computer performs BP imaging from PET brain image data. It is a figure which shows the screen 160 which illustrates the processing condition of the ellipse ROI setting part 27 in Example 3 of this invention. It is a figure which shows the graph which made the left side Y of Formula 23 the vertical axis | shaft, and made X of the right side of Formula 23 the horizontal axis. It is a flowchart which shows the flow of BP calculation methods (BP imaging program etc.) by the optimal starting point in Example 4 of this invention. FIG. 10 is a diagram illustrating a screen 170 illustrating a processing status of a BP calculation method using an optimum start point in the fourth embodiment. It is a block diagram which shows the internal circuit 180 of the computer 10 which executes the BP imaging program of this invention.

  In the following, for convenience of explanation, an MRI brain image is taken up as an example of a morphological (anatomical) brain image, and a PET brain image is taken up as an example of a functional brain image. However, the form (anatomical) brain image to which the receptor binding ability imaging program of the present invention is applied is not limited to the MRI brain image, but other forms (anatomical) such as a CT brain image. The same can be applied to brain images. Similarly, the functional brain image to which the receptor binding ability imaging program of the present invention is applied is not limited to a PET brain image, and the same applies to other functional brain images such as a SPECT brain image. Can be applied to. Therefore, a combination of a morphological (anatomical) brain image and a functional brain image to which the receptor binding ability imaging program of the present invention is applied is, for example, an MRI brain image and a PET brain image, an MRI brain image and a SPECT. Brain images, CT brain images and PET brain images, CT brain images and SPECT brain images, and the like. Hereinafter, a receptor binding ability imaging program for imaging BP from functional brain image data such as PET brain image data of the present invention is referred to as a “BP imaging program”. The receptor binding ability imaging method in which the computer of the present invention executes BP imaging from functional brain image data such as PET brain image data is referred to as “BP imaging method”. The BP imaging program and method are referred to as “BP imaging program or the like”. Hereinafter, embodiments will be described in detail with reference to the drawings.

  FIG. 1 shows a BP imaging system 1 in which a BP imaging program or the like according to the first embodiment of the present invention is executed. In FIG. 1, reference numeral 10 denotes a computer that executes a BP imaging program, 12 denotes a recording device such as a hard disk connected to the computer 10, and 14 denotes a database of PET brain image data recorded in the recording device 12. (PET-DB), 16 is a database (MRI-DB) of MRI brain image data recorded in the recording device 12, and 20 is a functional block showing the function of the BP imaging program. Hereinafter, each function shown in the function block 20 will be described.

PET brain image data input unit (functional brain image data input means. It may be a SPECT brain image data input unit as described above. The same applies hereinafter) 21 is a predetermined radiopharmaceutical that selectively binds to a receptor. The PET brain image data (radioactivity count value) of the subject imaged using is input. In this specification, neuroreceptors in the brain are treated as receptors. [ ¹¹ C] PE2I, [ ¹⁸ F] flumazenil and the like are suitable as the predetermined radiopharmaceutical. A three-dimensional collection type is suitable as a PET apparatus for collecting PET brain image data and imaging a predetermined radiopharmaceutical distribution. A PET / CT apparatus, a SPECT (Single Photon Emission Computed Tomography) / PET apparatus or the like may be used instead of the PET dedicated machine. FIG. 2 illustrates a PET brain image 40 based on the PET brain image data input by the PET brain image data input unit 21. In the following, “PET brain image” and “PET brain image data” are used in the same manner unless otherwise distinguished. As shown in FIG. 2, the matrix size of the PET brain image data 40 is preferably 128 × 128 (pixels), but is not limited to this matrix size.

  The MRI brain image data input unit (morphological brain image data input means. It may be a CT brain image data input unit as described above. The same applies hereinafter) 22 inputs the MRI brain image data of the subject. As an MRI apparatus used for collecting MRI brain image data and creating an MRI image, any of a tunnel type, an open type and the like may be used. FIG. 3 illustrates an MRI brain image 50 based on the MRI brain image data input by the MRI brain image data input unit 22. In the following, “MRI brain image” and “MRI brain image data” are used in the same manner unless otherwise distinguished. As shown in FIG. 3, the matrix size of the MRI brain image data 50 is preferably 256 × 256 (pixels), but is not limited to this matrix size.

  The registration unit (positioning means) 23 is input by the PET brain image data 40 and the MRI brain image data input unit 22 with the subject's PET brain image data 40 input by the PET brain image data input unit 21 as a reference. Alignment with MRI brain image data 50 of the same subject is performed. Specifically, first, reslice is performed to match the matrix size (256 × 256 (pixels)) of the MRI brain image data 50 with the matrix size (128 × 128 (pixels)) of the PET brain image data 40. In general, since the resolution of the MRI brain image data is better, the PET brain image data is re-sliced based on the MRI brain image data. However, in the BP imaging program of the present invention, the MRI brain image data 50 is re-sliced based on the PET brain image data 40 having a small matrix size in order to shorten the calculation time. Next, registration (registration) between the PET brain image data 40 and the MRI brain image data 50R (not shown) whose matrix size is re-sliced is performed. FIG. 4 illustrates the MRI brain image data 60 as a result of the alignment performed by the alignment unit 23.

  Registration refers to determining corresponding pixels for two different brain images (here, PET brain image 40 and MRI brain image 50R) of the same subject. There are various methods for registration, and in the case of two images (PET brain image and MRI brain image) having different properties as in the present application, for example, segmentation (partial extraction of brain image) is performed by pixel values of the MRI image, There is a method for calculating the variance of the ratio of both pixel values for each segment.

  In the above method, rigid transformation is used. Specifically, in order to align two brain images, in addition to a vector in three directions of a translation dx in the X direction, a translation dy in the Y direction, and a translation dz in the Z direction, the rotation dθx, Y around the X axis Six parameters having three rotation components, ie, rotation dθy around the axis and rotation dθ around the Z axis are used. The MRI brain image 50R is rotated / translated using these six parameters, and the result is evaluated using the PET brain image 40. As a result of the evaluation, it is determined whether or not a predetermined convergence condition is satisfied. If it is determined that the convergence is achieved, MRI brain image data 60 is obtained, and the registration ends. On the other hand, if it is not determined that it has converged, the six parameters are updated, and the process is repeated from the rotation / translation.

  The above evaluation can be performed using a desired evaluation standard. Here, a case where MI (Mutual Information) is used as an evaluation criterion will be described. The idea is that all pixels with a certain pixel value on the MRI brain image have the same partition, and the corresponding pixels in the PET (or SPECT) brain image will have approximately the same pixel value. Rely on. It is assumed that there is some shared information (mutual information) between the MRI brain image and the PET brain image. Since the mutual information amount decreases when the positional deviation between the two brain images occurs, the registration is performed so that the mutual information amount is maximized. Hereinafter, the mutual information amount will be described first.

  When a probability P (≦ 1.0) of occurrence of an event is given, an information amount (entropy) H is defined by the following formula 1.

As defined by Equation 1, the amount of information on rarely occurring events is very large. When an event probability distribution P _i is given, the average information amount H (P _i ) is defined by the following equation 2.

  Here, two events A and B are considered. The average information amount H (A, B) that the combined event p (A, B) of the events A and B has as a whole is defined by the following Equation 3.

The average information amount H (A, B) is referred to as the joint entropy of events A and B. Examples of events A and B include MRI brain images and PET or SPECT brain images. Now, in two events or information sources A (MRI brain image) and B (PET brain image) that are somewhat related to mutual information, an event B () obtained by knowing event A (or event B) Or it is defined as the amount of information regarding event A). FIG. 5 is a conceptual diagram for explaining the mutual information amount. In FIG. 5, a rectangle indicated by points a ₁ a ₂ a ₃ a ₄ indicates the average information amount H (A) possessed by event A, and a rectangle indicated by points b ₁ b ₂ b ₃ b ₄ is event B. Shows the average information amount H (B). The rectangles indicated by points b ₁ a ₂ a ₃ b ₄ where the average information amounts H (A) and H (B) overlap are average information amounts shared by the events A and B, and the average information amounts are mutually This is called information amount I (A, B). That is, the mutual information amount I (A, B) means the average information amount of event B (PET brain image) obtained by knowing event A (MRI brain image).

In FIG. 5, a rectangle indicated by points a ₁ b ₂ b ₃ a _{4 represents} the joint entropy H (A, B) of events A and B. A rectangle indicated by points a ₁ b ₁ b ₄ a ₄ indicates an average information amount (conditional entropy) H (A | B) possessed by event A on condition that event B has occurred, and point a ₂ A rectangle indicated by b ₂ b ₃ a ₃ indicates an average information amount (conditional entropy) H (B | A) possessed by event B on condition that event A has occurred. When conditional entropy is used, mutual information I (A, B) is given by the following equation (4).

  Here, conditional probabilities and mutual information are shown. If the probability of event A occurring is P (A), and the conditional probability of event B occurring on condition that event A occurs is P (B | A), then the combined event P (A, B) of events A and B Is given by Equation 5 below, and the conditional probability P (B | A) is given by Equation 6 by modifying Equation 5.

  Similarly, the conditional probability P (A | B) is given by the following formula 7, and the conditional entropy H (A | B) is given by the following formula 8. The mutual information I (A, B) is given by Equation 9 from Equation 4 (First Equation), Equation 7 and Equation 8.

