Methods, programs, and apparatus for evaluating the state of motor function

Abstract

The present disclosure provides a means for evaluating a state of a motor function of a patient who has or is suspected of having brain damage such as local brain damage.　The present disclosure relates to: a method for evaluating a state of a motor function of a patient who has or is suspected of having brain damage by using parameters obtained from a diffusion weighted image of the patient's brain; a program for executing the method in a computer; and an image processing device and an MRI device which can be used in practicing the method. According to the present disclosure, the motor function state of a patient who has or is suspected of having brain damage can be evaluated, and it is also possible to predict the recovery of the motor function after regeneration treatment. Accordingly, whether the patient is suitable for the regeneration treatment can be determined before the start of the treatment.

Description

[Technical Field]

[0001] This disclosure relates to a method for evaluating the motor function status of patients with or suspected of having brain injury, and to a program, image analysis device, and MRI device that can be used in implementing this method. In particular, this disclosure relates to a method for predicting motor function recovery after regenerative therapy in patients with focal brain injury. More specifically, this disclosure relates to a method that utilizes physiological index values ​​with the white matter region of interest on the injured hemisphere side of the brain, and to a program, image analysis device, and MRI device that can be used in implementing this method. [Background technology]

[0002] In recent years, regenerative medicine has attracted attention as a new treatment for central nervous system diseases (such as cerebral infarction, cerebral hemorrhage, head injury, and Parkinson's disease), and the development of several cell-based therapies is progressing. In particular, treatment by direct transplantation, which involves directly delivering cells into the brain, is thought to be able to deliver more cells into the brain because it can avoid being blocked by the blood-brain barrier.

[0003] In cell therapy, the degree of recovery varies among patients who actually receive the cells, so it is important to determine which patients are suitable for cell therapy before starting treatment (Non-Patent Literature 1). [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Stem Cell Therapies as an Emerging Paradigm in Stroke Participants, Stroke 40(2):510-5. 2009 [Disclosure of the Invention] [Means for solving the problem]

[0005] This disclosure provides means for evaluating the motor function status of patients who have or are suspected of having brain injury, such as focal brain injury. In particular, this disclosure provides means for determining whether such patients are suitable for regenerative therapy, that is, whether they are likely to respond to regenerative therapy, before the initiation of treatment. More specifically, this disclosure relates to a method using physiological index values ​​with the white matter region of interest on the side of the brain injury hemisphere.

[0006] The inventors have found that in patients with localized brain injury, the state of motor function correlates with parameters obtained from diffusion-weighted imaging with the white matter region of interest on the injured hemisphere of the patient's brain.

