Method for assisting in diagnosis of crush syndrome and program used therein

Abstract

To provide a method, a program, and a device, for making it possible to early diagnose a crush syndrome.SOLUTION: A method, a program, and a device includes a step of analyzing 31 P spectrum data on a subject's compression part obtained by MR spectroscopy and presenting a result of determining a crush syndrome when the 31 P spectrum data satisfies the following expression (1): PCr / (Pi+PCr)≤0.50(1), where in the expression (1), Pi represents the height of a peak of a spectrum corresponding to phosphate ions and PCr represents the height of a peak of the spectrum corresponding to creatine phosphate.SELECTED DRAWING: Figure 5

Description

[Technical field]

[0001] The present disclosure relates to aiding in the diagnosis of crush syndrome. [Background technology]

[0002] Crush syndrome refers to a condition in which muscle tissue is compressed and becomes ischemic due to an accident or disaster, and when the compression is released, symptoms such as fatal arrhythmia, cardiac arrest, acute renal failure, uremia, pulmonary edema, respiratory failure, and / or other organ failures throughout the body are caused. These symptoms are thought to be caused by potassium, myoglobin, lactic acid, creatine kinase, etc. accumulating at the compressed site over time during compression, and then suddenly circulating throughout the body as blood flow resumes when the compression is released.

[0003] According to Non-Patent Document 1, the conventional method for diagnosing crush syndrome is that it can be diagnosed based on the initial symptoms of crush syndrome, such as disproportionate pain, sensory abnormalities, swelling of the limbs, and cramps in the limbs. In addition, blood tests are also used to diagnose the condition, using creatine concentration, pH, and other indicators. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Ingrassia et al., Ciottone's Disaster Medicine 16:180, 2016 Summary of the Invention [Problem to be solved by the invention]

[0005] Crush syndrome includes fatal symptoms caused by pressure release, and early diagnosis is important. The early symptoms described in Non-Patent Document 1 are very similar to typical symptoms of external wounds, making it difficult to diagnose. Furthermore, it is even more difficult to accurately diagnose them in emergencies such as accidents and disasters. The conventional diagnostic method, blood tests, mainly detect substances that enter the bloodstream from the crush site. Therefore, they cannot detect substances before or immediately after the release of pressure, or the sensitivity is low, making them insufficient for early diagnosis. In addition, by the time crush syndrome is diagnosed, it is often already too late, making it difficult to diagnose crush syndrome early with blood tests. The present disclosure provides a method for early diagnosis of crush syndrome using MR spectroscopy measurements. [Means for solving the problem]

[0006] The gist of the present invention is as follows. [1] A method for assisting in the diagnosis of crush syndrome, comprising: MR spectroscopy of the subject's compressed area 31 Analyzing P spectral data 31 The method includes a step of presenting a determination result that the patient has crush syndrome when the P spectrum data satisfies the following formula (1): PCr / (Pi+PCr)≦0.50 (1) [In formula (1), Pi represents the height of the spectrum peak corresponding to phosphate ion, and PCr represents the height of the spectrum peak corresponding to creatine phosphate.] [2] In the step of presenting the result of the determination that the subject has crush syndrome, 31 The method according to [1], wherein crush syndrome is determined to occur when the P spectrum satisfies the following formula (2). PCr / (Pi+PCr)≦0.20 (2) [3] A method for assisting in the diagnosis of crush syndrome according to [1] or [2], comprising: In addition, the compression site of the subject was obtained by MR spectroscopy. 31 The method includes a step of presenting a determination result indicating crush syndrome when no spectral peak corresponding to creatine phosphate is present in the P spectral data. [4] A method for assisting in the diagnosis of crush syndrome according to any one of [1] to [3], In addition, the compression site of the subject was obtained by MR spectroscopy. 31 The method includes a step of presenting a determination result indicating crush syndrome when no spectral peak corresponding to the β-phosphorus of ATP is present in the P spectral data. [5] The method according to any one of [1] to [4], wherein the compressed area is compressed muscle tissue. [6] A program for determining crush syndrome, comprising: MR spectroscopy of the subject's compressed area 31 analyzing the P spectral data and calculating the height of the spectral peak corresponding to phosphate ion and the height of the spectral peak corresponding to creatine phosphate; 31 A program for executing a step of displaying a determination result that the patient has crush syndrome when the P spectrum satisfies the following formula (1). PCr / (Pi+PCr)≦0.50 (1) [In formula (1), Pi represents the height of the spectrum peak corresponding to phosphate ion, and PCr represents the height of the spectrum peak corresponding to creatine phosphate.] [7] Furthermore, the following steps are performed: A means for detecting a spectrum corresponding to the phosphorus at the β position of ATP; and The program according to [6], further comprising a means for displaying a result of the determination that the patient has a crush syndrome when a spectrum peak corresponding to the phosphorus at the β-position of ATP is not present. [8] 31 An MR spectroscopy device capable of measuring a P spectrum, comprising the program according to [6] or [7]. Effect of the Invention

