JP7445599B2 - 高感度分子解析のための組成及び方法 - Google Patents
高感度分子解析のための組成及び方法 Download PDFInfo
- Publication number
- JP7445599B2 JP7445599B2 JP2020548972A JP2020548972A JP7445599B2 JP 7445599 B2 JP7445599 B2 JP 7445599B2 JP 2020548972 A JP2020548972 A JP 2020548972A JP 2020548972 A JP2020548972 A JP 2020548972A JP 7445599 B2 JP7445599 B2 JP 7445599B2
- Authority
- JP
- Japan
- Prior art keywords
- microbubbles
- region
- contrast
- image
- signal
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000000034 method Methods 0.000 title claims description 177
- 239000000203 mixture Substances 0.000 title description 16
- 238000007479 molecular analysis Methods 0.000 title 1
- 238000003384 imaging method Methods 0.000 claims description 148
- 230000008685 targeting Effects 0.000 claims description 75
- 210000001519 tissue Anatomy 0.000 claims description 69
- 239000002872 contrast media Substances 0.000 claims description 53
- 201000010099 disease Diseases 0.000 claims description 42
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 42
- 210000004165 myocardium Anatomy 0.000 claims description 41
- 230000002861 ventricular Effects 0.000 claims description 26
- 238000009825 accumulation Methods 0.000 claims description 19
- 239000008280 blood Substances 0.000 claims description 17
- 210000004369 blood Anatomy 0.000 claims description 17
- 210000002216 heart Anatomy 0.000 claims description 17
- 230000007423 decrease Effects 0.000 claims description 13
- 238000001914 filtration Methods 0.000 claims description 12
- 239000003147 molecular marker Substances 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 210000000481 breast Anatomy 0.000 claims description 9
- 230000008859 change Effects 0.000 claims description 9
- 210000003734 kidney Anatomy 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 238000009499 grossing Methods 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 2
- 230000001360 synchronised effect Effects 0.000 claims description 2
- 238000002604 ultrasonography Methods 0.000 description 54
- 239000003446 ligand Substances 0.000 description 32
- 241001465754 Metazoa Species 0.000 description 28
- 239000004094 surface-active agent Substances 0.000 description 23
- 230000027455 binding Effects 0.000 description 19
- 239000007789 gas Substances 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 108010035766 P-Selectin Proteins 0.000 description 16
- 102000008212 P-Selectin Human genes 0.000 description 16
- 208000028867 ischemia Diseases 0.000 description 16
- 229920001223 polyethylene glycol Polymers 0.000 description 15
- 230000001066 destructive effect Effects 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 230000003902 lesion Effects 0.000 description 14
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 239000006185 dispersion Substances 0.000 description 13
- 230000004044 response Effects 0.000 description 13
- 101000622137 Homo sapiens P-selectin Proteins 0.000 description 12
- 241000282472 Canis lupus familiaris Species 0.000 description 11
- 102100023472 P-selectin Human genes 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 11
- 230000006378 damage Effects 0.000 description 11
- 239000013642 negative control Substances 0.000 description 11
- 238000012285 ultrasound imaging Methods 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 9
- 150000002632 lipids Chemical class 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 9
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 238000009826 distribution Methods 0.000 description 8
- 210000002027 skeletal muscle Anatomy 0.000 description 8
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 7
- 206010063837 Reperfusion injury Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000006835 compression Effects 0.000 description 7
- 238000007906 compression Methods 0.000 description 7
- 238000011833 dog model Methods 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 230000000302 ischemic effect Effects 0.000 description 7
- 208000031225 myocardial ischemia Diseases 0.000 description 7
