Diagnostic aid, program and diagnostic aid method

Abstract

The present application addresses the technical problem of reducing false negatives and false positives in nuclear medicine image diagnosis. The diagnostic assistance device of the embodiments has a collating section and a presuming section. The collating section collates information on the accumulation site of a diagnostic drug, i.e., first site information, obtained from nuclear medicine imaging of a subject, and information on the source site of exosomes including the diagnostic drug, i.e., second site information, collected from the subject. The presuming section presumes that a tumor exists at a site where the collated results are consistent between the first site information and the second site information.

Description

[0001] Cross-reference to related applications

[0002] This application is based on and claims priority to Japanese Patent Application No. 2021-186486, filed on November 16, 2021, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The embodiments disclosed in this specification and accompanying drawings relate to diagnostic aids, procedures, and methods. Background Technology

[0004] Regarding nuclear medicine imaging diagnosis, the following techniques are known: inferring tumor location based on the accumulation site of diagnostic drugs; however, significant variability in interpretation due to the skill level of the radiologist can lead to false negatives and false positives. For example, in cases of suspected lung malignancy, 18.4% of false negatives and 4.35% of false positives were reported. Furthermore, in cases of residual or suspected recurrence after chemoradiotherapy for squamous cell carcinoma of the oral pharynx, 59.2% of false positives were reported.

[0005] [Existing Technical Documents]

[0006] [Patent Literature]

[0007] [Patent Document 1] Japanese Patent Application Publication No. 2012-149994 Summary of the Invention

[0008] One of the technical problems to be solved by the embodiments disclosed in this specification and accompanying drawings is to reduce false negatives and false positives in nuclear medicine imaging diagnosis. However, the technical problems to be solved by the embodiments disclosed in this specification and accompanying drawings are not limited to the above-mentioned technical problems. It is also possible to identify other technical problems as corresponding to the effects of the various structures shown in the embodiments described below.

[0009] The diagnostic aid device of this embodiment includes a control unit and a presumption unit. The control unit compares information about the aggregation site (region) of the diagnostic drug obtained from nuclear medicine imaging of the specimen, i.e., first site information, with information about the origin site of exosomes, including the diagnostic drug, collected from the subject, i.e., second site information. The presumption unit presumes that the result of the comparison indicates the presence of a tumor at a site in the first site information that matches the second site information. Attached Figure Description

[0010] Figure 1 This is a block diagram illustrating an example of the diagnostic aid device according to the first embodiment.

[0011] Figure 2 This is a flowchart illustrating an example of the method executed by the diagnostic assistance method of the second embodiment and the diagnostic assistance procedure of the third embodiment.

[0012] Figure 3 This is a flowchart illustrating an example of the diagnostic assistance method of the fourth embodiment.

[0013] Figure 4 This is a flowchart illustrating an example of the diagnostic assistance method of the fourth embodiment.

[0014] Figure 5 This is a schematic diagram illustrating an example of the metabolism of a diagnostic drug in the diagnostic aid method of the fourth embodiment.

[0015] Figure 6 This is a schematic diagram illustrating an example of the metabolism of a diagnostic drug in the diagnostic aid method of the fourth embodiment.

[0016] Figure 7 This is a Venn diagram illustrating an example of the presumed conditions in the diagnostic aid method of the fourth embodiment.

[0017] Figure 8 This is a flowchart illustrating an example of a presumed step in the diagnostic assistance method of the second embodiment and the diagnostic assistance procedure of the third embodiment.

[0018] Figure 9 This is a flowchart illustrating an example of a diagnostic aid method for implementing an embodiment.

[0019] Figure 10 This is an image illustrating an example of a photograph taken during an implementation of the method. Figure 10 (a) is a simple chest CT scan. Figure 10 (b) is a PET / CT scan of the chest. Figure 10 (c) is a simple CT scan of the abdomen.

[0020] Figure 11 These are images showing examples of the presumed results of the implementation method.

[0021] Figure 12 This is a block diagram illustrating an example of a diagnostic aid device according to an embodiment. Detailed Implementation

[0022] Hereinafter, with reference to the accompanying drawings, the implementation methods of the diagnostic aid device, program, and diagnostic aid method will be described in detail.

[0023] (First Implementation)

[0024] One example of the diagnostic aid device in the first embodiment is a device used in a diagnostic aid method, which combines information on the aggregation site of diagnostic drugs obtained from nuclear medicine imaging of a subject with information on the source site obtained from the analysis of exosomes of the same subject, thereby presuming the location of a tumor in the subject.

[0025] Figure 1 This is a diagram illustrating a structural example of the diagnostic aid device according to the first embodiment. For example, such as... Figure 1 As shown, the diagnostic aid device 1 of this embodiment includes at least a control unit 2 and a presumption unit 3. The control unit 2 compares information on the aggregation site of the diagnostic drug obtained from nuclear medicine imaging of the subject (hereinafter also referred to as "first site information") with information on the source site of exosomes, including the diagnostic drug, collected from the subject (hereinafter also referred to as "second site information"). The presumption unit 3 presumes that the result of the comparison is that a tumor exists at the site in the first site information that matches the second site information.