[0007] According to the present disclosure, it is possible to provide a method for assisting in the early diagnosis of crush syndrome, and also to provide a program and an apparatus for the early diagnosis of crush syndrome. [Brief description of the drawings]

[0008] [Figure 1] Photograph of the right groin of a rat. [Diagram 2] 31P spectrum before avascularization (PRE) in Group A. [Diagram 3] 31P spectrum after 2 hours of avascularization (ACS 120 min) in Group A. [Figure 4] 31P spectrum in Group A, 1.5 hours after release of blood vessels (RPF90min). [Diagram 5] A graph showing the PCr / (Pi+PCr) value over time in the 31P spectrum of Group A. [Figure 6] Graph showing blood CPK concentrations over time in Group A. [Figure 7] 31P spectrum before avascularization (PRE) in Group B. [Figure 8] 31P spectrum after 3 hours of avascularization (ACS 180 min) in Group B. [Figure 9] 31P spectrum in Group B, 1.5 hours after release of blood vessels (RPF90min). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] According to the present disclosure, 31 Based on the P spectrum, it can assist in the early diagnosis of crush syndrome. That is, the method of the present invention is a method for assisting in the diagnosis of crush syndrome, comprising: MR spectroscopy of the subject's compressed area 31 When the P spectrum data satisfies the following formula (1), a determination result that the patient has crush syndrome is presented, Pi≧Pcr (1) In the formula (1), P i indicates the height of the spectral peak corresponding to phosphate ion, and PC r indicates the height of the spectral peak corresponding to creatine phosphate.

[0010] Crush syndrome occurs when tissue is compressed, becomes ischemic, and then the compression is released. The compressed tissue typically includes muscle tissue. Tissue compression includes compression accompanied by ischemia. Tissue compression typically includes compression accompanied by complete ischemia.

[0011] Release of compression typically involves resumption of blood flow. Thus, by way of example, crush syndrome includes the phenomenon that occurs when muscle tissue and / or vascular tissue is compressed with ischemia and then released with resumption of blood flow.

[0012] Compression of tissues may be due to external factors such as being pinched between heavy objects such as rubble or blood flow from a string-like object, or may be due to internal factors such as an increase in the internal pressure of a compartment due to hematoma formation or muscle swelling. Crush syndrome caused by internal factors is also called compartment syndrome.

[0013] Crush syndrome can be experimentally reproduced. For example, crush syndrome can be reproduced by tightly tying the groin of a subject with a cable tie and avascularization. The subject may be a mouse or a rat, and is not particularly limited as long as it is not a human, but is preferably a rat.

[0014] The above-mentioned method is excellent as a model of crush syndrome because it can avascularize by compression accompanied by complete ischemia. The avascularization in the above-mentioned method is preferably for 2 hours or more, more preferably for 3 hours or more.

[0015] In crush syndrome, substances derived from the compressed tissue, such as potassium, myoglobin, lactate, and creatine kinase, accumulate at the site of compression and are released into the bloodstream, causing symptoms such as fatal arrhythmias, cardiac arrest, acute renal failure, uremia, pulmonary edema, respiratory failure, and / or other organ failure throughout the body.

[0016] In the conventional method, crush syndrome is diagnosed by an increase in the substance derived from the compressed tissue in the blood. The substance derived from the compressed tissue used for the diagnosis is, for example, creatine phosphokinase (CPK). In other words, crush syndrome may be diagnosed when the concentration of CPK in the blood increases.

[0017] The substances derived from the compressed tissue are accumulated at the compressed site and released into the blood when the compressed tissue is damaged. Therefore, the degree of damage to the compressed tissue is an important indicator of the crush syndrome. Thus, crush syndrome can be diagnosed based on the state of the compressed tissue, which can be shown, for example, by measuring the compressed area with magnetic resonance spectroscopy (MR spectroscopy: MRS).

[0018] In view of the above, the method for assisting in the diagnosis of crush syndrome uses the results of measuring the compressed site, and preferably the results of measuring the compressed muscle tissue.

[0019] The concentrations of inorganic phosphate, creatine phosphate, and ATP change due to tissue damage, so the degree of tissue damage can be known by measuring inorganic phosphate, creatine phosphate, and ATP. Measurement of inorganic phosphate, creatine phosphate, and ATP can be achieved, for example, by measuring phosphorus by MR spectroscopy. Measurement of phosphorus by MR spectroscopy typically includes the following results: 31 This is shown by the P spectral data.

[0020] In the method for assisting in the diagnosis of crush syndrome of the present invention, 31 P spectrum data obtained by MR spectroscopy. 31 By using P spectrum data, it is possible to determine whether or not crush syndrome has occurred even before or immediately after pressure is released, and this can be used for early diagnosis of crush syndrome.