- 108090000765 processed proteins & peptides Proteins 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 230000002123 temporal effect Effects 0.000 description 7
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 6
- 230000001154 acute effect Effects 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 230000002209 hydrophobic effect Effects 0.000 description 6
- 150000003904 phospholipids Chemical class 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 238000012805 post-processing Methods 0.000 description 6
- 238000012545 processing Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 238000012800 visualization Methods 0.000 description 6
- 241000282412 Homo Species 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 230000021615 conjugation Effects 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 230000033001 locomotion Effects 0.000 description 5
- 229920001427 mPEG Polymers 0.000 description 5
- 230000003211 malignant effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000002107 myocardial effect Effects 0.000 description 5
- 230000002611 ovarian Effects 0.000 description 5
- 230000001023 pro-angiogenic effect Effects 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 4
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 4
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 4
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 4
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000006427 angiogenic response Effects 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 210000001715 carotid artery Anatomy 0.000 description 4
- XCJYREBRNVKWGJ-UHFFFAOYSA-N copper(II) phthalocyanine Chemical compound [Cu+2].C12=CC=CC=C2C(N=C2[N-]C(C3=CC=CC=C32)=N2)=NC1=NC([C]1C=CC=CC1=1)=NC=1N=C1[C]3C=CC=CC3=C2[N-]1 XCJYREBRNVKWGJ-UHFFFAOYSA-N 0.000 description 4
- 102000037865 fusion proteins Human genes 0.000 description 4
- 108020001507 fusion proteins Proteins 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 210000002796 renal vein Anatomy 0.000 description 4
- 230000010410 reperfusion Effects 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000002525 ultrasonication Methods 0.000 description 4
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 3
- 230000031016 anaphase Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 210000004351 coronary vessel Anatomy 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002961 echo contrast media Substances 0.000 description 3
- 238000002592 echocardiography Methods 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000001747 exhibiting effect Effects 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- -1 fatty acid ester Chemical class 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- 208000012947 ischemia reperfusion injury Diseases 0.000 description 3
- 239000002960 lipid emulsion Substances 0.000 description 3
- 230000031864 metaphase Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 229960004065 perflutren Drugs 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000527 sonication Methods 0.000 description 3
- 125000006850 spacer group Chemical group 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 description 3
- 230000001052 transient effect Effects 0.000 description 3
- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
- KWVJHCQQUFDPLU-YEUCEMRASA-N 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KWVJHCQQUFDPLU-YEUCEMRASA-N 0.000 description 2
- NITXODYAMWZEJY-UHFFFAOYSA-N 3-(pyridin-2-yldisulfanyl)propanehydrazide Chemical compound NNC(=O)CCSSC1=CC=CC=N1 NITXODYAMWZEJY-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 238000012935 Averaging Methods 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 2
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 2
- 239000004971 Cross linker Substances 0.000 description 2
- 239000012591 Dulbecco’s Phosphate Buffered Saline Substances 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 206010015866 Extravasation Diseases 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 108010040082 Junctional Adhesion Molecule A Proteins 0.000 description 2
