Abstract
Introduction. Tissue iron measurements with magnetic resonance imaging (MRI) have given doctors a reliable way to monitor iron overload in thalassemias, sickle-cell disease and other disorders. However, MRI remains too expensive for widespread use in the countries where the largest numbers of patients with these disorders live. This abstract describes a test in human subjects of a potentially less expensive method of quantifying excess iron: measurement of liver iron concentrations (LIC) by magnetic susceptometry, using magnetic sensors that work at room temperature.
Methods. The room-temperature susceptometer (RTS) in this study was a close copy of the one described by Maliken et al. [Room-temperature susceptometry predicts biopsy-determined hepatic iron in patients with elevated serum ferritin. Ann. Hepatol. 2012;11:77-84]. LIC measurements with the RTS were compared to those of an existing SQUID (superconducting quantum interference device) biosusceptometer [Starr, TN et. al. A new generation SQUID biosusceptometer. Proceedings, 12th International Conference on Biomagnetism. 2000].
84 patients, mostly with transfusion-dependent thalassemia major, participated in this comparison. Their LICs based on SQUID ranged from zero to 5250 μg/g wet weight, with median 920 μg/g and standard deviation 960 μg/g. Body-mass indices ranged from 16.6 to 31.7 kg/m2 (median 21.8 kg/m2, standard deviation 3.1 kg/m2). Liver-skin distances measured by ultrasound imaging ranged from 13.0 to 30.0 mm (median 17.5 mm, standard deviation 3.1 mm). For each patient, SQUID and RTS measurements were done in a single session.
The agreement of the two susceptometers was assessed in terms of their Pearson product moment correlation coefficient r and the standard deviation σ of the differences between the SQUID results and the least-squares Deming regression line. This standard deviation was slightly dependent on the value of λ, the ratio of the variances of errors for the two susceptometers, that was assumed in the Deming regression. This dependence was estimated by calculating σ for a range of λ values.
Results. LICs from RTS and SQUID had a Pearson product moment correlation coefficient r = 0.93. The differences between the two systems had a standard deviation σ = 363 μg/g assuming that the RTS's variance was four times the SQUID's and 353 μg/g assuming equal variances. As a point of reference, applying a similar analysis to published data yielded r = 0.975 and σ = 320 μg/g for a comparison of the Torino-based SQUID used in this study with another SQUID susceptometer at Hamburg [Engelhardt R et al. Agreement of liver iron quantification measurements with low Tc-SQUID biosusceptometers in Oakland, Torino and Hamburg. Elsevier International Congress Series 2007;1300: 279-282].
Conclusions. These results indicate that a less expensive susceptometer using room-temperature magnetic sensors can make liver iron measurements that are well correlated with those of the biopsy-validated SQUID technology. Based on the standard deviation of the differences between the two systems, the RTS used in this study was approaching accuracy levels that would be useful clinically, especially in screening patients for dangerously high iron. Since the RTS's errors in measurements on phantoms are significantly lower than those found in this study on human subjects, the room-temperature susceptometer's accuracy appears to be limited not by the noise of the room-temperature magnetic sensors, but by the relationship of the susceptometer to the patient's body. With improvement in areas such as patient positioning, measurement of the sensor-skin distance, and correction for the magnetic response of tissue between the liver and the susceptometer, low-cost susceptometers may ultimately achieve accuracies comparable to those of existing SQUIDs. Such technologies can potentially improve the management of iron overload, especially in regions where MRI is too expensive for routine use.
Piga:Acceleron: Research Funding; La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Apopharma: Honoraria, Research Funding; Bluebird Bio: Honoraria; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding. Avrin:Insight Magnetics: Employment, Other: Proprietor of company developing the study device, Patents & Royalties: Own rights to patents on the study device.
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