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WO1993006869A1 - Agents gazeux de contraste a ultrasons - Google Patents

Agents gazeux de contraste a ultrasons Download PDF

Info

Publication number
WO1993006869A1
WO1993006869A1 PCT/US1992/008385 US9208385W WO9306869A1 WO 1993006869 A1 WO1993006869 A1 WO 1993006869A1 US 9208385 W US9208385 W US 9208385W WO 9306869 A1 WO9306869 A1 WO 9306869A1
Authority
WO
WIPO (PCT)
Prior art keywords
gas
ultrasound
mixture
composition
oxygen
Prior art date
Application number
PCT/US1992/008385
Other languages
English (en)
Inventor
Donald R. Vanderipe
Original Assignee
Mallinckrodt Medical, Inc.
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 Mallinckrodt Medical, Inc. filed Critical Mallinckrodt Medical, Inc.
Publication of WO1993006869A1 publication Critical patent/WO1993006869A1/fr

Links

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

Definitions

  • the present invention relates to composition useful for ultrasound imaging and to the use of such compositions.
  • An object of the present invention is to provide ultrasound agents which would obviate or lessen the problems and disadvantages cited above.
  • This invention relates to ultrasound contrast agents comprising pharmaceutically acceptable gases or gas mixtures capable of forming gas bubbles after administration in the arterial and/or arteriolar circulation and the tissues supplied by said circulation of a warm blooded animal.
  • the gas bubbles are of appropriate size to enhance ultrasound imaging It was quite surprising, and contrary to teachings i physiology and pharmacology, that selected gases o gas mixtures after administration form gas bubble within the arterial circulation under conditions whic provide for diagnostic ultrasound contrast imaging in both 2D echo and Doppler contrast procedures. More importantly, these gases can be transported across the capillary and cell membranes and reform bubbles within the extracellular and intracellular space of the tissue to be imaged.
  • Another feature of this invention is the use of these agents to enhance the contrast of a diagnostic ultrasound procedure on a warm blooded animal. Still another feature is a sterile composition comprising the agent. Another feature is the use of said compositions to enhance the contrast of magnetic resonance imaging.
  • gases and gas mixtures useful in the practice of this invention are best composed of gases which tend to form larger bubbles in the blood and tissues and might be typified by xenon and nitrous oxide and other weakly active general anesthetics such as sulfur hexafluoride.
  • gases which tend to form larger bubbles in the blood and tissues
  • many other types of nontoxic gases, such as other perfluorocarbons would be useful, provided they form bubbles in the blood of the appropriate size.
  • gas mixtures under varying conditions of barometri pressure are useful and advantageous. For example maximum blood/tissue contrast might be expected i cases where the inhaled partial pressure of the ga mixture is retained at a high percentage of th inhaled gases and the barometric pressure of th environment is reduced.
  • the siz of the bubbles should grow and provide enhanced tissu contrast.
  • decreased contrast might b expected with smaller bubbles and, in cases wherei the subject is imaged under hyperbaric conditions, th latter compressing the gas back into solution.
  • composition of such ultrasound contrast gas mixtures may be varied, but in practice should always contain oxygen to insure proper oxygenation if the gas is to be inhaled for a significant period of time.
  • the mixture would be of two or three gases, but might, on occasion, include more complex mixtures.
  • the gas mixtures would be prepared according to th art using those available from the fractionation o air (oxygen, carbon dioxide, nitrogen, xenon, argon, krypton, neon, helium, etc.) and those prepare synthetically, such as the perfluorocarbons, etc.
  • Agents which would not generally be acceptable include the highly potent anesthetic methoxyflurane, and those less potent, but very effective, anesthetics such as chloroform, cyclopropane, halothane, enflurane, diethyl ether, fluoroxene and enflurane.
  • Gases with maximum efficacy would include nitrous oxide, xenon, ethylene, sulfur hexafluoride, argon, and the like.
  • the basis on which the various gases might b optimized would be based on their oil:gas partitio coefficients being reflected in the size of the ga bubbles which they form in the body formed within th body.
  • the potent and clinically use anesthetics listed above form gas bubbles of 4 microns or less, most of which are less than two microns. Ultrasound is poorly reflected by such small bubbles and therefore these agents would be predicted to provide poor contrast especially at safe and/or subanesthetic concentrations.
  • nitrous oxide can form gas bubbles in the body as large as 7-8 microns, a size which provides for excellent ultrasound reflectivity and those gases with similar oil:gas partition coefficients, namely, xenon and ethylene, would be expected to produce similar sized bubbles in the body (Goodman & Gilman above) .
  • gases with very low oil:gas partition coefficients might become less effective by virtue of being too soluble in water.
  • Nitrogen might be such a gas under most physiologic conditions and it has an oil:gas partition coefficient of about 0.1.
  • the gases to provide in vivo ultrasound contrast when inhaled should optimally include those with olive oil:gas partition coefficients between about 10:1 (high) and about 0.01:1 (low), preferably from about 5:1 (high) to 0.1:1 (low).
  • any gas mixture which needs to be inhaled for any significant length of time in order to provide optimal contrast would need to have oxygen as a necessary component gas, usually at about 20% by volume. Examples of effective gas mixtures would include:
  • the agents are used in the usual manner.
  • the gas or gas mixtures may be sterilized prior to administration or administered through a sterile filter.
  • an organ or tissue would be imaged prior to the administration of the gas mixture(s) in order to obtain a control tissue ultrasound signal level.
  • an agent o this invention would be administered by inhalation b the use of equipment well known to the art, eithe from a single gas container with the gases premixed or via the use of gas mixing valves and using two or more gas containers as appropriate.
  • the inhaled gas mixture would then circulate to the tissues via the blood stream and be distributed to each tissue in a manner consistent with the blood supply to the tissue.
  • control (normal) test as described above would be repeated after exercise or following the administration of pharmacologic stress agents to assess blood flow deficits or slower signal build up in low flow areas of the body.
  • Such rest and stress protocols have been used for some time in nuclear medicine as the thallium (Tl-201) stress test.
  • the inhalation of gases to provide the above ultrasound contrast will be for times suitable for ultrasound imaging, usually short periods generally less than about five minutes, but could b prolonged depending on the clinical application, e.g. monitoring of the return of tissue perfusion after period of ischemia.
  • the gas or gas mixtures might be inhaled over broad time frames with the clinical use determining the individual administration protocol.