[0007] Therefore, this disclosure provides the following: (Item 1) A step of obtaining one or more physiological index values ​​with the white matter region of interest being on the side of the damaged hemisphere of the brain of a patient with or suspected of having brain damage, The steps include: comparing the aforementioned physiological index value with a control physiological index value and performing calculations to calculate a value that indicates the state of the patient's motor function; A method for evaluating the motor function status of the patient, including the following: (Item 2) The method according to the above item, wherein the physiological index value is obtained from a diffusion-weighted image of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI). (Item 3) The method according to any one of the above items, wherein the physiological index value includes MD (mean diffusivity) value and AD (axial diffusivity) value. (Item 4) The method according to any one of the above items, wherein the region of interest is set in the posterior limb of the internal capsule of the brain. (Item 5) The method according to any one of the above items, wherein the state of motor function is the state of motor function after regenerative therapy. (Item 6) The method according to any one of the above items, wherein the control physiological index value is obtained with the white matter region on the non-damaged hemisphere side of the patient's brain as the region of interest. (Item 7) The method according to any one of the above items, wherein the step of performing the calculation is to calculate a value represented by the physiological index value / the control physiological index value. (Item 8) The method according to any one of the above items, wherein the step of performing the calculation involves substituting the calculated value indicating the state of the patient's motor function into a pre-prepared regression line whose variables are the value indicating the state of the patient's motor function and the degree of motor function recovery, thereby evaluating the state of the patient's motor function. (Item 9) The method according to any one of the above items, wherein the step of performing the calculation involves comparing the calculated value indicating the state of the patient's motor function with a pre-prepared reference value to calculate the likelihood of the patient achieving a desired degree of motor function recovery after regenerative therapy. (Item 10) A computer program that causes a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, the method comprising the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: causing the computer to perform calculations to compare the physiological index value with a control physiological index value and to calculate a value indicating the state of the patient's motor function; A program that includes this. (Item 10A) A computer program product that causes a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, wherein the method consists of the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: causing the computer to perform calculations to compare the physiological index value with a control physiological index value and to calculate a value indicating the state of the patient's motor function; A program product including (Item 10-2) The program or program product according to the above item, wherein the physiological index value is obtained from a diffusion-weighted image of the brain of the patient obtained by a diffusion tensor imaging (DTI) method or a diffusion kurtosis imaging (DKI) method. (Item 10-3) The program or program product according to any one of the above items, wherein the physiological index value includes an MD (mean diffusivity) value and an AD (axial diffusivity) value. (Item 10-4) The program or program product according to any one of the above items, wherein the region of interest is set in the posterior limb of the internal capsule of the brain. (Item 10-5) The program or program product according to any one of the above items, wherein the state of the motor function is the state of the motor function after regenerative treatment. (Item 10-6) The program or program product according to any one of the above items, wherein the control physiological index value is obtained with the white matter region on the non-lesioned hemisphere side of the brain of the patient as the region of interest. (Item 10-7) The program or program product according to any one of the above items, wherein the step of causing the calculation to be performed calculates a value represented by the physiological index value / the control physiological index value. (Item 10-8) The program or program product according to any one of the above items, wherein the step of causing the calculation to be performed substitutes a value indicating the state of the motor function of the patient, which has been calculated, into a regression line prepared in advance with a value indicating the state of the motor function of the patient and the degree of motor function recovery as variables, thereby evaluating the state of the motor function of the patient. (Item 10-9) The program or program product according to any one of the above items, wherein the step of causing the calculation to be performed compares a value indicating the state of the motor function of the patient, which has been calculated, with a previously prepared reference value, thereby calculating the likelihood of the patient reaching a desired degree of motor function recovery after regenerative treatment. (Item 10B) A program as described in Item 10 or a program product as described in Item 10A, further comprising any or more of the features described in Items 1-9. (Item 11) A recording medium for storing a computer program that causes a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, wherein the method involves the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: causing the computer to perform calculations to compare the physiological index value with a control physiological index value and to calculate a value indicating the state of the patient's motor function; A recording medium that includes this. (Item 11-2) The recording medium described above, wherein the physiological index values ​​are obtained from a diffusion-weighted image of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI). (Item 11-3) A recording medium according to any one of the above items, wherein the physiological index value includes MD (mean diffusivity) value and AD (axial diffusivity) value. (Item 11-4) A recording medium according to any one of the above items, wherein the region of interest is set in the posterior limb of the internal capsule of the brain. (Item 11-5) A recording medium as described in any one of the above items, wherein the state of motor function is the state of motor function after regenerative therapy. (Item 11-6) The recording medium according to any one of the above items, wherein the control physiological index value is obtained with the white matter region on the non-damaged hemisphere side of the patient's brain as the region of interest. (Item 11-7) The recording medium according to any one of the above items, wherein the step of performing the calculation calculates a value represented by the physiological index value / the control physiological index value. (Item 11-8) A recording medium according to any one of the above items, wherein the step of performing the calculation involves substituting the calculated value indicating the state of the patient's motor function into a pre-prepared regression line whose variables are the value indicating the state of the patient's motor function and the degree of motor function recovery, thereby evaluating the state of the patient's motor function. (Item 11-9) The recording medium according to any one of the above items, wherein the step of performing the calculation involves comparing the calculated value indicating the state of the patient's motor function with a pre-prepared reference value to calculate the likelihood that the patient will reach a desired degree of motor function recovery after regenerative therapy. (Item 11A) The recording medium described in Item 11, further comprising any or more of the features described in Items 1 to 9. (Item 12) A system for evaluating the motor function of the brain in patients who have or are suspected of having brain damage, A means for obtaining physiological index values ​​with the white matter region of interest being the white matter region on the side of the damaged hemisphere of the patient's brain, means for comparing the aforementioned physiological index value with a control physiological index value and performing calculations to calculate a value indicating the state of the patient's motor function, and A system that includes this. (Item 12-2) The system described above, wherein the physiological index values ​​are obtained from diffusion-weighted images of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI). (Item 12-3) The system according to any one of the above items, wherein the physiological index value includes MD (mean diffusivity) value and AD (axial diffusivity) value. (Item 12-4) The system described in any one of the above items, wherein the region of interest is set in the posterior limb of the internal capsule of the brain. (Item 12-5) The system described in any one of the above items, wherein the state of motor function is the state of motor function after regenerative therapy. (Item 12-6) The system according to any one of the above items, wherein the control physiological index value is obtained with the white matter region on the non-damaged hemisphere side of the patient's brain as the region of interest. (Item 12-7) The system according to any one of the above items, wherein the means for performing the calculation calculates a value represented by the physiological index value / the control physiological index value. (Item 12-8) The system according to any one of the above items, wherein the means for performing the calculation evaluates the state of the patient's motor function by substituting the calculated value indicating the state of the patient's motor function into a pre-prepared regression line whose variables are the value indicating the state of the patient's motor function and the degree of motor function recovery. (Item 12-9) The system according to any one of the above items, wherein the means for performing the calculation compares the calculated value indicating the state of the patient's motor function with a pre-prepared reference value to calculate the likelihood that the patient will reach a desired degree of motor function recovery after regenerative therapy. (Item 12A) The system described in Item 12, further comprising any or more of the features described in Items 1-9. (Item 13) A region of interest setting unit that, in diffusion-weighted imaging of the brain of a patient with or suspected of having brain damage, sets the white matter region on the damaged hemisphere side as the first region of interest and the white matter region on the undamaged hemisphere side as the second region of interest, A physiological index value calculation unit that calculates physiological index values ​​for the injured hemisphere and the uninjured hemisphere in the first and second regions of interest, respectively, A calculation unit that performs calculations to calculate a value indicating the state of motor function of the patient by comparing the physiological index value of the injured hemisphere with the physiological index value of the uninjured hemisphere. An image analysis device characterized by comprising the following features. (Item 13-2) The image analysis device described above, wherein the physiological index values ​​are obtained from diffusion-weighted images of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI). (Item 13-3) An image analysis device according to any one of the above items, wherein the physiological index value includes MD (mean diffusivity) value and AD (axial diffusivity) value. (Item 13-4) An image analysis device according to any one of the above items, wherein the region of interest is set to the posterior limb of the internal capsule of the brain. (Item 13-5) An image analysis device according to any one of the above items, wherein the state of motor function is the state of motor function after regenerative therapy. (Item 13-7) The image analysis apparatus according to any one of the above items, wherein the calculation unit calculates a value represented by the physiological index value on the injured hemisphere side / the physiological index value on the uninjured hemisphere side. (Item 13-8) The image analysis device according to any one of the above items, wherein the calculation unit evaluates the state of the patient's motor function by substituting the calculated value indicating the state of the patient's motor function into a pre-prepared regression line whose variables are the value indicating the state of the patient's motor function and the degree of motor function recovery. (Item 13-9) The image analysis device according to any one of the above items, wherein the calculation unit compares the calculated value indicating the state of the patient's motor function with a pre-prepared reference value to calculate the likelihood of the patient achieving a desired degree of motor function recovery after regenerative therapy. (Item 13A) An image analysis device as described in Item 13, further comprising the features described in any or more of Items 1 to 9. (Item 14) A magnetic resonance imaging unit for imaging the brains of patients with or suspected of having brain damage, An image generation unit that generates diffusion-weighted images from echo data acquired by the nuclear magnetic resonance imaging unit, In diffusion-weighted imaging, a region of interest setting unit sets the white matter region on the damaged hemisphere side as the first region of interest and the white matter region on the undamaged hemisphere side as the second region of interest. A physiological index value calculation unit that calculates physiological index values ​​for the injured hemisphere and the uninjured hemisphere in the first and second regions of interest, respectively, A calculation unit that performs calculations to calculate a value indicating the state of motor function of the patient by comparing the physiological index value of the injured hemisphere with the physiological index value of the uninjured hemisphere. An MRI apparatus characterized by comprising the following features. (Item 14-2) The MRI apparatus described above, wherein the physiological index values ​​are obtained from diffusion-weighted images of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI). (Item 14-3) An MRI apparatus according to any one of the above items, wherein the physiological indicator values ​​include MD (mean diffusivity) values ​​and AD (axial diffusivity) values. (Item 14-4) An MRI apparatus according to any one of the above items, wherein the region of interest is set to the posterior limb of the internal capsule of the brain. (Item 14-5) An MRI device as described in any one of the above items, wherein the state of motor function is the state of motor function after regenerative therapy. (Item 14-7) The MRI apparatus according to any one of the above items, wherein the calculation unit calculates a value represented by the physiological index value on the injured hemisphere side / the physiological index value on the uninjured hemisphere side. (Item 14-8) The MRI apparatus according to any one of the above items, wherein the calculation unit evaluates the state of the patient's motor function by substituting the calculated value indicating the state of the patient's motor function into a pre-prepared regression line whose variables are the value indicating the state of the patient's motor function and the degree of motor function recovery. (Item 14-9) The MRI apparatus according to any one of the above items, wherein the calculation unit compares the calculated value indicating the state of the patient's motor function with a pre-prepared reference value to calculate the likelihood that the patient will achieve a desired degree of motor function recovery after regenerative therapy. (Item 14A) An MRI apparatus as described in Item 14, further comprising any or more of the features described in Items 1-9.

[0008] In this disclosure, one or more of the above features may be provided in combinations other than those explicitly stated. Further embodiments and advantages of this disclosure will be apparent to those skilled in the art, by reading and understanding the detailed description below as necessary.