- 206010027336 Menstruation delayed Diseases 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010061481 Renal injury Diseases 0.000 description 2
- 102000003800 Selectins Human genes 0.000 description 2
- 108090000184 Selectins Proteins 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 210000000577 adipose tissue Anatomy 0.000 description 2
- 230000003444 anaesthetic effect Effects 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000012754 cardiac puncture Methods 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000036251 extravasation Effects 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000000684 flow cytometry Methods 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 229940055390 glycerin / propylene glycol Drugs 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011503 in vivo imaging Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 208000037806 kidney injury Diseases 0.000 description 2
- 210000005240 left ventricle Anatomy 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 230000004089 microcirculation Effects 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 230000003285 pharmacodynamic effect Effects 0.000 description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 2
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 2
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 239000003440 toxic substance Substances 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 210000000689 upper leg Anatomy 0.000 description 2
- 238000009423 ventilation Methods 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 1
- YFWHNAWEOZTIPI-DIPNUNPCSA-N 1,2-dioctadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCCCC YFWHNAWEOZTIPI-DIPNUNPCSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- VYMHBQQZUYHXSS-UHFFFAOYSA-N 2-(3h-dithiol-3-yl)pyridine Chemical compound C1=CSSC1C1=CC=CC=N1 VYMHBQQZUYHXSS-UHFFFAOYSA-N 0.000 description 1
- 241000269350 Anura Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 240000006829 Ficus sundaica Species 0.000 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101000945318 Homo sapiens Calponin-1 Proteins 0.000 description 1
- 101000652736 Homo sapiens Transgelin Proteins 0.000 description 1
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102100022304 Junctional adhesion molecule A Human genes 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 108010054395 P-selectin ligand protein Proteins 0.000 description 1
- 241000282579 Pan Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 101001000212 Rattus norvegicus Decorin Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241001116459 Sequoia Species 0.000 description 1
- 102100031013 Transgelin Human genes 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 208000009729 Ventricular Premature Complexes Diseases 0.000 description 1
- 206010047289 Ventricular extrasystoles Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- FVJZSBGHRPJMMA-DHPKCYQYSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-octadecanoyloxypropyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-DHPKCYQYSA-N 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 229940008201 allegra Drugs 0.000 description 1
- 230000001668 ameliorated effect Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 108010045325 cyclic arginine-glycine-aspartic acid peptide Proteins 0.000 description 1
- 150000001923 cyclic compounds Chemical group 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 150000001945 cysteines Chemical group 0.000 description 1
- 108091007930 cytoplasmic receptors Proteins 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- FVJZSBGHRPJMMA-UHFFFAOYSA-N distearoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-UHFFFAOYSA-N 0.000 description 1
- 238000004945 emulsification Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 229920005570 flexible polymer Polymers 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 102000055590 human KDR Human genes 0.000 description 1
- 102000058223 human VEGFA Human genes 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000005865 ionizing radiation Effects 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 1
