WO2004105802A1 - Traceur d'imagerie medicale - Google Patents

Traceur d'imagerie medicale Download PDF

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Publication number
WO2004105802A1
WO2004105802A1 PCT/IB2004/050704 IB2004050704W WO2004105802A1 WO 2004105802 A1 WO2004105802 A1 WO 2004105802A1 IB 2004050704 W IB2004050704 W IB 2004050704W WO 2004105802 A1 WO2004105802 A1 WO 2004105802A1
Authority
WO
WIPO (PCT)
Prior art keywords
tracer
micro
bubbles
imaging system
visible
Prior art date
Application number
PCT/IB2004/050704
Other languages
English (en)
Inventor
Ingwer Carlsen
Original Assignee
Philips Intellectual Property & Standards Gmbh
Koninklijke Philips Electronics N.V.
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Philips Intellectual Property & Standards Gmbh, Koninklijke Philips Electronics N.V. filed Critical Philips Intellectual Property & Standards Gmbh
Publication of WO2004105802A1 publication Critical patent/WO2004105802A1/fr

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Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1217—Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols

Definitions

  • the present invention relates to the field of medical imaging.
  • the present invention relates to a tracer which may be used for medical imaging and may be suitable for introduction into a bloodstream of a subject, to a tracer suitable for delivery to a region of interest, to a method of imaging a tracer and to the use of a tracer for medical imaging.
  • Ultrasonic imaging has a wide application in the field of medical practice.
  • Ultrasonic diagnostics refers to the imaging of a region of the human or animal patient or any kind of mammal using an ultrasound transducer to generate and receive ultrasound waves.
  • the transducer is placed on the patient's body over the region to be imaged and high frequency sound waves are generated by the transducer and directed at the region.
  • the transducer receives reflected ultrasonic waves from the region and converts the received waves into electrical signals, from which an image may be generated.
  • contrast means comprising gas bubbles with and without encapsulating shells may be used to improve the quality of ultra-sound images by high-lighting the blood pool and the vascular profusion of organs within the body.
  • US 2002/0151792 Al describes a method for site specific delivering therapeutic or diagnostic agents to a region in a fluid-filled cavity, vessel or tissue using an agent-loaded micro-bubble population.
  • the population has controlled fragility characterized by a uniform wall thickness to diameter ratio which defines the discrete threshold intensity value of ultrasonic power, where micro-bubble rupture occurs in the population.
  • the location of the micro-bubble population may be monitored by ultrasound to determine its presence at the region prior to application of the ultrasonic power to rupture micro-bubbles. Thus, an image generated or reconstructed from these ultrasound readings shows these micro-bubbles such that a location of the micro- bubbles can be detected.
  • the above object may be solved with a tracer comprising micro-bubbles visible in ultrasound imaging.
  • the micro-bubbles may have a structure and materials such as, for example, disclosed in the US 2002/0151792 Al, which is hereby incorporated by reference.
  • the micro-bubbles contain a contrast agent, which is visible in images registered by means of a nuclear medical imaging system.
  • the tracer may be suitable for introduction into a blood stream of a subject, such as a patient, animal or mammal.
  • this exemplary embodiment of the present invention allows for the registration and fusion of ultrasound with nuclear images within a common reference system.
  • This tracer is applicable in combination with any two- or three-dimensional dataset which is generated by nuclear medical imaging systems, such as, for example, PET or SPECT to be combined with corresponding datasets by ultrasound imaging systems.
  • the micro-bubbles have a controlled fragility, corresponding to a threshold of ultrasonic energy, such that, when an ultrasonic energy supplied to the micro-bubbles which exceeds the threshold, the rupture of the micro-bubbles occurs and the contrast agent, i.e. a radio-pharmaceutical visible in nuclear medical devices is released from the micro-bubbles.
  • the contrast agent i.e. a radio-pharmaceutical visible in nuclear medical devices is released from the micro-bubbles.
