Chemistry Reference
In-Depth Information
Hallervorden
Spatz syndrome (due to a mutation in the gene encoding pantothenate kinase 2). The MRI picture is
aT
2
-weighted image which shows diffuse bilateral low signal intensity of the globus pallidus (due to iron
deposition) with a region of hyperintensity in the internal segment (the high signal is thought to represent tissue
oedema). Neuroferritinopathy is another neurological disorder, in which the insertion of an adenine residue in the
gene for the ferritin light chain results in an altered carboxy terminal sequence of the protein. The T
2
-weighted
MRI image in
Figure 22.12
(
b) is quite characteristic, with symmetrical degeneration of the globus pallidus and
putamen and low signal intensity in the internal capsule.
The use of MRI allows accurate, noninvasive diagnosis of many pathological conditions. However, the use of
contrast agents, often in the form of paramagnetic metallochelates, makes the method even more sensitive and the
diagnosis more specific. MRI contrast agents are not directly visualised in the resulting image, only their effects
are observed. They enhance image contrast as a result of their influence on the relaxation times of nearby water
protons, and as a consequence on the NMR signal. Paramagnetic molecules, because of their unpaired electrons,
are potent MRI contrast agents, decreasing the T
1
and T
2
relaxation times of nearby proton spins, and enhancing
the signal observed. The most extensively studied paramagnetic metal ions are transition metal ions (high-spin
Mn(II) and Fe(III), each with five unpaired electrons) and lanthanides (often Gd(III) with its seven unpaired
electrons). Since free metal ions are toxic to biological systems they have to be administered in a nontoxic form
bound to suitable ligands or chelates. The first contrast agent to be approved for clinical use, Gd-DTPA, which we
encountered in Chapter 1, was introduced in the 1980s as a contrast agent for obtaining MR images in humans, and
e
(a)
(b)
FIGURE 22.13
(a) Structure of Gd-HPDO3A. (b) Schematic representation of the dissociation of apoferritin into subunits at pH 2, followed
by its reforming at pH 7. In this way the solution components are trapped within its interior.
Copyright 2002 with permission from John Wiley and Sons.)