- 238000004137 mechanical activation Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000008155 medical solution Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000005063 microvascular endothelium Anatomy 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 239000002101 nanobubble Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- KAVGMUDTWQVPDF-UHFFFAOYSA-N perflubutane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)F KAVGMUDTWQVPDF-UHFFFAOYSA-N 0.000 description 1
- 229950003332 perflubutane Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920001308 poly(aminoacid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000001542 size-exclusion chromatography Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- ALPWRKFXEOAUDR-GKEJWYBXSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)([O-])=O)OC(=O)CCCCCCCCCCCCCCCCC ALPWRKFXEOAUDR-GKEJWYBXSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- JJAHTWIKCUJRDK-UHFFFAOYSA-N succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate Chemical compound C1CC(CN2C(C=CC2=O)=O)CCC1C(=O)ON1C(=O)CCC1=O JJAHTWIKCUJRDK-UHFFFAOYSA-N 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 229920003176 water-insoluble polymer Polymers 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/48—Diagnostic techniques
- A61B8/481—Diagnostic techniques involving the use of contrast agent, e.g. microbubbles introduced into the bloodstream
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
- A61B8/0891—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of blood vessels
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
- A61B8/0833—Detecting organic movements or changes, e.g. tumours, cysts, swellings involving detecting or locating foreign bodies or organic structures
- A61B8/085—Detecting organic movements or changes, e.g. tumours, cysts, swellings involving detecting or locating foreign bodies or organic structures for locating body or organic structures, e.g. tumours, calculi, blood vessels, nodules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/08—Detecting organic movements or changes, e.g. tumours, cysts, swellings
- A61B8/0883—Detecting organic movements or changes, e.g. tumours, cysts, swellings for diagnosis of the heart
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/44—Constructional features of the ultrasonic, sonic or infrasonic diagnostic device
- A61B8/4416—Constructional features of the ultrasonic, sonic or infrasonic diagnostic device related to combined acquisition of different diagnostic modalities, e.g. combination of ultrasound and X-ray acquisitions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/46—Ultrasonic, sonic or infrasonic diagnostic devices with special arrangements for interfacing with the operator or the patient
- A61B8/461—Displaying means of special interest
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/52—Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves
- A61B8/5215—Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves involving processing of medical diagnostic data
- A61B8/5223—Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves involving processing of medical diagnostic data for extracting a diagnostic or physiological parameter from medical diagnostic data
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
- G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
- G16H50/30—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indices; for individual health risk assessment
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Medical Informatics (AREA)
- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Pathology (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Biophysics (AREA)
- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Acoustics & Sound (AREA)
- Vascular Medicine (AREA)
- Databases & Information Systems (AREA)
- Primary Health Care (AREA)
- Data Mining & Analysis (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Physiology (AREA)