[0009] Furthermore, any other features and notable effects of this disclosure will become clear to those skilled in the art by referring to the following sections on embodiments of the invention and the drawings. [Effects of the Invention]

[0010] According to this disclosure, it is possible to evaluate the motor function status of patients who have or are suspected of having brain damage, such as focal brain injury, and thereby predict the recovery of motor function after regenerative therapy in such patients, and to determine whether such patients are suitable for regenerative therapy before the start of treatment. [Brief explanation of the drawing]

[0011] [Figure 1] Figure 1 is a block diagram showing the overall configuration of an MRI apparatus, which is one embodiment of the present disclosure. [Figure 2] Figure 2 is a functional block diagram showing the configuration of the storage unit, calculation unit, input unit, and output unit in an MRI apparatus, which is one embodiment of the present disclosure. [Figure 3] Figure 3 is a flowchart showing each step in a prediction method, which is one embodiment of the present disclosure. [Figure 4] Figure 4 is a flowchart detailing the calculation steps in a prediction method, which is one embodiment of the present disclosure. [Figure 5] Figure 5 is a flowchart detailing the calculation steps in a prediction method, which is one embodiment of the present disclosure. [Figure 6] Figure 6 is a schematic diagram illustrating the procedure of image processing by DKI in one embodiment of the present disclosure. [Figure 7]Figure 7 is a graph showing the correlation between the ratio of AD in the posterior limb of the middle internal capsule on the lesioned side and the healthy side (lesion / healthy) and the change in BI in one embodiment of the present disclosure. [Figure 8] Figure 8 is a graph showing the correlation between the ratio of medial mass (MD) of the posterior limb of the middle internal capsule on the lesioned side and the healthy side (lesion / healthy) and the change in BI in one embodiment of the present disclosure. [Figure 9A] Figure 9A is a photograph showing a case of left cerebral hemisphere infarction with a poor degree of functional recovery. It can be seen that the AD and MD in the posterior limb of the left internal capsule are lower than on the right side. [Figure 9B] Figure 9B is a photograph showing a case of left cerebral hemisphere infarction with a high degree of functional recovery. It can be seen that the left-right difference in AD and MD of the posterior limb of the internal capsule is small. [Modes for carrying out the invention]

[0012] The present disclosure is described below in best form. Throughout this specification, singular expressions should be understood to include the concept of their plural form unless otherwise specified. Accordingly, singular articles (e.g., "a," "an," "the" in English) should be understood to include the concept of their plural form unless otherwise specified. Furthermore, terms used herein should be understood to have the meaning commonly used in the art unless otherwise specified. Accordingly, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which this disclosure pertains. In case of any conflict, this specification (including definitions) shall prevail.

[0013] The following provides definitions of terms used specifically in this specification and / or basic technical concepts as appropriate.

[0014] In this specification, "approximately" means ±10% of the following number.

[0015] In this specification, "white matter region" refers to the area within the central nervous system, which consists of the brain and spinal cord, where nerve fibers primarily accumulate and run. In the cerebrum and cerebellum, it is located in the deep layers, while in the spinal cord, it occupies the superficial layer. For example, the white matter region includes the anterior limb of the internal capsule, the posterior limb of the internal capsule, the genu of the internal capsule, the corpus callosum, the center of the semioval, the anterior column of the spinal cord, the lateral column of the spinal cord, and the posterior column of the spinal cord.

[0016] In this specification, the "posterior limb of the internal capsule" refers to the part of the internal capsule, a collection of nerve fibers, through which the pyramidal tract and fibers connecting the temporal, parietal, and occipital lobes to the brainstem run, and is mainly located in the space between the thalamus and the lentiform nucleus. The posterior limb of the internal capsule consists of a group of fibers running in a nearly vertical direction. Corticospinal fibers are located in the anterior part, and the corticorubral tract runs lateral to the corticospinal fibers.

[0017] In this specification, "physiological index value" refers to index values ​​obtained from diffusion-weighted imaging of the brain, such as diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI), and includes MK (mean kurtosis), AK (axial kurtosis), RK (radial kurtosis), FA (fractional anisotropy), KFA (kurtosis fractional anisotropy), MD (mean diffusivity), AD (axial diffusivity), and RD (radial diffusivity). Of these, the MD value is the average of three eigenvalues ​​(λ1 to λ3) that represent ADC, an index that represents the magnitude of diffusion itself, and the AD value refers to the value of λ1 among those eigenvalues.

[0018] In this specification, "state of motor function" refers to the state of motor function as comprehensively controlled by brain function, and "assessment of the state of motor function" includes evaluating or predicting, based on the state of the subject's brain, whether motor function is normal, partially or completely paralyzed, currently or after treatment. For example, "assessment of the state of motor function" includes predicting the recovery of brain function that controls movement through regenerative therapy, etc.

[0019] (Preferred embodiment) Preferred embodiments of the Disclosure are described below. The embodiments provided below are provided for a better understanding of the Disclosure, and the scope of the Disclosure should not be limited to the descriptions below. It will be apparent that those skilled in the art can make appropriate modifications within the scope of the Disclosure, taking into consideration the descriptions herein. Furthermore, the embodiments of the Disclosure below can be used individually or in combination.

[0020] In one aspect of this disclosure, a method is provided for evaluating the motor function status of a patient, comprising the steps of: obtaining one or more physiological index values ​​with the white matter region of interest on the side of the injured hemisphere of the brain of a patient who has or is suspected of having brain damage; and performing calculations to compare the physiological index values ​​with control physiological index values ​​to calculate a value indicating the motor function status of the patient.

[0021] In one embodiment, physiological indicator values ​​can be obtained from images of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI). In diffusion tensor imaging (DTI), the corticospinal tract can be tracked by setting a region of interest (ROI) created by tracing anatomical structures and measuring physiological indicator values ​​such as FA and MD values ​​within the region of interest.

[0022] While ROI setting in diffusion tensor imaging (DTI) is generally done manually, corticospinal tract tracking using this method depends on the experience of the examiner. Therefore, in one embodiment, the DKI method can be used as a quantitative image index that is independent of the examiner. Furthermore, the DTI method assumes that water molecule diffusion follows a normal distribution, but it is known that water molecule diffusion in living organisms does not follow a normal distribution. Therefore, a diffusion imaging method that does not assume a normal distribution, such as the DKI method, can more accurately reflect the diffusion of water molecules in living organisms. Thus, in one embodiment of this disclosure, the DKI method makes it possible to obtain a diffusion image index that can predict the effect of cell administration therapy in stroke patients with high accuracy and without depending on the experience of the examiner.

[0023] In one embodiment, the physiological index values ​​obtained from diffusion-weighted images of a patient's brain obtained by the diffusion tensor imaging (DTI) method or diffusion kurtosis imaging (DKI) method described above are not particularly limited as long as they are indices obtained by diffusion-weighted imaging that visualizes the direction and speed of water molecule diffusion in tissue as parameters. For example, diffusion indices such as MK (mean kurtosis), AK (axial kurtosis), RK (radial kurtosis), FA (fractional anisotropy), KFA (kurtosis fractional anisotropy), MD (mean diffusivity), AD (axial diffusivity), and RD (radial diffusivity) can be used. In another embodiment, these diffusion indices can be used individually or in combination of two or more.