[0021] MR spectroscopy is a type of magnetic resonance imaging (MRI) technique that utilizes the phenomenon of nuclear magnetic resonance. MRS can measure the signal strength of each resonance frequency, and can obtain a spectrum with the horizontal axis representing frequency and the vertical axis representing signal strength. The signal strength is proportional to the concentration.

[0022] In measurements using the phenomenon of nuclear magnetic resonance, atoms of the same isotope exhibit slightly different resonance frequencies depending on the magnetic environment of each atom. By measuring the signal strength of each different resonance frequency, MRS can measure the signal strength of the atom in each magnetic environment.

[0023] The difference in the magnetic environment of an atom depends on, for example, the bonding state of the atom. That is, atoms of the same isotope species exhibit different resonance frequencies depending on the structure of the molecule that contains the atom.

[0024] As described above, MRS can measure the signal intensity of the bond state of the measured atom and the molecular structure having the atom separated by frequency. The signal for each bond state and molecular structure is seen as a peak in a spectrum with the horizontal axis being frequency and the vertical axis being signal intensity. In addition, the signal intensity for each bond state and molecular structure can be calculated as the height of the peak in a spectrum with the horizontal axis being frequency and the vertical axis being signal intensity.

[0025] The signal strength is proportional to the concentration of the molecule, and the peak height is proportional to the signal strength. In other words, the concentration of molecules can be calculated for each atomic bonding state and molecular structure based on the spectrum obtained from MR spectroscopy.

[0026] The frequency can be expressed, for example, as a shift in resonant frequency. The shift in resonant frequency is calculated, for example, by dividing the difference between the resonant frequency of an atom in a reference substance (reference frequency) and the resonant frequency of an atom in a substance to be measured by the reference frequency, and is also called a chemical shift. The chemical shift is typically expressed in parts per million (ppm). Therefore, the measurement results of MRS can be expressed, for example, as a spectrum in which the horizontal axis represents chemical shift (unit: ppm) and the vertical axis represents signal intensity (relative value to a standard substance).

[0027] For the measurement of MR spectroscopy, an MR device such as an MRI device can be used. The output of the magnetic field in the device for measuring MR spectroscopy is preferably 1.5 T or more, more preferably 3 T or more. Since the higher the magnetic field, the higher the sensitivity, there is no particular upper limit on the output of the magnetic field.

[0028] The spectral data used to determine crush syndrome may be data measured before compression is released or may be data measured after compression is released, but is preferably data measured before compression is released.

[0029] 31 P spectrum data is one of the isotopes of phosphorus measured by MR spectroscopy. 31 It can be obtained by measuring P by MR spectroscopy. 31 To measure P, for example, 31 A probe for measuring P can be used. Preferably, a probe capable of measuring each muscle compartment can be used. 31 A probe for measuring P can be used.

[0030] of the body in its normal state 31 Signal peaks detected in the P spectrum include those of inorganic phosphate, creatine phosphate, and the α-, β-, or γ-position phosphorus of ATP. 31 In the P spectrum, the signal peaks are typically arranged in descending order of resonance frequency as follows: inorganic phosphate, creatine phosphate, γ-phosphorus of ATP, α-phosphorus of ATP, and β-phosphorus of ATP.

[0031] 31In the P spectrum, the horizontal axis may be, for example, a chemical shift (ppm) based on an 85% phosphoric acid aqueous solution, and the vertical axis may be, for example, a relative value or a concentration (Absolute mmol:Ammol) calculated by analysis software such as jMRUI.

[0032] As an example, the horizontal axis is shown as chemical shift (ppm) based on 85% phosphoric acid solution. 31 In the case of P spectra, the frequency at which each signal peak exists is shown.

[0033] That is, 31 In the P spectrum, the signal peak of inorganic phosphate is a peak observed at 0 ppm to 5 ppm, and preferably a peak observed at 2 ppm to 4 ppm. 31 In the P spectrum, the signal peak of inorganic phosphate is preferably seen at a higher ppm than the signal peak of creatine phosphate. In addition, 31 In the P spectrum, the signal peak of creatine phosphate is a peak observed between -5 ppm and 0 ppm, and preferably between -3 ppm and 0 ppm. 31 In the P spectrum, the signal peak of creatine phosphate is preferably observed at a ppm lower than the signal peak of inorganic phosphate and higher than the signal peak of phosphorus at the γ position of ATP.