- Computer Vision & Pattern Recognition (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
Description
a.単一の視野を示す時系列の画像を提供し、
b.1つ又は複数の関心領域及び1つ又は複数の対応する参照領域を選択し、
c.参照スケーリングされた画像及び/又は参照スケーリングされた信号強度を生成し、前記関心領域及び参照領域は前記時系列内の同じ瞬間に取得され、
d.参照スケーリングされた前記信号強度の時間強度関係を定量的に判定するために前記時系列内の2つ以上の画像に対して(c)のスケーリング処理を実行し、参照スケーリングされた前記信号は前記罹患領域で増加し非罹患領域で減少する、ことを含む
超音波を用いたコントラストイメージング
標的結合マイクロバブルの検出
後期におけるイメージング
バーストリフィルイメージング
動きに基づく方法及びフィルタリング法
動的スケーリング
参照スケーリングされた画像の生成
I*a、b(t)=Ia、b(t)/Iref(t)
ケーリングされた画像は、画像内の画素毎にIa、b(t)をI*a、b(t)で置き換えることにより生成される。この処理は参照領域のピーク信号と関心領域内のコントラスト信号の完全な損失の間の一時点又は各時点で実行してもよい。
比率画像の生成
I**a、b(t)=[I*a、b(t2)-I*a、b(t1)]/[t2―t1]
ここで、I*a、b(t)は時点tにおける画素(a、b)のスケーリングされたコントラスト信号強度、t1は参照領域のピーク信号が達成される時点、t2はt1と関心領域からのコントラストの除去の間の任意の時点である。
実験
線形化
7.イメージング条件
8. コントラスト剤(例えば、マイクロバブル)の調製に関する考察
定義
実施例
実施例1.脂質エマルジョンの調製
実施例2.超音波処理による典型的なマイクロバブルの調製
実施例3.振盪による典型的なマイクロバブルの調製
実施例4.典型的な標的指向性マイクロバブルの一工程調製
実施例5.典型的な標的指向性マイクロバブルの2工程調製
実施例6.典型的なP-セレクチンを標的とするマイクロバブルの調製
実施例7:イヌ心筋におけるP-セレクチンのイメージング
実施例8:典型的なマイクロバブルの調製
実施例9:ヒトの心筋における急性虚血再灌流損傷のイメージング
実施例10:ヒトにおける虚血後腎臓損傷の検出
実施例11:ヒトにおける不安定なアテローム性動脈硬化性プラークの検出
実施例12:卵巣病変の特定
実施例13:ヒトにおける悪性***病変の特定
実施例14:ヒトにおける血管新生療法に対する反応の評価
Claims (27)
- 関心領域(ROI)内のコントラスト信号の強度を定量化する方法であって、
被験者の標的組織の血液プール内を循環する標的指向性のコントラスト剤の量を示す参照領域を動的スケーリング時間変動式手順で選択し、
選択された前記参照領域を含む前記標的組織をイメージングし、
前記動的スケーリング時間変動式手順で罹患領域の強度を定量的に判定することを含み、
前記標的指向性コントラスト剤は前記罹患領域内で発現された前記疾患の1つ又は複数の分子マーカーに結合されるように構成され、
前記動的スケーリング時間変動式手順は、
a.単一の視野を示す時系列の画像を提供し、
b.1つ又は複数の関心領域及び1つ又は複数の対応する参照領域を選択し、
c.参照スケーリングされた画像及び/又は参照スケーリングされた信号強度を生成し、前記関心領域及び参照領域は前記時系列内の同じ瞬間に取得され、
d.参照スケーリングされた前記信号強度の時間強度関係を定量的に判定するために前記時系列内の2つ以上の画像に対して(c)のスケーリング処理を実行し、参照スケーリングされた前記信号は前記罹患領域で増加し非罹患領域で減少する、方法。 - 前記参照領域及び関心領域について同期した別々の画像シーケンスが取得される、請求項1に記載の方法。
- 動的にスケーリングされた画像内の各画素の値を定数でスケーリングすることを含む、請求項1に記載の方法。
- 前記手順は線形化された音響出力の単位で実行される、請求項1に記載の方法。
- 前記手順は線形化された音響振幅の単位で実行される、請求項1に記載の方法。
- 動的にスケーリングされた前記画像又は動的にスケーリングされた前記画像の変化率に由来する比率画像を色分けすることを更に含む、請求項1に記載の方法。
- 動的にスケーリングされた前記画像にローパスフィルタをかけることにより平滑化を行うことを更に含む、請求項1に記載の方法。
- 動的にスケーリングされた前記画像を非線形に圧縮することを更に含む、請求項1に記載の方法。
- 前記参照領域はマイクロバブルの蓄積がごく僅かか全く起こらない領域と定義される、請求項1に記載の方法。
- 参照スケーリングされた前記コントラスト信号の強度は、前記参照領域のピーク信号と除去との間のいくつかの時点において1つ又は複数の標的領域内で算出される、請求項1に記載の方法。
- 参照スケーリングされた前記コントラスト信号の強度はピーク信号において及びその後の関心時点において算出され、前記ピーク信号の時点とその後の前記関心時点と間の平均勾配が算出される、請求項1に記載の方法。
- 前記標的指向性コントラスト剤は、0.1umと2.0umとの間、0.2umと2.0umとの間、0.3umと2.0umとの間、0.4umと2.0umとの間、0.5umと2.0umとの間、0.6umと2.0umとの間、又は0.7umと2.0umとの間の数量平均直径を有するマイクロバブルである、請求項1に記載の方法。
- 前記標的指向性コントラスト剤は、0.7umと2.0umとの間の数量平均直径を有するマイクロバブルである、請求項1に記載の方法。
- 前記標的指向性コントラスト剤はマイクロバブルである、請求項1に記載の方法。
- 被験者内の疾患領域の強度を表示する方法であって、
1~10分間前記被験者内の視野をイメージングしかつコンピュータ可読媒体に一連の画像を保存し、
取得された前記時系列の画像に対し請求項1に記載の動的スケーリング時間変動式手順を実行し、
スケーリングされた前記一連の画像又は時間強度曲線などのスケーリングされた信号グラフをユーザに表示することを含む方法。 - 前記視野は心臓、腎臓、肝臓、胸部、腫瘍、または前立腺を含む、請求項15に記載の方法。
- 前記視野は心臓を含む、請求項16に記載の方法。
- 左室腔が参照領域であり、心筋が標的領域である、請求項16に記載の方法。
- 線形化された前記コントラスト信号に対して動的スケーリング手順が行われる、請求項18に記載の方法。
- 標的組織内のコントラスト剤に結合するように構成された関心分子マーカーのレベルを判定するために用いられる動的スケーリング時間変動式手順であって、
a.経時的に前記標的組織の一連の画像を取り込み、
b.前記画像内で標的指向コントラスト剤信号を有する標的領域を選択し、
c.前記画像内で標的指向コントラスト剤信号を有しないが循環するコントラスト剤信号を有する関心参照領域を選択し、
d.前記関心参照領域の信号強度を用いて各時点における前記標的領域の信号強度をスケーリングし、
e.前記各時点における前記標的組織の参照スケーリングされた画像又は強度を生成し、
f.参照スケーリングされた前記画像又は強度を用いて前記標的組織内の前記関心分子マーカーのレベルを判定することを含む手順。 - 前記手順は線形化された音響出力の単位で実行される、請求項20に記載の手順。
- 前記手順は線形化された音響振幅の単位で実行される、請求項20に記載の手順。
- 動的にスケーリングされた前記画像の変化率に由来する画像を含み動的にスケーリングされた前記画像を色分けすることを更に含む、請求項20に記載の手順。
- 動的にスケーリングされた前記画像にローパスフィルタをかけることにより平滑化を行うことを更に含む、請求項20に記載の手順。
- 動的にスケーリングされた前記画像を非線形に圧縮することを更に含む、請求項20に記載の手順。
- 参照スケーリングされた前記信号強度は、前記関心参照領域のピーク信号と除去との間のいくつかの時点において1つ又は複数の前記標的領域内で算出される、請求項20に記載の手順。
- 参照スケーリングされた前記信号強度はピーク信号において及びその後の関心時点において算出され、前記ピーク信号の時点とその後の前記関心時点と間の平均勾配が算出される、請求項20に記載の手順。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201862642017P | 2018-03-13 | 2018-03-13 | |
PCT/IB2019/000242 WO2019175664A1 (en) | 2018-03-13 | 2019-03-13 | Composition and methods for sensitive molecular analysis |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022513542A JP2022513542A (ja) | 2022-02-09 |
JP7445599B2 true JP7445599B2 (ja) | 2024-03-07 |
Family
ID=67907605
