A method for correcting the amount of light emitted from biological tissues that produce bioluminescence.

Abstract

A method for correcting the amount of light emitted from living tissue that produces a light emission phenomenon is provided. [Solution] A method for correcting the amount of light emitted by a biological tissue causing a luminescence phenomenon inside a living organism by applying an AC magnetic field to a magnetic fluid injected into the biological tissue causing a luminescence phenomenon to heat the biological tissue causing the luminescence phenomenon, and correcting the measured amount of light emitted by the biological tissue causing the luminescence phenomenon before and after heating includes the steps of determining, outside the living organism, the change in the amount of light emitted relative to the amount of magnetic fluid; heating the biological tissue causing the luminescence phenomenon and calculating the amount of magnetic fluid contained in the biological tissue causing the luminescence phenomenon based on a time constant related to the temperature change of the biological tissue causing the luminescence phenomenon; measuring the amount of light emitted by the biological tissue causing the luminescence phenomenon into which magnetic fluid has been injected; and calculating a correction value for the measured amount of light emitted based on the calculated amount of magnetic fluid.

Description

Technical Field

[0001] The present invention relates to a magnetic thermotherapy method for cancer treatment by applying an alternating magnetic field to a living tissue such as a tumor tissue that exhibits a luminescence phenomenon due to luciferase activity and is injected with a magnetic fluid to heat the tumor tissue, and a method for correcting the luminescence amount (luciferase activity value) of the tumor tissue.

Background Art

[0002] As a treatment method for tumors, hyperthermia has attracted attention. In this treatment method, by utilizing the fact that tumor tissues are more vulnerable to heat than normal tissues, only the tumor tissues can be selectively necrotized or regressed. Therefore, it is expected as a minimally invasive treatment method with less burden on patients compared to the current common cancer treatment methods such as surgical treatment, drug treatment, and radiation therapy.

[0003] Conventional heating methods in hyperthermia, such as RF dielectric heating method and ultrasonic heating method, have been proposed and are already used in the medical field. However, in these methods, it is relatively difficult to control the heating area, and there are cases where only the tumor tissue cannot be selectively heated. To effectively perform hyperthermia, it is necessary to continuously heat to a temperature at which the tumor tissue can be necrotized for a certain period of time. Furthermore, if the treatment temperature is increased, the tumor tissue can be more surely necrotized. However, the surrounding normal tissues are also exposed to high temperatures and there is a risk of necrosis. Therefore, the establishment of hyperthermia requires elucidation of the temperature and heating time that can treat only the tumor tissue without harming the normal tissues and the development of a temperature control system. Therefore, as shown in FIG. 10, a magnetic thermotherapy method has been proposed and studied in which a magnetic body is used as a heating element and implanted in the tumor tissue to enable local heating by applying an alternating magnetic field. FIG. 10 is a diagram conceptually showing the magnetic thermotherapy.

[0004] In magnetic thermotherapy, a soft heating method has been proposed in which a low-Curie-temperature magnetic material called a thermosensitive magnet is implanted in the body, and the heating temperature is controlled by the change in the magnetic properties of the material with respect to temperature. However, with this method, the thermosensitive magnet is on the order of μm to mm, making it difficult to remove after treatment. Furthermore, precise temperature control for various tumor tissues with different heat tolerances is also a challenge. Therefore, in animal experiments, a method has been adopted in which nanometer-order magnetic nanoparticles are implanted in the affected area, and the strength of the applied magnetic field is manipulated while measuring the temperature with an optical fiber thermometer.

[0005] Patent Document 1 discloses a method for injecting a low-osmotic suspension of magnetic particles into a patient's body and applying an alternating magnetic field to the patient for magnetic thermotherapy.

[0006] Furthermore, Non-Patent Document 1 discloses a research by the present inventors concerning temperature control when heating magnetic nanoparticles injected into a living organism by applying an alternating magnetic field in animal experiments. This method precisely controls the applied magnetic field to maintain a constant temperature without fluctuations at the target temperature without overshooting.