Landscapes

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

Abstract

Procédés d'imagerie à ultrasons utilisant un gaz ou un mélange de gaz capable de former des bulles après administration.
PCT/US1992/008385 1991-10-04 1992-10-02 Agents gazeux de contraste a ultrasons WO1993006869A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US77130091A 1991-10-04 1991-10-04
US07/771,300 1991-10-04

Publications (1)

Publication Number Publication Date
WO1993006869A1 true WO1993006869A1 (fr) 1993-04-15

Family

ID=25091377

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1992/008385 WO1993006869A1 (fr) 1991-10-04 1992-10-02 Agents gazeux de contraste a ultrasons

Country Status (2)

Country Link
AU (1) AU2789192A (fr)
WO (1) WO1993006869A1 (fr)

Cited By (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5348016A (en) * 1989-12-22 1994-09-20 Unger Evan C Apparatus for preparing gas filled liposomes for use as ultrasonic contrast agents
WO1995003835A1 (fr) * 1993-07-30 1995-02-09 Alliance Pharmaceutical Corp. Compositions a mocrobulles stabilisees pour applications mettant en ×uvre des ultrasons
US5393524A (en) * 1991-09-17 1995-02-28 Sonus Pharmaceuticals Inc. Methods for selecting and using gases as ultrasound contrast media
US5406950A (en) * 1993-12-23 1995-04-18 Mallinckrodt Medical, Inc. Inhalable contrast agent
WO1995016467A1 (fr) * 1993-12-15 1995-06-22 Bracco Research S.A. Melanges gazeux utiles comme agents de contraste ultrasonores
US5456901A (en) * 1989-12-22 1995-10-10 Unger; Evan C. Liposomes as contrast agents for ultrasonic imaging
US5469854A (en) * 1989-12-22 1995-11-28 Imarx Pharmaceutical Corp. Methods of preparing gas-filled liposomes
WO1996009793A1 (fr) * 1994-09-28 1996-04-04 Alliance Pharmaceutical Corp. Mise en evidence des harmoniques d'ultrasons par des microbulles
US5542935A (en) * 1989-12-22 1996-08-06 Imarx Pharmaceutical Corp. Therapeutic delivery systems related applications
US5558855A (en) * 1993-01-25 1996-09-24 Sonus Pharmaceuticals Phase shift colloids as ultrasound contrast agents
US5558094A (en) * 1991-09-17 1996-09-24 Sonus Pharmaceuticals, Inc. Methods for using persistent gases as ultrasound contrast media
US5558853A (en) * 1993-01-25 1996-09-24 Sonus Pharmaceuticals Phase shift colloids as ultrasound contrast agents
US5558854A (en) * 1991-09-17 1996-09-24 Sonus Pharmaceuticals Ultrasound contrast media comprising perfluoropentane and perfluorohexane gas
US5580575A (en) * 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
WO1996040288A1 (fr) * 1995-06-07 1996-12-19 Mallinckrodt Medical, Inc. Agents de contraste ultrasonore gazeux et procede associe
WO1998003205A3 (fr) * 1996-07-19 1998-03-05 Sonus Pharma Inc Renforcement des contrastes d'echographie par utilisation de gaz inhales
US5798091A (en) * 1993-07-30 1998-08-25 Alliance Pharmaceutical Corp. Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement
US5804162A (en) * 1995-06-07 1998-09-08 Alliance Pharmaceutical Corp. Gas emulsions stabilized with fluorinated ethers having low Ostwald coefficients