[0024] In one embodiment of this disclosure, the ROI in DTI and DKI may be set anywhere in the white matter region of the brain and is not particularly limited. In one embodiment, the ROI is preferably set in the posterior limb of the internal capsule. In particular, since there are very few nerve cells in the posterior limb of the internal capsule, a remarkable effect of this disclosure is that the state of motor function can be evaluated or the prognosis after treatment can be predicted by the value obtained by placing the ROI in the posterior limb of the internal capsule using the method of this disclosure.

[0025] In one embodiment of this disclosure, the motor function status of a subject can be evaluated from physiological index values ​​obtained from images of the patient's brain obtained by the diffusion tensor imaging (DTI) method or diffusion kurtosis imaging (DKI) method described above. This motor function may be current or post-treatment, and it is also possible to predict the state of motor function recovery after regenerative therapy.

[0026] In one embodiment of this disclosure, the state of motor function can be evaluated by comparing physiological index values ​​obtained when the ROI is placed on the side of the damaged hemisphere of the brain with physiological index values ​​obtained when the ROI is placed on the side of the undamaged hemisphere of the brain (referred to as control physiological index values), and preferably by calculating a value expressed as physiological index value / control physiological index value.

[0027] In one embodiment of this disclosure, the evaluation of motor function status can also be performed by substituting a value expressed as physiological index value / control physiological index value into a regression line where the variables are a value indicating the state of the patient's motor function status and the degree of motor function recovery. In another embodiment, the possibility can also be indicated by comparing the value expressed as physiological index value / control physiological index value with a reference value indicating the likelihood that the patient will reach a desired degree of motor function recovery after regenerative therapy.

[0028] As described above, the method of this disclosure makes it possible to evaluate the motor function status of a subject and to evaluate the motor function status after regenerative therapy, that is, to predict whether motor function will recover through regenerative therapy. Therefore, it becomes possible to determine which patients are suitable for cell therapy before starting treatment and to select patients who will be highly likely to receive treatment. This disclosure also provides a computer program for executing the above method on a computer, a recording medium for storing the program, and a system for executing the above method.

[0029] In other words, in one aspect of this disclosure, a computer program causes a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, the method comprising the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: causing the computer to perform calculations to compare the physiological index value with a control physiological index value and to calculate a value indicating the state of the patient's motor function; A program including the following will be offered.

[0030] In other aspects of this disclosure, a recording medium storing a computer program causing a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, wherein the method involves the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: causing the computer to perform calculations to compare the physiological index value with a control physiological index value and to calculate a value indicating the state of the patient's motor function; A recording medium including the above is provided.

[0031] In other aspects of this disclosure, a system for evaluating the motor function of the brain of a patient who has or is suspected of having brain damage, A means for obtaining physiological index values ​​with the white matter region of interest being the white matter region on the side of the damaged hemisphere of the patient's brain, means for comparing the aforementioned physiological index value with a control physiological index value and performing calculations to calculate a value indicating the state of the patient's motor function, and A system including this is provided.

[0032] Furthermore, in one aspect of this disclosure, we can provide an image analysis device and an MRI device that can be used in implementing a method for evaluating the motor function of patients who have or are suspected of having the brain injury described above.

[0033] In other words, in one aspect of this disclosure, a region of interest setting unit sets the white matter region on the injured hemisphere side as the first region of interest and the white matter region on the uninjured hemisphere side as the second region of interest in a diffusion-weighted image of the brain of a patient with or suspected of having brain injury, A physiological index value calculation unit that calculates physiological index values ​​for the injured hemisphere and the uninjured hemisphere in the first and second regions of interest, respectively, A calculation unit that performs calculations to calculate a value indicating the state of motor function of the patient by comparing the physiological index value of the injured hemisphere with the physiological index value of the uninjured hemisphere. An image analysis device is provided, characterized by comprising the following features.

[0034] In other aspects of this disclosure, a magnetic resonance imaging unit for imaging the brain of a patient who has or is suspected of having brain damage, An image generation unit that generates diffusion-weighted images from echo data acquired by the nuclear magnetic resonance imaging unit, In diffusion-weighted imaging, a region of interest setting unit sets the white matter region on the damaged hemisphere side as the first region of interest and the white matter region on the undamaged hemisphere side as the second region of interest. A physiological index value calculation unit that calculates physiological index values ​​for the injured hemisphere and the uninjured hemisphere in the first and second regions of interest, respectively, A calculation unit that performs calculations to calculate a value indicating the state of motor function of the patient by comparing the physiological index value of the injured hemisphere with the physiological index value of the uninjured hemisphere. An MRI device is provided, characterized by having the following features.

[0035] The detailed configuration of the image analysis device and MRI device described herein may be similar to that of the image analysis device and MRI device described in detail elsewhere in this specification.

[0036] Other aspects of this disclosure relate to a method for predicting motor function recovery after regenerative therapy in patients with focal brain injury, as well as a program, image analysis device, and MRI device that can be used in carrying out said method.

[0037] A method for predicting motor function recovery after regenerative therapy in patients with localized brain injury, and exemplary embodiments of MRI devices that can be used in implementing this method, will be described with reference to Figures 1 to 5.

[0038] Figure 1 shows a block diagram illustrating the overall configuration of an MRI apparatus, which is one embodiment of the present disclosure. The MRI apparatus 1 comprises a nuclear magnetic resonance imaging unit 10 and a computer 20.

[0039] The nuclear magnetic resonance imaging unit 10 is an imaging unit used in any known MRI apparatus that can acquire echo data necessary for diffusion-weighted imaging such as DTI and DKI. In one example, the nuclear magnetic resonance imaging unit 10 has a patient bed; a magnet stand equipped with a static magnetic field magnet, gradient magnetic field coils and an RF coil; and a sequence control unit. In the nuclear magnetic resonance imaging unit 10, the patient bed on which the patient sits is inserted into the opening of the magnet stand unit. The static magnetic field magnet of the magnet stand unit generates a static magnetic field, and the gradient magnetic field coils apply a gradient magnetic field. Next, the transmitting RF coil generates a high-frequency magnetic field, which is used to receive the echo signal emitted from the patient by the receiving RF coil. The received echo signal is digitized and transmitted as echo data to the sequence control unit. The sequence control unit controls imaging based on sequence information transmitted from the computer 20 and also transfers the received echo data to the computer 20.

[0040] The computer 20 is a device that controls the nuclear magnetic resonance imaging unit 10, acquires data, reconstructs images, and performs image analysis, and includes an interface unit 21, an input unit 22, a storage unit 23, a calculation unit 24, an output unit 25, and a control unit 26.

[0041] The interface unit 21 controls the input and output of various data, such as echo data, exchanged with the sequence control unit of the nuclear magnetic resonance imaging unit 10. The interface unit 21 transmits sequence information for controlling the nuclear magnetic resonance imaging unit 10 to the sequence control unit. The interface unit 21 also receives echo data from the sequence control unit and stores it in the storage unit 23.