[0007] Furthermore, Patent Document 2 discloses a cancer treatment device that applies an alternating magnetic field of a specific frequency, without relying on the thermal effect of magnetic heating. [Prior art documents] [Patent Documents]

[0008] [Patent Document 1] International Publication No. 2014 / 140543 [Patent Document 2] International Publication No. 2018 / 097185 [Non-patent literature]

[0009] [Non-Patent Document 1] A. Shikano, L. Tonthat, and S. Yabukami: IEEJ Trans. Electr. Electron. Eng. , 16 , 807 - 809 (2021) [Overview of the Initiative] [Problems that the invention aims to solve]

[0010] In research on magnetic thermotherapy, animal experiments to confirm the therapeutic effect of magnetic heating involve transplanting tumor cells that constitutively express the luciferase gene (i.e., tumor cells that produce luminescence due to luciferase activity) into the lymph nodes of experimental mice. A magnetic fluid containing magnetic nanoparticles is then injected into these lymph nodes, and treatment is performed using magnetic heating. Changes in tumor tissue during treatment (whether the tumor tissue is actually proliferating or decreasing) can be estimated by measuring the amount of luminescence using, for example, a bioluminescence imaging device.

[0011] One of the inventors has developed a method using genetic engineering to prepare tumor cells that constitutively express the luciferase gene, i.e., tumor cells that produce luminescence due to luciferase activity, as known research tumor cells, and transplanting them into the lymph nodes of lymph node-swollen mice, which are experimental animals. The tumor tissue constitutively emits light, and by measuring the amount of light emitted, it is possible to determine the location of the tumor tissue in the body, as well as track its behavior such as proliferation, regression, and metastasis, and observe changes in real time and over time.

[0012] The luminescence imaging device is, for example, an in vivo imaging system that measures luminescence due to luciferase activity, by receiving light emitted by chemical reactions within a living organism and measuring the amount of luminescence.

[0013] In magnetic thermotherapy, a magnetic fluid containing metal nanoparticles (e.g., nano-sized iron nanoparticles) for magnetic heating is injected into tumor tissue. However, when measuring luminescence using a bioluminescence imaging device, there is a problem in accurately measuring changes in tumor cells due to the absorption of luminescence by metal nanoparticles (magnetic nanoparticles) such as iron contained in the magnetic fluid that remain near the tumor tissue. In other words, when measuring the amount of luminescence using a bioluminescence imaging device to observe changes in tumor tissue over time after injecting magnetic fluid into tumor tissue, changes in luminescence due to absorption by metal nanoparticles contained in the magnetic fluid occur in addition to changes in luminescence due to changes in tumor tissue. Therefore, it may not be possible to accurately measure changes in luminescence due to changes in tumor tissue.

[0014] Therefore, the object of the present invention is to provide a method for correcting the amount of light emitted from biological tissue that produces a light-emitting phenomenon, in order to accurately observe changes in the biological tissue (tumor tissue) in magnetic thermotherapy, which involves injecting a magnetic fluid containing a metal component into biological tissue that produces a light-emitting phenomenon due to luciferase activity and treating the biological tissue by heating it with magnetic heating. [Means for solving the problem]

[0015] To achieve the above objective, the present invention provides a method for correcting the amount of light emitted from biological tissue that produces a light-emitting phenomenon, comprising: applying an alternating magnetic field to a magnetic fluid injected into biological tissue that produces a light-emitting phenomenon inside a living body to heat the biological tissue that produces the light-emitting phenomenon, and correcting the measured amount of light emitted from the biological tissue that produces the light-emitting phenomenon, characterized in that the method comprises: determining the change in the amount of light emitted with respect to the amount of the magnetic fluid outside the living body; heating the biological tissue that produces the light-emitting phenomenon and calculating the amount of the magnetic fluid contained in the biological tissue that produces the light-emitting phenomenon based on a time constant related to the temperature change of the biological tissue that produces the light-emitting phenomenon; measuring the amount of light emitted from the biological tissue that produces the light-emitting phenomenon into which the magnetic fluid has been injected; and calculating a correction value for the measured amount of light emitted based on the calculated amount of the magnetic material.

