Estimating tissue iron burden: current status and future prospects

Abstract

SUMMARY Iron overload is becoming an increasing problem as haemoglobinopathy patients gain greater access to good medical care and as therapies for myelodysplastic syndromes improve. Therapeutic options for iron chelation therapy have increased and many patients now receive combination therapies. However, optimal utilization of iron chelation therapy requires knowledge not only of the total body iron burden but the relative iron distribution among the different organs. The physiological basis for extrahepatic iron deposition is presented in order to help identify patients at highest risk for cardiac and endocrine complications. This manuscript reviews the current state of the art for monitoring global iron overload status as well as its compartmentalization. Plasma markers, computerized tomography, liver biopsy, magnetic susceptibility devices and magnetic resonance imaging (MRI) techniques are all discussed but MRI has come to dominate clinical practice. The potential impact of recent pancreatic and pituitary MRI studies on clinical practice are discussed as well as other works-in-progress. Clinical protocols are derived from experience in haemoglobinopathies but may provide useful guiding principles for other iron overload disorders, such as myelodysplastic syndromes.

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“…However ferritin is subject to many variations, and even when measured frequently, may not accurately reflect tissue iron burden [39]. Recently, scientific studies have led to better understanding of iron trafficking, including how iron accumulates in tissues which were not intended to store iron [40]. These studies have elucidated the need to monitor not only serum parameters but also tissue iron: hepatic iron and even iron in other tissues.…”

“…Liver biopsy (which is invasive) was previously considered the "gold standard" but both only measured hepatic iron stores. Currently, there are several types of magnetic resonance imaging (MRI) which can noninvasively measure liver, cardiac, pancreatic, and even pituitary iron [40]. MRI measures iron indirectly by the influence of iron on nearby water molecules.…”

“…MRI measures iron indirectly by the influence of iron on nearby water molecules. Tissue iron disrupts the magnetic field for a period of time which can be measured in units of time (designated T2 or T2* by spin echo imaging or gradient echo imaging) or by rate (R2 and R2* by spin and gradient echo imaging, respectively) [40]. Quantitation of liver iron by R2* has been validated by liver biopsy results [40].…”

“…Since cardiac mortality is the major cause of mortality in nonchelated patients, cardiac T2*, which has been validated clinically [40] has become the standard of care in industrialized countries. As such, the use of cardiac MRI has contributed to prolonging life expectancy in countries where this tool is available, such as the UK and other parts of Europe [42].…”

“…As such, the use of cardiac MRI has contributed to prolonging life expectancy in countries where this tool is available, such as the UK and other parts of Europe [42]. An algorithm has been developed for routine use of cardiac MRI to guide long term optimum chelation [40]. Ferritin remains useful in young children, for whom the use of MRI requiring sedation is problematic and needs to be weighed individually [33].…”