The mutual information described above is applied to a medical brain image. The average information amount (entropy) in the case of a medical brain image can be defined by using a histogram (frequency distribution) of the medical brain image. FIG. 6 is a diagram for explaining the average information amount (entropy) of a medical brain image. For the data of the MRI brain image 200 as shown in FIG. 6, if the number of pixels having a certain signal intensity is calculated and graphed, a histogram of the medical brain image can be obtained. Reference numeral 202 denotes a histogram of the MRI brain image 200 in which the horizontal axis indicates the signal intensity and the vertical axis indicates the appearance frequency. In the histogram 202, the signal strength is representative of the range of _{d 1} to _{d 2} (in the original drawing shows in blue.) (Shown in yellow at the original drawing.) Range of from _{d 2} to _{d 3} on MRI brain image, A range shown in blue corresponds to a substantially gray matter region as shown in the MRI brain image 204, and a range shown in yellow corresponds to a substantially white matter region as shown in the MRI brain image 206. . Thus, the histogram of the medical brain image is strongly related to the anatomical structure of the brain.

  In the case of a histogram of a combined event P (A, B) between an event A such as an MRI brain image and an event B such as a SPECT or PET brain image, a two-dimensional histogram (Joint Histogram) may be considered. . FIG. 7 is a diagram for explaining a histogram of binding events. In FIG. 7, the parts denoted by the same reference numerals as those in FIG. As shown in FIG. 7, reference numeral 212 is a histogram of a SPECT brain image (event B) with the horizontal axis representing the count (value) and the vertical axis representing the appearance frequency. A two-dimensional histogram of the combined event P (A, B) between the MRI brain image 200 (event A) and the SPECT brain image 210 (event B) is represented by a joint histogram 300 shown in FIG. In the joint histogram 300, the horizontal axis represents the signal intensity in the histogram 202 of the MRI brain image 200, and the vertical axis represents the count in the histogram 212 of the SPECT brain image 210. The value of the coordinates (Ai, Bj) in the joint histogram 300 is a value calculated from the appearance frequency of the histogram 202 corresponding to the signal intensity Ai and the appearance frequency of the histogram 212 corresponding to the count Bj. Expressed in terms of brightness. However, for convenience of explanation, the signal intensity and the count close to 0 in the histograms of both brain images are cut out.

  FIG. 8 shows a three-dimensional joint histogram 400 when the joint histogram 300 shown in FIG. 7 is viewed from the viewpoint VP (see FIG. 7). As shown in the coordinate axis at the bottom of FIG. 8, the brightness intensity (appearance frequency, count magnitude) in FIG. 7 is represented by a three-dimensional vertical axis, and the signal intensity axis extends from the origin 0 on the right side to the upper left side. The count axis increases from the origin 0 on the right side toward the lower left side. As shown in FIG. 8, the regions of white matter, gray matter, and cerebrospinal fluid are clearly shown as peaks in the vertical axis direction in the three-dimensional joint histogram 400, and the three-dimensional joint histogram 400 and the anatomy of the brain are shown. It is clear that it is strongly related to the structural structure.

FIG. 9 is a diagram for explaining a method for calculating mutual information from a two-dimensional joint histogram. In FIG. 9, reference numeral 260 is a floating image (SPECT brain image, event B) to be deformed, and 270 is a (fixed) reference image (SPECT brain image. Event A) to which the floating image 260 is to be combined. Although not explicitly shown in FIG. 9, like the histogram 212 of the SPECT brain image 210 shown in FIG. 7, each of the floating image 260 and the reference image 270 has a histogram in which the horizontal axis is the count and the vertical axis is the appearance frequency. ing. Subsequently, in FIG. 9, reference numeral 310 denotes a two-dimensional joint histogram G (A, B) that is a combined event of the floating image 260 (event B) and the reference image 270 (event A), and the horizontal axis represents the reference image. The count A is 270, and the vertical axis is the count B of the floating image 260. As shown in FIG. 9, a histogram such as a histogram 212 is created only for a portion where the floating image 260 and the reference image 270 overlap, for example, only the portion of coordinates (x _m , y _n ). That is, the image count for the portion where the floating image 260 and the reference image 270 do not overlap is not taken into the appearance frequency in the histogram of the image. Thereafter, as in the case of the joint histogram 300 shown in FIG. 7, the value G (A _i , B _j ) of the coordinates (A _i , B _j ) in the joint histogram 310 is the reference image corresponding to the count A _i. This is a value calculated from the appearance frequency of the histogram (not shown) of 270 and the appearance frequency of the histogram (not shown) of the floating image 260 corresponding to the count B _j , and the magnitude of the value is expressed by the intensity of brightness. .

FIG. 10 shows a joint probability distribution p (A, B) between the reference image 270 (event A) and the floating image 260 (event B) calculated from the two-dimensional joint histogram G (A, B) (histogram 310). . As shown in FIG. 10, the horizontal axis of the joint probability distribution p (A, B) is the count A of the reference image 270, and the vertical axis is the count B of the floating image. The joint probability p (A _i , B _j ) can be obtained by normalizing the two-dimensional joint histogram G (A _i , B _j ) with the sum as shown in Equation 10.

As shown in FIG. 10, the sum of the coupling probabilities p (A _i , B _j ) in the direction of the variable B is the marginal probability p _A (A _i ) (Equation 11), and the variable A The sum of the directions is the marginal probability p _B (B _j ) (Formula 12).

The mutual information MI can be calculated as shown in Expression 13 by referring to Expression 9 using Expressions 11 and 12 and the connection probability p (A _i , B _j ). The mutual information MI shown in Equation 13 is a physical difference that measures the difference between the appearance frequency (probability distribution) of event A and the appearance frequency (probability distribution) of event B, and is called Kullbac-Leibler divergence. Registration is performed so that the mutual information MI shown in Expression 13 is maximized. The mutual information MI is maximized by reducing the variation (reducing the spread) of the two-dimensional joint histogram G (A _i , B _j ) and increasing the peak of the three-dimensional joint histogram 400. become.

  The case where MI is used as the evaluation function has been described above. Next, a case where RIU (Ratio Image Uniformity) is used as another evaluation function will be described. This relies on the idea that all pixels with a certain pixel value on an MRI brain image have the same partition, and the corresponding pixels of the PET brain image will have approximately the same pixel value. It is. That is, the uniformity of the pixel values of the PET brain image (the above-mentioned segment) corresponding to each tissue of the MRI brain image is maximized, that is, the weighted average of the standard deviation is minimized. Specifically, the pixel value on the PET brain image 40 corresponding to the pixel having the pixel value j on the MRI brain image 50R is set to aij. Next, an average aj 'for all the pixels i in aij is obtained. The standard deviation σj for all the pixels i in aij is obtained. σj ′ = σj / aj ′ is obtained. Σj ″ obtained by the following equation (14) is minimized.

  σj ″ = Σjσj ′ × nj / N (14)

  Here, Σj means the sum of the subscript j. nj is the number of pixels of the pixel value j on the MRI image 50R, and N = Σjnj.

  The segmentation unit (separating means) 24 separates the gray matter portion data and the white matter portion data from the MRI brain image data 50 of the subject aligned by the alignment unit 23 (segmentation). FIG. 11 shows an example in which the gray matter portion data 55 and the white matter portion data 56 are separated from the MRI brain image data 60 of the subject by the segmentation unit 24. One of the purposes of the BP imaging program of the present invention is to finally obtain separately the BP in the gray matter region and the BP in the white matter region. Therefore, gray matter portion data 55 in which only the gray matter region is extracted and white matter portion data 56 in which only the white matter region is extracted are prepared in advance and used as a gray matter mask and a white matter mask, as will be described later. The segmentation can be performed using free software SPM (statistical parametric mapping) 2 or 99. In SPM2 or the like, the MRI brain image data 60 of the subject is matched with the standard brain template by affine transformation, and then the gray matter and white matter template previously cut out for the standard brain are inversely transformed to obtain the gray matter partial data 55 of the subject. The white matter portion data 56 is cut out.

  The gray matter portion data 55 and the white matter portion data 56 separated by the segmentation unit 24 can be used as they are as a gray matter mask and a white matter mask, respectively, but noise may remain. A processing unit (noise removing means) 25 is provided. The fine line / expansion processing unit 25 performs predetermined noise removal processing on the gray matter portion data 55 and / or the white matter portion data 56 separated by the segmentation portion 24. In this specification and claims, “and / or” means, for example, gray matter portion data 55 and / or white matter portion data 56, only gray matter portion data 55, only white matter portion data 56, gray matter. It means both the quality portion data 55 and the white matter portion data 56.

As the predetermined noise removal processing, expansion and thin line processing are suitable. In the thin line / expansion processing unit 25, thinning is performed after expansion by using operations corresponding to dilation (erosion, scraping, expansion) and erosion (erosion, scraping, thin line) defined by Mathematical Morphology. Or the process which expand | swells after thinning is performed. Dilation and erosion for the sets A and B are defined by the following equations 15 and 16. The process of thinning after expansion in the thin line / expansion processing unit 25 corresponds to the closing operation (A ^B ) by the set B (structural element) of the set A shown by Expression 17, and the process of expanding after thinning is expressed by Expression 18. This corresponds to an opening operation (A _B ) by a set B (structural element) of the set A.

Specifically, the opening operation (A _B ) or the closing operation (A ^B ) by the structural element B of the set A is performed with the gray matter portion data 55 and the white matter portion data 56 as images to be processed (set A). A structural element B having a desired size may be used. FIG. 12 illustrates a fine line / expansion process (closing operation) by the fine line / expansion processing unit 25. 12A shows gray matter portion data 55 before the thin line / expansion processing, and FIG. 12B shows gray matter portion data 55+ as a result of the expansion processing performed on the gray matter portion data 55. FIG. C) shows gray matter portion data 55- as a result of performing thin line processing on the gray matter portion data 55+. The thin line / expansion processing unit 25 performs the above-described thin line / expansion processing (opening operation (A _B ), closing operation (A ^B )) on the gray matter portion data 55 and the white matter portion data 56 any number of times in any order. Can do. Alternatively, the thin line / expansion processing unit 25 can perform dilation and erosion processing any number of times in an arbitrary order regardless of the opening operation (A _B ) and the closing operation (A ^B ).