[0016] A further luminescence amount correction method for correcting the luminescence amount of a biological tissue that causes a luminescence phenomenon in the present invention is a luminescence amount correction method for heating a preparation containing a light absorption component injected into a biological tissue that causes a luminescence phenomenon inside the living body and correcting the measured luminescence amount of the biological tissue that causes the luminescence phenomenon. The method includes, outside the living body, a step of obtaining a change in the luminescence amount with respect to the amount of the preparation containing the light absorption component, heating the biological tissue that causes the luminescence phenomenon, and calculating the amount of the preparation containing the light absorption component contained in the biological tissue that causes the luminescence phenomenon based on a time constant related to the temperature change of the biological tissue that causes the luminescence phenomenon, a step of measuring the luminescence amount of the biological tissue that causes the luminescence phenomenon into which the preparation containing the light absorption component is injected, and a step of calculating a corrected value of the measured luminescence amount based on the calculated amount of the preparation containing the light absorption component.

Advantages of the Invention

[0017] According to the present invention, the luciferase activity value (luminescence amount) measured for a biological tissue that causes a luminescence phenomenon due to, for example, luciferase activity inside the living body can be corrected with high precision, and changes in the biological tissue can be accurately measured.

Brief Description of the Drawings

[0018] [Figure 1] It is a diagram showing a configuration example of a magnetic heating system in an embodiment of the present invention. [Figure 2] It is a graph showing the relationship between the biological surface temperature measured by the biological surface temperature measurement unit 16 and the temperature of the magnetic fluid 20. [Figure 3] It is a diagram schematically showing the measurement of the (luminescence) amount by a biological luminescence imaging device. [Figure 4] It is a flowchart showing a method for measuring the luminescence amount due to luciferase activity in this embodiment example. [Figure 5] It is a graph showing the measurement results of the luminescence decay rate. [Figure 6] It is a graph showing the measurement results of the luminescence amount. [Figure 7]It is a graph showing an example of measurement results of temperature changes during magnetic hyperthermia treatment. [Figure 8] It is a graph showing the value of time constant -1 corresponding to the passage of time. [Figure 9] It is a graph showing the calibrated light emission amount. [Figure 10] It is a conceptual diagram for explaining magnetic hyperthermia therapy.

Embodiments for Carrying Out the Invention

[0019] Hereinafter, embodiments of the present invention will be described with reference to the drawings. However, such example embodiments do not limit the technical scope of the present invention.

[0020] [Example Configuration of Magnetic Heating System] FIG. 1 is a diagram showing an example configuration of a magnetic heating system 100 in an embodiment of the present invention. Tumor tissue, which is the target of magnetic heating in living tissue, is a tumor tissue near a lymph node in a living body 30, and magnetic fluid 20 is injected into it.

[0021] In research on magnetic hyperthermia therapy, in an animal experiment to confirm the therapeutic effect of magnetic heating, tumor cells that constantly express the luciferase gene, that is, tumor cells that produce a luminescence phenomenon, are transplanted into the lymph nodes of experimental mice, and a magnetic fluid containing magnetic nanoparticles is injected into the lymph nodes, and the treatment process by the magnetic heating system 100 in this embodiment is executed. Then, the change in luciferase activity of the tumor tissue during the treatment process (whether the tumor tissue actually grows or decreases) can be estimated by measuring the luminescence phenomenon due to luciferase activity using, for example, a bioluminescence imaging device.

[0022] Using known research tumor cells, genetic engineering is employed to prepare tumor cells that constitutively express the luciferase gene, i.e., tumor cells that produce luminescence due to luciferase activity, and these are transplanted into the lymph nodes of experimental mice. The amount of change in the tumor lesion after treatment with the magnetic heating system 100 is measured using a bioluminescence imaging device. The bioluminescence imaging device is, for example, an in vivo imaging system that receives light emitted from the luciferase gene in the body and measures its luciferase activity value, i.e., the amount of light emitted.

[0023] Luciferase activity causes tumor tissue to emit light, and by measuring this light emission with a bioluminescence imaging device, it is possible to determine the location of tumor tissue within the body, track its growth and regression, and observe changes in real time and over time.

