13-05 Further Applications
The spleen, pancreas, bone marrow, lymph nodes, adrenals, muscles, in particular the heart, as well as inflammations and specific tumors have been proposed as additional target regions for some contrast agents. None of these, nor a number of other agents not mentioned here, are available for clinical imaging.
Agents for contrast-enhanced MR angiography (i.e., ECF space and blood pool agents) are discussed in Chapter 14.
13-05-01 Ventilation Imaging
Not all contrast agents are aimed at proton magnetic resonance imaging. One can also exploit magnetic properties of nuclei different from hydrogen, for instance fluorine. The feasibility of in vivo application of perfluorinated compounds has been demonstrated for lung ventilation and perfusion studies (Figure 20-33b) [⇒ Rinck 1984].
Gadolinium-based aerosols, hyperpolarized gases, and oxygen were also proposed to be used as possible ventilation agents. In the case of hyperpolarized gases helium seems better suited than xenon [⇒ Albert, ⇒ Middleton]. However, special hardware is necessary: devices for production, storage, and installation of the hyperpolarized gases, as well as special coils and receivers for imaging. This makes ventilation imaging with these gases more difficult than comparable methods. The methods are not applied in clinical settings.
13-05-02 Enteral Contrast Agents
Problems in abdominal MR imaging are created by motion artifacts from respiration, cardiac motion, peristalsis, and blood flow, as well as a general lack of contrast between feces- and fluid-filled or collapsed bowel loops and adjacent organs or pathological structures. Cardiac and respiratory gating, special software, faster imaging sequences, and the use of contrast agents have solved some of these problems.
A number of substances were proposed and studied during the last years in phantom, animal, and clinical trials. Among them were positive and negative contrast agents. Gadolinium-containing contrast agents belonged to the first group, while fluorine-containing compounds and magnetic particles are found in the second group (Figure 13-16) [⇒ Hamm, ⇒ Rinck 1991]. For studies of the upper abdomen blueberry or pineapple juices are also useable.
The use of enteral contrast agents has been limited, and with today’s imaging techniques, in particular custom-tailored pulse sequences, most clinical questions can be answered without the application of oral or rectal agents.
In addition to imaging of the liver, manganese-enhanced MRI (MEMRI) with Mn-DPDP (mangafodipir) has a wide range of potential applications. Research is focused upon both depiction of brain damage and functional mapping of neural pathways to map brain activation independently and with higher contrast than measurements of hemodynamics in fMRI [review: ⇒ Koretsky].
Manganese also has an affinity for the myocardium and can act as biomarker in heart disease. Manganese ions compete with calcium for entry into cardiac cells. There the ions bind to macromolecules and influence the relaxation of cell and tissue water. Heart diseases gradually inactivate calcium transport mechanisms (due to lower metabolic activity). Thus, manganese uptake is reduced accordingly; manganese-induced changes of tissue relaxation reflect tissue calcium homeostasis and thus myocardial viability (Figure 13-17) [⇒ Skjold].
During the development of mangafodipir (Mn-DPDP) as an MR contrast agent for liver studies, it was discovered that this compound and its metabolite manganese pyridoxyl ethyldiamine (Mn-PLED) also possess therapeutic properties. Mn-DPDP has been studied in cancer patients and in patients with myocardial infarctions. The contrast enhancement in MR imaging relies on the release of manganese from the chelate, the therapeutic activity depends on manganese that remains bound to DPDP or PLED.
Mn-PLED's stabilized derivate calmangafodipir [Ca4Mn(DPDP)5] has even superior therapeutic properties [⇒ Karlsson]. These compounds are some of the prime examples of theragnostics, combining image contrast enhancement and therapy.
Dysprosium can be used as an intravenous negative contrast agent, as was shown with Dy-DTPA-BMA, a paramagnetic bulk susceptibility perfusion agent. It possesses a large magnetic moment and a poor T1 relaxivity, despite its relationship with gadolinium and manganese. It can be used as T2-relaxation contrast agent at extremely high fields [⇒ Haraldseth, ⇒ vander Elst 2002].