[0042] The input unit 22 is a device such as a keyboard, mouse, buttons, or switches, and it receives signals corresponding to the operator's actions on these devices.

[0043] The storage unit 23 includes a storage medium such as a hard disk, flash memory, RAM, or ROM, and a reading device for reading information stored in the storage medium. The storage unit 23 stores echo data transmitted from the sequence control unit, various MRI image data generated from the echo data, reference information for evaluating the patient's motor function, programs for image generation and analysis, programs for controlling each functional unit of the MRI apparatus 1 executed by the control unit 26, and various setting information.

[0044] The arithmetic unit 24 is composed of hardware such as a CPU. The arithmetic unit 24 reads a program stored in the memory unit 23, reconstructs an image from the echo data stored in the memory unit 23, and generates images such as DTI and DKI from the reconstructed image. The arithmetic unit 24 also analyzes the images of the patient's brain, such as DTI and DKI, stored in the memory unit 23 and performs calculations to evaluate the state of the patient's motor function.

[0045] The output unit 25 outputs various information, such as MRI images generated by the calculation unit 24 and values ​​for evaluating the state of motor function obtained through calculations, to an external display, typically connected to the output unit 25, outside the computer 20.

[0046] The control unit 26 is connected to each functional unit that constitutes the MRI apparatus 1 and reads programs stored in the memory unit 23 to control their operations. For example, the control unit 26 generates sequence information from imaging conditions set by the operator and transmits this to the sequence control unit to control imaging by the nuclear magnetic resonance imaging unit 10. Here, imaging conditions refer to the setting values ​​of various imaging parameters such as b-value, TR, TE, NEX, voxel size, number of slices, and diffusion gradient direction, and those skilled in the art can appropriately set these values ​​to be suitable for acquiring images such as DTI and DKI.

[0047] Next, the functions of the arithmetic unit 24 will be described while referring to FIG. 2, including its relationship with the input unit 22, the storage unit 23, and the output unit 25. FIG. 2 is a functional block diagram showing the configurations of the storage unit, the arithmetic unit, the input unit, and the output unit in one embodiment of the present disclosure. The storage unit 23 includes an echo data storage unit 231, a reconstructed image storage unit 232, a DTI / DKI image storage unit 233, and a reference information storage unit 234. The arithmetic unit 24 includes an image generation unit 241 and an image analysis unit 242. Further, the image generation unit 241 includes an image reconstruction unit 241a and a DTI / DKI image generation unit 241b, and the image analysis unit 242 includes an interest region setting unit 242a, a physiological index value calculation unit 242b, a physiological index value comparison unit 242c, and a motor function state evaluation arithmetic unit 242d.

[0048] The function of the image generation unit 241 that generates images such as DTI and DKI from echo data will be described. The echo data storage unit 231 stores the echo data transmitted from the sequence control unit for each patient. The image reconstruction unit 241a generates a reconstructed image such as a diffusion-weighted image (DWI image) by performing a reconstruction process such as a Fourier transform on the echo data stored by the echo data storage unit 231. The reconstructed image storage unit 232 stores the generated reconstructed image.

[0049] The DTI / DKI image generation unit 241b analyzes the generated reconstructed image for DTI, DKI, etc., and generates a DTI / DKI image. For example, in DTI analysis, for each voxel, the diffusion coefficients D xx , D xy , D xz , D yy , D yz , D zz which are the components of the diffusion tensor D represented by the 3×3 symmetric matrix of Equation 1 are calculated, and by diagonalizing the matrix of Equation 1, the eigenvalues (λ1, λ2, λ3) shown in Equation 2 are calculated. Here, D xx , D yy and D zz are the diffusion coefficients when the gradient magnetic field is applied in the x-axis direction, y-axis direction, and z-axis direction of the MRI apparatus coordinate system, respectively. are the diffusion coefficients when the gradient magnetic field is applied in the x-axis direction, y-axis direction, and z-axis direction of the MRI apparatus coordinate system, respectively.

number

number

[0050] From the calculated eigenvalues ​​(λ1, λ2, λ3), the diffusion tensor parameters ADC (apparent diffusion coefficient) and FA (fractional anisotropy) are derived (Equations 3 and 4). Note that ADC and MD will have the same value.

number

number

[0051] The DTI / DKI image generation unit 241b generates images such as DTI and DKI, including λ1 map, λ2 map, λ3 map, ADC map, or FA map, by mapping these parameters. The DTI / DKI image storage unit 233 stores the generated DTI and DKI images.

[0052] Next, the functions of the image analysis unit 242, which analyzes images such as DTI and DKI to perform calculations for evaluating motor function status, will be described in conjunction with a method for predicting motor function recovery after regenerative therapy in patients with localized brain injury, which is one embodiment of the present disclosure, with reference to Figures 2 to 5. Figure 3 is a flowchart showing each step in the prediction method, which is one embodiment of the present disclosure and is performed using each of the above-mentioned functional units, and Figures 4 and 5 are flowcharts detailing the calculation steps in the prediction method.

[0053] The region of interest setting unit 242a sets a first region of interest (ROI-1) at a position corresponding to the white matter region on the injured hemisphere and a second region of interest (ROI-2) at a position corresponding to the white matter region on the uninjured hemisphere, on a DTI image, such as an FA map, stored in the DTI / DKI image storage unit 233 (step S10). The ROIs may be set manually based on anatomical positions, set by overlaying with other medical images, or set automatically based on the functions of known image analysis software. When setting ROIs manually, the input unit 22 accepts the operator's operation to set the ROIs.

[0054] The physiological index value calculation unit 242b calculates the physiological index values ​​for the injured hemisphere and the uninjured hemisphere, respectively, which are the physiological index values ​​for ROI-1 and ROI-2 (step S11). The physiological index values ​​for the injured hemisphere and the uninjured hemisphere are the average values ​​of the physiological index values ​​of all voxels contained in ROI-1 and ROI-2, respectively.

[0055] The physiological index value comparison unit 242c calculates a value represented by the physiological index value of the injured hemisphere / the physiological index value of the uninjured hemisphere (step S12).

[0056] The motor function state evaluation calculation unit 242d performs calculations to predict, for example, the recovery of the motor function of the patient after regenerative therapy, based on the values ​​calculated by the physiological index value comparison unit 242c (step S13), and outputs the calculation results to the output unit 25 (step S14). The calculations for evaluating the motor function state are performed based on the calculated values ​​as well as the reference information stored in the reference information storage unit 234. It breaks.

[0057] In one embodiment, the reference information is a regression line in which the variables are a pre-prepared value represented by the physiological index value of the injured hemisphere / physiological index value of the uninjured hemisphere of a patient who has or is suspected of having brain injury before regenerative therapy, and the degree of motor function recovery of the same patient after treatment. Here, the degree of motor function recovery is the degree of recovery of motor function due to treatment, as evaluated using a known evaluation method that can assess motor function, such as the Bathel Index (BI) or the Fugl-Meyer Assessment (FMA), and can be expressed as the difference between the score before treatment and the score after treatment for the same patient.