[0026] For example, the estimation section may also

[0027] The result of the comparison indicates that a tumor (positive) exists in a location included in both the first and second location information.

[0028] If the result of the comparison is determined to be a false positive, indicating that a tumor exists in a location other than the location included in the first location information but not included in the second location information.

[0029] The result of the comparison indicates that a tumor exists in a location that is not included in the first location information but is included in the second location information (false negative).

[0030] (Second Implementation)

[0031] like Figure 2 As shown in (a), the diagnostic aid method of the second embodiment may be a diagnostic aid method that uses information on the location of the accumulation of diagnostic drugs obtained from nuclear medicine imaging of the subject and information on the source of exosomes, including the diagnostic drugs, included in the subject, to estimate the location of the tumor in the subject (step S).

[0032] Figure 2 (b) is a flowchart illustrating a structural example of the diagnostic assistance method according to the second embodiment. For example, such as... Figure 2 As shown in (b), the diagnostic assistance method of this embodiment can include the following steps:

[0033] The information on the aggregation site of the diagnostic drug obtained from nuclear medicine imaging of the subject, i.e., the first site information, is compared with the information on the origin site of exosomes, including the diagnostic drug, collected from the subject, i.e., the second site information (process S1); and

[0034] It is presumed that a tumor exists in the location where the first location information matches the second location information (step S2).

[0035] For example, step S1 can be performed in the comparison section 2 of the diagnostic aid device 1 in the first embodiment, and step S2 can be performed in the estimation section 3.

[0036] As a third implementation, for example, it may also be provided in Figure 1 Performed in the diagnostic aid device shown Figure 2 (a) and Figure 2 The procedure for the diagnostic aid method shown in (b) is an example of such a diagnostic aid procedure.

[0037] The method is characterized by comparing information about the aggregation site of the diagnostic drug obtained from nuclear medicine imaging of the subject, i.e., first site information, with information about the origin of exosomes, including the diagnostic drug, collected from the subject, i.e., second site information (S1); and presuming that a tumor exists at a site in the first site information that matches the second site information as a result of the comparison (S2). For example, such a procedure is a diagnostic aid method that can be implemented by a processing system such as a computer, and may be a diagnostic aid program that executes steps S1 and S2.

[0038] For example, process S1 may also include the following steps:

[0039] Nuclear medicine imaging images were obtained from subjects who had been given diagnostic drugs;

[0040] Information about the location where the diagnostic drug accumulates, i.e., the first location information, is obtained from the acquired camera images;

[0041] Molecular information of exosomes collected from the subject, including the diagnostic drug, is obtained;

[0042] The source site information of the exosomes, i.e., the second site information, is obtained from the molecular information of the exosomes; and

[0043] Compare the information of the first part with the information of the second part.

[0044] In other words, another structural example of the diagnostic assistance method of the second embodiment includes the following steps:

[0045] Nuclear medicine imaging images were obtained from subjects who had been given diagnostic drugs;

[0046] Information about the location where the diagnostic drug accumulates, i.e., the first location information, is obtained from the acquired camera images;

[0047] Molecular information of exosomes collected from the subject, including the diagnostic drug, is obtained;

[0048] The source site information of the exosomes, i.e., the second site information, is obtained from the molecular information of the exosomes;

[0049] Compare the information of the first part with the information of the second part; and

[0050] It is presumed that the tumor exists in the location where the first site information is consistent with the second site information, based on the results of the comparison.

[0051] (Fourth Implementation)

[0052] The diagnostic assistance method of the fourth embodiment can also be performed using the diagnostic assistance device 1. The diagnostic assistance method of the fourth embodiment can, as... Figure 4 As shown, it includes the following steps:

[0053] Administer diagnostic drugs to the subject (process S1);

[0054] Perform nuclear medicine imaging on the subject (procedure S2);

[0055] Information about the location where the diagnostic drug accumulates is obtained from the camera image, i.e., the first location information (process S3);

[0056] Exosomes, including diagnostic drugs, are collected from the subject (process S4);

[0057] Obtain molecular information of exosomes (step S5);

[0058] Obtain the source site information of exosomes, i.e., the second site information, from the molecular information of exosomes (step S6);

[0059] Compare the information from the first part with the information from the second part (process S7); and

[0060] It is presumed that a tumor exists in the location where the information in the first location matches the information in the second location (process S8).

[0061] The following uses Figure 3 and Figure 4 Examples of detailed steps of the diagnostic assistance method according to the fourth embodiment will be described.

[0062] like Figure 3 and Figure 4 As shown, firstly, diagnostic drug 5 is administered to the subject 4 (process S1).

[0063] Subject 4 is preferably a human. However, it can also be an animal other than a human. Animals other than humans include mammals, birds, amphibians, reptiles, or fish. Mammals include primates such as monkeys, rodents such as mice, rats, and guinea pigs, companion animals such as dogs, cats, and pigs, livestock such as horses, cattle, and pigs, or mammals that are exhibit animals.