[0024] The magnetic heating system 100 controls the heating of magnetic fluid 20 injected into a site within a living body 30, for example, near a lymph node into which tumor cells have been transplanted. It comprises a heating unit 12 that applies a magnetic field to the magnetic fluid 20 on the living surface near the lymph node into which tumor cells have been transplanted to heat the magnetic fluid, a temperature measuring unit 16 that measures the temperature of the living body 30 near the lymph node containing the tumor tissue and magnetic fluid 20, and a control unit 18 that controls the heating unit 12 based on the measured temperature.

[0025] The heating unit 12 can use a drive coil 12a and a high-frequency induction heating power supply 12b to drive it. The drive coil 12a is positioned so that the magnetic fluid 20 injected into the living organism 30 is located approximately on the center line of its coil axis. The alternating magnetic field generated from the drive coil 12a heats the magnetic fluid 20 in the living organism. A chiller (not shown) for cooling the heating unit 12 may be provided if necessary.

[0026] The temperature measuring unit 16 is a radiation thermometer (thermograph) and is a temperature sensor that measures the surface temperature of an object, including the living organism 30, using infrared radiation. The temperature measuring unit 16 measures the living organism's surface temperature due to the heating of the magnetic fluid 20, rather than the temperature of the magnetic fluid 20 itself. Lymph nodes are tissues relatively close to the living organism's surface, and the living organism's surface temperature near the magnetic fluid 20 injected into the lymph node changes in a highly correlated manner with the temperature of the magnetic fluid 20. Therefore, by measuring the living organism's surface temperature, the temperature of the magnetic fluid 20 can be detected. The temperature measuring unit 16 is not limited to thermography; for example, it can also be applied to optical fiber thermometers that are directly inserted into tumor tissue within the living organism 30 to measure temperature.

[0027] Figure 2 shows the relationship between the biological surface temperature measured by the biological surface temperature measurement unit 16 and the temperature of the magnetic fluid 20. As the temperature of the magnetic fluid 20 increases (or decreases), the biological surface temperature also increases (or decreases) linearly, and the temperature of the magnetic fluid 20 can be measured based on the temperature measured by the biological surface temperature measurement unit 16.

[0028] The control unit 18 is a computer device that executes the temperature control method in this embodiment. The control unit 18 can be a general-purpose computer device such as a laptop computer or a desktop computer, and is configured to have storage means (such as RAM, ROM, or magnetic disks) for storing computer programs and various data for executing the temperature control method in this embodiment, and arithmetic processing means (such as a CPU) for executing computer programs. Based on the temperature data acquired from the temperature measurement unit 16, the control unit 18 controls the output of the heating unit 12 that heats the magnetic fluid 20. For example, constant temperature heating control is performed to maintain a therapeutic temperature of 40-43°C.

[0029] [Magnetic fluid] The magnetic fluid used in magnetic thermotherapy is implanted in the body, so it must be safe as a pharmaceutical product. Therefore, when selecting a magnetic fluid, it is desirable that it be a pharmaceutical product approved through preclinical trials and clinical trials. For this reason, in this embodiment, we selected Resovist® (Kyowa CritiCare, Tokyo), a medical magnetic fluid that has already been approved as a pharmaceutical product and is used in research on magnetic thermotherapy. Resovist® is a magnetic fluid containing magnetic nanoparticles made of iron oxide with a particle size of approximately 57 nm in liquid, coated with carboxydextran.

[0030] In magnetic thermotherapy, a magnetic fluid containing magnetic nanoparticles is injected into tumor tissue, and treatment is performed by magnetic heating. Changes in tumor tissue due to treatment can be observed by measuring the amount of luminescence due to luciferase activity before and after magnetic heating. For example, a decrease in luminescence suggests that the tumor tissue is shrinking, while an increase in luminescence suggests that the tumor tissue is growing. The amount of luminescence is measured using a bioluminescence imaging device.