US6001332A (en) * 1995-02-16 1999-12-14 The Boc Group Plc Medical gas mixture
US6110443A (en) * 1990-04-02 2000-08-29 Bracco International N.V. Dry stable formation to produce microbubble suspension for ultrasound
WO2002054946A3 (fr) * 2001-01-12 2002-10-10 Nycomed Imaging As Procede d'imagerie en perfusion
US6569404B1 (en) 1993-01-25 2003-05-27 Amersham Health A/S Phase shift colloids as ultrasound contrast agents
US6613306B1 (en) 1990-04-02 2003-09-02 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US6881397B2 (en) 1990-04-02 2005-04-19 Bracco International B.V. Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof
US6884407B1 (en) 1996-09-11 2005-04-26 Bristol-Myers Squibb Pharma Company Methods for diagnostic imaging involving the use of a contrast agent and a coronary vasodilator
EP1588699A3 (fr) * 1994-09-16 2006-01-18 Imarx Pharmaceutical Corp. Récipient contenant une composition polyphasique et s'utilisant dans des applications diagnostiques et thérapeutiques
US6989141B2 (en) 1990-05-18 2006-01-24 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US6998107B2 (en) 1991-04-05 2006-02-14 Bristol-Myers Squibb Pharma Comapany Composition comprising low density microspheres
USRE39146E1 (en) 1990-04-02 2006-06-27 Bracco International B.V. Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof
US7078015B2 (en) 1989-12-22 2006-07-18 Imarx Therapeutics, Inc. Ultrasound imaging and treatment
US7083778B2 (en) 1991-05-03 2006-08-01 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US7083572B2 (en) 1993-11-30 2006-08-01 Bristol-Myers Squibb Medical Imaging, Inc. Therapeutic delivery systems
US7105151B2 (en) 1997-06-18 2006-09-12 Imarx Therapeutics, Inc. Oxygen delivery agents and uses for the same
US7329402B2 (en) 1995-06-07 2008-02-12 Imarx Pharmaceutical Corp. Methods of imaging and treatment
US7405241B2 (en) * 2003-01-15 2008-07-29 Air Liquide Sante (International) Use of N2O in the treatment of post-ischemic brain cell deterioration
US7452551B1 (en) 2000-10-30 2008-11-18 Imarx Therapeutics, Inc. Targeted compositions for diagnostic and therapeutic use
US7612033B2 (en) 1994-11-29 2009-11-03 Imarx Pharmaceutical Corp. Methods for delivering compounds into a cell
WO2011035140A1 (fr) 2009-09-18 2011-03-24 Paka Pulmonary Pharmaceuticals, Inc. Procédés et compositions pour la délivrance de moitiés de contraste aux poumons
US9545457B2 (en) 1998-01-14 2017-01-17 Lantheus Medical Imaging, Inc. Preparation of a lipid blend and a phospholipid suspension containing the lipid blend
US9789210B1 (en) 2016-07-06 2017-10-17 Lantheus Medical Imaging, Inc. Methods for making ultrasound contrast agents
US10022460B2 (en) 2014-12-31 2018-07-17 Lantheus Medical Imaging, Inc. Lipid-encapsulated gas microsphere compositions and related methods
US10588988B2 (en) 2016-05-04 2020-03-17 Lantheus Medical Imaging, Inc. Methods and devices for preparation of ultrasound contrast agents

