Drug – bio-affecting and body treating compositions – In vivo diagnosis or in vivo testing – Magnetic imaging agent
Patent
1985-10-31
1989-09-05
Warden, Robert J.
Drug, bio-affecting and body treating compositions
In vivo diagnosis or in vivo testing
Magnetic imaging agent
128653, 128654, 436173, 436806, A61K 4900, A61B 505, A61B 600
Patent
active
048637157
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a method of nuclear magnetic resonance (nmr) imaging involving the use of ferromagnetic particles as contrast agents and to compositions comprising ferromagnetic particles suitable for such use.
Nmr has found increasing use since the early 1970's as a medical diagnostic tool, in particular as an imaging technique. The technique provides high resolution and differentiation of soft tissue without the use of potentially harmful radiation. For several years radiologists believed that, with the high contrast achieved in nmr imaging in soft tissues without the use of contrast agents, the use of contrast agents would not be necessary.
However, it has recently been found that paramagnetic complexes can be used with advantage to achieve enhanced contrast in nmr imaging so extending the diagnostic utility of the technique.
The nuclei of many atoms have a property called spin which is associated with a small magnetic moment. In the absence of an external magnetic field the distribution of the orientations of the magnetic moments is random. In the presence of a static magnetic field the nuclear magnetic moments precess about the field direction and there will be a net alignment in the field
As R. S. First describes in "Nmr in medicine in the 1980's" (1983), in nmr imaging a patient is placed in a static field and a short radio frequency pulse is applied via a coil surrounding the patient. The radio frequency or RF signal is selected for the specific nuclei (e.g. .sup.1 H, .sup.19 F) which are to be resonated. The RF pulse causes the magnetic moments of the nuclei to align with the new field and to precess in phase, and on termination of the pulse the moments return to the original distribution of alignments with respect to the static field and to a random distribution of precession phases giving off a nuclear magnetic resonance signal which can be picked up by a receiving coil. The nmr signal is generally from .sup.1 H nuclei and represents a proton density map of the tissue being studied.
Two additional values can be determined when the RF pulse is turned off and the nuclear magnetic moments are relaxing or returning to equilibrium orientations and phases. These are T.sub.1 and T.sub.2, the spin-lattice and spin-spin relaxation times. T.sub.1 represents a time characteristic of the return to equilibrium spin distribution, i.e. equilibrium alignment of the nuclear magnetic moments in the static field. T.sub.2 on the other hand represents a time characteristic of the return to random precession phase distribution of the nuclear magnetic moments.
The nmr signal that is generated thus contains information on proton density, T.sub.1 and T.sub.2 and the images that are generated are generally the result of complex computer data reconstruction on the basis of that information.
The potential application of contrast agents in extending the diagnostic utility of nmr imaging is discussed by R. C. Brasch in Radiology 147 (1983) 781. Although numerous methods of contrast are available, many, such as manipulation of tissue temperature, viscosity or hydration, are clearly not clinically feasible and the most advantageous prior art technique appears to be the use of paramagnetic contrast agents to reduce the spin-lattice relaxation time T.sub.1.
A paramagnetic substance is one which contains one or more fundamental particles (electrons, protons or neutrons) with a spin whose effect is not cancelled out by another particle with like spin. These particles create a small magnetic field which can interact with neighbouring nuclear magnetic dipoles to cause a reorientation of the dipole, i.e. a change in nuclear spin and precession phase.
Since the magnetic field created by an electron is much greater than that created by a proton or a neutron, in practice only ions, molecules, radicals or complexes which are paramagnetic through containing one or more unpaired electrons are used as paramagnetic nmr contrast agents.
The contrast effect of paramagnetic ions and complexes is predominantly the result of reduction i
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Jacobsen Trond
Klaveness Jo
Nycomed /AS
Warden Robert J.
Wieder Stephen C.
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