Separate MRI quantification of dispersed (ferritin‐like) and aggregated (hemosiderin‐like) storage iron

Abstract

A new MRI method is proposed for separately quantifying the two principal forms of tissue storage (nonheme) iron: ferritin iron, a dispersed, soluble fraction that can be rapidly mobilized, and hemosiderin iron, an aggregated, insoluble fraction that serves as a long-term reserve. The method utilizes multiple spin echo sequences, exploiting the fact that aggregated iron can induce nonmonoexponential signal decay for multiple spin echo sequences. The method is validated in vitro for agarose phantoms, simulating dispersed iron with manganese chloride, and aggregated iron with iron oxide microspheres. To demonstrate feasibility for human studies, preliminary in vivo data from two healthy controls and six patients with transfusional iron overload are presented. For both phantoms and human subjects, conventional R 2 and R 2 * relaxation rates are also measured in order to contrast the proposed method with established MRI iron quantification techniques. Quantification of dispersed (ferritin-like) iron may provide a new means of monitoring the risk of iron-induced toxicity in patients with iron overload and, together with quantification of aggregated (hemosiderin-like) iron, improve the accuracy of estimates for total storage iron.

MRI-Based Liver Iron Content Determination at 3T in Regularly Transfused Patients by Signal Intensity Ratio Using an Alternative Analysis Approach Based on R2* Theory

“…Results differ only marginally, and only 8 (18 %) of our examinations were affected by this choice. Jensen et al point out that SE and GRE address complementary aspects of liver iron storage mechanisms [29]. Therefore, we have to keep in mind that differences observed between GRE-LIC and the reference method Ferriscan ® represent general deviations between GRE and SE.…”

Reference method for measurement of the hepatic iron concentration

“…In addition to considerations of calibration, MRI detects tissue iron indirectly by the effects of the storage (nonheme) forms of iron on hydrogen nuclei. The two forms of storage iron, ferritin and hemosiderin, have distinctively different effects on MRI signal decay [19]. Methods to measure the total storage (ferritin 1 hemosiderin) iron based on a single metric (T 2 , R 2 , T 2 *, and R 2 *) have an intrinsic uncertainty resulting from variations in the relative amounts of ferritin and hemosiderin iron.…”

Noninvasive MRI-Based Liver Iron Quantification: Methodic Approaches, Practical Applicability and Significance

“…The sum of the two components results in more precise determination of liver iron content than each individual component. The following should be noted: the results acquired by Jensen on the basis of a phantom indicate that the R 2 relaxation rate determined using spin-echo does not correlate significantly with the concentration of dissolved iron or of hemosiderin [48]. The correlation of R 2 to the total iron content is also only moderate.…”

“…3. Jensen et al were able to show that it is possible to differentiate between dissolved iron (associated with ferritin by the authors) and the aggregated form (hemosiderin) with the acquisition of multiple series with different echo intervals [48]. The sum of the two components results in more precise determination of liver iron content than each individual component.…”

“…The correlation of R 2 to the total iron content is also only moderate. However, gradient-echo data, i. e., the R 2 * relaxation rate, shows a good correlation with the hemosiderin concentration and a relatively good correlation with the total iron concentration [48]. The multi-contrast spin-echo method was used by Tang et al in patients with iron overload [49].…”