[0031] Figure 3 is a schematic diagram illustrating the measurement of luminescence using the bioluminescence imaging device 200. For example, in an animal experiment, tumor cells that produce luminescence due to luciferase activity are transplanted into the subiliac lymph nodes (SiLN) of experimental mice MXH10 / Mo / lpr, which are used as the organism 30. Magnetic fluid 20 is then injected, and the amount of luminescence is measured using the bioluminescence imaging device 200 before and after magnetic thermotherapy. The bioluminescence imaging device 200 captures the luminescence associated with luciferase activity emitted from the tumor tissue using the image sensor 204, and processes the image using the image processing unit 208.

[0032] In measuring the amount of luminescence using the bioluminescence imaging device 200, magnetic nanoparticles such as iron contained in the magnetic fluid 20 that remain near the tumor tissue absorb the luminescence associated with luciferase activity, which may prevent accurate measurement of changes in the tumor tissue. Specifically, when measuring the amount of luminescence using the bioluminescence imaging device 200 to observe changes in the tumor tissue over time during the process of injecting the magnetic fluid 20 into the tumor tissue and performing magnetic thermotherapy by magnetic heating, not only does the change in the amount of luminescence associated with luciferase activity due to changes in the tumor tissue occur, but there is also a decrease in the amount of luminescence due to luminescence absorption by magnetic nanoparticles contained in the magnetic fluid 20. Therefore, it may be difficult to accurately measure the change in the amount of luminescence due to changes in the tumor tissue.

[0033] Therefore, in order to accurately measure changes in tumor tissue, this embodiment proposes the following luminescence correction method, which corrects the measured luminescence amount using a time constant corresponding to the temperature change of the tumor tissue.

[0034] [Method for correcting light output] Next, the method for correcting the amount of light emitted in this embodiment will be described according to the flowchart shown in Figure 4. Figure 4 is a flowchart showing the method for correcting the amount of light emitted in this embodiment.

[0035] First, the luminescence attenuation rate corresponding to the amount of Resovist® used as the magnetic fluid 20 is measured in advance by an in vitro experiment (S101). Multiple samples are prepared, each containing a different amount of Resovist®, and for each sample, the absorbance of light at the same wavelength (e.g., 550 nm) as the luminescence associated with luciferase activity measured by the bioluminescence imaging device 200 is measured. Due to the light absorption of Resovist® itself, the intensity of the light emitted from the tumor tissue is weakened, and the amount of luminescence from the tumor tissue is attenuated.

[0036] Figure 5 is a graph showing the measurement results of the luminescence attenuation rate. As the amount of Resovist® increases, the luminescence attenuation rate increases, and this luminescence attenuation rate can be approximated by a predetermined approximation formula using an exponential function. In Figure 5, the dotted curve is the approximation curve of the luminescence attenuation rate.

[0037] In animal experiments using MXH10 / Mo / lpr mice, tumor cells that exhibit luciferase-induced luminescence were transplanted into the subiliac lymph nodes (SiLNs) of the mice, and a predetermined amount (e.g., 10 μl) of magnetic fluid 20, Resovist®, was injected into these cells using a syringe. Magnetic thermotherapy was then performed, and the amount of luminescence associated with luciferase activity before and after treatment was measured using a bioluminescence imaging device (S102). The amount of luminescence before injection of Resovist® was also measured.

[0038] Magnetic thermotherapy uses the magnetic heating system 100 shown in Figure 1 to excite the heating unit 12 with alternating current at a predetermined frequency using a high-frequency induction heating power supply. This heats the SiLN of MXH10 / Mo / lpr mice to a treatment temperature of, for example, 40°C, and maintains this temperature for a certain period of time. Magnetic thermotherapy is performed multiple times (for example, once a day for a predetermined duration over several days). By measuring the amount of light emitted before and after each magnetic thermotherapy session, the progress of tumor tissue growth or decline after each session can be confirmed.

[0039] Figure 6 is a graph showing the results of the luminescence measurement. In the measurement example in Figure 6, three MXH10 / Mo / lpr mice (Mouse 1: shown as a filled circle, Mouse 2: shown as a filled triangle, Mouse 3: shown as an open square) transplanted with tumor cells that produce a luminescence phenomenon due to luciferase activity were subjected to magnetic hyperthermia treatment four times over four days. The graph shows the changes in luminescence measured before and after injection of Resovist® and before and after the four magnetic hyperthermia treatments.

