Liver and Spleen Imaging
Liver and Spleen Imaging
The use of Gd-DTPA with routine imaging sequences of the liver is unsatisfactory. Particulate contrast agents targeted to the reticuloendothelial system (RES) of the liver and spleen, achieve the goals of improved detection and localization in the liver. This is analogous to the use of 99mTc-sulfur colloid in nuclear liver scans.
Two major cell types can be targeted for hepatic imaging. Hepatocytes comprise about 78% of the liver by volume, and Kupffer cells of the reticuloendothelial system comprise about 2% by volume. Originally, particulate contrast agents were targeted for the RES but recently ultra-small particles have been used that bind to a specific receptor site on the hepatocyte cell membrane.
Gadolinium oxide is a the prototype particulate contrast agent. This material accumulates in the liver and spleen of rabbits in both Kupffer cells and in the sinusoidal vascular spaces and effectively increases T1 and T2 relaxation as desired. The safety ratio (LD50/Imaging dose) is only about 7:1 raising concerns of acute and chronic toxicity. It is therefore precluded from clinical use.
As with its use as an oral contrast agent, superparamagnetic iron oxide (SPIO) causes marked shortening T2 relaxation time resulting in a loss of signal in the liver and spleen with all commonly used pulse sequences. The most common form of iron oxide used is magnetite, which is a mixture of Fe2O3 and FeO. A mixture using Fe3O4 instead of FeO may also be used. Three mechanisms have been postulated to explain the relaxation enhancement of SPIO.
SPIO particles for parenteral use are coated with various substances to facilitate uptake by the reticuloendothelial system. These coatings have included albumin, a hydrophilic polymer, starch, and dextran.
The following problems that can arise with detecting small lesions in the liver using SPIO: 1) Small lesions may be indistinguishable from the flow void in small blood vessels seen in cross-section; 2) Aortic pulsation artifacts are more noticeable; and 3) the one hour delay between injection and imaging make it impractical to decide at the last minute to give contrast.
A liposome is a spherical vesical consisting of one or more bilayer phospholipid membranes or lamella. Liposomes for hepatic imaging range in size from about 20 nm to 400 nm diameter. Reasons to use liposomes as a carrier for paramagnetic contrast materials include: 1) changing the interaction between water molecules and the contrast agent; 2) changing the rate of removal of the contrast agent from the blood pool; and 3) targeting specific organ systems, e.g., liver, spleen, and bone marrow. Paramagnetic materials can be incorporated into either the aqueous inner chamber or the bilayer membrane. Encapsulation of superparamagnetic iron oxide particles into liposomes (Ferrosomes) has been reported. Both Gd-DTPA and MnCl2 can be encapsulated into the aqueous inner chamber of liposomes.
Liposomes are taken up only by the Kupffer cells. Once in the Kupffer cells, Mn+2 or Gd-DTPA is slowly released and diffuses into adjacent hepatocytes, resulting in enhancement of normal liver but not malignancies.
Stable nitroxide free radicals have been attached to phospatidylcholine, a common constituent of liposome lamellae. They may also be attached to derivatives of the fatty acid, stearic acid, as have the DTPA chelates of Mn and Gd. This results in a lipophilic side chain that allows incorporation into the liposome membrane.