  FIG. 13 is a screen 70 illustrating a processing state by the thin line / expansion processing unit 25. The screen shown below including the screen 70 is displayed on the display of the computer 10. First, when the erosion button 72a shown on the screen 70 is clicked with a mouse or the like, the above-described erosion processing is performed on the unprocessed MRI brain image displayed in the upper left frame, and the MRI brain image as the processing result is displayed. Is displayed in the lower left frame. Next, when the dilatation (synonymous with dilation; the same applies hereinafter) button 73a shown on the screen 70 is clicked, the above-described dilation processing is performed on the MRI brain image that is the result of the previous erosion processing displayed in the lower left frame. The MRI brain image as the processing result is displayed in the same lower left frame. When the reset button 71a is clicked once, the original MRI brain image before the processing without erosion processing and dilation processing is displayed in the lower left frame. As described above, dilation and erosion processing can be performed any number of times in any order on the MRI brain image before processing displayed in the upper left frame. Since the Reset button 71b, the erosion button 72b, and the dilatation button 73b are similarly used for the MRI brain image displayed in the central upper and lower frames, description thereof is omitted.

  The MRI brain images illustrated on the screen 70 are as follows. The upper left frame shows gray matter data 55 before thin line / expansion processing, and the lower left frame shows gray matter data 55- after fine line / expansion processing (closing operation). The gray matter partial data 55- can be used as a gray matter mask. Similarly, the center upper frame shows the white matter portion data 56 before the thin line / expansion processing, and the center lower frame shows the white matter portion data 56- after the thin line / expansion processing (closing operation). The white matter partial data 56- can be used as a white matter mask. On the screen 70, the lower right frame shows a whole brain mask 51 that is a combination of a gray matter mask (gray matter portion data 55-) and a white matter mask (white matter portion data 56-). The upper right frame of the screen 70 is a PET brain image 41, which is displayed as a reference (described later).

A reference ROI setting unit (region of interest setting means) 26 is a reference region (reference region) that can be regarded as the above-mentioned predetermined radiopharmaceutical is not present for the MRI brain image data aligned by the alignment unit 23. Region of interest
Interest: ROI) is set, and the ROI is set in the PET brain image data of the subject input by the PET brain image data input unit 21. Since a predetermined radiopharmaceutical is selected that specifically binds to a target receptor, the reference region can be considered as a region where the receptor does not exist. The function of the reference ROI setting unit 26 is necessary for BP calculation, and details will be described later. FIG. 14 is a screen 80 illustrating the processing status of the reference ROI setting unit 26. The left image in the screen 80 is the subject's PET brain image data 42 input by the PET brain image data input unit 21, and the right image is MRI brain image data that is aligned with the PET brain image data 42 by the alignment unit 23. 61. In the screen 80, reference numeral 81 is an MRI option frame in which various options on the MRI brain image data side can be set, 82 is a registration box in which whether or not the MRI brain image data has been registered, and 85 is for the ROI An ROI frame 86 in which various options can be set is a polygon ROI box in which a polygon can be selected as the ROI shape.

  The reference ROI setting unit 26 sets the ROI (ROI 61) in the reference area MRef (indicated by a dotted line) for the MRI brain image data 61 shown in the right frame in the screen 80. Specifically, the user draws and inputs an ROI having a desired shape on the screen 80 using a cursor or the like, and sets the ROI 61 based on the coordinates of the input ROI. In FIG. 14, the ROI 61 is set in a slightly deformed iron array shape. When this setting is completed, the reference ROI setting unit 26 copies the ROI 61 into the reference area PRef corresponding to the reference area MRef with respect to the PET brain image data 42 shown in the left frame in the screen 80. As a result, the ROI 61 can be set on the PET brain image data 42. As described above, since the MRI brain image data 61 is aligned with the PET brain image data 42 by the alignment unit 23, both brain image data have the same coordinates. Thus, the ROI 61 is accurately set for the MRI image data 61 rich in anatomical information, and then the ROI 61 is set on the PET brain image data 42 by copying the ROI 61 to the PET brain image data 42. Yes. For this reason, the ROI 61 can be accurately set also on the PET brain image data 42.

  The elliptic ROI setting unit (predetermined shape region of interest setting means) 27 sets a ROI having a predetermined shape in the PET brain image data of the subject input by the PET brain image data input unit 21. In the BP imaging program of the present invention, BP is calculated for each pixel as described later. At this time, if the BP is calculated for all the pixels on the PET brain image, the BP is also calculated for a useless region such as a region where brain image data does not actually exist, and the processing time becomes long. . Therefore, in order not to calculate the BP for the useless region, a ROI (mask) having a predetermined shape is set on the PET brain image, the outside of the predetermined shape is cut, and only the inside is set as the target of the BP calculation. Yes. As the predetermined shape, an elliptical shape (elliptical mask) is preferable.

  FIG. 15 is a screen 90 illustrating the processing status of the ellipse ROI setting unit 27. In FIG. 15, the parts denoted by the same reference numerals as those in FIG. The left image in the screen 90 is the PET brain image data 43 of the subject input by the PET brain image data input unit 21, and the right image is MRI brain image data that is aligned with the PET brain image data 43 by the alignment unit 23. 62. In the screen 90, reference numeral 83 denotes a mask option frame in which various options relating to the above-described gray matter mask and the like can be set, 84 denotes a registration box which can select whether or not the gray matter mask etc. are aligned, and 87 denotes an ROI. This is an ellipse ROI box in which an ellipse can be selected as the shape.

  The elliptical ROI setting unit 27 sets an elliptical ROI 62 for the MRI brain image data 61 shown in the right frame in the screen 90. Specifically, the user draws and inputs an elliptical ROI on the screen 90 using a cursor or the like, and sets the ROI 62 based on the coordinates of the input ROI. In FIG. 9, the ROI 62 is set in an elliptical shape so that the entire brain image can be entered. When this setting is completed, the elliptical ROI setting unit 27 copies the elliptical ROI 62 to the PET brain image data 43 shown in the left frame in the screen 90. As a result, an elliptical ROI 62 (elliptical mask) can be set on the PET brain image data 43. As described above, since the MRI brain image data 62 is aligned with the PET brain image data 43 by the alignment unit 23, both brain image data have the same coordinates. As a result, the elliptical ROI 62 is accurately set for the MRI image data 63 rich in anatomical information, and then the elliptical ROI 62 is copied to the PET brain image data 43. An elliptical ROI 62 is set. Therefore, the elliptical ROI 62 can be accurately set even on the PET brain image data 43.

  In the case of setting the ROI 61 in the reference area PRef by the reference ROI setting unit 26 described above, the ROI 61 has a free shape by the user's freehand. However, the elliptical shape input by the user in the case of the elliptical ROI setting unit 27 is not freehand, but can be input by an automatic elliptical shape creation function using a conventional technique. In addition, since the oval ROI 62 may be created so that the entire brain image can be entered, it is not necessarily the MRI brain image data 61 shown in the right frame of the screen 90, but the PET brain image 43 shown in the left frame. Alternatively, an elliptical ROI 62 may be set directly. In this case, the elliptical ROI setting unit 27 can set the elliptical ROI 62 on the MRI brain image data 62 by copying the elliptical ROI 62 set on the PET brain image 43 onto the MRI brain image 62. it can.

  The radioactivity count value input unit (radioactivity count value input means) 28 inputs a time-radioactivity count value for each pixel with respect to the ROI in the reference region of the PET brain image data set by the reference ROI setting unit 26. . The function of the radioactivity count value input unit 28 is necessary for the calculation of BP, and details will be described later. FIG. 16 is a screen 100 showing the processing status of the radioactivity count value input unit 28. In FIG. 16, the parts denoted by the same reference numerals as those in FIGS. In the screen 100, reference numeral 101 is a table in which time-radioactivity count values inputted for one specific pixel are paired, and the radioactivity count values are shown as time passes from top to bottom. Reference numeral 102 is a graph corresponding to Table 101, and shows a time-radioactivity count value curve TAC (Time Activity Curve) with time on the horizontal axis and radioactivity count value on the vertical axis.

  As shown in FIG. 16, the radioactivity count value input unit 28 inputs a time-radioactivity count value for each pixel in the ROI 61 in the reference region PRef of the PET brain image data 42 set by the reference ROI setting unit 26. To do. The radioactivity count value input unit 28 can display the table 101 and display the time-radioactivity count value curve TAC in the graph 102 for one specific pixel. Here, specification (selection) of one pixel can be performed by placing a cursor on the ROI 61 on the PET brain image 42 or the ROI 61 on the MRI brain image 61 by the user. Alternatively, it is possible to specify (select) one pixel for designating the pixel number or coordinates by the user. Since the TAC curve is a curve for each pixel, it is easily affected by noise. Therefore, the radioactivity count value input unit 28 can smooth the TAC curve by performing smoothing by causing the user to click the S button indicated by reference numeral 103 in the screen 100. The R button indicated by reference numeral 104 performs a reset to restore smoothing.

