Friday, December 16, 2011

Gadolinium

While school children know the most famous elements listed in the periodic table (for example hydrogen, oxygen, and carbon), even many scientists are unfamiliar with those rare earth elements down at the bottom of the table, listed under the generic label of lanthanides. But one of these, gadolinium (Gd, element 64), has become crucial for modern medicine because of its use as a contrast agent during magnetic resonance imaging. In the 4th edition of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss gadolinium in Chapter 18.
“Differences in relaxation time are easily detected in an image. Different tissues have different relaxation times. A contrast agent containing gadolinium (Gd3+), which is strongly paramagnetic, is often used in magnetic resonance imaging. It is combined with many of the same pharmaceuticals used with 99mTc, and it reduces the relaxation time of nearby nuclei.”
In 1999, Peter Caravan and his coworkers published a major review article about the uses of gadolinium in imaging, which has been cited over 1500 times (Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications, Chemical Reviews, Volume 99, Pages 2293-2352). The review is well written, and I reproduce the introduction below.
“Gadolinium, an obscure lanthanide element buried in the middle of the periodic table, has in the course of a decade become commonplace in medical diagnostics.
Like platinum in cancer therapeutics and technetium in cardiac scanning, the unique magnetic properties of the gadolinium(III) ion placed it right in the middle of a revolutionary development in medicine: magnetic resonance imaging (MRI). While
it is odd enough to place patients in large superconducting magnets and noisily pulse water protons in their tissues with radio waves, it is odder still to inject into their veins a gram of this potentially toxic metal ion which swiftly floats among the water
molecules, tickling them magnetically.

The successful penetration of gadolinium(III) chelates into radiologic practice and medicine as a whole can be measured in many ways. Since the approval of [Gd(DTPA)(H2O)]2- in 1988, it can be estimated that over 30 metric tons of gadolinium have been administered to millions of patients worldwide. Currently, approximately 30% of MRI exams include the use of contrast agents, and this is projected to increase as new agents and applications arise; Table 1 lists agents currently approved or in clinical trials. In the rushed world of modern medicine, radiologists, technicians, and nurses often refrain from calling the agents by their brand names, preferring instead the affectionate 'gado.' They trust this clear, odorless 'magnetic light', one of the safest class of drugs ever developed. Aside from the cost ($50-80/bottle), asking the nurse to 'Give him some gado' is as easy as starting a saline drip or obtaining a blood sample.

Gadolinium is also finding a place in medical research. When one of us reviewed the field in its infancy, in 1987, only 39 papers could be found for that year in a Medline search for 'gado-' and MRI. Ten years later over 600 references appear each year. And as MRI becomes relied upon by different specialties, 'gado' is becoming known by neurologists, cardiologists, urologists, opthamologists, and others in search of new ways to visualize functional changes in the body.

While other types of MRI contrast agents have been approved, namely an iron particle-based agent and a manganese(II) chelate, gadolinium(III) remains the dominant starting material. The reasons for this include the direction of MRI development and the nature of Gd chelates.”
In Section 18.12 about Functional MRI, Russ and I again mention gadolinium.
"Magnetic resonance imaging provides excellent structural information. Various contrast agents can provide information about physiologic function. For example, various contrast agents containing gadolinium are injected intravenously. They leak through a damaged blood-tissue barrier and accumulate in the damaged region. At small concentrations T1 is shortened."
Here at Oakland University, several of our Biomedical Sciences: Medical Physics PhD students study brain injury using this method. See, for instance, the dissertation Magnetic Resonance Imaging Investigations of Ischemic Stroke, Intracerebral Hemorrhage and Blood-Brain Barrier Pathology by Karki, Kishor, 2009.

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