Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron

Wu, Ed X.; Kim, Daniel; Tosti, Christina L.; Tang, Haiying; Jensen, Jens Højgaard; Cheung, J. T.; Feng, Li; Au, Wing Y.; Ha, Shau Yin; Sheth, Sujit; Brown, Truman R.; Brittenham, Gary M.

doi:10.1111/j.1749-6632.2010.05587.x

Cited by 24 publications

(31 citation statements)

References 30 publications

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“…Iron is often associated with ferritin but may also bind to hemosiderin and magnetite. Hemosiderin-iron is an aggregate that induces greater spin dephasing [40] and so has a greater effect on T2* (and thus R2*) than ferritin-iron, which acts mostly through T2 relaxation [40]. Iron associated with biogenic magnetite also has a higher magnetic moment than that stored in ferritin and better at enhancing T2 relaxation [41].…”

Section: Discussionmentioning

confidence: 99%

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

Walker

Michaelides

Ekonomou

et al. 2016

Aging

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Despite regulation, brain iron increases with aging and may enhance aging processes including neuroinflammation. Increases in magnetic resonance imaging transverse relaxation rates, R2 and R2*, in the brain have been observed during aging. We show R2 and R2* correlate well with iron content via direct correlation to semi-quantitative synchrotron-based X-ray fluorescence iron mapping, with age-associated R2 and R2* increases reflecting iron accumulation. Iron accumulation was concomitant with increased ferritin immunoreactivity in basal ganglia regions except in the substantia nigra (SN). The unexpected dissociation of iron accumulation from ferritin-upregulation in the SN suggests iron dyshomeostasis in the SN. Occurring alongside microgliosis and astrogliosis, iron dyshomeotasis may contribute to the particular vulnerability of the SN. Dietary restriction (DR) has long been touted to ameliorate brain aging and we show DR attenuated agerelated in vivo R2 increases in the SN over ages 7 – 19 months, concomitant with normal iron-induction of ferritin expression and decreased microgliosis. Iron is known to induce microgliosis and conversely, microgliosis can induce iron accumulation, which of these may be the initial pathological aging event warrants further investigation. We suggest iron chelation therapies and anti-inflammatory treatments may be putative ‘antibrain aging’ therapies and combining these strategies may be synergistic.

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Section: Discussionmentioning

confidence: 99%

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

Walker

Michaelides

Ekonomou

et al. 2016

Aging

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“…A new, non-invasive imaging method proposed by Jensen that separately quantifies these two molecular forms of storage iron improves our ability to assess and monitor patients with iron overload and test the efficacy of iron-chelating therapies 6–10 . Non-invasive MR-based iron quantification methods are particularly desirable for cardiac tissue where the clinical consequences of iron-overload are severe, and the diagnostic methods to measure it are few.…”

Section: Discussionmentioning

confidence: 99%

Measurement and correction of stimulated echo contamination in T2-based iron quantification

Sammet

Swaminathan

Tang

et al. 2013

Magnetic Resonance Imaging

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The purpose of this study was to characterize the effects of stimulated echo contamination on MR-based iron measurement derived from quantitative T2 images and develop a method for retrospective correction. Two multiple spin echo (MSE) pulse sequences were implemented with different amounts of stimulated echo contamination. Agarose-based phantoms were constructed that simulate the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron. Additionally, myocardial iron was assessed in nine human subjects with transfusion iron overload. These data were used to determine the influence of stimulated echoes on iron measurements made by an MR-based iron quantification model that can separately measure dispersed and aggregated iron. The study found that stimulated echo contamination caused an underestimation of dispersed (ferritin-like) iron and an overestimation of aggregated (hemosiderin-like) iron when applying this model. The relationship between the measurements made with and without stimulated echo appears to be linear. The findings suggest that while it is important to use MSE sequences with minimal stimulated echo in T2-based iron quantification, it appears that data acquired with sub-optimal sequences can be retrospectively corrected using the methodology described here.

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“…We demonstrate that the contributions of dispersed and aggregated iron to the transverse relaxation rate (R 2 ) can be separated using the parameters RR 2 and A. Finally, the influnce of the stimulated echo (31) caused by the present MSE sequence on RR 2 and A (32, 33), and on iron measurement are analyzed based on phantom simulations. We hypothesize that tissue iron quantification based on the two parameters, RR 2 and A, rather than the single parameter, R 2 or R 2 *, will improve estimates of total storage iron.…”

Section: Introductionmentioning

confidence: 91%

MR characterization of hepatic storage iron in transfusional iron overload

Tang

Jensen

Sammet

et al. 2013

Magnetic Resonance Imaging

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Purpose To quantify the two principal forms of hepatic storage iron, diffuse, soluble iron (primarily ferritin), and aggregated, insoluble iron (primarily hemosiderin) using a new MRI method in patients with transfusional iron overload. Materials and Methods Six healthy volunteers and twenty patients with transfusion-dependent thalassemia syndromes and iron overload were examined. Ferritin- and hemosiderin-like iron were determined based on the measurement of two distinct relaxation parameters: the “reduced” transverse relaxation rate, RR2 and the “aggregation index,” A, using three sets of Carr-Purcell-Meiboom-Gill (CPMG) datasets with different interecho spacings. Agarose phantoms, simulating the relaxation and susceptibility properties of tissue with different concentrations of dispersed (ferritin-like) and aggregated (hemosiderin-like) iron, were employed for validation. Results Both phantom and in vivo human data confirmed that transverse relaxation components associated with the dispersed and aggregated iron could be separated using the two-parameter (RR2, A) method. The MRI-determined total hepatic storage iron was highly correlated (r = 0.95) with measurements derived from biopsy or biosusceptometry. As total hepatic storage iron increased, the proportion stored as aggregated iron became greater. Conclusion This method provides a new means for non-invasive MRI determination of the partition of hepatic storage iron between ferritin and hemosiderin in iron overload disorders.

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Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron

Cited by 24 publications

References 30 publications

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

Dissociation between iron accumulation and ferritin upregulation in the aged substantia nigra: attenuation by dietary restriction

Measurement and correction of stimulated echo contamination in T2-based iron quantification

MR characterization of hepatic storage iron in transfusional iron overload

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