Chemistry Reference
In-Depth Information
the chemIstry of LanthanIde mrI
contrast agents
Stephen Faulkner and Octavia A. Blackburn
Chemistry Research Laboratory, University of Oxford, Oxford, UK
8.1
IntroductIon
Over the last quarter century, the use of magnetic resonance imaging has revolutionised diagnostic medicine and soft tissue
imaging. Contrast agents containing gadolinium are widely used to assist in the acquisition and interpretation of MRI
images [1]. Normal NMR spectroscopy relies on the presence of a uniform magnetic field (B
0
) through a sample. When a
magnetic field is applied to the sample, the nuclear spin populations are perturbed by the magnetic field. A second field (B
1
)
is then applied at right angles to the first, giving rise to a realignment of the nuclear spins. Magnetic resonance imaging is
slightly different. In a typical biological sample, the vast majority of the NMR active nuclei belong to protons in water. The
NMR spectrum is therefore likely to be rather uninformative. However, while the spin alignment is hard to separate, the
relaxation of the water molecules from the aligned state is highly dependent on their environment, that is, some protons will
take longer to get back to normal than others. There are two kinds of relaxation time:
(a)
The spin-lattice, or longitudinal, relaxation time, T
1
: a measure of how long the nucleus takes to return to its
equilibrium state after the pulse has been applied. Essentially T
1
determines how often an experiment can be repeated.
(b)
The spin-spin relaxation time, T
2
: the rate at which nuclear spins get out of phase with one another. T
2
determines the
rate at which the signal dies away.
Whereas spectroscopy can be achieved with a uniform field, that in magnetic resonance imaging must be varied across
the sample, using what is called a gradient field to provide spatial resolution (usually mm). Following the transmitter pulse,
the nuclear spins induce small voltages in a receiver coil. These constitute the free induction decay and are amplified before
Fourier transform. This procedure is repeated at a range of field gradients, and the data are then processed to generate an
image. Images can be obtained either by taking spectra from a series of thin slices, or by imaging the whole area and then
deconvoluting the signal. Relaxation-sensitive pulse sequences are often used to provide contrast. Even in the absence of
probe molecules, the relaxation properties of water will vary in the body. Well-resolved NMR signals come from water
molecules in free solution, making MRI a very good method to probe the environment inside a patient. A number of pulse
sequences can be used to distinguish between different environments - inversion recovery, saturation recovery, spin echo
methods, and proton density imaging methods are all used to achieve this goal.
Up to this point, we have not mentioned the role of the contrast agent in imaging by MRI. Non-endogenous paramagnetic
species can provide enhanced image contrast and shorter image acquisition times through changing the local relaxation rates
of bulk water protons [2]. Both T
1
and T
2
can be influenced in this way, but for the purposes of this chapter we will only
consider the role of lanthanide complexes as T
1
contrast agents, which produce T
1
weighted images when suitable imaging
pulse sequences are applied and deconvoluted.