[0040] In the implementation of magnetic thermotherapy in S102, the heating unit 12 of the magnetic heating system 100 is activated to start heating the magnetic fluid, the temperature change during heating up to a predetermined treatment temperature is measured by the temperature measuring unit 16, and the time constant of the temperature change is calculated based on that temperature change (S104). The time constant is the time it takes to reach 63% of the equilibrium state at the treatment temperature, and the coefficient m3 when the measured temperature change is expressed by the following approximation formula (1) using an exponential function corresponds to the time constant. y = m1 + m2·exp(-m3·x) (1)

[0041] Figure 7 is a graph showing an example of measurement results for temperature changes during magnetic thermotherapy. In the measurement example in Figure 7, the temperature of the biological surface near the tumor tissue is measured by the thermographic temperature measurement unit 16. The average value (avg line) of the temperature distribution with a predetermined extent and the maximum temperature value of that temperature distribution (max line) are graphed. The time constant can be determined from either temperature change, but a time constant with a high signal-to-noise ratio can be obtained by calculating the time constant from the more sensitive maximum temperature value (max line).

[0042] Based on the calculated time constant, the amount of magnetic fluid 20 near the tumor tissue is calculated (S106). The time constant is the heating response characteristic of the magnetic fluid 20, and the larger the amount of magnetic fluid, the slower the heating rise becomes, so the time constant becomes a relatively small value. Therefore, there is a correlation between the time constant and the amount of magnetic fluid, and more specifically, the time constant of the temperature change is small (1 / time constant (time constant -1 The larger the value of (), the greater the amount of magnetic fluid 20 can be inferred. The magnetic fluid 20 is injected into the lymph node to which tumor cells have been transplanted. Immediately after injection, it remains near the lymph node, but over time, it gradually flows out of the lymph gland, and the amount of magnetic fluid 20 injected near the tumor tissue gradually decreases. The amount of decrease in magnetic fluid 20 and the amount of magnetic fluid 20 remaining near the tumor tissue at the time of measurement are calculated from the time constant.

[0043] The amount of magnetic fluid after X time has elapsed since the injection of the magnetic fluid is calculated from the following equation (2). Amount of magnetic fluid after time X = Initial amount of magnetic fluid injected (X=0) × Time constant -1 (Magnetic thermotherapy at time X=0 hours elapsed (injection time)) / Time constant -1 (Magnetic thermotherapy after X hours) (2)

[0044] Figure 8 shows the time constant corresponding to the passage of time for the three experimental mice in Figure 6. -1 This graph shows the values ​​and illustrates the change in the amount of magnetic fluid 20 remaining near the tumor tissue. Generally, it can be seen that the amount of magnetic fluid 20 decreases over time.

[0045] Based on the amount of magnetic fluid 20 after a predetermined time has elapsed, calculated in S106, a correction value for the amount of light emitted measured in S102 is calculated (S108). Since the measured amount of light emitted is affected not only by the amount of light emitted corresponding to the size of the tumor tissue but also by the light absorption by the magnetic fluid 20 remaining near the tumor tissue, the correction value for the amount of light emitted, which removes the effect of light absorption, is calculated in the simplest way, for example, by the following equation (3), using the light emission attenuation rate obtained in S101 corresponding to the amount of magnetic fluid 20. Correction value for luminescence = Measured luminescence amount × Luminescence attenuation rate corresponding to the amount of magnetic fluid (3)

[0046] Figure 9 is a graph showing the corrected values ​​of the luminescence measurements. The graph in Figure 6 above shows the luminescence measurements before correction. Comparing Figure 9 and Figure 6, the following can be inferred from the experimental results. Specifically, in the change in luminescence before and after injection of magnetic fluid before magnetic thermotherapy, in Figure 6, the luminescence decreases for mice 1 and 3 even before magnetic thermotherapy (dotted area P), whereas in Figure 9, it remains largely unchanged (dotted area Q). This suggests that the luminescence measurements before correction (actual values) include the effect of light absorption by the magnetic fluid 20, but the corrected luminescence values, obtained by correcting these measurements, exclude the effect of light absorption by the magnetic fluid 20 and show the luminescence corresponding only to the size of the tumor tissue. Even after magnetic thermotherapy, a difference in luminescence measurements before and after correction occurs for mice 1 and 3, suggesting that the luminescence is correctly corrected.

