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WO2001074245A1 - Procede d'imagerie par resonance magnetique - Google Patents

Procede d'imagerie par resonance magnetique Download PDF

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Publication number
WO2001074245A1
WO2001074245A1 PCT/NO2001/000137 NO0100137W WO0174245A1 WO 2001074245 A1 WO2001074245 A1 WO 2001074245A1 NO 0100137 W NO0100137 W NO 0100137W WO 0174245 A1 WO0174245 A1 WO 0174245A1
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WO
WIPO (PCT)
Prior art keywords
organ
contrast agent
subject
agent composition
vascularized
Prior art date
Application number
PCT/NO2001/000137
Other languages
English (en)
Inventor
Lars Johansson
Original Assignee
Amersham Health As
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 Amersham Health As filed Critical Amersham Health As
Priority to AU2001248921A priority Critical patent/AU2001248921A1/en
Priority to AT01922143T priority patent/ATE476916T1/de
Priority to EP01922143A priority patent/EP1267716B1/fr
Priority to JP2001571993A priority patent/JP5063847B2/ja
Priority to DE60142777T priority patent/DE60142777D1/de
Publication of WO2001074245A1 publication Critical patent/WO2001074245A1/fr
Priority to US10/256,397 priority patent/US7082326B2/en

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/05—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves
    • A61B5/055—Detecting, measuring or recording for diagnosis by means of electric currents or magnetic fields; Measuring using microwaves or radio waves involving electronic [EMR] or nuclear [NMR] magnetic resonance, e.g. magnetic resonance imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/42—Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems
    • A61B5/4222—Evaluating particular parts, e.g. particular organs
    • A61B5/4244—Evaluating particular parts, e.g. particular organs liver
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
    • A61K49/1806—Suspensions, emulsions, colloids, dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4519—Muscles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
    • G01R33/48—NMR imaging systems
    • G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
    • G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
    • G01R33/563—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution of moving material, e.g. flow contrast angiography
    • G01R33/56341—Diffusion imaging