[0034] In addition, 31 In the P spectrum, the signal peak of phosphorus at the γ-position of ATP is a peak observed at -8 ppm to -3 ppm, and preferably a peak observed at -7 ppm to -4 ppm. 31 In the P spectrum, the signal peak of phosphorus at the γ position of ATP is preferably observed at a ppm lower than the signal peak of creatine phosphate and higher than the signal peak of phosphorus at the α position of ATP. In addition, 31In the P spectrum, the signal peak of phosphorus at the α-position of ATP is a peak observed at -12 ppm to -7 ppm, and preferably a peak observed at -11 ppm to -8 ppm. 31 In the P spectrum, the signal peak of α-position phosphorus of ATP is preferably observed at a lower ppm than the signal peak of γ-position phosphorus of ATP and at a higher ppm than the signal peak of β-position phosphorus of ATP.

[0035] In addition, 31 In the P spectrum, the signal peak of phosphorus at the β-position of ATP is a peak observed at -20 ppm to -15 ppm, and preferably a peak observed at -19 ppm to -17 ppm. 31 In the P spectrum, the signal peak of β-position phosphorus of ATP is preferably observed at a lower ppm than that of α-position phosphorus of ATP. 31 In the P spectrum, the height of the signal peak of inorganic phosphate is Pi, the height of the signal peak of creatine phosphate is PCr, the height of the signal peak of the signal peak of phosphorus at the α position of ATP is ATPα, the height of the signal peak of phosphorus at the β position of ATP is ATPβ, and the height of the signal peak of phosphorus at the γ position of ATP is ATPγ.

[0036] At this time, the normal state of a healthy organism 31 In the P spectrum, the value of PCr / (Pi+PCr) is typically greater than 0.50.

[0037] In crush syndrome, the area of ​​compression of the body 31 The P spectrum has a PCr / (Pi+PCr) value of 0.50 or less, typically 0.20 or less, and more typically 0.10 or less. In addition, the area of ​​pressure on the body in crush syndrome 31In the P spectrum, typically, there is no spectral peak corresponding to creatine phosphate and / or no spectral peak corresponding to the β-position phosphorus of ATP. The absence of a spectral peak corresponding to creatine phosphate and / or no spectral peak corresponding to the β-position phosphorus of ATP includes the substantial absence of a spectral peak corresponding to creatine phosphate and / or no spectral peak corresponding to the β-position phosphorus of ATP.

[0038] The absence of a signal peak of creatine phosphate may mean that the PCr value is 1 / 10 or less, preferably 1 / 100 or less, compared to the normal state. In addition, when the vertical axis represents concentration, it may mean that the PCr value is 1.0 Ammol or less, preferably 0.10 Ammol or less, and more preferably 0.01 Ammol or less. Furthermore, the substantial absence of a signal peak of phosphorus at the β position of ATP may refer to an ATP β value that is 1 / 10 or less, preferably 1 / 100 or less, compared to the normal state. Furthermore, when the vertical axis is the concentration, it may refer to a case where the concentration is 1.0 Ammonium or less, preferably 0.10 Ammonium or less, more preferably 0.01 Ammonium or less.

[0039] Therefore, methods to aid in the diagnosis of crush syndrome include: 31 The method may include a step of presenting a determination result that the patient has crush syndrome when the P spectrum data satisfies the following formula (1): PCr / (Pi+PCr)≦0.50 (1) At this time, 31 The P spectrum is obtained by MR spectroscopy of the subject's compressed area. 31 P spectrum data.

[0040] In the above step, when the following formula (2) is satisfied instead of formula (1), a determination result indicating the occurrence of crush syndrome may be presented. PCr / (Pi+PCr)≦0.20 (2)

[0041] In addition, in the above step, when the following formula (3) is satisfied instead of formula (1), a determination result indicating the occurrence of crush syndrome may be presented. PCr / (Pi+PCr)≦0.10 (3)

[0042] Methods to aid in the diagnosis of crush syndrome include: 31 The method may further include a step of presenting a result of the determination that the patient has crush syndrome when there is no peak in the spectrum corresponding to creatine phosphate in the P spectrum. In addition, at this time, the patient may be determined to have severe crush syndrome. The absence of a peak in the spectrum corresponding to creatine phosphate includes the case where there is substantially no peak in the spectrum corresponding to creatine phosphate.

[0043] Methods to aid in the diagnosis of crush syndrome include: 31 The method may further include a step of presenting a result of the determination that the patient has crush syndrome when there is no peak in the spectrum corresponding to phosphorus at the β position of ATP in the P spectrum. In addition, at this time, the patient may be determined to have severe crush syndrome. The absence of a peak in the spectrum corresponding to phosphorus at the β position of ATP includes the substantial absence of a peak in the spectrum corresponding to phosphorus at the β position of ATP.

[0044] The present invention further relates to a program for determining crush syndrome. The program may be a program for causing a computer to execute the above-mentioned method.