[0064] Diagnostic agent 5 is, for example, a substance that accumulates in tumor cells and can be detected by nuclear medicine imaging equipment. For example, diagnostic agent 5 is a compound containing a radioactive isotope. Such a compound is, for example, […]. 18 F]2-Fluorodeoxy-D-glucose([ 18 F]FDG), [ 18 F]6-Fluoro-m-tyrosine, L-[3- 18 F]-a-Methyltyrosine, S-[Methyl- 11 C]-methionine, trans-1-Amino-3-[ 18 F]fluorocyclobutanecarboxylic acid, 3'-Deoxy-[3'- 18 F]thymidine, [ 11 C-Methyl]thymidine, 2-[ 11 C]Tymidine, [ 11 C]Methionine、[ 18 F]Fluorothymidine、4'-[Methyl- 11 [C]-thiotymidine, [ 11 C]Acetate、[ 11 C]Choline、[ 18 F]Fluorocholine、[ 18 F] Fluoromisonidazole, [ 18 F]Fluoroa zomycin arabinofuranoside, and / or [ 62 Cu]Diacetyl-bis(N4-methylthiose micarbazone) etc.

[0065] There are no particular restrictions on the method of administering the diagnostic drug 5 to the subject 4, as long as it is any known method that can deliver the diagnostic drug to the target site of the diagnostic aid method of the implementation method. For example, it can be administered intravenously, intra-arterially, intradermally, subcutaneously, intramuscularly, or orally. For example, for whole-body imaging, it can be administered intravenously.

[0066] In process S1, the diagnostic drug 5 is injected and diffused into the subject 4, where it can be absorbed by various cells. For example, ... Figure 5As shown in section (a), diagnostic drug 5 accumulates in cells 50 (tumor cells) where the metabolism of diagnostic drug 5 (“X”) does not progress. There are also cases where diagnostic drug 5 accumulates in a multi-stage metabolic state (“X’” or “X””) in the figure.

[0067] Next, nuclear medicine imaging was performed on subject 4. Figure 4 Process S2).

[0068] Nuclear medicine imaging, such as Figure 3 As shown, this is performed, for example, using a nuclear medicine imaging device 6. When the radioactive isotope included in the diagnostic agent 5 emits positrons (cations), as a result of the annihilation of the positrons released from the radioactive isotope with nearby electrons, two annihilation radiation rays (gamma rays) are emitted in opposite directions of 180 degrees. For example, by simultaneously counting the gamma rays emitted in these two directions, the nuclear medicine imaging device 6 can use the detection signals to create an image. That is, in such a device, by simultaneously detecting two gamma rays using multiple gamma-ray detectors arranged in a ring around the sample, data such as a sine curve showing the presence of radioactive isotopes on the line connecting the gamma-ray detectors that detected the gamma rays is obtained. By reconstructing the image from this data, the distribution of the radioactive isotopes is obtained as a tomographic image. For example, such devices can be positron emission tomography (PET) devices, PET-CT devices that combine PET devices with X-ray computed tomography (CT) devices, or TOF-PET (time-of-flight PET) devices.

[0069] In cases where radioactive isotopes emit gamma rays, a nuclear medicine imaging device 6 can be used, for example, to detect such gamma rays using a gamma ray detector equipped with a collimator, such as a parallel collimator. As a result of the detection, data such as the position of the gamma ray detector where the gamma rays arrived and output power pulses, and the number of power pulses detected, can be obtained, and a planar image can be created based on this data. By collecting planar images by detecting gamma rays from various directions of the sample using a gamma ray detector, and reconstructing the images by a computer, the distribution of the radioactive isotope can be obtained as a tomographic image. For example, a single-photon emission computed tomography (SPECT) device or a SPECT / CT device combining a SPECT device and a CT device can be used as such a device.

[0070] Through the aforementioned imaging, information (first site information) 7 regarding the location where the diagnostic drug 5 accumulates in the subject 4 can be obtained. Since the diagnostic drug 5 accumulates in tumor cells, the first site information 7 is the information regarding the location where nuclear medicine imaging has determined the presence of a tumor.

[0071] In this instruction manual, "site" refers to the organ (viscera) or tissue of the subject 4. There are no limitations on the organ; for example, it includes the brain, lungs, breast, esophagus, stomach, large intestine, colon, rectum, liver, pancreas, bladder, prostate, cervix, or ovary. Tissue refers to the tissue further subdivided from the aforementioned organs; in the case of the lungs, it could be non-small cell, small cell, glandular, squamous epithelium, or large cell tissues.

[0072] The information 7 for the first part can be obtained either by a technician or radiologist visually examining the video data, or automatically using image analysis software. Alternatively, it can be obtained by accessing a database stored inside or outside the nuclear medicine imaging device 6 and comparing the video data with the information stored in the database.

