|
Tissue iron can be visualized and quantified by a variety of imaging modalities, including MRI [22–24], SQUID [25–28], computed tomography [29–32] and nuclear resonance scattering [33, 34]. With the exception of MRI, these methods are still investigational, and not available in widespread clinical practice.
MRI provides a non-invasive, quantitative method of estimating parenchymal iron levels by measuring tissue iron concentration indirectly via the detection of the paramagnetic influences of storage iron (ferritin and hemosiderin) on the proton resonance behavior of tissue water [35]. The longitudinal (R1) and transverse (R2) nuclear magnetic relaxation rates of nearby solvent water protons can then be calculated. Both R1 and R2 rates are increased when interacting with paramagnetic particles such as iron. R2 (or spin-echo imaging) is more preferable than R1 for determining LIC, since ferritin enhances the relaxation of both R1 and R2, while hemosiderin only has a strong R2 relaxation accelerating effect. Gradient echo imaging produces images for calculating T2* and R2*, where R2* = 1000/T2*. As such, a T2* of 20 ms is equivalent to an R2* of 50 Hz.
Evaluation of hepatic iron
Liver iron levels determined using MRI shows excellent correlation with that obtained from liver biopsy [36–38]. Furthermore, unlike liver biopsy, MRI has the ability to evaluate the entire organ. It may therefore be a more accurate measurement of LIC, particularly in patients with heterogeneous iron content. In addition, the pathologic status of the liver can also be assessed using MRI.
Correlation between R2 MRI and liver biopsy
The solid line is the calibration established by curve fitting to the data. Error bars represent the ±19% uncertainties for biopsy measurement of average LICs. This percentage has been determined by studies of LIC heterogeneity in fibrosis-free livers. The dashed lines show the 95% limits of agreement between R2-LIC and LIC by biopsy. High levels of sensitivity and specificity were observed at various clinically important thresholds. The sensitivity of R2 to biopsy starts to decrease at higher LICs, partly due to the increase in biopsy sampling error at high LICs. This research was originally published in Blood. St Pierre et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood. 2005;105(2):855-61. © American Society of Hematology
The wide availability of MRI makes this technique suitable for ongoing assessment of body iron levels and regular evaluation of chelation.
MRI detection of hepatic iron overload
An MRI image (R2 map, inverse, false color) clearly displays iron overloading in the liver.
Evaluation of cardiac iron
MRI remains the only non-invasive modality in clinical use with the ability to detect cardiac iron deposition. Though this technique is neither widely available nor standardized, it holds promise in the monitoring of patients at high risk for cardiac damage due to iron overload, such as patients with thalassemia.
Reductions in cardiac iron assessed by MRI correlate with improvements in cardiac function [36, 39].
Anderson et al [36]. © 2001 Oxford University Press, reprinted with permission. MRI detection of cardiac iron overload. The cardiac T2* MRI image shows myocardial iron stores; the lighter ventricle walls in the left image indicate heavy iron loading.
T2* MRI is rapidly becoming the new standard for measuring cardiac iron levels. One study found that below a myocardial T2* of 20 ms there was a progressive and significant decline in left ventricular ejection fraction (LVEF) [36]. In general, the lower the T2* the higher the risk of cardiac dysfunction, with a T2* <8 ms suggestive of severe iron overload [36].
Correlation between T2* and cardiac function
Anderson et al [36]. © 2001 Oxford University Press, reprinted with permission.
The effect of different iron chelation therapies on myocardial T2* has been evaluated in a number of studies. One randomized trial comparing deferiprone (Ferriprox®) with subcutaneous deferoxamine (Desferal®, DFO) in thalassemia major patients with no symptoms of heart failure observed a significant improvement in myocardial T2* with both treatments, although the improvement was greater with deferiprone than DFO [40]. Another recent study has evaluated the effect of combination therapy with these agents on T2* and found the combination regimen to be more effective than DFO alone [41]. A study using the oral chelator deferasirox (Exjade®, ICL670) observed a significant improvement in myocardial T2* in deferasirox-treated patients with various transfusion dependent anemias over a median follow-up of 13 months (T2* geometric mean improved by 5.1 ms; P=0.013) and no significant change in LVEF was observed [42].
Evaluation of endocrine organs
Functional correlations have been demonstrated in MRI studies of the iron-loaded anterior pituitary gland [43–46].
Although MRI shows promise as an accurate, non-invasive test for iron overload, variability in its quantitative accuracy currently limits its usefulness as a definitive diagnostic test, especially when non-validated image acquisition protocols are used. Where available, however, it may provide a useful means of detecting iron overload and monitoring iron chelation therapy.
1 | 2 | 3 | 4 | next >
|
Français
Español
Deutsch
Italiano
