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Magnetic resonance imaging of liver and spleen with superparamagnetic contrast agents
| Details |
Inventors: Widder, Kenneth J.;
Assignee: Molecular Biosystems, Inc. (San Diego, CA)
Primary Examiner: Warden; Robert J.
Assistant Examiner: Wieder; Stephen C.
Attorney, Agent or Firm: Tilton, Fallon, Lungmus & Chestnut
A method of imaging a tumor by magnetic resonance imaging (MRI) of liver and/or spleen is provided which employes microspheres composed of a biodegradeable matrix material with a particulate superparamagnetic contrast agent therein. The microspheres have diameters of less than 1.5 microns, and the ferromagnetic contrast agent, such as magnetite, has a particle size below 300 Angstroms. The superparamagnetic microspheres when administered intravenously segregate through the reticuloendothelial system in the liver and spleen where they reduce the T.sub.2 relaxation time to obtain improved MR imaging. In the T.sub.2 or mixed T.sub.1 and T.sub.2 images obtained by the MRI examination, the normal liver and spleen tissues appear dark and the tumor appears light with distinct margins therebetween. |
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DETAILED DESCRIPTION The superparamagnetic contrast agent is used in particulate form, for example, as particles of 50 to 300 Angstroms diameter.
Particle size of not over 300 Angstroms provides ferromagnetic iron compounds with the desired superparamagnetic characteristics; namely, enhanced magnetic susceptibility and low residual magnetization.
Preferably, the particulate forms are substantially water-insoluble, such as insoluble oxides or salts.
The superparamagnetic contrast agent may also be in the form of particles of an elemental metal such as particularly iron particles sized below 300 Angstroms.
A preferred particulate contrast agent is magnetite, which is a magnetic iron oxide sometimes represented as Fe.
sub.
3 O.
sub.
4 (or as FeO.
Fe.
sub.
2 O.
sub.
3 .
) Commercially, fine powders or suspensions of magnetite are available from Ferrofluidics Corporation, Burlington, Massachusetts.
The size range of the particles is submicron, viz.
50 to 200 Angstroms.
Other water-insoluble superparamagnetic iron compounds can be used such as ferrous oxide (Fe.
sub.
2 O.
sub.
3), iron sulfide, iron carbonate, etc.
For purposes of this invention, the microspheres comprise relatively spherical particles consisting of protein, carbohydrate or lipid as the biodegradable matrix for the paramagnetic contrast agent.
For effective targeting to the liver and spleen, the microspheres comprising the encapsulated contrast agents should have diameters up to about a maximum size of 8 microns.
An advantageous size range appears to be from about 2 to 5 micro diameter.
Less than 1.
5 micron microspheres can be used as a livery spleen contrast agent (viz.
1.
0 micron size), but circulation time is prolonged, that is, fewer spheres will be rapidly taken up by the RES.
Microspheres of larger size than 8 microns may be sequestered in the first capillar bed encountered, and thereby prevented from reaching the liver and spleen at all.
Large microspheres (viz.
10 microns or more) can be easily trapped in the lungs by arteriolar and capillary blockade
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