[0058] In another embodiment, the reference information is a pre-defined baseline value. The baseline value is a cutoff value used to distinguish between patients who have or are suspected of having brain damage that is expected to result in the desired degree of motor function recovery after regenerative therapy, and patients who have or are suspected of having brain damage that is not expected to result in the desired degree of motor function recovery.

[0059] As will be shown in later examples, the inventors have found that in patients with localized brain injury, the degree of motor function recovery after regenerative therapy correlates with a value expressed as the ratio of the physiological index value of the injured hemisphere to the physiological index value of the uninjured hemisphere before treatment. Therefore, by referring to the values ​​calculated from the DTI and DKI images of the brain of patients who have already undergone regenerative therapy and the degree of motor function recovery after treatment, it is possible to predict the motor function recovery after treatment for patients who are about to undergo regenerative therapy, and to evaluate whether this patient is likely to be suitable for regenerative therapy, that is, whether the regenerative therapy is likely to be successful.

[0060] Specifically, for example, a regression line can be prepared in advance with the values ​​calculated from the DTI and DKI images of the brain of patients who have already received regenerative therapy and the degree of motor function recovery after treatment as variables. By substituting the values ​​calculated from the DTI and DKI images of the brain of a subject who is about to receive regenerative therapy into this regression line, a predicted value for the degree of motor function recovery after regenerative therapy for that subject can be calculated (steps S130a, S130b).

[0061] Similarly, for example, based on a scatter plot or regression line with variables being values ​​calculated from pre-treatment DTI and DKI images of the brain of patients who have already received regenerative therapy and the degree of motor function recovery after treatment, a value expressed as the pre-treatment physiological index value on the damaged hemisphere / physiological index value on the undamaged hemisphere corresponding to the desired degree of motor function recovery can be predetermined as a reference value, and by determining whether the values ​​calculated from the DTI and DKI images of the brain of a subject who is about to receive regenerative therapy exceed the reference value, it is possible to calculate the likelihood that the subject will reach the desired degree of motor function recovery after regenerative therapy (steps S130b to S133b). The reference value can be set appropriately according to the target degree of motor function recovery.

[0062] Reference information such as regression lines and reference values ​​is preferably obtained from patients with the same type of disease as the patient whose motor function recovery after regenerative therapy is being predicted. For example, if the patient being predicted is a stroke patient, the reference information is preferably prepared using values ​​calculated from pre-treatment DTI and DKI images of the brain of stroke patients who underwent regenerative therapy, and the degree of motor function recovery after treatment.

[0063] The reference information should also preferably be obtained from patients who have received the same type of treatment as the treatment being applied. For example, if the treatment is the administration of bone marrow mesenchymal stem cells (BMSCs), the reference information should preferably be prepared using values ​​calculated from pre-treatment brain DTI and DKI images of patients who received BMSCs, and the degree of motor function recovery after treatment.

[0064] The above describes a method for evaluating the motor function of patients with or suspected of having brain injury, and exemplary embodiments of an MRI apparatus that can be used in carrying out the said method. An exemplary embodiment of the image analysis apparatus according to the present disclosure that can be used in carrying out the said method is an apparatus having an image analysis unit 242 of an MRI apparatus 1, the details thereof as described above.

[0065] Furthermore, the program relating to this disclosure that can be used in carrying out the above method is a program that causes a computer to execute each step of the above method, and its details are as described above. The computer-readable storage medium storing the program can be any storage medium such as a hard disk, flash memory, CD, or DVD.

[0066] According to this disclosure, it is possible to evaluate the state of a patient's motor function, thereby predicting, for example, the recovery of motor function after treatment in a patient undergoing regenerative therapy. Furthermore, according to this disclosure, it is possible to evaluate whether a patient is expected to be suitable for regenerative therapy, that is, whether the regenerative therapy is likely to be successful. Therefore, the methods and programs according to this disclosure can also be described as methods and programs for evaluating a patient's suitability for regenerative therapy, or methods and programs to assist in evaluating a patient's suitability for regenerative therapy. The same applies to other aspects of this disclosure.

[0067] In this specification, "brain injury" means any damage to the brain, including damage to the blood vessels of the brain. The causes of the injury are not particularly limited; for example, "brain injury" may include traumatic brain injury, stroke, cerebral infarction, oxygen-deficiency brain injury, brain tumor encephalitis, and focal brain injury.

[0068] In this specification, “focal brain injury” refers to a condition in which damage occurs in a specific area of ​​the brain, and “patient with focal brain injury” refers to a patient who has suffered damage to a specific area of ​​the brain. Examples of focal brain injury include cerebral infarction, traumatic head injury, and cerebral hemorrhage. Furthermore, in this disclosure, there are no limitations on patients with focal brain injury, as long as they have suffered damage to a specific area of ​​the brain and have impaired motor function, and they may be patients in the acute, subacute, or chronic phases.

[0069] In this specification, "regenerative therapy for patients with focal brain injury" means a treatment that uses the patient's own cells (autologous) or cells or secretions from another person (allogeneic) to regenerate the patient's damaged nervous system cells and restore various functional impairments resulting from the injury.

[0070] Cells that can be used for regenerative therapy in patients with brain injury or localized brain injury are any cells that have the ability to differentiate into neural cells. Examples include multipotent stem cells such as mesenchymal stem cells and neural stem cells, induced pluripotent stem cells (iPS cells), embryonic stem cells (ES cells), embryonic tumor cells (EC cells), and embryonic germ cells (EG cells). In this disclosure, the cells preferably used for therapy are mesenchymal stem cells, particularly bone marrow mesenchymal stem cells (BMSCs, also called bone marrow stem cells).

[0071] The cells exemplified above are thought to exert their therapeutic effects through the transdifferentiation of the transplanted cells themselves into nerve cells, and through the activation of the patient's own neural stem cells and the promotion of nerve repair (nursing effect) by cytokines, trophic factors, exosomes, etc., contained in secretions from the transplanted cells. Therefore, secretions from the cells exemplified above, such as exosomes and cell culture supernatants derived from these cells, can also be used for the treatments described in this disclosure.

[0072] The cells and their secretions described above can be prepared by known methods using biological samples isolated from the patient or another person. Multipotent stem cells may also be obtained by differentiating pluripotent stem cells.

[0073] Furthermore, the dosage and route of administration of the above-mentioned cells and their secretions are appropriately determined by those skilled in the art, with reference to known drug regimens relating thereto. For example, the cells may be administered systemically by intravenous or intra-arterial administration at a dose of 10 per kg of patient body weight. 4 ~10 9 pieces, preferably 10 5 ~10 8The individual can be administered locally, such as directly into the brain or intrathecally, at a rate of 10 per kg of patient body weight. 2 ~10 9 pieces, preferably 10 4 ~10 6 The drug can be administered to the patient in one or more divided doses.

[0074] In this specification, "or" is used when "at least one" of the items listed in the text can be adopted. The same applies to "or else". In this specification, when it is specified that "within the range" of "two values", that range includes the two values ​​themselves.

[0075] References such as scientific literature, patents, and patent applications cited herein are incorporated herein by reference to the same extent as they are specifically described herein.