From the time-radioactivity count value for each pixel in the ROI 61 in the reference region PRef obtained as described above, the behavior of a predetermined radiopharmaceutical in the ROI 61 in the reference region PRef is known. BP can be obtained by calculating the behavior of the pixels in other regions with respect to this behavior. That is, it is possible to know how much radiopharmaceutical has been taken into other regions based on the radioactivity count value in the reference region PRef. The BP calculating unit (receptor binding capacity calculating means) 29 includes the PET brain image data 43 in the elliptical ROI 62 set by the elliptic ROI setting unit 27 and the reference region PRef input by the radioactivity count value input unit 28. Using the time-radioactivity count value in the ROI 61, a BP is calculated for each pixel of the PET brain image data 43 in the elliptical ROI 62 based on the reference region method which is a mathematical model representing the dynamics of the radiopharmaceutical. . The BP calculation unit 29 cuts the outside of the ROI 62 (ellipse mask) on the PET brain image data 43 set by the ellipse ROI setting unit 27 and sets only the inside as a BP calculation target. In other words, the BP calculation unit 29 applies an ellipse mask to the PET brain image data 43 and uses the PET brain image data only within the ellipse mask as a calculation target. For this reason, it is possible to calculate at a faster speed with less waste than when all the PET brain image data 43 is calculated. In the BP imaging program of the present invention, the SRTM method (Lammertsma AA, Hume SP, Simplified reference tissue model for PET receptor studies.) Is one of the non-linear least square fitting as the reference region method.
NeuroImage 4: 153-158, 1996) and non-invasive Logan method (Logan, J., Fowler, JS, Volkow, ND, et al. Distribution Volume Ratios Without Blood Sampling from Graphical) Analysis of PET Data. Journal of Cerebral Blood Flow and Metabolism, 16, 834-840, 1996.). The outline of each method will be described below.

SRTM method.
FIG. 17 shows a compartment model for explaining the SRTM method. FIG. 17A shows a three-compartment model indicating a target region. In FIG. 17A, reference numeral 110 is plasma (Plasma), 111 is tissue (Tissue), 112 is a non-displaceable area where a radiopharmaceutical is released in the tissue 111, and 113 is radioactive in the tissue 111. It is a receptor (Receptor sites or Receptor rich region) to which a drug is bound, and the blood-brain barrier (not shown) is between the plasma 110 and the tissue 111. As shown in FIG. 17A, the radioactivity concentration of plasma 110 at time t is Cp (t), the radioactivity concentration of free region 112 is Cf (t), and the radioactivity concentration of receptor 113 is Cb (t ). The rate constant that defines the amount of radiopharmaceutical movement between each part is K ₁ from plasma 110 to free region 112 (due to diffusion from capillaries, unit is [ml / min / cm ³ ]), free region 112 to receptor 113 is k ₃ (due to binding, unit is [1 / min]), and receptor 113 to free region 112 is k ₄ (due to divergence, unit is {1 / min}), The free region 112 to the plasma 110 is k ₂ (due to the clearance to the vein and the unit is [1 / min]). FIG. 17B is a two-compartment model showing a reference region. In FIG. 17B, portions denoted by the same reference numerals as those in FIG. 11A indicate the same elements, and thus description thereof is omitted. In FIG. 17B, reference numeral 114 denotes a tissue, and reference numeral 115 denotes a reference region that can be regarded as having no radiopharmaceutical. As shown in FIG. 17B, the radiopharmaceutical migration constant is K ₁ ′ from plasma 110 to reference region 115, and K ₂ ′ from reference region 115 to plasma 110. In each compartment model shown in FIGS. 17A and 17B, the following equations 19 to 21 are established (refer to the homepage of the Department of Cyclotron Nuclear Medicine, Tohoku University).

  Here, for simplification, it is assumed that the volume of distribution (DV) of the radiopharmaceutical in the target area and the reference area is equal. The volume of distribution is an index indicating how much the drug administered to the human body has transferred to the tissue, and can be calculated by dividing the amount of drug in the body (dose) by the drug concentration of plasma when the equilibrium state is reached. (Refer nonpatent literature 1). A linear relationship represented by the following Expression 22 is assumed for the transition constant between the plasma 110 and the tissues 111 and 114 in the target region and the reference region. When Formula 22 is transformed, Formula 23 is obtained.

When the behavior of the radiopharmaceutical bound to the receptor 113 is not much different from that before binding, the target region can be shown by a two-compartment model as shown in FIG. In FIG. 17C, portions denoted by the same reference numerals as those in FIG. 17A indicate the same elements, and thus description thereof is omitted. In FIG. 17C, reference numeral 116 denotes a target portion obtained by combining the free region 112 and the receptor 113, and k _2a is an apparent rate constant from the target portion 116 to the plasma 110. In the target region shown in FIG. 17C, the following Expression 24 is established.

Considering the distribution volume DV in the target region shown in FIG. 17C, since the target region has reached an equilibrium state from the definition of the distribution volume described above, dC _t (t) / dt = 0 in Expression 24, In Expression 20, dC _f (t) / dt = 0, and in Expression 21, dC _b (t) / dt = 0. From the above and C _t (t) = C _f (t) + C _b (t), the following Expression 25 can be obtained. As shown in Equation 26, BP is expressed as a ratio of the transition constants k ₃ and k ₄ . The SRTM method has a non-invasive advantage because no blood is collected.

  When Expressions 19 and 24 are solved using Laplace transform and Expression 25, Expression 27 is obtained.

In Equation 27, λ is a decay constant (decay constant), and is unnecessary when attenuation correction is performed. In the BP imaging program of the present invention, Expression 28 where λ = 0 is used in Expression 27. In BP imaging program formula 28 of the present invention, C r _(t) is for each one pixel obtained by the radioactivity count input unit 28 described above time - using the radioactivity count, C _{t (t)} is PET Using the PET brain image data (radioactivity count value) input by the brain image data input unit 21, both sides of Equation 28 become equal while changing the values of R ₁ (see Equation 23), k ₂ and BP. The values of R ₁ , k ₂ and BP were determined. The value of BP at this time is the value of BP to be obtained.

Non-invasive Logan method.
This method is generally called the Logan plot method, and there are blood sampling methods and non-blood sampling methods. In the present specification, since a non-blood sampling method is adopted, the non-invasive Logan method will be hereinafter described. When the distribution volume DV (Equation 25) in the target region described above is transformed using the relationship of Equation 26, the following Equation 25 ′ is obtained. The DV in the reference region is expressed by Equation 29, and the ratio DVR of both can be expressed by Equation 30 (see Waseda University Dspace).
(Http://dspace.wul.waseda.ac.jp/dspace/bitstream/2065/356/9/Honbun-05_chapter5.pdf).

Here, if DVR _f is defined as in the following Expression 31,

K ₃ / k _{4 in} Expression 30 is expressed by Expression 32.

Here, when K ₁ / k ₂ of the target area is equal to K ₁ ′ / k ₂ ′ of the reference area, DVR _f = 1, so Expression 32 can be expressed as Expression 33.

  According to the graph method proposed by Logan et al. (Or the Logan plot method as described above), the DVR in Equation 33 is a graph in which the left side is a variable Y and the term excluding the DVR in the first term on the right side is a variable X in Equation 34. It can be estimated from the slope of the (regression line).

In the BP imaging program of the present invention, it is assumed that C _r (t) and C _t (T) in the second term of Equation 34 are balanced over time, and the second term is changed to the third term. The expression 35 was used as int ′ in the constant term int.

  In Expression 35, if the left side is the variable Y and the fraction on the right side is the variable X, Expression 36 is obtained. In Expression 36, Y is calculated for each pixel using the value input by the PET brain image data input unit 21 described above, and X is the value input by the PET brain image data input unit 21 and the radioactivity count described above. A graph was created by calculation for each pixel using the value input by the value input unit 28. The slope of the graph is DVR from Equation 36. Using this DVR, BP was obtained for each pixel from Equation 33.

  As described above, the time-radioactivity count value is obtained for each pixel of the PET brain image, and the BP is obtained for each pixel. For this reason, even when a normal region and an abnormal region are mixed in the ROI 62 (elliptical mask) on the PET brain image data 43 set by the elliptic ROI setting unit 27, the behaviors of the two are distinguished. can do. The BP calculation unit 29 described above can calculate the BP using only the SRTM method or the non-invasive Logan method, and can also calculate the BP using both.

  The BP image display unit (receptor binding capacity display means) 30 converts the BP for each pixel calculated by the BP calculation unit 29 and the gray matter portion data 55 and / or the white matter portion data 56 separated by the segmentation unit 24. Based on this, the gray matter portion and / or BP of the white matter portion data is displayed in a predetermined display format. As described above, the BP calculating unit 29 obtains BP for each pixel in the area of the ellipse ROI 62 in which the ellipse mask is applied to the PET brain image data 43, and BP brain image data including the entire pixels is obtained. By using the gray matter portion data 55 as a mask for the BP brain image data composed of the entire pixel, BP brain image data of only the gray matter portion can be obtained, and the BP brain image data of only the gray matter portion is obtained. By displaying, a BP brain image of only the gray matter portion can be obtained. Similarly, with respect to the white matter portion, by using the white matter portion data 56 as a mask for the BP brain image data composed of the entire pixels, BP brain image data of only the white matter portion can be obtained. By displaying image data, a BP brain image of only the white matter portion can be obtained. As described above, in the BP imaging program of the present invention, the BP is obtained for each of the gray matter and the white matter. For this reason, accurate BP according to a disease state is computable. Of course, the BP brain image of the whole brain can be displayed using the whole brain mask 51 in which the gray matter portion data 55 and the white matter portion data 56 are combined.