  • a transport of the radio-pharmaceutical to a region of interest can easily be carried out. Then, when the micro-bubbles are destroyed or ruptured, the contrast agent is released directly in the region of interest.
  • Such localized release of the contrast agent or radio-pharmaceutical reduces the tracer up-take outside the region of interest and leads to less background signal and thus to an improved image quality. Furthermore, advantageously, the localized release of the radio-pharmaceutical reduces the radiation dose for a patient.
  • Claims 3 and 4 provide for further exemplary embodiments of the tracer according to the present invention.
  • a tracer is provided suitable for delivery to a region of interest by, for example, a bloodstream of a subject.
  • the tracer is visible in an ultrasound image and in a nuclear medical image.
  • a tracer which can be detected by means of ultrasound imaging systems and nuclear medical imaging systems and thus provides for a cross-modality fusion of ultrasound with nuclear medical images.
  • Claim 6 provides for another exemplary embodiment of the tracer according to the present invention.
  • a method of imaging a tracer is provided, wherein the tracer is firstly imaged by means of an ultrasound imaging system and then imaged by means of a nuclear medical imaging system, thereby allowing for a cross-modality fusion of ultrasound with nuclear medical images within a common reference system.
  • this allows a geometrically correct combination of contrasts visible in either one of the modalities and thereby improves the information content of the combined image of both modalities.
  • this advantageously may allow for the assignment of active tumors (hot spots) to anatomical details visible in the ultrasound images.
  • this may allow, for example, the targeting of biopsies directly to the tumor centers by the use of ultrasound and nuclear imaging.
  • ultrasonic energy is applied to the micro-bubbles such that the micro- bubbles are ruptured and the contrast agent provided in the micro-bubbles is released.
  • this allows for a precise delivery of the contrast agent to the region of interest and thereby prevents the up-take of the contrast agent by tissue outside the region of interest.
  • this also reduces the radiation dose applied to a patient.
  • the localized release of the contrast agent leads to less background signal in the images since the contrast agent is released in the region of interest only.
  • the ultrasound image and the nuclear medical image are overlaid to form a composite image allowing for the presentation of details only visible in ultrasonic images and details only visible in nuclear medical images in a combined manner in a common reference system.
  • the tracer is introduced into a bloodstream of a subject such as a human or a mammal.
  • a subject such as a human or a mammal.
  • Another exemplary embodiment of the present invention as set forth in claim 11 relates to the use of a tracer for medical imaging.
  • the tracer uses micro-bubbles that can be imaged by ultrasound, which contain radio-pharmaceuticals visible in nuclear medical imaging devices.
  • this tracer allows to turn the vascular structure visible for ultrasound and nuclear imaging devices and thus allows for the registration of ultrasound and nuclear data to a common reference. Furthermore, it allows for the transport of the radio-pharmaceuticals to a target area but prevents the up-take thereof outside a region of interest until the micro-bubbles are destroyed or ruptured and thereby leads to a reduced background signal.
  • Fig. 1 shows a first exemplary embodiment of a tracer according to the present invention.
  • Fig. 2 shows a flowchart describing the use of the tracer of Fig. 1 according to an exemplary embodiment of the present invention.
  • Fig. 3 shows a second exemplary embodiment of a micro-bubble of a tracer according to the present invention.
  • Fig. 4 shows an exemplary embodiment of the use of the tracer of Fig. 3 according to the present invention.
  • Fig. 1 shows a simplified graphic representation of a tracer according to a first exemplary embodiment of the present invention.
  • the tracer comprises a plurality of micro-bubbles 2.
  • these micro-bubbles 2 are visible in an ultrasound image registered by means of an ultrasound imaging system and are furthermore visible in a nuclear medical image registered by means of a nuclear medical imaging system such as, for example, PET or SPECT.