Definitions

  • This invention relates to improvements in and relating to magnetic resonance (MR) imaging of blood perfusion in vascularized organs of interest, e.g. the myocardium, the kidneys, the brain, the liver and in particular imaging of myocardial perfusion.
  • MR magnetic resonance
  • the invention provides a method of first pass, contrast enhanced organ perfusion magnetic resonance imaging of a human or vascularized animal subject, wherein a MR contrast agent composition is administered into the vasculature of said subject and magnetic resonance images are generated of slices through a vascularized organ of said subject during the passage of said agent through the vasculature of said organ, and wherein said contrast agent comprises a particulate superparamagnetic metal oxide and in that said images are generated using a T 2 -weighted Turbo (fast) spin-echo sequence and wherein said vascularized organ preferably is the myocardium, the kidneys, the brain or the liver, and more preferably the myocardium.
  • Perfusion deficits revealed by such studies indicate areas of actual or potential damage to heart muscle, for example as a result of coronary infarction or total or partial arterial occlusion, and the technique can be used to monitor and assess the success of pharmacological or surgical attempts to reperfuse areas of perfusion deficit .
  • MR image acquisition sequences used have been very fast gradient-echo sequences or multishot echo planar imaging (EPI) sequences which rely on fast read out and a short TR in order to achieve sufficient resolution and acquire images of multiple slices through the heart in each heart beat.
  • EPI multishot echo planar imaging
  • Such sequences usually acquire 3 or 4 slices each heart beat or 6 to 8 interleaved slices in two heart beats and the in-plane resolution is generally about 2 to 3 mm.
  • the invention therefore provides a method of first pass, contrast enhanced myocardial perfusion magnetic resonance imaging of a human or vascularized animal (e.g. mammalian, avian or reptilian, but preferably mammalian) subject, wherein an MR contrast agent composition is administered into the vasculature of said subject and magnetic resonance images are generated of slices through the heart of said subject during the passage of said agent through the vasculature of said heart, and wherein said contrast agent comprises a particulate superparamagnetic metal oxide (preferably an USPIO) and in that said images are generated using a T 2 -weighted Turbo (fast) spin-echo sequence .
  • a human or vascularized animal e.g. mammalian, avian or reptilian, but preferably mammalian
  • an MR contrast agent composition is administered into the vasculature of said subject and magnetic resonance images are generated of slices through the heart of said subject during the passage of said agent through the vasculature of said heart
  • the invention provides a method of generating MR images of a human or vascularized animal subject, previously administered with a MR contrast agent composition comprising a particulate superparamagnetic metal oxide (preferably an USPIO) , which method comprises generating a first pass contrast enhanced organ perfusion MR image of slices through the vascularized organ of said subject and in that said images are generated using a T 2 -weighted Turbo (fast) spin echo sequence.
  • a MR contrast agent composition comprising a particulate superparamagnetic metal oxide (preferably an USPIO)
  • a MR contrast agent composition comprising a particulate superparamagnetic metal oxide (preferably an USPIO)
  • a MR contrast agent composition comprising a particulate superparamagnetic metal oxide (preferably an USPIO)
  • a MR contrast agent composition comprising a particulate superparamagnetic metal oxide (preferably an USPIO)
  • the invention provides the use of a particulate superparamagnetic metal oxide (preferably an USPIO) for the manufacture of a MR contrast agent composition for use in a method of diagnosis involving first pass contrast enhanced organ perfusion magnetic resonance imaging of perfusion deficits in a vascularized organ using a T 2 -weighted Turbo (fast) spin-echo sequence.
  • a particulate superparamagnetic metal oxide preferably an USPIO
  • the organ is the myocardium (heart) , the kidneys, the brain or the liver and more preferably the organ is the myocardium- (heart) .
  • the invention provides the use of a MR contrast agent composition comprising a particulate superparamagnetic metal oxide in MR imaging of a human or vascularized animal subject by generating a MR image of slices through a vascularized organ of said subject using a T 2 -weighted Turbo (fast) spin-echo sequence following administration of said composition into the vasculature of said subject .
  • the organ is the myocardium (heart), the kidneys, the brain or the liver and more preferably the organ is the myocardium (heart) .
  • the methods of the invention are preferably used to generate images of at least two slices per vascularized organ cycle, preferably cardiac cycle, e.g. 2 to 10 slices/cycle, preferably 3 to 5 slices/cycle.
  • cardiac cycle e.g. 2 to 10 slices/cycle, preferably 3 to 5 slices/cycle.
  • the slices from separate cycles are preferably interleaved.
  • superparamagnetic contrast agents especially USPIOs, have both T 1 and T 2 /T 2 * reducing effects, the latter of which can dominate at high concentrations.
  • the T 2 /T 2 * effect can be used for the first pass imaging, e.g. in a T 2 -weighted Turbo (fast) spin echo sequence.
  • a sequence is preferably used in a single shot acquisition (i.e. where an entire image rather than a single image line is read out per rf- excitation) allowing the use of pre-saturating slabs, generally in the phase-encoding direction. In this way outer volume suppression, i.e.
  • the extra-cardiac signal can be achieved without unduly prolonging the image acquisition time since a smaller field of view (FOV) , and hence fewer phase-encoding lines, are necessary to achieve the required image resolution.
  • FOV field of view
  • the field of view for the cardiac image can be reduced significantly, e.g. to a value commensurate with the heart cross section dimension, so causing an increase in resolution.
  • This reduction in FOV cannot be done using conventional ⁇ -weighted gradient echo imaging with gadolinium chelates since the pre-saturation pulses would need to be applied within each sequence cycle, i.e. within each TR, and would accordingly increase TR so much that it would not be possible to acquire sufficient slices within each cardiac cycle.