[0076] The present disclosure has been described above with reference to preferred embodiments for ease of understanding. The present disclosure will now be described based on examples, but the above description and the following examples are provided for illustrative purposes only and not to limit the present disclosure. Accordingly, the scope of the present disclosure is not limited to the embodiments or examples specifically described herein, but is limited only by the claims. [Examples]

[0077] (Example 1: Evaluation of motor function status using DTI) With the approval of the Institutional Review Board of Hokkaido University Hospital, the following research was conducted. (1) Target patients Six patients were included in this study who met five criteria: being in the acute phase (early stage) of ischemic stroke, being between 20 and 80 years old at the time of consent; being within 14 days of ischemic stroke onset at the time of consent; having ischemic stroke in the internal carotid artery perfusion area; having an mRS score of 0 or 1 before ischemic stroke onset; and having moderate to severe neurological symptoms due to ischemic stroke (NIHSS (National Institutes of Health Stroke Scale): ≥6) (provided that the total score for the "5. Upper Limb Movement" and "6. Lower Limb Movement" items of the NIHSS was 6 or more), did not violate the prescribed exclusion criteria, and gave consent to participate in this study. Of the six patients, five had hemorrhagic infarction, i.e., ischemic stroke accompanied by cerebral hemorrhage.

[0078] (2) Preparation and administration of bone marrow stem cells After patient registration, bone marrow was promptly collected, and cell culture and bone marrow stem cell preparation were performed at the Cell Processing Laboratory of the Clinical Research and Development Center, Hokkaido University Hospital. The prepared bone marrow stem cells (20 million or 50 million per patient) were directly administered into the patient's brain 3 to 5 weeks after bone marrow collection.

[0079] (3) Assessment of motor function Patient motor function was assessed using the Bathel Index (BI), modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), and functional independence measure (FIM). These indices are recommended for use in the stroke rehabilitation assessment section of the 2015 Stroke Treatment Guidelines published by the Japanese Stroke Society. Motor function assessments were performed at the time of case registration (14 days after stroke), 7 days before cell administration (average 50 days after stroke), and 1 year after cell administration. The scores for each motor function index, such as BI, in the subacute phase (10 to 50 days after stroke onset, hereafter referred to as the subacute phase), when acute treatment was almost complete, were subtracted from the scores for the same motor function index at 12 months after cell administration (6 months for patients who had not reached 12 months at the time of this application, hereafter referred to as the chronic phase) to determine the degree of motor function recovery: ΔBI, ΔmRS, ΔNIHSS, and ΔFIM.

[0080] (4) DTI / DKI imaging For each patient, DTI / DKI images of the brain were acquired during the subacute and chronic phases. The images were acquired using an MRI machine (3T Achieva TX (Philips Medical Systems)) with default settings (b = 0, 1000, 2000 s mm). -2 , TR / TE = 5032 / 85 msec, NEX = 1, voxel size =3 x 3 x 3 mm 3 The process was carried out using the following method: (number of slices = 43, 32 diffusion gradient directions).

[0081] (5) Image analysis Diffuse image data acquired from a 3T MRI system (Achieva TX, Philips Medical Systems, Best, the Netherlands) (TR / TE = 5032 / 85 msec, voxel size = 3 x 3 x 3 mm) 3, plane = axial, no. of slices = 43, interslice gap = 0 mm, b=0, 1000, 2000 sec mm -2 From the data (NSA = 1, MPG directions = 32), the main DTI / DKI indices, mean kurtosis (MK), axial kurtosis (AK), radial kurtosis (RK), fractional anisotropy (FA), kurtosis fractional anisotropy (KFA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were calculated for each voxel (DKE2.6, MUSC Center for Biomedical Imaging, South Carolina, USA). Next, the data was converted to a standard brain using SPM12 (Wellcome Centre for Human Neuroimaging, London, UK). Regions other than the brain parenchyma were removed by segmentation using anatomical images (3D-SSFP images in this study) of each patient. Using ROIs in the posterior limbs of the internal capsule on both sides, the main DTI / DKI indices of these regions were measured using the IBASPM Atlas (http: / / www.thomaskoenig.ch / Lester / ibaspm.htm) and the JHU White-Matter Tractionography Atlas (http: / / cmrm.med.jhmi.edu / ). The ratio of the DTI / DKI index between the lesioned side and the healthy side (lesion / healthy) at the time before cell administration (10-47 days after stroke onset, mean = 19.0 ± 13.8 days) was calculated, and its correlation with changes in the Barthel index (BI), modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), and functional independence measure (FIM) (1 year after cell administration - before cell administration), which indicate the degree of functional recovery, was evaluated (Figure 6). The number of days from stroke onset to MRI imaging was used as an inhibitory variable.

[0082] (6)DTI results Table 1 shows the results of evaluating the correlation between BI, mRS, NIHSS, or FIM and motor function using DTI. From these results, a correlation was found between the ADC value and improvement in motor function when the ROI was placed only in the posterior limb of the internal capsule (ADC value of the posterior limb ROI of the internal capsule and the degree of improvement in BI 14 days after onset). [Table 1]

[0083] (Example 2: Evaluation of motor function status using DKI) Diffuse kurtosis imaging (DKI) was used to obtain diffusion image indices that can predict the efficacy of cell therapy in stroke patients with high accuracy and without depending on the experience of the measurer. In this example, a map of the main indices was created using diffuse kurtosis imaging (DKI), converted to a standard brain, and then the values ​​of the posterior limbs of the internal capsule on both sides were measured. Image analysis was performed in the same manner as described in "(5) Image Analysis" above.

[0084] Table 2 shows the correlation between diffusion image data before cell administration by DKI and the degree of functional recovery. [Table 2]

[0085] The ratios of AD (r=0.90, P=0.04) and MD (r=0.93, P=0.02) in the posterior limb of the internal capsule on the lesioned and healthy sides, obtained from diffusion imaging data before cell administration, showed a significant positive correlation with the change in BI (Figures 7 and 8, respectively). The degree of decrease in AD or MD associated with cerebral infarction is thought to reflect functional recovery. From Figures 7 and 8, it was found that in order to obtain a change in BI of 30% or more, the ratio of AD to MD in the posterior limb of the internal capsule on the lesioned and healthy sides needed to be 0.83 or 1.01 or higher, respectively. The left-right differences in AD and MD in cases with different degrees of functional recovery are shown in Figures 9A and 9B.

[0086] The results above show that the ratio of the DKI index from the lesion side to the healthy side before cell administration shows a strong correlation with the degree of functional recovery.

[0087] (Example 3: Example of a program product) In this embodiment, an example of a program product is described. The program product prepared is one that can perform the shooting and analysis described in (4) and (5) of Example 1. The program of this disclosure can be provided as a program product that stores a device-readable command code in memory, with the program described in Example 1 or 2 as the memory. In this program product, when the command code is read via a device, the image processing and its applications of this disclosure are performed. In this disclosure, storage media (such as hard disks, optical disks, magneto-optical disks, memory cards, memory sticks, etc.) for accepting program products that store device-readable command codes for the programs described in Example 1 or 2 are also applicable to this disclosure. This program product allows a computer to perform processing to capture DTI / DKI images of the brain in patients with or suspected of having brain damage, and to calculate diffusion image data for those patients. Furthermore, by using this program product to have a computer perform processing, the ratio of the DTI / DKI index (pathological / healthy) between the affected side and the healthy side is calculated, and the change in a numerical value indicating the degree of functional recovery is calculated.