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020548972A Active JP7445599B2 (ja) | 2018-03-13 | 2019-03-13 | 高感度分子解析のための組成及び方法 |
Country Status (5)
Country | Link |
---|---|
US (2) | US11766243B2 (ja) |
EP (1) | EP3764878A4 (ja) |
JP (1) | JP7445599B2 (ja) |
CN (1) | CN111902074A (ja) |
WO (1) | WO2019175664A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP3777699A4 (en) * | 2018-03-30 | 2021-05-26 | FUJIFILM Corporation | ULTRASONIC DIAGNOSTIC DEVICE AND CONTROL METHOD FOR ULTRASONIC DIAGNOSTIC DEVICE |
EP4076211A2 (en) * | 2019-12-18 | 2022-10-26 | Insightec Ltd. | Systems and methods for providing tissue information in an anatomic target region using acoustic reflectors |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014138761A (ja) | 2012-12-18 | 2014-07-31 | Toshiba Corp | 超音波診断装置、画像処理装置及び画像処理方法 |
JP2016501599A (ja) | 2012-12-21 | 2016-01-21 | ブラッコ・シュイス・ソシエテ・アノニムBracco Suisse SA | 時間に対する統計的分析に基づく画像診断応用におけるセグメンテーション |
JP2017527355A (ja) | 2014-12-18 | 2017-09-21 | コーニンクレッカ フィリップス エヌ ヴェKoninklijke Philips N.V. | 超音波撮像システム及び方法 |
JP2018086075A (ja) | 2016-11-28 | 2018-06-07 | 株式会社日立製作所 | 超音波画像処理装置 |
JP2018536460A (ja) | 2015-12-10 | 2018-12-13 | ブラッコ・シュイス・ソシエテ・アノニムBracco Suisse SA | ダイナミック閾値を有する固定化造影剤の検出 |
Family Cites Families (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10064768B4 (de) * | 2000-12-22 | 2006-12-07 | Siemens Ag | Verfahren zur Untersuchung eines Lebewesens mittels eines bildgebenden Verfahrens |
JP4706003B2 (ja) * | 2003-06-12 | 2011-06-22 | ブラッコ・シュイス・ソシエテ・アノニム | 超音波造影画像において補充曲線フィッティングを用いる血流評価法 |
US9545237B2 (en) * | 2007-02-27 | 2017-01-17 | Koninklijke Philips N.V. | Method and device for recording a vascular struture during intervention |
US8493306B2 (en) | 2007-09-06 | 2013-07-23 | Himax Technologies Limited | Source driver and method for restraining noise thereof |
WO2009083557A1 (en) * | 2007-12-28 | 2009-07-09 | Bracco Research S.A. | Quantification analisys of immobilized contrast agent in medical imaging applications |
US9042967B2 (en) * | 2008-05-20 | 2015-05-26 | University Health Network | Device and method for wound imaging and monitoring |
US20110208061A1 (en) * | 2008-11-11 | 2011-08-25 | Koninklijke Philips Electronics N.V. | Ultrasonic lesion identification using temporal parametric contrast images |
EP2419020A4 (en) * | 2009-04-17 | 2014-01-15 | Visualsonics Inc | METHOD FOR NONLINEAR IMAGING OF ULTRASONIC CONTRASTING AT HIGH FREQUENCIES |
US8493406B2 (en) | 2009-06-19 | 2013-07-23 | Microsoft Corporation | Creating new charts and data visualizations |
GB2498519A (en) * | 2012-01-11 | 2013-07-24 | Univ Erasmus Medical Ct | Ultrasound imaging |
GB2509168B (en) * | 2012-12-21 | 2020-04-01 | James Shue Min Yeh | Method of quantifying the characteristics of an object treated with a contrast agent |
KR101595795B1 (ko) * | 2014-03-19 | 2016-02-22 | (주)아이엠지티 | 약물을 함유한 나노입자가 결합된 이중-목적 pat/초음파 조영제 및 이의 제조방법 |
CN115919256A (zh) * | 2014-07-24 | 2023-04-07 | 大学健康网络 | 用于诊断目的的数据的收集和分析 |
CN107207379B (zh) * | 2014-11-25 | 2021-08-10 | 百时美施贵宝公司 | 用于生物制品的18f-放射性标记的方法和组合物 |
CN105727318A (zh) * | 2014-12-09 | 2016-07-06 | 中国科学院苏州纳米技术与纳米仿生研究所 | 靶向间充质干细胞的多肽分子影像探针、其制备方法及由该探针标记的间充质干细胞 |
CN106456108A (zh) * | 2015-08-10 | 2017-02-22 | 深圳迈瑞生物医疗电子股份有限公司 | 超声弹性成像***和方法 |
US11185361B2 (en) * | 2015-10-12 | 2021-11-30 | Landy Toth | Controlled and precise treatment of cardiac tissues |
WO2018045222A1 (en) * | 2016-08-31 | 2018-03-08 | The Regents Of The University Of California | Ultrasound responsive micro-composite markers |
SG11201908827YA (en) * | 2017-03-24 | 2019-10-30 | Burl Concepts Inc | Portable ultrasound device |
US20190154822A1 (en) * | 2017-11-21 | 2019-05-23 | The Charles Stark Draper Laboratory, Inc. | System and method for imaging and localization of contrast-enhanced features in the presence of accumulating contrast agent in a body |
-
2019
- 2019-03-13 WO PCT/IB2019/000242 patent/WO2019175664A1/en unknown
- 2019-03-13 CN CN201980019188.5A patent/CN111902074A/zh active Pending
- 2019-03-13 EP EP19767195.1A patent/EP3764878A4/en active Pending
- 2019-03-13 JP JP2020548972A patent/JP7445599B2/ja active Active