[0045] The program for determining crush syndrome includes a means for executing a step of calculating the height of a spectral peak corresponding to phosphate ion and the height of a spectral peak corresponding to creatine phosphate. Furthermore, the program of the present invention may include a means for executing a step of calculating the height of a spectral peak corresponding to phosphorus at the γ-position of ATP, the height of a spectral peak corresponding to phosphorus at the α-position of ATP, and the height of a spectral peak corresponding to phosphorus at the β-position of ATP.

[0046] 31As an example of a method for analyzing P spectrum data and calculating the height of the spectrum peak, the horizontal axis is expressed as chemical shift (ppm) based on 85% phosphoric acid aqueous solution. 31 The case of P spectrum data is shown below, but the present invention is not limited to this and any appropriate method can be used.

[0047] The above 31 In the P spectrum data, the peaks observed at 0 ppm to 5 ppm, preferably 2 to 4 ppm, are taken as signal peaks of inorganic phosphate. In addition, 31 In the P spectrum data, the peaks observed between −5 ppm and 0 ppm, preferably between −3 ppm and 0 ppm, are taken as signal peaks of creatine phosphate. Note that the signal peak of creatine phosphate is preferably a peak at a lower ppm than the signal peak of inorganic phosphate.

[0048] In addition, 31 In the P spectrum data, the peaks observed between -8 ppm and -3 ppm, preferably between -7 ppm and -4 ppm, are taken as the signal peaks of phosphorus at the γ position of ATP. Note that the signal peak of phosphorus at the γ position of ATP is preferably taken as a peak at a lower ppm than the signal peak of creatine phosphate. In addition, 31 In the P spectrum data, the peaks observed between -12 ppm and -7 ppm, preferably between -11 ppm and -8 ppm, are taken as the signal peaks of phosphorus at the α-position of ATP. Note that the signal peak of phosphorus at the α-position of ATP is preferably a peak at a lower ppm than phosphorus at the γ-position of ATP.

[0049] In addition, 31In the P spectrum data, the peaks observed at −20 ppm to −15 ppm, preferably at −19 ppm to −17 ppm, are regarded as signal peaks of phosphorus at the β position of ATP. Note that the signal peak of phosphorus at the β position of ATP is preferably a peak at a lower ppm than phosphorus at the α position of ATP.

[0050] The height of the apex of each of the above spectrum peaks is calculated as the height of the spectrum peak. For example, the height of the apex of the spectrum peak of an 85% phosphoric acid aqueous solution is set to 1, and the height of the apex of each spectrum peak can be calculated as a relative value.

[0051] The above method allows for the detection of compression sites in living tissue using MR spectroscopy. 31 By analyzing the P spectral data, the height of the spectral peak corresponding to inorganic phosphate, the height of the spectral peak corresponding to creatine phosphate, the height of the spectral peak corresponding to phosphorus at the γ position of ATP, the height of the spectral peak corresponding to phosphorus at the α position of ATP, and the height of the spectral peak corresponding to phosphorus at the β position of ATP can be calculated.

[0052] The calculated signal peak height of inorganic phosphate is Pi, the signal peak height of creatine phosphate is PCr, the signal peak height of the α-position phosphorus of ATP is ATPα, the signal peak height of the β-position phosphorus of ATP is ATPβ, and the signal peak height of the γ-position phosphorus of ATP is ATPβ. The height is ATPγ.

[0053] The program for determining crush syndrome is 31 The method includes a step of displaying the result of the determination that the patient is suffering from crush syndrome based on the P spectrum.

[0054] The step of displaying the determination result that there is a crush syndrome may be a step of displaying the determination result that there is a crush syndrome when the following formula (1) is satisfied, preferably a step of displaying the determination result that there is a crush syndrome when the following formula (2) is satisfied, and more preferably a step of displaying the determination result that there is a crush syndrome when the following formula (3) is satisfied. PCr / (Pi+PCr)≦0.50 (1) PCr / (Pi+PCr)≦0.20 (2) PCr / (Pi+PCr)≦0.10 (3)

[0055] Furthermore, the step of displaying the determination result that there is crush syndrome may be a step of displaying the determination result that there is crush syndrome when there is no spectral peak corresponding to creatine phosphate and / or no spectral peak corresponding to phosphorus at the β position of ATP. The absence of a spectral peak corresponding to creatine phosphate and / or no spectral peak corresponding to phosphorus at the β position of ATP includes the substantial absence of a spectral peak corresponding to creatine phosphate and / or a spectral peak corresponding to phosphorus at the β position of ATP. The absence of a signal peak of creatine phosphate may mean that the PCr value is 1 / 10 or less, preferably 1 / 100 or less, compared to the normal state. In addition, when the vertical axis represents concentration, it may mean that the PCr value is 1.0 Ammol or less, preferably 0.10 Ammol or less, and more preferably 0.01 Ammol or less. Furthermore, the substantial absence of a signal peak of phosphorus at the β position of ATP may refer to an ATP β value that is 1 / 10 or less, preferably 1 / 100 or less, compared to the normal state. Furthermore, when the vertical axis is the concentration, it may refer to a case where the concentration is 1.0 Ammonium or less, preferably 0.10 Ammonium or less, more preferably 0.01 Ammonium or less.