  When the noise removal processing by the fine line / expansion processing unit 25 is performed, the BP image display unit 30 is separated by the BP for each pixel calculated by the BP calculation unit 29 and the segmentation unit 24 and processed by the thin line expansion processing unit 25. Based on the gray matter portion data 55- and / or white matter portion data 56-, the BP of the gray matter portion and / or white matter portion data is displayed in a predetermined display format. As described above, the BP calculating unit 29 obtains BP for each pixel in the area of the ellipse ROI 62 in which the ellipse mask is applied to the PET brain image data 43, and BP brain image data including the entire pixels is obtained. By using the gray matter portion data 55- as a mask for the BP brain image data composed of the entire pixels, it is possible to obtain BP brain image data of only the gray matter portion from which noise has been removed. By displaying this BP brain image data, it is possible to obtain a BP brain image of only the gray matter portion. Similarly, with respect to the white matter portion, by using the white matter portion data 56- as a mask with respect to the BP brain image data composed of the entire pixels, BP brain image data of only the white matter portion from which noise has been removed can be obtained. By displaying the BP brain image data of only the white matter portion, the BP brain image of only the white matter portion can be obtained.

FIG. 18 shows screens 120a to 120d displayed by the BP image display unit 30 when [ ¹¹ C] PE2I is used as a radiopharmaceutical for a subject. In FIG. 18, reference numeral 44 is a PET brain image, 121 is a BP image corresponding to the PET brain image 44, 122 is an image of R ₁ (see Expression 10) when both sides of Expression 15 are equal as described above, and 123 is an image of k ₂ when the both sides of the equation 15 as described above is equal. As shown in the screen 120b, in the BP image 121 (in the original image), the region where the radiopharmaceutical is likely to be taken in (the region where the BP is large) is displayed in red, and the region where the radiopharmaceutical is difficult to capture (the region where the BP is small) is displayed in blue These areas are displayed in an intermediate color from red to blue (predetermined display format). As shown in the BP image 121, it can be understood at a glance that [ ¹¹ C] PE2I is easily taken into a part of the brain. As shown in the screen 120c, the area is a large value of (the originals) R ₁ is displayed in red, and displays a small area in blue, those of the middle region is displayed in the middle of the color from red to blue ing. As shown in screen 120d, (in originals) value of k ₂ the region is large is displayed in red, and displays a small area in blue, those of the middle region is displayed in the middle of the color from red to blue ing. The above display format is an example, and it is needless to say that other display formats may be used.

FIG. 19 shows screens 130a to 130d displayed by the BP image display unit 30 when [ ¹⁸ F] flumazenil is used as a radiopharmaceutical for a subject. 19, reference numeral 45 is a PET brain image, 131 is a BP image corresponding to the PET brain image 45, 132 is an image of R ₁ (see Expression 10) when both sides of Expression 15 are equal as described above, 133 is an image of k ₂ when the both sides of the equation 15 as described above is equal. The display format of the BP image 131 is the same as that of the BP image 121 in FIG. As shown in the BP image 131, it can be understood at a glance that [ ¹⁸ F] flumazenil is easily taken into a wide part of the brain. The display format of the R ₁ image 132 shown on the screen 130c and the display format of the k ₂ image 133 shown on the screen 130d are the same as those of the R ₁ image 122 and the k ₂ image 123 of FIG. 12, respectively. Omitted.

  FIG. 20 shows a screen 140 displayed by the BP image display unit 30. As shown on the screen 140, the BP image display unit 30 can also display the size of the BP by using a shade of a specific color (red in the original screen 140) (predetermined display format). Of course, the specific color is not limited to red, and may be other colors. Furthermore, as shown on the screen 140, BP images of a cross section of the brain can be displayed side by side from the top of the head to the neck. Although FIG. 20 shows a BP image of the cross section of the brain, the coronal section and the sagittal section can be displayed in the same manner. As described above, since the obtained BP is displayed as an image in the BP imaging program of the present invention, it is possible to easily evaluate BP in the entire region of the brain in a short period of time.

  FIG. 21 is a flowchart showing the flow of processing such as a BP imaging program in which the computer executes BP imaging from PET brain image data in the first embodiment of the present invention. As shown in FIG. 21, first, PET brain image data 40 of a subject imaged using a predetermined radiopharmaceutical that selectively binds to a receptor is input (step S10, PET brain image data input step). Next, the MRI brain image data 50 of the same subject is input (step S12. MRI brain image data input step). These PET brain image data input step (step S10) and MRI brain image data input step (step S12) may be executed in the reverse order.

  Based on the PET brain image data 40 of the subject input in the PET brain image data input step (step S10), the MRI brain of the same subject input in the PET brain image data 40 and the MRI brain image data input step (step S12) Alignment with the image data 50 is performed (step S14, alignment step). The gray matter portion data 55 and the white matter portion data 56 are separated from the MRI brain image data 60 of the subject aligned in the alignment step (step S14) (step S16, separation step or segmentation step).

  The gray matter portion data 55 and white matter portion data 56 separated in the separation step (step S16) can be used as gray matter mask and white matter mask, respectively, but noise may remain. For this reason, the user selects whether noise removal is necessary (step S18), and noise removal is performed if necessary. A predetermined noise removal process is performed on the gray matter portion data 55 and / or the white matter portion data 56 separated in the separation step (step S16) (step S20, noise removal step). In the noise removal step (step S20), it is preferable to perform the noise removal processing by subjecting the gray matter portion data 55 and / or the white matter portion data 56 separated in the separation step (step S16) to expansion and thin line processing. It is. The noise removal step (step S20) may be executed after the separation step (step S16) and before the BP image display step (step S30) described later. If noise removal is not selected in step S18, the process proceeds to the next step 22.

  For the MRI brain image data 61 and the like that have been aligned in the alignment step (step S14), the ROI 61 and the like are set in a reference region that can be regarded as a predetermined radiopharmaceutical not present, and the ROI 61 and the like are input as PET brain image data The PET brain image data 42 of the subject input in step (step S10) is set (step S22, region of interest setting step). A region of interest having a predetermined shape is set in the PET brain image data 43 and the like of the subject input in the PET brain image data input step (step S10) (step S24, predetermined shape region of interest setting step). The predetermined shape is preferably an ellipse. The predetermined shape region-of-interest setting step (step S24) can be executed before each preceding step (steps S12, 14 and the like) as long as it is after the PET brain image data input step (step S10).

  A time-radioactivity count value is input for each pixel for the ROI 61 and the like in the reference region such as the PET brain image data 42 set in the region-of-interest setting step (step S22) (step S26, radioactivity count value input step). . The PET brain image data 43 and the like in the ROI 62 having the predetermined shape (elliptical shape) set in the predetermined shape region-of-interest setting step (step S24) and the reference region input in the radioactivity count value input step (step S26) Based on the reference region method which is a mathematical model representing the dynamics of the radiopharmaceutical using the time-radioactivity count value in the ROI 61 etc., the PET brain image data 43 etc. in the ROI 62 etc. of a predetermined shape (elliptical shape) etc. BP is calculated for each pixel (step S28, receptor binding ability calculating step or BP calculating step). As the reference region method, the SRTM method and / or the non-invasive Logan method are suitable. Based on the BP for each pixel calculated in the receptor binding capacity calculation step (step S28) and the gray matter portion data 55 and / or white matter portion data 56 separated in the separation step (step S16), the gray matter portion and BP of the white matter portion is displayed in a predetermined display format (step S30, receptor binding ability display step or BP image display step). Of course, in the receptor binding ability display step (step S30), a BP brain image of the whole brain can be displayed using the whole brain mask 51 in which the gray matter portion data 55 and the white matter portion data 56 are combined.

  When noise removal is selected in step 18, the receptor binding ability display step (step S30) is the BP for each pixel calculated in the receptor binding ability calculation step (step S28) and the separation step (step S16). Based on the gray matter portion data 55- and / or the white matter portion data 56- that have been separated and subjected to the predetermined noise removal processing in the noise removal step (step S20), the BP of the gray matter portion and / or the white matter portion is determined as a predetermined value. Display in display format.