  • the superparamagnetic MR contrast agent used according to the invention may be any physiologically tolerable agent comprising superparamagnetic iron oxide (or doped iron oxide) particles.
  • particles which have a blood half life (measured for example in the pig) of at least 10 minutes, preferably at least 30 minutes, more preferably at least 1 hour, are especially preferred.
  • Such particles are often referred to as blood pool contrast agents.
  • the contrast agent will be a particulate material having a particle size of 1 to 8000 nm, preferably 5 to 500 nm, more preferably 5 to lOOnm. Blood residence times for such particles can be enhanced by provision of an opsonization inhibiting coating, e.g. polyalkylene oxides (e.g.
  • glycosaminoglycans e.g. heparin or heparinoids, dermatan, hyaluronic acid, keratan, chondroitin, etc.
  • Particularly suitable as USPIO agents are dextran or carboxy-dextran-coated USPIOs, the degraded starch coated USPIOs of WO97/25073 (preferably also provided with a PEG coating) , AMI 7228 and the particulate agents described in WO95/05669, W091/12526, WO91/12025, WO90/01899, WO88/00060, WO92/11037 and WO90/01295.
  • the superparamagnetic agents are especially preferably members of the subclass known as ultra small superparamagnetic iron oxides (USPIO) . More particularly the superparamagnetic agent is preferably a water- dispersible material comprising magnetic iron oxide particles having on their surfaces (e.g. as a coating), an optionally modified carbohydrate or polysaccharide or derivative thereof, e.g. a glucose unit containing optionally modified polysaccharide or derivative thereof, preferably an optionally modified dextran or starch or derivative thereof, for example a cleaved (e.g. oxidatively cleaved) starch or carboxylated dextran.
  • Such iron oxide complexes preferably also comprise a further material (e.g.
  • coating material especially one which inhibits opsonization, e.g. a hydrophilic polymer, preferably a functionalized polyalkylene oxide, more preferably a functionalized polyethylene glycol (PEG) , in particular methoxy PEG phosphate (MPP) .
  • a hydrophilic polymer preferably a functionalized polyalkylene oxide, more preferably a functionalized polyethylene glycol (PEG) , in particular methoxy PEG phosphate (MPP) .
  • PEG polyethylene glycol
  • MPP methoxy PEG phosphate
  • the iron oxide complexes preferably have a core (i.e. iron oxide particle) diameter (mode diameter) of 1 to 15 nm, more preferably 2-10 nm, especially 3-7 nm, a total diameter (mode particle size) of 1 to 100 nm, more preferably 5-50 nm, especially preferably 10-25 nm, an r 2 /r 1 ratio at 0.47T and 40°C of less than 3, more preferably less than 2.3, still more preferably less than 2.0, especially preferably less than 1.8.
  • the saturation magentization (Msat) at IT is preferably 10 to 100 emu/gFe, more preferably 30-90 emu/gFe.
  • NC100150 a blood pool contrast agent coated with a starch residue and further coated with a PEG component, (ClariscanTM ,Nycomed Imaging AS, Oslo, Norway), e.g. disclosed in WO 97/25073 (see Ex. 12).
  • the superparamagnetic contrast agent composition is preferably administered by bolus injection into the vasculature, particularly a vein, e.g. a limb vein or in the case of an animal a tail vein.
  • the bolus is preferably administered over a period of less than 3 minutes, more preferably less than 100 seconds, still more preferably less than 60 seconds, e.g. 0.3 to 10 seconds.
  • Contrast medium injection rates will desirably be in the range 0.01 to 10 mL/sec, especially 0.3 to 3.0 mL/sec.
  • the bolus should desirably be as tight as possible and may be sharpened by the use of a physiological saline chaser.
  • the superparamagnetic MR contrast agent is preferably administered in a dose of 0.5 to 8 mg Fe/kg bodyweight, more preferably 1 to 6 mg Fe/kg, especially 2 to 5 mg Fe/kg.
  • the superparamagnetic contrast agent may be formulated for use in the method of the invention with conventional pharmaceutical carriers and excipients . Typically they will be in aqueous dispersion form, e.g. at an iron content of 10 to 50 mg Fe/mL, preferably 20 to 40 mg Fe/mL. Excipients that may be present include pH modifiers, chelating agents, viscosity modifiers, osmolality modifiers, etc.
  • the T 2 -weighted Turbo (fast) spin echo sequence is preferably effected with a repetition time of one cardiac cycle and a FOV which is 80 to 120% of the cardiac dimension, e.g. 20 to 150 mm, especially 50 to 100 mm.
  • Turbo (fast) spin echo imaging is described in by Henning et al in MRM 2: 823-833 (1986) .
  • Pre- saturation slabs are preferably positioned so as to avoid signal from phase wrapping and so as to enable the small FOV values to be achieved.
  • Figure 1 is a short-axis view of a pig heart with an occluded left anterior descending coronary artery generated by first pass myocardial imaging using a T 2 - weighted single shot Turbo (fast) spin echo sequence following iv administration of an USPIO content agent.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Health & Medical Sciences (AREA)
  • Radiology & Medical Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Medical Informatics (AREA)
  • Biophysics (AREA)
  • Pathology (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Endocrinology (AREA)
  • Physiology (AREA)
  • General Physics & Mathematics (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Signal Processing (AREA)
  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne un procédé d'imagerie par résonance magnétique (RM) de perfusion sanguine dans des organes vascularisés, notamment le myocarde, les reins, le cerveau, le foie, dans lesquels est administrée une composition d'agent de contraste contenant un oxyde métallique superparamagnétique particulaire.
PCT/NO2001/000137 2000-03-31 2001-03-30 Procede d'imagerie par resonance magnetique WO2001074245A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
AU2001248921A AU2001248921A1 (en) 2000-03-31 2001-03-30 Method of magnetic resonance imaging
AT01922143T ATE476916T1 (de) 2000-03-31 2001-03-30 Verfahren zur magnetresonanzbildgebung
EP01922143A EP1267716B1 (fr) 2000-03-31 2001-03-30 Procede d'imagerie par resonance magnetique
JP2001571993A JP5063847B2 (ja) 2000-03-31 2001-03-30 磁気共鳴画像法
DE60142777T DE60142777D1 (de) 2000-03-31 2001-03-30 Verfahren zur magnetresonanzbildgebung
US10/256,397 US7082326B2 (en) 2000-03-31 2002-09-27 Method of magnetic resonance imaging