[0056] The program for diagnosing crush syndrome may execute the step of displaying the determination result that crush syndrome is present, either alone or in combination, but includes means for executing at least one or more steps of displaying the determination result that crush syndrome is present.

[0057] The program for determining the crush syndrome may include, for example, a means for issuing an alert when at least one of the above conditions is satisfied in the step of displaying the determination result that the crush syndrome is present. The said means may be a means for executing the step of displaying the determination result. The alert may be issued by any suitable means, including but not limited to emitting a sound, displaying a warning on a screen, or turning on a lamp.

[0058] The program for determining crush syndrome may be stored in a CD-ROM, DVD-ROM, USB drive, or other appropriate storage medium and used. The program for determining crush syndrome may be installed in an apparatus, an analysis computer, or other appropriate device and used. The program for determining crush syndrome may be stored in the storage medium and installed in the device and used.

[0059] The present invention further relates to an apparatus for determining crush syndrome.

[0060] The device that judges crush syndrome uses MR spectroscopy to measure the area of ​​the subject's compression. 31 The device includes a means for measuring the P spectrum. 31 The means for measuring the P spectrum includes, for example, an MR device and 31 Using a P measurement probe, 31 In other words, the device for determining the crush syndrome may be, for example, an MR device. 31 The device may include a probe for measuring P. In addition, the above MR device and / or 31The probe for measuring P is preferably an MR device and / or a probe capable of measuring each muscle compartment.

[0061] The apparatus for determining crush syndrome is 31 The present invention also includes a means for determining whether or not a patient has crush syndrome using the P spectrum. The means for determining the presence of crush syndrome may be a means for determining the presence of crush syndrome when the following formula (1) is satisfied, preferably a means for determining the presence of crush syndrome when the following formula (2) is satisfied, and more preferably a means for determining the presence of crush syndrome when the following formula (3) is satisfied. Furthermore, these means may be based on a program incorporated in the device. PCr / (Pi+PCr)≦0.50 (1) PCr / (Pi+PCr)≦0.20 (2) PCr / (Pi+PCr)≦0.10 (3)

[0062] The means for determining the presence of crush syndrome may be a means for determining the presence of crush syndrome when a spectral peak corresponding to creatine phosphate and / or a spectral peak corresponding to phosphorus at the β position of ATP is not present. These means may be implemented by a program installed in the device. The absence of a spectral peak corresponding to creatine phosphate and / or a spectral peak corresponding to the beta phosphorus of ATP includes the substantial absence of a spectral peak corresponding to creatine phosphate and / or a spectral peak corresponding to the beta phosphorus of ATP. The absence of a signal peak of creatine phosphate may mean that the PCr value is 1 / 10 or less, preferably 1 / 100 or less, compared to the normal state. In addition, when the vertical axis represents concentration, it may mean that the PCr value is 1.0 Ammol or less, preferably 0.10 Ammol or less, and more preferably 0.01 Ammol or less. Furthermore, the substantial absence of a signal peak of phosphorus at the β position of ATP may refer to an ATP β value that is 1 / 10 or less, preferably 1 / 100 or less, compared to the normal state. Furthermore, when the vertical axis is the concentration, it may refer to a case where the concentration is 1.0 Ammonium or less, preferably 0.10 Ammonium or less, more preferably 0.01 Ammonium or less.

[0063] The device for determining the crush syndrome may include a means for issuing an alert when the crush syndrome is determined to be present. The alert may be issued by any suitable means, including but not limited to issuing a sound, displaying a warning on a screen, or turning on a lamp.

[0064] By using the method, program, or device of the present invention, early diagnosis of crush syndrome is possible, which allows appropriate treatment to be administered and facilitates the decision to select the appropriate treatment. An appropriate treatment may be, for example, but is not limited to, treatment including compression relief, limb amputation, or treatment based on a prediction of functional outcome. Furthermore, the method, program, or device of the present invention may be used to perform early diagnosis of severe crush syndrome, which may facilitate the decision to select an appropriate treatment for severe crush syndrome, such as amputation of a lower limb to save a life. EXAMPLES

[0065] The present invention will be described below with reference to specific experimental data, but the present invention is not limited to the following embodiments.