- 2019-03-13 US US16/980,416 patent/US11766243B2/en active Active
-
2023
- 2023-05-08 US US18/144,244 patent/US20230270413A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2014138761A (ja) | 2012-12-18 | 2014-07-31 | Toshiba Corp | 超音波診断装置、画像処理装置及び画像処理方法 |
JP2016501599A (ja) | 2012-12-21 | 2016-01-21 | ブラッコ・シュイス・ソシエテ・アノニムBracco Suisse SA | 時間に対する統計的分析に基づく画像診断応用におけるセグメンテーション |
JP2017527355A (ja) | 2014-12-18 | 2017-09-21 | コーニンクレッカ フィリップス エヌ ヴェKoninklijke Philips N.V. | 超音波撮像システム及び方法 |
JP2018536460A (ja) | 2015-12-10 | 2018-12-13 | ブラッコ・シュイス・ソシエテ・アノニムBracco Suisse SA | ダイナミック閾値を有する固定化造影剤の検出 |
JP2018086075A (ja) | 2016-11-28 | 2018-06-07 | 株式会社日立製作所 | 超音波画像処理装置 |
Also Published As
Publication number | Publication date |
---|---|
US11766243B2 (en) | 2023-09-26 |
CN111902074A (zh) | 2020-11-06 |
EP3764878A4 (en) | 2022-03-09 |
US20210000448A1 (en) | 2021-01-07 |
WO2019175664A1 (en) | 2019-09-19 |
EP3764878A1 (en) | 2021-01-20 |
JP2022513542A (ja) | 2022-02-09 |
US20230270413A1 (en) | 2023-08-31 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Wang et al. | Targeting of microbubbles: contrast agents for ultrasound molecular imaging | |
US8275449B2 (en) | Overlay image contrast enhancement | |
Agrawal et al. | Chitosan-based systems for molecular imaging | |
US6444192B1 (en) | Diagnostic imaging of lymph structures | |
Klibanov | Ultrasound molecular imaging with targeted microbubble contrast agents | |
Greis | Ultrasound contrast agents as markers of vascularity and microcirculation | |
Calliada et al. | Ultrasound contrast agents: basic principles | |
Harvey et al. | Developments in ultrasound contrast media | |
Chertok et al. | Circulating magnetic microbubbles for localized real-time control of drug delivery by ultrasonography-guided magnetic targeting and ultrasound | |
Liu et al. | Nanoparticles as image enhancing agents for ultrasonography | |
US20230270413A1 (en) | Composition and methods for sensitive molecular analysis | |
JP6430958B2 (ja) | 造影剤で処置した物体の特徴を定量化する方法 | |
Liao et al. | Evaluation of 18F-labeled targeted perfluorocarbon-filled albumin microbubbles as a probe for microUS and microPET in tumor-bearing mice | |
Villanueva | Molecular imaging of cardiovascular disease using ultrasound | |
Novell et al. | Ultrasound contrast imaging in cancer–technical aspects and prospects | |
Sirlin et al. | Effect of acquisition rate on liver and portal vein enhancement with microbubble contrast | |
EP2934599B1 (en) | Microparticle compositions | |
Kaufmann et al. | High-resolution myocardial perfusion imaging in mice with high-frequency echocardiographic detection of a depot contrast agent | |
Kiessling et al. | Molecular ultrasound imaging and its potential for paediatric radiology | |
Hughes et al. | Perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics | |
Klibanov | Targeted microbubbles: ultrasound contrast agents for molecular imaging | |
KR20140065763A (ko) | 간 종양 표적화 초음파 조영제 및 그 제조방법 | |
Schneider | Ultrasound Contrast Agents | |
Uchimoto et al. | Comparison of the efficacy of two air-based contrast agents in dogs | |
Yeh et al. | Molecular imaging of inflammation using echocardiography. advances with the use of microbubbles |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220310 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20220309 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220422 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230131 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230202 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230501 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230607 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20230905 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20231102 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240122 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20240202 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20240226 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7445599 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |