MRI is now well established as a medical diagnostic tool. The ability of the technique to generate high quality images and to differentiate between soft tissues without requiring the patient to be exposed to ionizing radiation has contributed to this success.
Although MRI can be performed without using added contrast media, it has been found that substances which affect the nuclear spin reequilibration of the nuclei (hereinafter the "imaging nuclei"--generally water protons in body fluids and tissues) responsible for the magnetic resonance (MR) signals from which the images are generated may be used to enhance image contrast and, accordingly, in recent years, many such materials have been suggested as MRI contrast agents.
The enhanced contrast obtained with the use of contrast agents enables particular organs or tissues to be visualized more clearly by increasing or by decreasing the signal level of the particular organ or tissue relative to that of its surroundings. Contrast agents raising the signal level of the target site relative to that of its surroundings are termed "positive" contrast agents whilst those lowering the signal level relative to surroundings are termed "negative" contrast agents.
The majority of materials now being proposed as MRI contrast media achieve a contrast effect because they contain paramagnetic, superparamagnetic or ferromagnetic species.
Paramagnetic contrast agents may be either positive or negative MRI contrast agents. The effect of paramagnetic substances on magnetic resonance signal intensities is dependent on many factors, the most important of which are the concentration of the paramagnetic substance at the imaged site, the nature of the paramagnetic substance itself and the pulse sequence and magnetic field strength used in the imaging routine. Generally, however, paramagnetic contrast agents are positive MRI contrast agents at low concentrations where their T.sub.1 lowering effect dominates and negative MRI contrast agents at higher concentrations where their T.sub.2 (or T.sub.2 *) lowering effect is dominant.
An example of a physiologically tolerable paramagnetic material known for use as an MRI contrast agent is manganese ion, which may conveniently be used in the form of its salts or chelates.
Manganese, when administered intravenously as a contrast agent, may be teratogenic at clinical dosages. Administered intravenously, manganese is also known to interfere with the normal functioning of the heart by replacement of calcium in the calcium pump of the heart.
In order to reduce the direct effect on the heart, oral administration of manganese has been proposed. A result of the vascularisation of the upper gastrointestinal tract is that orally administered material taken up into the blood from the gut passes to the liver before passing to the heart. In the case of manganese, absorption by the hepatocytes in the liver prevents cardiotoxic levels of manganese reaching the heart. This hepatocyte uptake of manganese has led to the use of orally administered manganese as a liver imaging contrast agent.
However, development of MRI as a technique for imaging the gastrointestinal (g.i.) tract has been hindered by problems particular to the g.i. tract in which natural inter-tissue contrast is relatively poor and in the absence of a particularly effective contrast medium.
U.S. Pat. No. 5,143,716 concerns methods of imaging of the gastrointestinal region to detect the presence of tumorous tissue. The contrast medium described comprises a combination of at least one polyphosphorylated compound and at least one paramagnetic ion, including Mn.sup.2+. Whilst it is suggested that such a contrast medium is capable of providing images showing any diseased tissue in the g.i. tract, this does not permit the detection of regions of the gut, in particular the gut wall, which may be functioning abnormally.