  • the micro-bubbles may comprise a radio pharmaceutical such as, e.g.
  • the micro-bubbles 2 are designed such that they are suitable for introduction into a bloodstream of a subject, for example of a patient.
  • the micro-bubbles may have diameters within the range of about 1 to 10 microns. Details with respect to the material of the micro-bubbles and the construction of the micro-bubbles may, for example, be taken from US 2002/0151792 Al, which is hereby incorporated by reference.
  • Fig. 2 shows a flowchart of a use of the tracer of Fig. 1 according to an exemplary embodiment of the present invention.
  • the method continues to step S2 where the tracer is applied to the subject.
  • the tracer is introduced into the bloodstream of a person.
  • the method continues to step S3, where the tracer is transported to the region of interest, i.e. the region to be examined.
  • the transport of the tracer may be carried out by means of the bloodstream of the patient.
  • the method continues to step S4, where, by means of an ultrasound imaging system, the ultrasound image is registered.
  • step S4 On the ultrasound image registered in step S4, the tracer is visible in the region of interest. Then, the method continues to step S5, where the nuclear medical image is registered by means of a nuclear medical imaging system. In the nuclear medical image, the tracer applied in step S2 is visible. Steps S4 and S5 may be carried out in separate ultrasound imaging systems and nuclear medical imaging systems in timely succession. However, in case, for example, a diagnostic hybrid probe such as the one disclosed in US 6, 212,423 Bl, which is hereby incorporated by reference, is used, steps S4 and S5 can also be carried out in one and the same medical imaging system, comprising a scintillator and an ultrasonic sensor. With such a device, steps S4 and S5 can also be carried out at the same time.
  • a diagnostic hybrid probe such as the one disclosed in US 6, 212,423 Bl, which is hereby incorporated by reference
  • step S6 the ultrasound image and the nuclear medical image are overlaid to form a composite image.
  • this allows for the cross-modality fusion of ultrasound with nuclear medical images.
  • a physician to, for example, see a position of tumors visible in the nuclear medical image with respect to anatomical structures such as bones, visible in the ultrasound image.
  • the composite image may be output to a user via a suitable display or output means.
  • step S7 the method continues to step S7, where it ends.
  • the above described method is applicable to any two or three- dimensional nuclear medical imaging systems, such as PET and or SPECT in combination with an ultrasound imaging system.
  • Fig. 3 shows a micro-bubble of a tracer according to a second exemplary embodiment of the present invention.
  • the micro-bubble 4 shown in Fig. 3 comprises a cavity 6.
  • the wall 8 of the micro-bubble 4 has a controlled fragility such that a rupture can be created in the wall 8 by means of a predetermined ultrasound energy.
  • the cavity 6 of the micro-bubble 4 contains a contrast agent 10 visible in nuclear medical imaging, such as a radio-pharmaceutical.
  • a radio-pharmaceutical may be, e.g.
  • isotopes 18 F, U C, 13 N or 15 0 for PET in compounds like, for example, 18 F-FDG (fluor deoxy glucose), ⁇ C-acetate and ⁇ C-methionine, 13 N-NH 3 and H 2 15 0, or Tc -99 m for SPECT.
  • 18 F-FDG fluor deoxy glucose
  • ⁇ C-acetate and ⁇ C-methionine 13 N-NH 3 and H 2 15 0, or Tc -99 m for SPECT.
  • the cavity 6, apart from containing the contrast agent 10 may contain air or other suitable gas allowing for sufficient compressibility and oscillation capability of the micro-bubble 4 in case it is subjected to ultrasound.
  • the air or gas in the wall 8 of the micro-bubble 4.
  • the wall 8 may be made of a lipid material.
  • the contrast agent 10 may also be comprised in the wall 8 of the micro-bubble 4 or may be attached to an outside of the wall 8 of the micro-bubble 4.
  • the micro-bubble 4 shown in Fig. 3 may have the same size, construction and design as the micro-bubbles 2 described with reference to Fig. 1.
  • a plurality or a population of micro-bubbles 4 form the tracer according to the present invention.
  • the tracer may comprise gas-filled microspheres or liposomes containing the contrast agent visible in nuclear medical imaging.
  • the contrast agent may be located in cavities of the microspheres or liposomes, in the walls or may be attached to an outside of the walls of the microspheres or liposomes.
  • the contrast agent may be arranged in the microspheres or liposomes in the same manner as the therapeutic compounds of the therapeutic drug delivery system disclosed in the US 5,580,575, which is hereby incorporated by reference.
  • the composition of the walls of the microspheres or liposomes according to this exemplary embodiment of the present invention may be the same as of the microspheres or liposomes comprising the therapeutic compounds of the therapeutic drug delivery system disclosed in the US 5,580,575, which is hereby incorporated by reference.
  • the gas-filled microspheres or liposomes are visible in ultrasound imaging.
  • Fig. 4 shows the use of the tracer with the micro-bubbles shown in Fig. 3 according to an exemplary embodiment of the present invention.
  • the tracer is applied to the bloodstream of a patient.
  • step SI 2 by means of the bloodstream of the patient, the tracer is transported to the region of interest of the patient to be examined.
  • step S13 where the ultrasound image data is registered by means of an ultrasound imaging system.
  • step S14 where a query is made with respect to whether nuclear imaging is required or not. For example, this decision in step S14 can be made on the basis of whether there is a suspicious element or shape in the ultrasound image acquired in step S13. In case it is determined in step S14 that no nuclear imaging is required, the method directly continues to step SI 8.
  • step S14 the method continues to step SI 5, where an ultrasonic energy is applied to the region of interest.
  • an ultrasonic energy exceeding the rupture threshold of the micro-bubbles 4 in the tracer is applied such that the wall 8 of the micro-bubbles 4 ruptures and the contrast agent, i.e. the radio-pharmaceutical is released in step S16.
  • step S17 where a nuclear medical image is acquired or registered by means of a nuclear medical imaging system, such as, for example, PET or SPECT.
  • step SI 8 where a query is made, whether an overlaying of the nuclear medical image and the ultrasound image acquired or registered in step S13 is desired and possible.
  • An overlaying of both images is, for example, not possible in case no nuclear imaging was acquired in step S14.
  • the overlaying of the nuclear medical image and the ultrasound image may be desired and advantageous in case, for example, a suspicious region is determined in the ultrasound image where a physician was not sure whether it corresponded to an image artifact or to a shape of a tumor.
  • the examination of the region of interest with the nuclear medical imaging system allows for a further examination of the region of interest and in this case allows for the imaging of the tumor.
  • An overlaying of both images then advantageously shows the position of the tumor with respect to anatomic structures such as, for example, bones of the patient.
  • the above method turns the vascular structure visible for ultrasound and nuclear imaging devices and thus allows for the registration of ultrasound and nuclear data in a common reference system. Furthermore, the transport of the radio-pharmaceutical to the region of interest within the micro-bubbles and the localized release of the radio-pharmaceutical in the region of interest prevents the uptake of the radio-pharmaceutical outside the region of interest. Due to this localized release of the radio-pharmaceuticals, the tracer up-take outside the region of interest is reduced, which leads to a reduced background signal and thus to a improved image quality.
  • the localized release of the radio-pharmaceuticals reduces the radiation dose applied to the patient.
  • the generation of the composite image advantageously allows the correlation of data acquired in nuclear medical imaging systems to data acquired with ultrasound imaging systems.
  • this allows, for example, the assignment of tumors such as hot spots visible in nuclear medical imaging to anatomical details visible in the ultrasound image.
  • this allows to, for example, directly target biopsies by the use of ultrasound to tumor centers. Since the contrast means, i.e. the tracer is only taken up by tissue of the region of interest, the signal intensity in the acquired images is improved, allowing for a better image quality.