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4657756A (en) * 1980-11-17 1987-04-14 Schering Aktiengesellschaft Microbubble precursors and apparatus for their production and use
US4681119A (en) * 1980-11-17 1987-07-21 Schering Aktiengesellschaft Method of production and use of microbubble precursors
US4718433A (en) * 1983-01-27 1988-01-12 Feinstein Steven B Contrast agents for ultrasonic imaging
US5078146A (en) * 1989-09-08 1992-01-07 Kabushiki Kaisha Toshiba Ultrasonic diagnosis apparatus
US5088499A (en) * 1989-12-22 1992-02-18 Unger Evan C Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4657756A (en) * 1980-11-17 1987-04-14 Schering Aktiengesellschaft Microbubble precursors and apparatus for their production and use
US4681119A (en) * 1980-11-17 1987-07-21 Schering Aktiengesellschaft Method of production and use of microbubble precursors
US4718433A (en) * 1983-01-27 1988-01-12 Feinstein Steven B Contrast agents for ultrasonic imaging
US5078146A (en) * 1989-09-08 1992-01-07 Kabushiki Kaisha Toshiba Ultrasonic diagnosis apparatus
US5088499A (en) * 1989-12-22 1992-02-18 Unger Evan C Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same

Cited By (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5456901A (en) * 1989-12-22 1995-10-10 Unger; Evan C. Liposomes as contrast agents for ultrasonic imaging
US5580575A (en) * 1989-12-22 1996-12-03 Imarx Pharmaceutical Corp. Therapeutic drug delivery systems
US5542935A (en) * 1989-12-22 1996-08-06 Imarx Pharmaceutical Corp. Therapeutic delivery systems related applications
US5469854A (en) * 1989-12-22 1995-11-28 Imarx Pharmaceutical Corp. Methods of preparing gas-filled liposomes
US5348016A (en) * 1989-12-22 1994-09-20 Unger Evan C Apparatus for preparing gas filled liposomes for use as ultrasonic contrast agents
US7078015B2 (en) 1989-12-22 2006-07-18 Imarx Therapeutics, Inc. Ultrasound imaging and treatment
USRE39146E1 (en) 1990-04-02 2006-06-27 Bracco International B.V. Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof
US6136293A (en) * 1990-04-02 2000-10-24 Bracco International B.V. Stable microbubbles suspensions containing saturated lamellar phospholipids
US6485705B1 (en) 1990-04-02 2002-11-26 Bracco International B.V. Mixable combination for generating a suspension of stable microbubbles for ultrasonic imaging
US6110443A (en) * 1990-04-02 2000-08-29 Bracco International N.V. Dry stable formation to produce microbubble suspension for ultrasound
US6613306B1 (en) 1990-04-02 2003-09-02 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US6881397B2 (en) 1990-04-02 2005-04-19 Bracco International B.V. Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof
US6896875B2 (en) 1990-04-02 2005-05-24 Bracco International B.V. Mixable combination for generating a suspension of stable microbubbles for ultrasonic imaging
US6989141B2 (en) 1990-05-18 2006-01-24 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US6998107B2 (en) 1991-04-05 2006-02-14 Bristol-Myers Squibb Pharma Comapany Composition comprising low density microspheres
US7344705B2 (en) 1991-04-05 2008-03-18 Bristol-Myers Squibb Medical Imaging, Inc. Composition comprising low density microspheres
US7083778B2 (en) 1991-05-03 2006-08-01 Bracco International B.V. Ultrasound contrast agents and methods of making and using them
US5558094A (en) * 1991-09-17 1996-09-24 Sonus Pharmaceuticals, Inc. Methods for using persistent gases as ultrasound contrast media
US5573751A (en) * 1991-09-17 1996-11-12 Sonus Pharmaceuticals, Inc. Persistent gaseous bubbles as ultrasound contrast media