[0088] (Note) As described above, while the present disclosure has been illustrated using preferred embodiments thereof, it is understood that the scope of this disclosure should be interpreted solely by the claims. Patents, patent applications and other documents cited herein should be incorporated by reference to this specification as if their contents were specifically described herein. This application claims priority to Japanese Patent Application No. 2020-219126, filed with the Japan Patent Office on 28 December 2020, and its contents are incorporated by reference as if they constitute the contents of this application in whole. [Industrial applicability]

[0089] This disclosure is useful in industries such as the treatment and diagnosis of central nervous system diseases. This disclosure can also be used in fields such as the development of regenerative medicine and cell therapies. [Explanation of symbols]

[0090] 1 MRI machine 10. Nuclear Magnetic Resonance Imaging Unit 20 Computers 21 Interface section 22 Input section 23 Memory section 231 Echo Data Storage Unit 232 Reconstructed Image Storage Unit 233 DTI / DKI Image Storage Unit 234 Reference information storage unit 24 Arithmetic section 241 Image generation unit 241a Image reconstruction unit 241b DTI / DKI image generation section 242 Image Analysis Department 242a Area of ​​Interest Setting Unit 242b Physiological Indicator Value Calculation Unit 242c Physiological Indicator Value Comparison Section 242d Motor Function State Evaluation Calculation Unit 25 Output section 26 Control Unit

Claims

1. A step of obtaining one or more physiological index values ​​with the white matter region of interest being on the side of the damaged hemisphere of the brain of a patient with or suspected of having brain damage, The steps include comparing the aforementioned physiological index values ​​with control physiological index values, and performing calculations to calculate a value indicating the state of the patient's motor function using a regression line prepared with the values ​​obtained from the patient with brain injury, expressed as the ratio of the physiological index value on the injured hemisphere to the physiological index value on the uninjured hemisphere, and the degree of motor function recovery of the patient after treatment as variables. A method for evaluating the motor function status of the patient, including the following.

2. The method according to claim 1, wherein the physiological index values ​​are obtained from a diffusion-weighted image of the patient's brain obtained by diffusion tensor imaging (DTI) or diffusion kurtosis imaging (DKI).

3. The method according to claim 1 or 2, wherein the physiological indicator value includes an MD (mean difficulty) value and an AD (axial difficulty) value.

4. The method according to any one of claims 1 to 3, wherein the region of interest is set in the posterior limb of the internal capsule of the brain.

5. The method according to any one of claims 1 to 4, wherein the state of motor function is the state of motor function after regenerative therapy.

6. The method according to any one of claims 1 to 5, wherein the control physiological index value is obtained with the white matter region on the non-damaged hemisphere side of the patient's brain as the region of interest.

7. The method according to any one of claims 1 to 6, wherein the step of performing the calculation calculates a value represented by the physiological index value / the control physiological index value.

8. The method according to any one of claims 1 to 7, wherein the step of performing the calculation evaluates the state of the patient's motor function by substituting the calculated value indicating the state of the patient's motor function into the regression line.

9. The method according to any one of claims 1 to 8, wherein the step of performing the calculation involves comparing the calculated value indicating the state of the patient's motor function with a pre-prepared reference value to calculate the likelihood of the patient achieving a desired degree of motor function recovery after regenerative therapy.

10. A computer program that causes a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, the method comprising the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: having the computer compare the physiological index value with a control physiological index value, and performing calculations to calculate a value indicating the state of the patient's motor function using a prepared regression line with the values ​​obtained from the patient with brain injury, expressed as the ratio of the physiological index value on the injured hemisphere side to the physiological index value on the uninjured hemisphere side, and the degree of motor function recovery of the patient after treatment as variables; A program that includes this.

11. A recording medium for storing a computer program that causes a computer to perform a process for evaluating the motor function state of the brain of a patient who has or is suspected of having brain damage, wherein the method consists of the following steps: The steps include: causing the computer to obtain physiological index values ​​with the white matter region on the side of the damaged hemisphere of the patient's brain as the region of interest; The steps include: having the computer compare the physiological index value with a control physiological index value, and performing calculations to calculate a value indicating the state of the patient's motor function using a prepared regression line with the values ​​obtained from the patient with brain injury, expressed as the ratio of the physiological index value on the injured hemisphere side to the physiological index value on the uninjured hemisphere side, and the degree of motor function recovery of the patient after treatment as variables; A recording medium that includes this.

12. A system for evaluating the motor function of the brain in patients who have or are suspected of having brain damage, A means for obtaining physiological index values ​​with the white matter region of interest being the white matter region on the side of the damaged hemisphere of the patient's brain, A means for performing calculations to compare the aforementioned physiological index values ​​with control physiological index values, and to calculate a value indicating the state of the patient's motor function using a regression line prepared with the values ​​obtained from the patient with brain injury, expressed as the ratio of the physiological index value on the injured hemisphere to the physiological index value on the uninjured hemisphere, and the degree of motor function recovery of the patient after treatment as variables. A system that includes this.

13. A region of interest setting unit that, in diffusion-weighted imaging of the brain of a patient with or suspected of having brain damage, sets the white matter region on the damaged hemisphere side as the first region of interest and the white matter region on the undamaged hemisphere side as the second region of interest, A physiological index value calculation unit that calculates physiological index values ​​for the injured hemisphere and the uninjured hemisphere in the first and second regions of interest, respectively, A calculation unit compares the physiological index values ​​of the injured hemisphere with those of the uninjured hemisphere, and performs calculations to calculate a value indicating the motor function state of a patient using a prepared regression line with the values ​​obtained from the patient with brain injury, expressed as the ratio of the physiological index value of the injured hemisphere to the physiological index value of the uninjured hemisphere, and the degree of motor function recovery of the patient after treatment as variables. An image analysis device characterized by comprising the following features.

14. A magnetic resonance imaging unit for imaging the brains of patients with or suspected of having brain damage, An image generation unit that generates diffusion-weighted images from echo data acquired by the nuclear magnetic resonance imaging unit, In diffusion-weighted imaging, a region of interest setting unit sets the white matter region on the damaged hemisphere side as the first region of interest and the white matter region on the undamaged hemisphere side as the second region of interest. A physiological index value calculation unit that calculates physiological index values ​​for the injured hemisphere and the uninjured hemisphere in the first and second regions of interest, respectively, A calculation unit compares the physiological index values ​​of the injured hemisphere with those of the uninjured hemisphere, and performs calculations to calculate a value indicating the motor function state of a patient using a prepared regression line with the values ​​obtained from the patient with brain injury, expressed as the ratio of the physiological index value of the injured hemisphere to the physiological index value of the uninjured hemisphere, and the degree of motor function recovery of the patient after treatment as variables. An MRI apparatus characterized by comprising the following:

Images