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0007872.5 2000-03-31
US21091100P 2000-06-12 2000-06-12

Related Child Applications (1)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005006356A1 (fr) 2003-07-10 2005-01-20 Micromod Partikeltechnologie Gmbh Nanoparticules magnetiques aux proprietes magnetiques ameliorees
JP2006500099A (ja) * 2002-09-19 2006-01-05 コーニンクレッカ　フィリップス　エレクトロニクス　エヌ　ヴィ 画像データ情報の表示
US7332909B2 (en) 2003-04-23 2008-02-19 Koninklijke Philips Electronics N.V. MR imaging method

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996027394A1 (fr) * 1995-03-08 1996-09-12 Schering Aktiengesellschaft Utilisation de ferrites pour determiner la perfusion de tissus humains au moyen d'un diagnostic par resonance magnetique
US5855868A (en) * 1996-04-01 1999-01-05 Nycomed Imaging As Method of T1 -weighted resonance imaging of RES organs
WO1999006849A1 (fr) * 1997-08-01 1999-02-11 Nycomed Imaging As Imagerie par resonance nucleaire, amelioree par un agent de contraste, d'une perfusion dans un tissu
WO2000072037A1 (fr) * 1999-05-21 2000-11-30 Nycomed Imaging As Procede d'imagerie par resonance magnetique

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996027394A1 (fr) * 1995-03-08 1996-09-12 Schering Aktiengesellschaft Utilisation de ferrites pour determiner la perfusion de tissus humains au moyen d'un diagnostic par resonance magnetique
US5855868A (en) * 1996-04-01 1999-01-05 Nycomed Imaging As Method of T1 -weighted resonance imaging of RES organs
WO1999006849A1 (fr) * 1997-08-01 1999-02-11 Nycomed Imaging As Imagerie par resonance nucleaire, amelioree par un agent de contraste, d'une perfusion dans un tissu
WO2000072037A1 (fr) * 1999-05-21 2000-11-30 Nycomed Imaging As Procede d'imagerie par resonance magnetique

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SMALL W C ET AL: "Dual Contrast Enhancement of Both T1- and T2-Weighted Sequences Using Ultrasmall Superparamagnetic Iron Oxide", MAGNETIC RESONANCE IMAGING, vol. 11, no. 5, 1993, pages 645 - 654, XP002901813 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006500099A (ja) * 2002-09-19 2006-01-05 コーニンクレッカ　フィリップス　エレクトロニクス　エヌ　ヴィ 画像データ情報の表示
US7332909B2 (en) 2003-04-23 2008-02-19 Koninklijke Philips Electronics N.V. MR imaging method
WO2005006356A1 (fr) 2003-07-10 2005-01-20 Micromod Partikeltechnologie Gmbh Nanoparticules magnetiques aux proprietes magnetiques ameliorees
DE10331439B3 (de) * 2003-07-10 2005-02-03 Micromod Partikeltechnologie Gmbh Magnetische Nanopartikel mit verbesserten Magneteigenschaften
US7691285B2 (en) 2003-07-10 2010-04-06 Micromod Partikeltechnologie Gmbh Magnetic nanoparticles having improved magnetic properties

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