[0073] On the other hand, after step S1, exosomes, including diagnostic drugs, are collected from the subject 4. Figure 4 (Process S4).

[0074] Such as about Figure 5 As explained in section (a), diagnostic drug 5 accumulates in cells 50 where its metabolism does not progress due to the administration of diagnostic drug 5. However, as Figure 5 As shown in section (b), when exosomes 9 are produced from cell 50, the accumulated diagnostic drug 5 can be taken up into the exosomes 9. As a result, exosomes 9, including the diagnostic drug 5, are released into the bloodstream.

[0075] Reference Figure 6 For diagnostic drug 5, [ 18 F]2-Fluorodeoxy-D-glucose([ 18 The example of F]FDG) will be used to illustrate this. The [F]FDG was placed on subject 4. 18 F]FDG was ingested into cells 50 of subject 4. The ingested [ 18 F]FDG is metabolized by hexokinase to produce [ 18 F]FDG-6-P. Accumulated in cells 50 [ 18 F]FDG-6-P is ingested into exosomes 9 and released into the bloodstream.

[0076] Exosome 9 consists of tiny vesicles with a diameter of approximately 100 nm found within organisms. Secreted by cells, exosome 9 possesses a lipid bilayer structure containing nucleic acids and proteins, and plays a role in transporting substances and transmitting information between separate organs. Cases have also been reported where the lipid bilayer contains proteins or glycoproteins, with nucleic acids such as DNA attached to it. The types or combinations of these molecules are specific to the cell type from which they originate; by analyzing them, information about the cell 50 from which exosome 9 originated can be obtained. Hereinafter, such exosome-specific molecules will be referred to as "exosome molecules 10".

[0077] Exosomes can be collected, for example, through methods such as... Figure 3 As shown, blood is collected from subject 4, and exosomes 9, including diagnostic drugs 5, are separated from the obtained blood 8.

[0078] To isolate the exosomes 9 containing the diagnostic drug 5, blood collection is preferably performed before the half-life of the radioactive isotope contained in the diagnostic drug 5 has elapsed. For example, [ 18 F]FDG's [ 18 The half-life of [F] is approximately 2 hours, therefore when using [ 18 When FDG is used as a diagnostic drug, blood collection is preferably performed within 2 hours after administration.

[0079] The diagnostic aid device 1 can also display the time of blood collection or the time elapsed until blood collection. When blood 8 is collected from multiple subjects 4, the diagnostic aid device 1 can also display the time of blood collection or the time elapsed for each of the multiple subjects 4. This display can be on a display unit that is also included in the diagnostic aid device 1, or it can be on a display unit that is included in the nuclear medicine imaging device 6 or the molecular information comparison device 14 connected to the diagnostic aid device 1. In addition to display, the time can also be indicated by signals such as sound or light.

[0080] The separation of exosomes 9 can be performed using known methods, such as commercially available exosome separation kits. In this case, it is also possible to separate exosomes 9 containing the diagnostic drug 5 from those not containing the diagnostic drug 5.

[0081] Next, molecular information 11 of exosome 9 was obtained. Figure 4 (Process S5).

[0082] Molecular information 11 includes information such as the type and / or quantity of exosome molecules 10 contained in the collected exosomes 9. For example... Figure 3 As shown, molecular information 11 can be obtained, for example, by extracting the above-mentioned exosome molecules 10 from the isolated exosomes 9 and identifying and / or quantifying them.

[0083] Exosome molecules 10 may include, for example, nucleic acids, enzymes, membrane proteins, cytoskeletal proteins, single molecules and / or chaperone proteins. Exosome molecules 10 may include, for example, exosome molecules 10 that can be associated with information from the producing cell 50 (source) and exosome molecules 10 that are themselves exosomes.

[0084] For example, the exosome molecule 10, which can be associated with information from the generated cell 50 (source), is not limited, and may include, for example, exosomal microRNA (miRNA), messenger RNA (mRNA), and / or DNA.

[0085] In addition, the exosome molecules 10 that can be associated with their own exosome status are not limited, such as enzymes such as GAPDH, PK, ATPase, PGK, and enolase; cytoskeletal proteins such as Actin, Myosin, Vimentin, Tubulin, Cofilin, Profilin, and Fibronectin; signaling molecules such as EGF-R, HIF-1a, CDC42, PI-3K, ARF1, and Rab5b; chaperone proteins such as HSP70, HSP90, HSP60, and HSC70; tetraspanins such as CD9, CD63, and CD81; integrins such as α6β4, α6β1, and αvβ5; MHC class I molecules and class II molecules; multivesicle constituent molecules such as TSG101, Clathrin, Ubiquitin, and Alix; and lipid rafts such as Flotillin-1.

[0086] Extraction of exosome molecule 10 can be performed by dissolving the exosomes in a buffer solution close to water, or by a known method appropriate to the species. For example, commercially available nucleic acid extraction kits or protein extraction kits can also be used.