[0066] The crush syndrome model animal was created as follows: 31 The P spectrum was measured. Male normotensive SD rats, 9-12 weeks old and weighing 276-499g, were purchased from Japan SLC. They were induced and maintained with 2-3% isoflurane (Pfizer Pharmaceuticals), adjusted appropriately within the range of 1.5-3% depending on the respiratory rate. This concentration of isoflurane is a concentration commonly used in MRI experiments without affecting the results obtained. First, the rat was placed in a supine position and, after sufficient warming, a 22G Surflow (Terumo) was percutaneously inserted into the ventral tail artery, and only the outer tube was left in place and fixed. 0.25 ml of arterial blood was collected from the Surflow, and an arterial blood collection line filled with heparinized saline (Terumo) was connected. After that, a cable tie for avascularization was loosely wrapped around the right groin as shown in Figure 1, and the skin was sutured in three places to prevent the band from moving. The rats were then placed in a supine position on an MR cradle connected to a small animal ventilator (Shinano SF486, Shinano Seisakusho) and their hind limbs were firmly fixed with tape. Body temperature was maintained at 37°C using a circulating hot water system to the MRI scanner. Complete avascularization of the right lower limb was achieved by tightening a cable tie. The duration of avascularization was divided into two groups: 2 hours and 3 hours, with the 2-hour group designated Group A and the 3-hour group designated Group B. After that, the cable tie was cut to allow reperfusion and release the avascularization. 31 P spectra were obtained using an MR system (Bruker) and 31 Measurements were taken on the right thigh using a P measurement probe (manufactured by Bruker). 31 The P spectrum was measured before the start of avascularization, at the end of the avascularization duration, and 1.5 hours after the avascularization was released. In addition, measurements were also taken over time every 12 to 20 minutes from the start of avascularization until 2 hours after the avascularization was released. 31 The measurement results of the P spectrum are shown with the horizontal axis representing the chemical shift (ppm) and the vertical axis representing the relative value. At the same time, as a comparative example, the blood concentration of creatine phosphokinase (CPK) was measured using arterial blood obtained from the tail artery with a blood analyzer i-STAT1 (Abbott) and a blood tester (Fujifilm). Measurements using arterial blood were performed before the start of avascularization, every hour during avascularization, and 5 minutes, 60 minutes, and 90 minutes after the end of avascularization. In addition, the respiratory rate of the rats was continuously monitored (SA Instruments, Stony Brook).

[0067] Regarding Group A, before avascularization 31 Figure 2 shows the P spectrum after 2 hours of avascularization. 31 P spectrum in Fig. 3, 1.5 hours after release of blood vessel avascularization 31 The P spectrum is shown in Figure 4. In Figures 2 to 4, Pi indicates the apex and height of the signal peak of inorganic phosphate, PCr indicates the apex and height of the signal peak of creatine phosphate, γ indicates the apex and height of the signal peak of ATPγ, α indicates the apex and height of the signal peak of ATPα, and β indicates the apex and height of the signal peak of ATPβ. Before the start of avascularization, the spectrum had a high PCr and a slight visible peak for Pi, but after 2 hours of avascularization, the heights of the peaks were reversed, with Pi high and PCr only slightly visible. At this time, the PCr / (Pi+PCr) value was below 0.10. 1.5 hours after avascularization was released, the spectrum had a high PCr and only slightly visible peak for Pi, recovering to a spectrum roughly similar to that before the start of avascularization. From the above, 31 From PCr and Pi calculated from the P spectrum, if the PCr / (Pi+PCr) value is below 0.10, it can be determined that the tissue is in an ischemic state, and this can be an indicator of crush syndrome.

[0068] Furthermore, for Group A, 31 From the time-dependent measurement results of P spectrum, PCr / The (Pi+PCr) values ​​were calculated and are shown in FIG. The PCr / (Pi+PCr) value decreased over time after the start of avascularization, and fell below 0.50 about 30 minutes after the start of avascularization, i.e., the peak height was reversed. 80 minutes after the start of avascularization, the PCr / (Pi+PCr) value fell below 0.20, and 2 hours later, the PCr / (Pi+PCr) value fell below 0.10. After the end of avascularization, the PCr / (Pi+PCr) value recovered, and 3 hours after the start of avascularization (1 hour after the end of avascularization), the PCr / (Pi+PCr) value exceeded 0.50, but the variance was large and it was not stable. From the above, it was found that in tissues under ischemic conditions, PCr decreases and Pi increases over time. 31 By measuring the P spectrum, it is possible to determine the onset of crush syndrome earlier based on the value of PCr / (Pi+PCr) calculated from PCr and Pi. Although the tissue damage caused by complete avascularization for 2 hours was reversible, it is considered that the concentrations of inorganic phosphate and creatine phosphate were unstable and therefore did not completely recover.