US5558854A (en) * 1991-09-17 1996-09-24 Sonus Pharmaceuticals Ultrasound contrast media comprising perfluoropentane and perfluorohexane gas
US5409688A (en) * 1991-09-17 1995-04-25 Sonus Pharmaceuticals, Inc. Gaseous ultrasound contrast media
US5393524A (en) * 1991-09-17 1995-02-28 Sonus Pharmaceuticals Inc. Methods for selecting and using gases as ultrasound contrast media
US6183725B1 (en) 1992-12-16 2001-02-06 Bracco Research S.A. Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method
US5595723A (en) * 1993-01-25 1997-01-21 Sonus Pharmaceuticals Method for preparing storage stable colloids
US5558853A (en) * 1993-01-25 1996-09-24 Sonus Pharmaceuticals Phase shift colloids as ultrasound contrast agents
US6569404B1 (en) 1993-01-25 2003-05-27 Amersham Health A/S Phase shift colloids as ultrasound contrast agents
US5558855A (en) * 1993-01-25 1996-09-24 Sonus Pharmaceuticals Phase shift colloids as ultrasound contrast agents
US6372195B1 (en) 1993-07-30 2002-04-16 Alliance Pharmaceutical Corp. Mixed gas microbubble compositions
WO1995003835A1 (fr) * 1993-07-30 1995-02-09 Alliance Pharmaceutical Corp. Compositions a mocrobulles stabilisees pour applications mettant en ×uvre des ultrasons
US7005120B2 (en) 1993-07-30 2006-02-28 Imcor Pharmaceutical Company Osmotically stabilized microbubble preparations
US5720938A (en) * 1993-07-30 1998-02-24 Alliance Pharmaceutical Corp. Systems for the formation of microbubbles
US6953569B2 (en) 1993-07-30 2005-10-11 Imcor Pharmaceutical Company Mixed gas microbubble compositions
US6939531B2 (en) 1993-07-30 2005-09-06 Imcor Pharmaceutical Company Ultrasonic imaging system utilizing a long-persistence contrast agent
EP1550464A1 (fr) * 1993-07-30 2005-07-06 IMCOR Pharmaceutical Co. Composition à microbulles stabilisées pour application mettant en oeuvre des ultrasons
US5626833A (en) * 1993-07-30 1997-05-06 Alliance Pharmaceutical Corp. Ultrasound imaging method using microbubbles
US5798091A (en) * 1993-07-30 1998-08-25 Alliance Pharmaceutical Corp. Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement
US5639443A (en) * 1993-07-30 1997-06-17 Alliance Pharmaceutical Corp. Stabilized microbubble compositions
US6706253B2 (en) 1993-07-30 2004-03-16 Ernest G. Schutt Osmotically stabilized microbubble preparations
US7141235B2 (en) 1993-07-30 2006-11-28 Imcor Pharmaceutical Co. Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement
US6258339B1 (en) 1993-07-30 2001-07-10 Alliance Pharmaceutical Corp. Osmotically stabilized microbubble preparations
US6287539B1 (en) 1993-07-30 2001-09-11 Alliance Pharmaceuticals Corp. Methods of imaging using osmotically stabilized microbubble preparations
US6280704B1 (en) 1993-07-30 2001-08-28 Alliance Pharmaceutical Corp. Ultrasonic imaging system utilizing a long-persistence contrast agent
US6280705B1 (en) 1993-07-30 2001-08-28 Alliance Pharmaceutical Corp. Kits & systems for ultrasonic imaging
US5695741A (en) * 1993-07-30 1997-12-09 Alliance Pharmaceutical Corp. Stable microbubble precursors
US7083572B2 (en) 1993-11-30 2006-08-01 Bristol-Myers Squibb Medical Imaging, Inc. Therapeutic delivery systems
CN1068229C (zh) * 1993-12-15 2001-07-11 勃勒柯研究有限公司 超声对比介质、含该介质的对比剂及方法
AU679295B2 (en) * 1993-12-15 1997-06-26 Bracco Suisse S.A. Gas mixtures useful as ultrasound contrast media
WO1995016467A1 (fr) * 1993-12-15 1995-06-22 Bracco Research S.A. Melanges gazeux utiles comme agents de contraste ultrasonores
US5406950A (en) * 1993-12-23 1995-04-18 Mallinckrodt Medical, Inc. Inhalable contrast agent
EP0802767A4 (fr) * 1993-12-23 1999-06-23 Mallinckrodt Medical Inc Agent de contraste inhalable
EP1588699A3 (fr) * 1994-09-16 2006-01-18 Imarx Pharmaceutical Corp. Récipient contenant une composition polyphasique et s'utilisant dans des applications diagnostiques et thérapeutiques
US7374744B2 (en) 1994-09-28 2008-05-20 Imcor Pharmaceutical Co. Harmonic ultrasound imaging with microbubbles
US5733527A (en) * 1994-09-28 1998-03-31 Alliance Pharmaceutical Corp. Methods for harmonic imaging with ultrasound
AU693608B2 (en) * 1994-09-28 1998-07-02 Imcor Pharmaceutical Company Harmonic ultrasound imaging with microbubbles
WO1996009793A1 (fr) * 1994-09-28 1996-04-04 Alliance Pharmaceutical Corp. Mise en evidence des harmoniques d'ultrasons par des microbulles
US6056943A (en) * 1994-09-28 2000-05-02 Alliance Pharmaceutical Corp. Methods of ultrasound imaging using phospholipid stabilized microbubbles
US6036644A (en) * 1994-09-28 2000-03-14 Alliance Pharmaceutical Corp. Enhanced methods of ultrasound imaging using multiple frequencies
US6019960A (en) * 1994-09-28 2000-02-01 Alliance Pharmaceutical Corp. Systems for harmonic ultrasound imaging
US5540909A (en) * 1994-09-28 1996-07-30 Alliance Pharmaceutical Corp. Harmonic ultrasound imaging with microbubbles
US7612033B2 (en) 1994-11-29 2009-11-03 Imarx Pharmaceutical Corp. Methods for delivering compounds into a cell
US6001332A (en) * 1995-02-16 1999-12-14 The Boc Group Plc Medical gas mixture
EP0831935A4 (fr) * 1995-06-07 2001-08-29 Mallinckrodt Medical Inc Agents de contraste ultrasonore gazeux et procede associe
US6013243A (en) * 1995-06-07 2000-01-11 Mallinckrodt Inc. Gaseous inhalable ultrasound contrast agents and method therefor
WO1996040288A1 (fr) * 1995-06-07 1996-12-19 Mallinckrodt Medical, Inc. Agents de contraste ultrasonore gazeux et procede associe
US7329402B2 (en) 1995-06-07 2008-02-12 Imarx Pharmaceutical Corp. Methods of imaging and treatment
US5804162A (en) * 1995-06-07 1998-09-08 Alliance Pharmaceutical Corp. Gas emulsions stabilized with fluorinated ethers having low Ostwald coefficients
US6193952B1 (en) 1995-06-07 2001-02-27 Alliance Pharmaceutical Corp. Stabilized gas emulsions containing phospholipid for ultrasound contrast enhancement
WO1998003205A3 (fr) * 1996-07-19 1998-03-05 Sonus Pharma Inc Renforcement des contrastes d'echographie par utilisation de gaz inhales
US6884407B1 (en) 1996-09-11 2005-04-26 Bristol-Myers Squibb Pharma Company Methods for diagnostic imaging involving the use of a contrast agent and a coronary vasodilator
US7105151B2 (en) 1997-06-18 2006-09-12 Imarx Therapeutics, Inc. Oxygen delivery agents and uses for the same
US9545457B2 (en) 1998-01-14 2017-01-17 Lantheus Medical Imaging, Inc. Preparation of a lipid blend and a phospholipid suspension containing the lipid blend
US7452551B1 (en) 2000-10-30 2008-11-18 Imarx Therapeutics, Inc. Targeted compositions for diagnostic and therapeutic use
WO2002054946A3 (fr) * 2001-01-12 2002-10-10 Nycomed Imaging As Procede d'imagerie en perfusion
US7405241B2 (en) * 2003-01-15 2008-07-29 Air Liquide Sante (International) Use of N2O in the treatment of post-ischemic brain cell deterioration
WO2011035140A1 (fr) 2009-09-18 2011-03-24 Paka Pulmonary Pharmaceuticals, Inc. Procédés et compositions pour la délivrance de moitiés de contraste aux poumons
US12296029B2 (en) 2014-12-31 2025-05-13 Lantheus Medical Imaging, Inc. Lipid-encapsulated gas microsphere compositions and related methods
US10022460B2 (en) 2014-12-31 2018-07-17 Lantheus Medical Imaging, Inc. Lipid-encapsulated gas microsphere compositions and related methods
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Publication number Publication date
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