[0087] Next, the extracted exosome molecules 10 are identified and / or quantified. Protein identification and quantification can be performed, for example, by protein sequencing, dual-enzyme assays, or peptide mass spectrometry. Nucleic acids can be identified and quantified, for example, by nucleic acid amplification methods such as PCR, LAMP, or TRC, or sequencing methods.

[0088] Next, the source site information (second site information) 12 of the exosomes is obtained from the obtained exosome molecular information 11 (step S6). The second site information 12 is obtained, for example, by comparing the exosome molecular information 11 with a set of information obtained by associating multiple exosome molecules 10 obtained from past insights with their source sites.

[0089] For example, when the information contained in exosome molecular information 11 includes exosome molecules a, b, c, and d, comparisons are made between a, b, c, and d to obtain consistent information about the origin of exosome molecules 10. The obtained information about the origin can be relative to multiple exosome molecules 10. Examples of associating exosome molecules 10 with their origin include miR-30c with lung cancer, miR-181c with breast cancer or brain tumors, miR-34a with ovarian cancer, or MMP-1 mRNA with ovarian cancer, but are not limited to these.

[0090] Alternatively, sometimes a combination of multiple exosome molecules 10 is combined with specific source site information, and when this combination is included in the exosome molecule information 11 (e.g., a and b, etc.), the specific source site can be obtained. In addition, sometimes the amount of exosome molecules 10 is combined with specific source site information to obtain a source site consistent with the amount of exosome molecules (e.g., the amount of a, the amount of b, etc.).

[0091] Such a comparison and the acquisition of information 12 in the second part can also be achieved as follows: Figure 3 The molecular information comparison device 14 is used as shown. The molecular information comparison device 14 is, for example, a computer, which has a comparison unit 15 that compares the information group obtained by associating multiple exosome molecules 10 stored in the database (DB) 13 with their source sites with the exosome molecular information 11.

[0092] Database 13 can be configured within the molecular information comparison device 14 or externally. External database 13 can be stored in a web service (e.g., cloud 16), or accessed by connecting the molecular information comparison device 14 to the cloud 16. Database 13 can be, for example, domestic or international medical databases, chemistry databases, general introductions, explanations, or textbooks. Furthermore, the various data processed in this specification are typically digital data.

[0093] For example, if specific exosome molecular information 11 of a subject 4 is input into the molecular information comparison device 14, the comparison unit 15 accesses the database 13, reads the information set included therein, and compares the exosome molecular information 11 of the subject 4 with the information set. The comparison result, which is consistent with the source information of the exosome molecular information 11 of the subject 4, is output as the second site information 12. Alternatively, the database 13 may also have the function of the comparison unit 15. In this case, the exosome molecular information 11 is sent to the database 13 for comparison, and the second site information 12 is sent to the molecular information comparison device 14.

[0094] In the case of multiple subjects 4, for example, each subject 4 can be compared and its own comparison results can be returned.

[0095] Alternatively, the presence of exosomes in the collected sample can be determined simultaneously based on the exosome molecular information 11. For example, the exosome molecular information 11 can be compared with a database 13 containing information groups of exosome molecules 10 that may be associated with exosomes, as described earlier. If inconsistent comparison results are obtained, it is preferable to stop the process and collect exosomes again without proceeding to the next step. By performing this comparison, more accurate results can be obtained.

[0096] As explained above, information on the aggregation site of the diagnostic drug (first site information) 7 is obtained through nuclear medicine imaging procedures S2-S3, and information on the origin of the exosomes (second site information) 12 is obtained through exosome analysis procedures S4-S6. Procedures S2-S3 and S4-S6 can be performed one of them first or simultaneously. The steps up to this point can be determined, for example, by taking into account factors such as the half-life of the radioisotope of the diagnostic drug 5 to obtain accurate information.

[0097] Next, the first part information 7 and the second part information 12 are compared (step S7). This comparison is performed, for example, by the comparison unit 2 of the diagnostic aid device 1. The diagnostic aid device 1 receives the first part information 7 from the nuclear medicine imaging device 6 and the second part information 12 from the molecular information comparison device 14, and sends them to the comparison unit 2. The comparison unit 2 then compares the first part information 7 and the second part information 12. For example, the comparison can also be performed by investigating whether each part included in the first part information 7 is included in the second part information 12.

[0098] For sites in the first site information 7 that have consistent control results, a tumor is identified as present (positive) (step S7-1). In cases of inconsistency, a site is identified as either present in the first site information 7 but without a tumor (or possibly with a disease other than a tumor) (false positive), or present in a site not included in the first site information 7 but with a tumor (false negative). Figure 4 (Process S7-2).

[0099] Here, "positive", "false positive" and "false negative" are determined based on the information 7 from the first part obtained through nuclear medicine imaging.

[0100] False positives can be attributed to active inflammation such as acute inflammation, chronic inflammation, abscess, tuberculosis, nodules, or chronic thyroiditis, or to physiological accumulation of salivary gland tumors, benign bone tumors, hypermotility, enteritis, artificial anus sites, colorectal polyps, endometrium during menstruation, ovulation period, lactational breast, uterine fibroids, endometritis, benign ovarian tumors (chocolate cysts, teratomas), or brown adipose tissue (cold period).