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  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Acoustics & Sound (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Ultra Sonic Daignosis Equipment (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention porte sur un traceur visible dans les clichés d'imagerie nucléaire et d'imagerie ultrasonique utilisés à des fins médicales. Le traceur fait appel à des micro-bulles qui peuvent être visualisées par des dispositifs ultrasoniques, mais qui sont remplies de substances radiopharmaceutiques détectables dans les dispositifs d'imagerie nucléaire utilisés en médecine. Avantageusement, ce traceur permet une fusion à modalité croisée de l'imagerie ultrasonique avec l'imagerie nucléaire utilisées dans le domaine médical.
PCT/IB2004/050704 2003-05-27 2004-05-14 Traceur d'imagerie medicale WO2004105802A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP03101529.0 2003-05-27
EP03101529 2003-05-27

Publications (1)

Publication Number Publication Date
WO2004105802A1 true WO2004105802A1 (fr) 2004-12-09

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104415371A (zh) * 2013-08-28 2015-03-18 成都市绿科华通科技有限公司 一种生物相容性高分子超声成像造影剂
CN104415364A (zh) * 2013-08-27 2015-03-18 成都市绿科华通科技有限公司 含聚丙烯腈医用高分子造影剂微球
CN105561346A (zh) * 2015-12-31 2016-05-11 常州市长宇实用气体有限公司 一种超声造影剂的制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995019184A1 (fr) * 1994-01-14 1995-07-20 Massachusetts Institute Of Technology Microparticules de polymeres contenant des agents de contraste a des fins d'imageries
WO1996040277A2 (fr) * 1995-06-07 1996-12-19 Brown University Research Foundation Microparticules polymeres sechees par pulverisation contenant des agents d'imagerie
WO1998051284A1 (fr) * 1997-05-13 1998-11-19 Imarx Pharmaceutical Corp. Nouveaux systemes d'administration de medicaments actives par un procede acoustique
WO2001091805A2 (fr) * 2000-06-02 2001-12-06 Bracco Research Usa Composes pour le ciblage des cellules endotheliales, compositions les contenant et leurs procedes d'utilisation
WO2003002156A2 (fr) * 2001-06-26 2003-01-09 The Board Of Trustees Of The University Of Illinois Microspheres de proteines polymerisees paramagnetiques et procedes de fabrication de ces dernieres

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995019184A1 (fr) * 1994-01-14 1995-07-20 Massachusetts Institute Of Technology Microparticules de polymeres contenant des agents de contraste a des fins d'imageries
WO1996040277A2 (fr) * 1995-06-07 1996-12-19 Brown University Research Foundation Microparticules polymeres sechees par pulverisation contenant des agents d'imagerie
WO1998051284A1 (fr) * 1997-05-13 1998-11-19 Imarx Pharmaceutical Corp. Nouveaux systemes d'administration de medicaments actives par un procede acoustique
WO2001091805A2 (fr) * 2000-06-02 2001-12-06 Bracco Research Usa Composes pour le ciblage des cellules endotheliales, compositions les contenant et leurs procedes d'utilisation
WO2003002156A2 (fr) * 2001-06-26 2003-01-09 The Board Of Trustees Of The University Of Illinois Microspheres de proteines polymerisees paramagnetiques et procedes de fabrication de ces dernieres

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104415364A (zh) * 2013-08-27 2015-03-18 成都市绿科华通科技有限公司 含聚丙烯腈医用高分子造影剂微球
CN104415371A (zh) * 2013-08-28 2015-03-18 成都市绿科华通科技有限公司 一种生物相容性高分子超声成像造影剂
CN105561346A (zh) * 2015-12-31 2016-05-11 常州市长宇实用气体有限公司 一种超声造影剂的制备方法
CN105561346B (zh) * 2015-12-31 2018-05-18 李彬 一种超声造影剂的制备方法

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