  As described above, according to the first embodiment of the present invention, the PET brain image data input unit 21 captures PET brain image data (radioactivity count) of a subject imaged using a predetermined radiopharmaceutical that selectively binds to a receptor. Value). The MRI brain image data input unit 22 inputs the MRI brain image data of the subject. The alignment unit 23 uses the PET brain image data 40 of the subject input by the PET brain image data input unit 21 as a reference, and the MRI brain of the same subject input by the PET brain image data 40 and the MRI brain image data input unit 22. Alignment with the image data 50 is performed. Specifically, first, reslice is performed to match the matrix size (256 × 256 (pixels)) of the MRI brain image data 50 with the matrix size (128 × 128 (pixels)) of the PET brain image data 40. In the BP imaging program of the present invention, the MRI brain image data 50 is re-sliced based on the PET brain image data 40 having a small matrix size in order to shorten the calculation time. Next, registration (registration) between the PET brain image data 40 and the MRI brain image data 50R (not shown) whose matrix size is re-sliced is performed. The segmentation unit 24 separates the gray matter partial data and the white matter partial data from the MRI brain image data 50 of the subject aligned by the alignment unit 23 (segmentation). One of the purposes of the BP imaging program of the present invention is to finally obtain separately the BP in the gray matter region and the BP in the white matter region. Therefore, the gray matter portion data 55 from which only the gray matter region is extracted and the white matter portion data 56 from which only the white matter region is extracted are prepared in advance and used as a gray matter mask and a white matter mask, respectively. The gray matter portion data 55 and the white matter portion data 56 separated by the segmentation unit 24 can be used as they are as a gray matter mask and a white matter mask, respectively, but noise may remain. 25 is provided. The fine line / expansion processing unit 25 performs predetermined noise removal processing on the gray matter portion data 55 and / or the white matter portion data 56 separated by the segmentation portion 24. As the predetermined noise removal processing, expansion and thin line processing are suitable. The reference ROI setting unit 26 sets the ROI in the reference region for the MRI brain image data aligned by the alignment unit 23, and the subject's PET brain inputted by the PET brain image data input unit 21. Set to image data. As described above, since the MRI brain image data 61 is aligned with the PET brain image data 42 by the alignment unit 23, both brain image data have the same coordinates. Thus, the ROI 61 is accurately set for the MRI image data 61 rich in anatomical information, and then the ROI 61 is set on the PET brain image data 42 by copying the ROI 61 to the PET brain image data 42. Yes. For this reason, the ROI 61 can be accurately set also on the PET brain image data 42. The ellipse ROI setting unit 27 sets an ROI having a predetermined shape in the PET brain image data of the subject input by the PET brain image data input unit 21. In the BP imaging program of the present invention, the BP is calculated for each pixel. At this time, if the BP is calculated for all the pixels on the PET brain image, the BP is also calculated for a useless region such as a region where brain image data does not actually exist, and the processing time becomes long. . Therefore, in order not to calculate the BP for the useless region, a ROI (mask) having a predetermined shape is set on the PET brain image, the outside of the predetermined shape is cut, and only the inside is set as the target of the BP calculation. Yes. As the predetermined shape, an elliptical shape (elliptical mask) is preferable. The radioactivity count value input unit 28 inputs a time-radioactivity count value for each pixel with respect to the ROI in the reference region of the PET brain image data set by the reference ROI setting unit 26.

  From the time-radioactivity count value for each pixel in the ROI 61 in the reference region PRef obtained as described above, the behavior of a predetermined radiopharmaceutical in the ROI 61 in the reference region PRef is known. BP can be obtained by calculating the behavior of the pixels in other regions with respect to this behavior. That is, it is possible to know how much radiopharmaceutical has been taken into other regions based on the radioactivity count value in the reference region PRef. The BP calculation unit 29 includes the PET brain image data 43 in the elliptical ROI 62 set by the elliptical ROI setting unit 27 and the time-radioactivity count value in the ROI 61 of the reference region PRef input by the radioactivity count value input unit 28. BP is calculated for each pixel of the PET brain image data 43 in the elliptical ROI 62 based on the reference region method which is a mathematical model representing the dynamics of the radiopharmaceutical. The BP calculation unit 29 applies an ellipse mask to the PET brain image data 43 and uses the PET brain image data only within the ellipse mask as a calculation target. For this reason, it is possible to calculate at a faster speed with less waste than when all the PET brain image data 43 is calculated. In the BP imaging program of the present invention, the SRTM method, which is one of nonlinear least square fitting, and the non-invasive Logan method, which is one of graph analysis methods, are used as the reference region method. As described above, the time-radioactivity count value is obtained for each pixel of the PET brain image, and the BP is obtained for each pixel. For this reason, even when a normal region and an abnormal region are mixed in the ROI 62 (elliptical mask) on the PET brain image data 43 set by the elliptic ROI setting unit 27, the behaviors of the two are distinguished. can do. Based on the BP for each pixel calculated by the BP calculation unit 29 and the gray matter portion data 55 and / or the white matter portion data 56 separated by the segmentation unit 24, the BP image display unit 30 The BP of the white matter data is displayed in a predetermined display format. As described above, the BP calculating unit 29 obtains BP for each pixel in the area of the ellipse ROI 62 in which the ellipse mask is applied to the PET brain image data 43, and BP brain image data including the entire pixels is obtained. By using the gray matter portion data 55 as a mask for the BP brain image data composed of the entire pixel, BP brain image data of only the gray matter portion can be obtained, and the BP brain image data of only the gray matter portion is obtained. By displaying, a BP brain image of only the gray matter portion can be obtained. Similarly, with respect to the white matter portion, by using the white matter portion data 56 as a mask for the BP brain image data composed of the entire pixels, BP brain image data of only the white matter portion can be obtained. By displaying image data, a BP brain image of only the white matter portion can be obtained. As described above, in the BP imaging program of the present invention, the BP is obtained for each of the gray matter and the white matter. For this reason, accurate BP according to a disease state is computable. When the processing by the thin line / expansion processing unit 25 is performed, the BP image display unit 30 is separated by the BP for each pixel calculated by the BP calculation unit 29 and the segmentation unit 24 and processed by the thin line expansion processing unit 25. Based on the gray matter portion data 55- and / or the white matter portion data 56-, the BP of the gray matter portion and / or white matter portion data is displayed in a predetermined display format. Since the obtained BP is displayed as an image in the BP imaging program of the present invention, it is possible to easily evaluate the BP in the entire region of the brain in a short period of time.

  In Embodiment 1 of the present invention, the MRI brain image and the PET brain image are aligned so that both brain images have the same coordinates. Thereby, after setting an anatomical region for an MRI image rich in anatomical information, the anatomical region is set in the PET brain image. For this reason, an anatomical region can be accurately specified even on a PET brain image. The time-radioactivity count value is obtained for each pixel of the PET brain image, and the BP is obtained for each pixel. For this reason, even when a normal area and an abnormal area are mixed in the set (elliptical) ROI, the normal radioactivity count value and the abnormal radioactivity count value are not mixed. It is possible to clearly indicate whether the BP is a normal area BP or an abnormal area BP. Since the obtained BP is displayed as an image, the BP in the entire region in the brain can be instantly shown, and the BP in the entire region in the brain can be easily evaluated in a short period of time. The BP is obtained for each of the gray matter and the white matter. For this reason, it is possible to calculate an accurate BP corresponding to a disease state in which gray matter is damaged or a disease state in which white matter is damaged.

A BP image is displayed by the above-described BP imaging program of the present invention. A doctor or the like can accurately determine a normal region and an abnormal region by looking at the BP image data. Thereafter, a doctor or the like can set an ROI in a region that seems to be abnormal, and can calculate an average BP for the ROI as in the conventional technique. In the second embodiment, a desired ROI is set for the image data on which the BP is displayed by the BP image display unit 30 described above, for example, the BP image 121 shown in FIG. 12, and the PET brain image data corresponding to the ROI is set. The time-radioactivity count value is input for the region of, and another BP calculation unit (other receptor binding capacity calculation means, not shown) that calculates the average BP in the ROI based on the time-radioactivity count value is further included. Can be provided.

  As described above, according to the second embodiment of the present invention, a doctor or the like can accurately determine a normal region and an abnormal region by looking at the BP image data. Thereafter, a doctor or the like can set an ROI in a region that seems to be abnormal, and can calculate an average BP for the ROI as in the conventional technique.

  FIG. 22 is a screen 160 illustrating the processing status of the elliptical ROI setting unit 27 according to the third embodiment of the present invention. In FIG. 22, the portions denoted by the same reference numerals as those in FIG. As shown in FIG. 22, the elliptical ROI that the elliptical ROI setting unit 27 sets by the user is not necessarily the size or position that covers the entire brain like the ROI 62 but the size or position that covers a part of the brain like the ROI 62a. It may be a position. Furthermore, the ellipse can be inclined and set like the ROI 62a. As shown in FIG. 18, when it is known that some radiopharmaceuticals accumulate only in a specific region (PET brain image 44), an elliptical shape that covers the region can be set.

  As described above, according to the third embodiment of the present invention, the elliptical ROI setting unit 27 can cause the user to set the elliptical ROI 62a at a size or position that covers a part of the brain, and in addition, the elliptical ROI 62 can be set to be inclined. You can also. For this reason, when using a radiopharmaceutical known to accumulate only in a specific region, an elliptical shape that covers the region can be set, and a BP image can be displayed in a faster calculation time.

  In the BP imaging program in the first embodiment and the like described above, the BP calculation unit 29 uses both or one of the SRTM method and the non-invasive Logan method as the reference region method. In the fourth embodiment, another calculation example when the non-invasive Logan method is used will be described.

As described above, the BP calculation unit 29 calculates BP by using the non-invasive Logan method using the equations 35 and 36. FIG. 23 shows a graph in which the left side Y of Equation 36 is the vertical axis and the right side X is the horizontal axis. When obtaining the slope DVR of the regression line Y shown in FIG. 23, the slope DVR varies depending on whether the starting point of the straight line portion is B ₀ or B ₁ . Therefore, in the fourth embodiment, a method for causing the user to select an optimal starting point is used.

FIG. 24 is a flowchart showing the flow of a BP calculation method (BP imaging program or the like) based on the optimum start point in the fourth embodiment of the present invention. The flowchart shown in FIG. 24 starts after the radioactivity count value input step (step S26) of the flowchart shown in FIG. 21 (or before the BP calculation step (step S28)). First, in step S40, the user selects either the SRTM method or the non-invasive Logan method. If the SRTM method is selected, the process proceeds to the BP calculation step (step S28). When the non-invasive Logan method is selected in step S40, the start point B _i regarded as a regression line by the Logan-DVR method is changed from the initial value B ₀ to the end value B _n , and the BP for each start point B _i is obtained. The process of the calculation step (step S44 or S28) is repeated (repetition steps (steps S42, S46, S48). Details will be described later. Repetition means). Each BP obtained in the repetitive steps (steps SS42, S46, S48) is displayed in a predetermined format, and the user is made to select an optimum start point (specific start point) (start point selection step (step S49). Point selection means). This will be described in detail below. First, the initial value setting of the starting point are considered regression line Y at Logan-DVR method (starting point initial value setting step (step S42). The initial value of the starting point, and B ₀ shown in FIG. 17. Next, a BP calculation step (step S44 or S28) by the non-invasive Logan method is executed, and then it is determined whether or not the start point set in the start point initial value setting step (step S42) is finished (start) Point end determination step (step S46), for example, the end is determined if the start point is _Bn shown in Fig. 17. If the start point end determination step (step S46) determines that the start point is not the end, start The start point set in the point initial value setting step (step S42) is changed to the next start point, and the process of the BP calculation step (step S44 or S28) is repeated ( Step S48). Changing the starting point to change the. Following Similarly starting point _{B i} performed by the _{B 1} increments the starting point _{B 0} to _B 1 .about.B _n. Beginning end determination step (step S46 ), The BP calculated for each start point B _i (i = 0 to n) is shown to the user, and the user is allowed to select an optimal start point B _j (start point selection). Step S49) As a way of showing each BP to the user, a plot display in which the vertical axis is BP and the horizontal axis is each start point B _i (i = 0 to n) is preferable. (first BP became plateau) the starting point B _j corresponding to determined the optimum starting point B _j BP portions of shoulder became, enter the B _j. then, the starting point B _j The process proceeds to step S28. More, it is possible to obtain the BP by optimal starting point B _j.

FIG. 25 illustrates a screen 170 illustrating the processing status of the BP calculation method using the optimum start point according to the fourth embodiment. In the screen 170, numeral 171 is a BP image displayed when using the starting point B _i in the 172 is a graph displaying the regression line Y at that time.

As described above, according to the fourth embodiment of the present invention, when the non-invasive Logan method is used as the BP calculation method, the start point _Bi is changed when the slope DVR of the regression line Y shown in FIG. 23 is obtained. the user optimal starting point B _j while gradually can be selected. As a result, it is possible to obtain the BP by optimal starting point B _j.

  FIG. 26 is a block diagram showing an internal circuit 180 of the computer 10 that executes the BP imaging program of the present invention. As shown in FIG. 26, the CPU 181, ROM 182, RAM 183, image control unit 186, controller 187, input control unit 190, and external I / F unit 192 are connected to a bus 193. In FIG. 26, the above-described BP imaging program of the present invention is recorded on a recording medium (including a removable recording medium) such as a ROM 182, a disk 188, a DVD, or a CD-ROM 189. On the disk 188, the above-mentioned PET-DB14, MRI-DB16, etc. can be recorded. The BP imaging program is loaded into the RAM 183 from the ROM 182 via the bus 193 or from a recording medium such as the disk 188 or DVD or CD-ROM 189 via the controller 187 via the bus 193. The image control unit 186 sends image data such as various screens 70 displayed by the BP image display unit 30 or the like to the VRAM 185. A display device (display) 184 displays the above data sent from the VRAM 185. The VRAM 185 is an image memory having a capacity corresponding to the data capacity for one screen of the display device 184. The input operation unit 191 is an input device such as a mouse and a keyboard for performing input, designation, etc. (ROI setting, etc.) on the computer 10. The input control unit 190 is connected to the input operation unit 191 and performs input control and the like. The external I / F unit 192 has an interface function when connecting to the outside of the computer (CPU) 181.

  As described above, the computer (CPU) 181 executes the BP imaging program of the present invention, thereby achieving the object of the present invention. The BP imaging program can be supplied to the computer (CPU) 181 in the form of a recording medium such as a DVD or a CD-ROM 189 as described above, and a recording medium such as a DVD or a CD-ROM 189 on which the BP imaging program is recorded is also available. Similarly, the present invention is constituted. As a recording medium on which the BP imaging program is recorded, for example, a memory card, a memory stick, an optical disk, an FD, or the like can be used in addition to the recording medium described above.

  As an application example of the present invention, it can be applied to a PET brain image or a PET image of another part.

1 BP imaging system, 10 computer, 12 recording device, 14 PET-DB, 16 MRI-DB, 20 functional block, 21 PET brain image data input unit, 22 MRI brain image data input unit, 23 registration unit, 24 segmentation Unit, 25 thin line / expansion processing unit, 26 reference ROI setting unit, 27 elliptical ROI setting unit, 28 radioactivity count input unit, 29 BP calculation unit, 30 BP image display unit, 40, 41, 42, 43, 44, 45 PET brain image data, 50 MRI brain image data, 51 Whole brain mask, 55, 55+, 55- Gray matter partial data, 56, 56- White matter partial data, 60, 61, 62 (after alignment) MRI brain image data, 70, 80, 90, 100, 120, 130, 140 screen, 71a, 71b reset button 72a, 72b erosion button, 73a, 73b dilatation button, 81 MRI option frame, 82, 84 Registration box, 83 Mask option frame, 85 ROI frame, 86 Polygon ROI box, 87 Ellipse ROI box, 101 table, 102 , 172 graph, 103 S button, 104 R button, 110 plasma, 111, 114 tissue, 112 free region, 113 receptor, 115 reference region, 116 target region, 121, 131, 171 BP image, 122, 132 R ₁ image , 123, 133 k ₂ images, 181 CPU, 182 ROM, 183 RAM, 184 display device, 185 VRAM, 186 Image control unit, 187 controller, 188 disc, 189 CD-ROM, 190 input control unit, 191 input Operation unit, 192 External I / F unit, 192 bus.

Kazuya Sakaguchi, Yuichi Kimura, “Dynamic Analysis for Measurement of Neuronal Receptor Function in PET”, MEDICAL IMAGING TECHNOLOGY, Vol. 27, No. 5, pp. 286-291, November 2009, Japanese Medical Image Engineering Society.

The receptor binding ability imaging program of the present invention is a receptor binding ability imaging program for imaging receptor binding ability from functional brain image data (preferably PET or SPECT brain image data). A functional brain image data input means for inputting functional brain image data of a subject imaged by using a predetermined radiopharmaceutical that selectively binds to a receptor, and morphological brain image data of the subject (preferably Is a morphological brain image data input means for inputting MRI or CT brain image data), and the functional brain image data and the morphology are based on the functional brain image data of the subject input by the functional brain image data input means. Alignment means for aligning with the subject's morphological brain image data input by the brain image data input means; Separating means for separating gray matter partial data and white matter partial data from the morphological brain image data of the subject, and the predetermined radiopharmaceutical is not present in the morphological brain image data aligned by the alignment means A region of interest setting means for setting a region of interest in a reference region that can be regarded as a region of interest, and setting the region of interest in the functional brain image data of the subject input by the functional brain image data input means, the functional brain image data input About the region of interest in the reference region of the functional brain image data set by the region-of-interest setting means, the region of interest having the predetermined shape set in the functional brain image data of the subject inputted by the means , Radioactivity count value input means for inputting time-radioactivity count value for each pixel, set by the predetermined shape region of interest setting means Of the radiopharmaceutical using the functional brain image data in the region of interest of a predetermined shape and the time-radioactivity count value in the region of interest in the reference region input by the radioactivity count value input means. A receptor binding ability calculating means for calculating a receptor binding ability for each pixel of the functional brain image data in the region of interest of the predetermined shape based on a reference region method which is a mathematical model representing the receptor binding, The gray matter portion data and / or white matter portion data separated by the separating means is used as a mask for the receptor binding ability brain image data composed of the whole receptor binding ability calculated by the ability calculating means. , A receptor binding capacity image for functioning as a receptor binding capacity display means for displaying the receptor binding capacity of the gray matter portion and / or white matter portion data in a predetermined display format. An imaging program.

Here, in the receptor binding ability imaging program of the present invention, when the reference region method is the Logan-DVR method, the start point regarded as a regression line by the Logan-DVR method is changed from the initial value to the end value, Repeating means for repeating the processing of the receptor binding ability calculating means for each starting point, and starting point selection for displaying each receptor binding ability obtained by the repeating means in a predetermined format and selecting a specific starting point Means.
Here, in the receptor binding ability imaging program according to the present invention, the radioactivity count value input means includes the region of interest set for the morphological brain image data by the predetermined shape region-of-interest setting means, or the predetermined shape. In the region of interest set in the functional brain image data by the region-of-interest setting unit, a unit for displaying a time-radioactivity count curve for one pixel selected by the user can be further provided.

The receptor binding ability imaging method of the present invention is a receptor binding ability imaging method in which a computer executes imaging of receptor binding ability from functional brain image data, and selectively binds to a receptor. A functional brain image data input step for inputting functional brain image data of a subject imaged using a predetermined radiopharmaceutical, a morphological brain image data input step for inputting morphological brain image data of the subject, and the functional Using the functional brain image data of the subject input in the brain image data input step as a reference, the functional brain image data and the morphological brain image data of the subject input in the morphological brain image data input step are aligned. The gray matter portion data and the white matter portion data are separated from the morphological brain image data of the subject aligned in the alignment step to be performed and the alignment configuration step. A region of interest in a reference region in which the predetermined radiopharmaceutical can be regarded as non-existent with respect to the morphological brain image data aligned in the alignment step, and the region of interest in the functional brain A region-of-interest setting step set in the functional brain image data of the subject input in the image data input step, and a region of interest having a predetermined shape in the functional brain image data of the subject input in the functional brain image data input step A predetermined shape region-of-interest setting step for setting a region of interest, and a radioactivity count value for inputting a time-radioactivity count value for each pixel for the region of interest in the reference region of the functional brain image data set in the region-of-interest setting step Functional brain image data in a region of interest of a predetermined shape set in the input step; Based on the reference area method, which is a mathematical model representing the dynamics of the radiopharmaceutical, using the time-activity count value in the region of interest of the reference area input in the radioactivity count value input step, A receptor binding ability calculating step for calculating a receptor binding ability for each pixel of the functional brain image data in the region of interest of the shape, and a receptor binding ability for each pixel calculated by the receptor binding ability calculating step Receptor binding ability of the gray matter portion and / or white matter portion by using the gray matter portion data and / or white matter portion data separated by the separation step as a mask with respect to the whole receptor binding ability brain image data. A receptor binding capacity display step for displaying the functional brain image data in the predetermined display format, and the functional brain image data input step and the morphological brain image data input step. Can be executed in reverse, and the predetermined shape region-of-interest setting step can be executed before each preceding step as long as it is after the functional brain image data input step.