[0101] False negatives can occur in cases where the tumor diameter is less than 9 mm, in cases of high G-6-P phosphatase activity such as primary liver cancer, in cases of low cell density such as gastric marker ring cell carcinoma and ovarian mucinous cystadenocarcinoma, in cases where the tumor is in contact with the urinary tract such as kidney cancer, bladder cancer, or prostate cancer, or in cases of well-differentiated tumors such as well-differentiated lung adenocarcinoma or ovarian borderline malignant tumors.

[0102] Through this process S7, the presence of a tumor in the subject 4 can be presumed. Presuming the presence of a tumor means inferring the location of the tumor in the subject 4 based on the assessment of each of the above-mentioned sites. For example, it can be presumed that a tumor exists in a site that is positive in the above-mentioned assessments.

[0103] The determination and estimation can be performed, for example, by the estimation unit 3 of the diagnostic aid device 1. The estimation unit 3 performs the above determination and estimation based on the comparison results sent from the comparison unit 2, and outputs the estimation result.

[0104] In another embodiment, the estimation can also be performed in the estimation section 3. Figure 7 The determination of the Venn diagram shown. For example, if the information on the aggregation site of the diagnostic drug obtained from nuclear medicine imaging (first site information) 7 is set as "A", and the information on the source site of the exosomes obtained from exosome analysis (second site information) 12 is set as "B", then the determination can be made according to the conditions in Table 1 below.

[0105] [Table 1]

[0106] Table 1

[0107]

[0108] In the determination according to the conditions in Table 1, firstly, all part information contained in both the first part information 7 and the second part information 12 (A∪B) is obtained, and then each part contained therein is applied to the above four conditions for the next determination:

[0109] For the locations included in conditions A and B, the presence of a tumor is determined (true positive).

[0110] For the location in condition 2 that is included in A but not in B, it is determined that there may be no tumor or a disease other than a tumor (false positive).

[0111] For the location in condition 3 that is not included in A but is included in B, it is determined to be a tumor that cannot be detected by nuclear medicine imaging (false negative).

[0112] In addition, for locations that are not included in conditions A and B of condition 4, it can be determined that there is no tumor (true negative).

[0113] Based on the above judgment results, the presence of a tumor in subject 4 can be presumed (process S8).

[0114] Such judgments and presumptions can be made through the presumption section 3, for example... Figure 8 The process is as shown. First, all part information contained in both the first part information 7 and the second part information 12 (A∪B) is obtained (parse parent group) (process S10). Then, each part contained therein is applied to the next process.

[0115] First, determine whether the region is included in the first region information 7 (step S11). If it is included (yes), then determine whether it is included in the second region information 12 (step S12). If it is included (yes), it is determined to be a true positive (step S13). If it is not included (no), it is determined to be a false positive (step S14).

[0116] If the result of step S11 is that it is not included (No), the next step is to determine whether it is included in the second part information 12 (step S15). If it is included (Yes), it is determined to be a false negative (step S16). Here, if it is not included in the parsed parent group obtained in S10, but is determined not to be included (No) in step S15, it is determined to be a true negative (step S17).

[0117] This process is repeated for all parts included in the parent group of the analysis. As a result, each part undergoes three determinations in steps S13, S14, and S16, and four determinations, including S17, are made as needed. Based on the information from these determinations for each part, the location of the tumor in the subject 4 is inferred (step S8). According to this inference method, the first part information 7 can be classified into four determination results based on four conditions.

[0118] The following is for reference Figure 9 Instructions for administering [treatment] to subject 4 (female) suspected of having right lobe lung cancer. 18 F]FDG is an example of a diagnostic drug.

[0119] First, [the following was applied to subject 4] 18 After FDG (process S20), whole-body FDG-PET / CT imaging (S21) and blood collection (S23) are performed after 60 minutes.

[0120] The FDG-PET / CT images are shown in Figure 10 . Figure 10 (a) is a simple CT image of the chest, showing the presence of […] in the right lobe and right hilar lymph nodes and the left breast (in the direction of the arrow). 18 High aggregation of F]FDG. Figure 10 (b) is a PET / CT image of the same chest, similarly confirming [the presence of lymph nodes in the right lobe and right hilum, and the left breast (circled area)]. 18 High aggregation of F]FDG. Figure 10 (c) is a simple CT image of the abdomen, in which [[] was confirmed in the ovary] 18 High aggregation of F]FDG. Therefore, as the first part information 7, the right lung lobe, left breast, and ovary are obtained (process S22).

[0121] Next, exosomes were isolated from the blood collected (S24). Proteins and nucleic acids were extracted from the exosomes and identified (S25). The results showed that the exosomes were rich in miR-30c and miR-181c, which are exosome molecules 10. That is, as exosome molecule information 11, the exosomes were found to be rich in miR-30c and miR-181c. Comparing this with the information set in database 13, it was found that miR-30c is a specific molecule for lung cancer, and miR-181c is a specific molecule for breast cancer and brain metastases. Here, miR-34a and MMP-1 mRNA, which are specific molecules for ovarian cancer, were not included. Therefore, as second site information 12, lung, breast, and brain were obtained (step 26).

[0122] Next, the information of the first part 7 is compared with the information of the second part 12. In the comparison, the part information (lung, breast, ovary, brain) contained in both the information of the first part 7 and the information of the second part 12 is first obtained (step 27). Then, each part is applied to the conditions shown in Table 1. For each part, the determination is made as follows (step S28): the lung and breast are contained in both the information of the first part 7 and the information of the second part 12, so they are true positives; the ovary is contained in the information of the first part 7 but not in the information of the second part 12, so it is a false positive; the brain is not contained in the information of the first part 7 but is contained in the information of the second part 12, so it is a false negative.

[0123] Based on the above, it is presumed that the subject has tumors in the lungs and breasts (step S29). Here, FDG-PET / CT imaging shows that the lung is the right lobe and the breast is the left breast, so it is not simply presumed that the tumors are in the lungs and breasts, but rather that they are in the right lobe of the lungs and the left breast.

[0124] For example, the estimation result obtained by the estimation unit 3 of the diagnostic aid device 1 can also be as follows: Figure 11 As shown, these are displayed along with the imaging images, categorized by the location of each diagnostic drug accumulation. Additionally, false-negative brain metastases can be indicated as "other suspicious."

[0125] In addition, for brain metastases that were initially identified as false negatives, brain FDG-PET / CT imaging was performed (step S30). The results confirmed multiple brain metastases. Therefore, it was presumed that brain metastases were present in subject 4 (step S31). For sites that were identified as false negatives, the determination can be reconfirmed by performing further examinations.

[0126] The diagnostic aid device and diagnostic aid method according to the above-described embodiments can reduce false positives and false negatives when nuclear medicine imaging diagnosis is used alone, and can make more accurate diagnoses.

[0127] In addition, it can reduce the deviation in medical quality caused by the different proficiency levels of the interpreters of nuclear medicine imaging, and make the quality more uniform.

[0128] Furthermore, the diagnostic aid device and method of the implementation method only require imaging and blood sampling, which is minimally invasive. Therefore, it can reduce the burden on the examinee and medical personnel.

[0129] According to a further embodiment, the diagnostic aid device 1 may have further components in addition to the comparison unit 2 and the estimation unit 3. One example is... Figure 12 As shown in the diagram, the diagnostic aid device 100 includes, for example, a receiving unit 110, a processing unit 120 including a comparison unit 2 and an estimation unit 3, a storage unit 130, a display unit 140, and an input unit 150. These units are electrically connected via a bus 160.

[0130] The receiving unit 110 receives first site information 7 from the nuclear medicine imaging device 6 and second site information 12 from the molecular information comparison device 14. The received information is sent to the storage unit 130.

[0131] The storage unit 130 includes, for example, a non-volatile memory and a volatile memory, and stores the first part information 7 and the second part information 12 sent from the receiving unit 110, the comparison result 131 sent from the comparison unit 2, the estimation result 132 sent from the estimation unit 3, and the program P for performing comparison and estimation and controlling other units.

[0132] The processing unit 120 includes a comparison unit 2 and an estimation unit 3. The comparison unit 2 compares the first part information 7 and the second part information 12 according to program P, and sends the comparison result 131 to the storage unit 130. The estimation unit 3 retrieves the comparison result 131 stored in the storage unit 130 and performs an estimation based on the comparison result 131 according to program P. In addition, it sends the estimation result 132 to the storage unit 130.

[0133] The display unit 140 includes, for example, a monitor or printer, and displays or outputs the estimated result 132.

[0134] The input unit 150 may include, for example, a mouse, keyboard, touch panel, button, or scanner, for inputting references and estimated start and end times, or parameters required for various processes.

[0135] The diagnostic aid device 100 may also be integrated with the nuclear medicine imaging device 6 and / or the molecular information comparison device 14.

[0136] As described above, the diagnostic assistance procedure of the third embodiment, as a further embodiment, may be a procedure that performs part of, or the entirety of, the steps or processes described herein, or any combination thereof. For example, according to a further embodiment, a procedure is provided for presuming the location of a tumor in a subject. The procedure compares information on the aggregation site of a diagnostic drug obtained from nuclear medicine imaging of the subject as first site information, and information on the source site of exosomes containing the diagnostic drug collected from the subject as second site information (second site information), and presumes that a tumor exists at a site in the first site information that matches the second site information.

[0137] For example, the program may also include partitioning according to the conditions in Table 1 and / or Figure 8 The procedure described is compared and estimated.

[0138] According to at least one embodiment described above, the false negatives and false positives in nuclear medicine image diagnosis can be reduced. Furthermore, according to at least one embodiment described above, the quality of medical treatment can be homogenized.

[0139] Several embodiments have been described, but these embodiments are given by way of example and are not intended to limit the scope of the invention. These embodiments can be implemented in various other ways, and various omissions, substitutions, modifications, and combinations of embodiments are possible without departing from the spirit of the invention. These embodiments and their variations are included in the scope or spirit of the invention, as well as in the scope of the invention as described in the claims and its equivalents.

[0140] [Explanation of reference numerals in the attached figures]

[0141] 1… Diagnostic aid device, 2… Control unit, 3… Control unit, 4… Subject, 5… Diagnostic drug, 6… Nuclear medicine imaging device, 7… First information site, 8… Blood, 9… Exosome, 10… Exosome molecule, 11… Exosome molecule information, 12… Second site information, 13… Database, 14… Molecular information control device, 15… Control unit, 16… Cloud, 50… Cell, 100… Diagnostic aid device, 110… Receiving unit, 120… Processing unit, 130… Storage unit, 131… Control result, 132… Estimated result, 140… Display unit, 150… Input unit, 160… Bus, P… Program.

Claims

1. A diagnostic auxiliary device, comprising: The comparison section compares information from a first region with information from a second region. The first region information is information about the aggregation region of the diagnostic drug obtained from nuclear medicine imaging of the subject, and the second region information is information about the source region of the exosomes, which are collected from the subject and include the diagnostic drug. The presumption unit presumes regions in the first region information that are consistent with the second region information as areas where tumors exist; and The display unit shows the result of the comparison, which is the area in the first area information that is consistent with the second area information, i.e., the area where the tumor exists.

2. The diagnostic auxiliary device according to claim 1, wherein, The display unit, The region in the first region information that is consistent with the second region information is represented on the image obtained from the nuclear medicine camera, and a message is displayed indicating that the consistent region is presumed to be a tumor region.

3. The diagnostic auxiliary device according to claim 1, wherein, The information about the source region of the exosomes is information collected from the subject before the half-life of the diagnostic drug has elapsed.

4. The diagnostic auxiliary device according to claim 2, wherein, The display unit, The results for the control group show a positive result indicating the presence of tumors in regions included in both the first and second region information. The results for the control group show that areas included in the first region information but not included in the second region information are identified as false positives, indicating the presence of areas other than tumors. The results for the control group show false negatives indicating the presence of tumors in areas that are not included in the first region information but are included in the second region information.

5. A diagnostic assistance program product for causing a computer to perform the following steps: The information of the first region and the information of the second region are compared. The first region information is the information of the aggregation region of the diagnostic drug obtained from nuclear medicine imaging of the subject. The second region information is the information of the source region of the exosomes, which are collected from the subject and include the diagnostic drug. The results of the comparison are used to presume that the regions in the first region information that are consistent with the second region information are the regions where tumors are present; and The results of the comparison show that the area in the first area information that matches the second area information is the area where the tumor exists.

6. The diagnostic assistance program product according to claim 5, wherein, The collection was performed before the half-life of the diagnostic drug had elapsed.

7. The diagnostic assistance program product according to claim 5, wherein, The results of the comparison show that regions included in both the first and second region information are identified as positive for tumors and are displayed. The results of the comparison, which show regions included in the first region information but not included in the second region information, are determined to be false positives other than tumors and are displayed. The results of the comparison are used to identify areas that are not included in the first area information but are included in the second area information as false negatives indicating the presence of tumors, and these are then displayed.

8. A diagnostic aid method, comprising the following steps: The aggregation region information of the diagnostic drug aggregation area obtained from nuclear medicine imaging of the subject is compared with the source region information of the exosomes, including the diagnostic drug, included in the subject; The regions in the aggregation region information that are consistent with the source region information are presumed to be the regions where tumors exist. as well as The results of the comparison show that the regions in the aggregation region information that are consistent with the source region information are the regions where the tumor exists.

9. A diagnostic aid method, comprising the following steps: Obtain video images of subjects who have been given diagnostic drugs by using a nuclear medicine imaging device; Information about the region where the diagnostic drugs are concentrated, i.e., the first region information, is obtained from the obtained camera images; Exosomes containing the diagnostic drug were collected from the subject. Obtain the molecular information of the exosomes; The source region information of the exosomes, i.e., the second region information, is obtained from the molecular information of the exosomes; as well as Compare the information of the first region with the information of the second region. The regions in the first region information that are consistent with the second region information are presumed to be the regions where tumors exist. as well as The results of the comparison show that the area in the first area information that matches the second area information is the area where the tumor exists.

10. The diagnostic aid method according to claim 9, wherein, The collection was performed before the half-life of the diagnostic drug had elapsed.

11. The diagnostic aid method according to claim 9, wherein, The diagnostic drug is [ 18 F]FDG.

12. The diagnostic aid method according to claim 9, wherein, The second region information is obtained by comparing the molecular information of the exosome with the following information group, which is obtained by establishing an association between the molecular information of multiple exosomes stored in the database and the source region of the exosome.

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