[0047] In the case of mouse 2, the measurement results showed no change in the amount of luminescence before and after the injection of magnetic fluid prior to the magnetic thermotherapy. This is presumed to be due to the fact that the magnetic fluid 20 was not properly injected into the lymph nodes of mouse 2. The luminescence measurement values ​​for mouse 2 overlapped and were almost identical before and after correction throughout the entire period, suggesting that the magnetic fluid was not present near the lymph nodes where the thermotherapy was performed. If the magnetic fluid 20 is not present near the tumor tissue, the tumor tissue will not be heated even if thermotherapy is performed, and no changes will occur in the tumor tissue. Therefore, even if the luminescence correction in this embodiment is performed, the magnetic fluid 20 will not be present, the tumor tissue will not change, and the amount of luminescence should not change. The measurement results for mouse 2 are thought to support this, and complementarily suggest that the above-described luminescence correction method in this embodiment is effective.

[0048] As described above, by correcting the measured luminescence amount using a time constant determined based on the temperature change measured during magnetic heating therapy, the luminescence amount measurement can be corrected, and an accurate luminescence amount (luciferase activity value) can be measured.

[0049] In the above embodiment example, an example was described in which a magnetic fluid such as Resovist® is injected into bioluminescent tissue. However, the formulation administered into the body is not limited to this, and the method can also be applied to formulations containing other light-absorbing components that absorb light and change temperature when heated. The light-absorbing component may be, for example, a metallic component such as the iron oxide component contained in the above-mentioned Resovist®, or another inorganic or organic component. Furthermore, the formulation is not limited to a fluid, but may be in other forms such as powder or solid. In addition, the bioluminescent phenomenon used for measurement is not limited to luminescence due to luciferase activity, but may be a different bioluminescent phenomenon.

[0050] The present invention is not limited to the embodiments described above, and of course, design changes that do not depart from the spirit of the invention, including various modifications and alterations that can be conceived by a person with ordinary skill in the art of the present invention, are also included in the present invention. [Explanation of Symbols]

[0051] 100: Magnetic heating system, 12: Heating unit, 12a: Drive coil, 12b: High-frequency induction heating power supply, 16: Temperature measurement unit, 18: Control unit, 20: Magnetic fluid (magnetic nanoparticles), 30: Living organism, 200: Bioluminescence imaging device, 204: Image sensor, 208: Image processing unit

Claims

1. A method for correcting the amount of light emitted by a biological tissue that produces a light emission phenomenon inside the body of an animal other than a human, wherein an alternating magnetic field is applied to a magnetic fluid injected into the biological tissue that produces the light emission phenomenon to heat the biological tissue that produces the light emission phenomenon, and the measured amount of light emitted by the biological tissue that produces the light emission phenomenon is corrected, A step of determining the change in the amount of light emitted in relation to the amount of magnetic fluid in an animal other than a human, A step of heating the biological tissue that produces the light-emitting phenomenon, and calculating the amount of magnetic fluid contained in the biological tissue that produces the light-emitting phenomenon based on a time constant related to the temperature change of the biological tissue that produces the light-emitting phenomenon, A step of measuring the amount of light emitted from the biological tissue that produces the light emission phenomenon into which the magnetic fluid has been injected, A method for correcting the amount of light emitted, characterized by comprising the step of calculating a correction value for the measured amount of light emitted based on the calculated amount of magnetic fluid.

2. The method for correcting the amount of luminescence according to claim 1, characterized in that the time constant is determined based on the largest temperature change of the biological tissue that produces the luminescence phenomenon.

3. The method for correcting the amount of luminescence according to claim 1, characterized in that the biological tissue that produces the luminescence phenomenon emits light due to luciferase activity.

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