[0069] The results of measuring the blood CPK concentration using arterial blood for Group A are shown in Figure 6. In Figure 6, Pre indicates the time before the start of avascularization, Isc indicates the time elapsed during avascularization, and Rep indicates the time elapsed after avascularization was released. The blood CPK concentration did not change from the start of avascularization while avascularization was continued. Five minutes after the release of avascularization after two hours, the blood CPK concentration increased slightly, but no significant difference was observed before and after the release of avascularization. One hour after the release of avascularization, a significant increase in the blood CPK concentration was observed compared to before avascularization and while avascularization was continued. From the above, we found that the increase in the blood CPK concentration in Group A reproduced the crush syndrome. Furthermore, with conventional blood tests, there was no significant difference in the blood CPK concentration during and immediately after the release of avascularization, making it difficult to determine the crush syndrome at an early stage.

[0070] Regarding Group B, before avascularization 31 P spectrum after 2 hours of avascularization 31 P spectrum in Fig. 8, 1.5 hours after release of blood vessel avascularization 31The P spectrum is shown in Figure 9. In Figures 7 to 9, Pi indicates the apex and height of the signal peak of inorganic phosphate, PCr indicates the apex and height of the signal peak of creatine phosphate, γ indicates the apex and height of the signal peak of ATPγ, α indicates the apex and height of the signal peak of ATPα, and β indicates the apex and height of the signal peak of ATPβ. Before the start of avascularization, the spectrum showed high PCr and only a slight peak for Pi, but after 3 hours of avascularization, the spectrum showed high Pi and PCr decreased to the point where no peak existed. Furthermore, after 3 hours of avascularization, ATPγ, ATPα, and ATPβ decreased significantly compared to before the start of avascularization, and in particular, ATPβ decreased to the point where no peak existed. In the spectrum 1.5 hours after the end of avascularization, Pi was high and PCr recovered to the point where a slight peak was visible, while ATPγ, ATPα, and ATPβ remained significantly low and did not recover or had no peaks.

[0071] In addition, gait disturbance persisted in Group B. These results indicate that irreversible tissue damage occurs when avascularization is continued for 3 hours. In addition, the PCr peak disappears, and ATPγ and ATPα decrease, while the ATPβ peak disappears.

Claims

1. 1. A method for aiding in the diagnosis of crush syndrome, comprising: MR spectroscopy of the subject's compression site ３１ Analyzing the P spectrum data ３１ The method includes a step of determining whether P spectrum data satisfies the following formula (1) and presenting the determination result. PCr / (Pi+PCr)≦0.50 (1) [In formula (1), Pi represents the height of the spectrum peak corresponding to phosphate ion, and PCr represents the height of the spectrum peak corresponding to creatine phosphate.]

2. In the step of presenting the determination result, ３１ The method according to claim 1 , further comprising determining whether the P spectrum data satisfies the following formula (2) and presenting the determination result: PCr / (Pi+PCr)≦0.20 (2)

3. A method for assisting in the diagnosis of crush syndrome according to claim 1 or 2, comprising: Furthermore, the compression site of the subject obtained by MR spectroscopy ３１ determining whether or not a spectral peak corresponding to creatine phosphate is present in the P spectral data, and presenting the determination result.

4. A method for assisting in the diagnosis of crush syndrome according to any one of claims 1 to 3, comprising: Furthermore, the compression site of the subject obtained by MR spectroscopy ３１ The method includes a step of determining whether or not a spectral peak corresponding to the β-phosphorus of ATP is present in the P spectral data, and presenting the determination result.

5. A method for assisting in the diagnosis of crush syndrome according to claim 3 or 4, comprising: The method, wherein said diagnosis of crush syndrome is a diagnosis of severe crush syndrome.

6. The method according to any one of claims 1 to 5, wherein the compression site is compressed muscle tissue.

7. A program for determining crush syndrome, comprising: MR spectroscopy of the subject's compression site ３１ Analyzing the P spectrum data calculating the height of the spectral peak corresponding to phosphate ion and the height of the spectral peak corresponding to creatine phosphate; and ３１ A program for executing a process of displaying a judgment result that the patient has crush syndrome when the P spectrum data satisfies the following formula (1). PCr / (Pi+PCr)≦0.50 (1) [In formula (1), Pi represents the height of the spectrum peak corresponding to phosphate ion, and PCr represents the height of the spectrum peak corresponding to creatine phosphate.]

8. Furthermore, the following steps are performed: detecting a spectrum corresponding to the phosphorus at the β position of ATP; and The program according to claim 7, further comprising a step of displaying a result of the determination that the patient has crush syndrome when no spectral peak corresponding to phosphorus at the β position of ATP is present.

9. The program according to claim 8, wherein in the step of displaying the result of the diagnosis that the patient has crush syndrome when there is no spectral peak corresponding to the phosphorus at the beta position of ATP, the result of the diagnosis that the patient has crush syndrome is displayed as being severe.

10. ３１ An MR spectroscopy apparatus capable of measuring P spectrum data, comprising the program according to any one of claims 7 to 9.

11. The apparatus of claim 10, wherein the MR spectroscopy apparatus is an MR spectroscopy apparatus equipped with a probe capable of measuring each muscle compartment.

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