Here, in the receptor binding ability imaging method of the present invention, when the reference region method is the Logan-DVR method, before the receptor binding ability calculation step, the starting point considered as a regression line by the Logan-DVR method Is changed from the initial value to the end value, and the process of the receptor binding capacity calculation means is repeated for each starting point, and each receptor binding capacity obtained in the repetition step is displayed in a predetermined format. And a starting point selection step of selecting a specific starting point.
Here, in the receptor binding ability imaging method of the present invention, the radioactivity count value input step includes the region of interest set for the morphological brain image data in the predetermined shape region of interest setting step, or the predetermined shape. The method may further include displaying a time-radioactivity count curve for one pixel selected by the user in the region of interest set in the functional brain image data in the region-of-interest setting step.

Claims (15)

A receptor binding ability imaging program for imaging receptor binding ability from functional brain image data, comprising:
Functional brain image data input means for inputting functional brain image data of a subject imaged using a predetermined radiopharmaceutical that selectively binds to a receptor;
Morphological brain image data input means for inputting morphological brain image data of the subject,
Based on the functional brain image data of the subject input by the functional brain image data input means, the functional brain image data and the morphological brain image data of the subject input by the morphological brain image data input means Alignment means for performing alignment,
Separating means for separating gray matter portion data and white matter portion data from the morphology brain image data of the subject aligned by the alignment means;
A region of interest is set in a reference region that can be considered that the predetermined radiopharmaceutical does not exist for the morphological brain image data aligned by the alignment unit, and the region of interest is set by the functional brain image data input unit. Region-of-interest setting means for setting functional brain image data of the input subject,
A predetermined shape region-of-interest setting means for setting a region of interest having a predetermined shape in the functional brain image data of the subject input by the functional brain image data input unit;
Radioactivity count value input means for inputting a time-radioactivity count value for each pixel for a region of interest in a reference area of functional brain image data set by the region of interest setting means,
Functional brain image data in a region of interest of a predetermined shape set by the predetermined shape region-of-interest setting means, and time-radioactivity count value in the region of interest of the reference region input by the radioactivity count value input unit. And a receptor that calculates a receptor binding capacity for each pixel of the functional brain image data in the region of interest of the predetermined shape based on a reference region method that is a mathematical model representing the dynamics of the radiopharmaceutical. Binding ability calculation means,
Based on the receptor binding capacity for each pixel calculated by the receptor binding capacity calculating means and the gray matter part data and / or white matter part data separated by the separating means, the gray matter part and / or white matter part of A receptor binding ability imaging program for functioning as a receptor binding ability display means for displaying receptor binding ability of data in a predetermined display format.   The receptor binding ability imaging program according to claim 1, wherein the reference region method is an SRTM (Simplified Reference Tissue Model) method and / or a non-invasive Logan method. The receptor binding ability imaging program according to claim 2, further comprising noise removal means for performing predetermined noise removal processing on gray matter partial data and / or white matter partial data separated by the separation means,
The receptor binding capacity display means is a gray-white that has been separated by the receptor binding capacity for each pixel calculated by the receptor binding capacity calculation means and separated by the separation means and subjected to predetermined noise removal processing by the noise removal means. A receptor binding ability imaging program for displaying a receptor binding ability of a gray matter portion and / or a white matter portion in a predetermined display format based on the quality portion data and / or the white matter portion data.   4. The receptor binding ability imaging program according to claim 3, wherein the noise removing means performs noise reduction by performing expansion and fine line processing on the gray matter partial data and / or white matter partial data separated by the separating means. A receptor binding ability imaging program characterized by performing processing.   The receptor binding ability imaging program according to any one of claims 1 to 4, wherein a region of interest is set for image data on which receptor binding ability is displayed by the receptor binding ability display means, and the region of interest Other receptor binding capacity calculating means for inputting a time-radioactivity count value for a functional brain image data area corresponding to, and calculating an average receptor binding capacity in the region of interest based on the time-radioactivity count value And a receptor binding ability imaging program.   6. The receptor binding ability imaging program according to claim 1, wherein the predetermined shape set by said predetermined shape region-of-interest setting means is an ellipse. . The receptor binding ability imaging program according to any one of claims 2 to 6, wherein the reference region method is a Logan-DVR method.
A repeating means for changing the starting point regarded as a regression line in the Logan-DVR method from an initial value to an ending value, and repeating the processing of the receptor binding ability calculating means for each starting point;
A receptor binding capacity imaging program, further comprising start point selection means for displaying each receptor binding capacity obtained by the repeating means in a predetermined format and selecting a specific start point.   A computer-readable recording medium on which the receptor-binding ability imaging program according to claim 1 is recorded. A receptor binding ability imaging method, wherein the computer performs imaging of receptor binding ability from functional brain image data, comprising:
A functional brain image data input step of inputting functional brain image data of a subject imaged using a predetermined radiopharmaceutical that selectively binds to a receptor;
A morphological brain image data input step for inputting morphological brain image data of the subject,
Using the functional brain image data of the subject input in the functional brain image data input step as a reference, the functional brain image data and the morphological brain image data of the subject input in the morphological brain image data input step An alignment step for alignment;
A separation step of separating the gray matter portion data and the white matter portion data from the morphology brain image data of the subject aligned in the alignment configuration step;
A region of interest is set in a reference region that can be considered that the predetermined radiopharmaceutical does not exist for the morphological brain image data registered in the registration step, and the region of interest is set in the functional brain image data input step. A region-of-interest setting step to be set in the functional brain image data of the input subject;
A predetermined shape region-of-interest setting step for setting a region of interest of a predetermined shape in the functional brain image data of the subject input in the functional brain image data input step;
A radioactivity count value input step for inputting a time-radioactivity count value for each pixel for the region of interest in the reference region of the functional brain image data set in the region of interest setting step;
Functional brain image data in a region of interest having a predetermined shape set in the predetermined shape region-of-interest setting step, and time-radioactivity count value in the region of interest in the reference region input in the radioactivity count value input step. And a receptor that calculates a receptor binding capacity for each pixel of the functional brain image data in the region of interest of the predetermined shape based on a reference region method that is a mathematical model representing the dynamics of the radiopharmaceutical. A binding ability calculating step;
Based on the receptor binding capacity for each pixel calculated by the receptor binding capacity calculation step and the gray matter part data and / or white matter part data separated by the separation step, the gray matter part and / or the white matter part A receptor binding capacity display step for displaying the receptor binding capacity in a predetermined display format,
The functional brain image data input step and the morphological brain image data input step can be executed in reverse, and the predetermined shape region-of-interest setting step is after each of the functional brain image data input steps. Receptor binding ability imaging method characterized in that it can be carried out before.   10. The receptor binding ability imaging method according to claim 9, wherein the reference region method is an SRTM (Simplified Reference Tissue Model) method and / or a non-invasive Logan method. The receptor binding ability imaging method according to claim 10.
After the separation step and before the receptor binding ability display step, a noise removal step of performing a predetermined noise removal process on the gray matter portion data and / or white matter portion data separated in the separation step is further provided. ,
In the receptor binding capacity display step, the receptor binding capacity for each pixel calculated in the receptor binding capacity calculation step is separated from the receptor binding capacity in the separation step and is subjected to predetermined noise removal processing in the noise removal step. A receptor binding ability imaging method, wherein the receptor binding ability of a gray matter part and / or a white matter part is displayed in a predetermined display format based on the substance part data and / or the white matter part data.   12. The receptor binding ability imaging method according to claim 11, wherein the noise removal step performs expansion and thin line processing on the gray matter portion data and / or white matter portion data separated in the separation step, thereby removing noise. Receptor binding ability imaging method characterized by performing processing.   13. The receptor binding ability imaging method according to claim 9, wherein a region of interest is set for the image data on which receptor binding ability is displayed in the receptor binding ability display step, and the region of interest is displayed. Another receptor binding capacity calculation step of inputting a time-radioactivity count value for a functional brain image data area corresponding to, and calculating an average receptor binding capacity in the region of interest based on the time-radioactivity count value And a receptor binding ability imaging method.   14. The receptor binding ability imaging method according to claim 9, wherein the predetermined shape set in the predetermined shape region of interest setting step is an ellipse. . The receptor binding ability imaging method according to any one of claims 10 to 14, wherein the reference region method is a Logan-DVR method.
Before the receptor binding ability calculation step,
A repeating step of changing the starting point regarded as a regression line in the Logan-DVR method from an initial value to an ending value, and repeating the processing of the receptor binding ability calculating means for each starting point;
A receptor binding ability imaging method, further comprising: a starting point selection step of displaying each receptor binding ability obtained in the repetition step in a predetermined format and selecting a specific starting point.