Influence of iron chelation on R1 and R2 calibration curves in gerbil liver and heart

Abstract

MRI is gaining increasing importance for the noninvasive quantification of organ iron burden. Since transverse relaxation rates depend on iron distribution as well as iron concentration, physiologic and pharmacologic processes that alter iron distribution could change MRI calibration curves. This article compares the effect of three iron chelators, deferoxamine, deferiprone, and deferasirox, on R1 and R2 calibration curves according to two iron loading and chelation strategies. Thirty-three Mongolian gerbils underwent iron loading (iron dextran 500 mg/kg/wk) for 3 weeks followed by 4 weeks of chelation. An additional 56 animals received less aggressive loading (200 mg/kg/week) for 10 weeks, followed by 12 weeks of chelation. R1 and R2 calibration curves were compared to results from 23 iron-loaded animals that had not received chelation. Acute iron loading and chelation-biased R1 and R2 from the unchelated reference calibration curves but chelator-specific changes were not observed, suggesting physiologic rather than pharmacologic differences in iron distribution. Long-term chelation deferiprone treatment increased liver R1 50% (P < 0.01), while long-term deferasirox lowered liver R2 30.9% (P < 0.0001). The relationship between R1 and R2 and organ iron concentration may depend on the acuity of iron loading and unloading as well as the iron chelator administered. Magn Reson Med 60:82-89, 2008.

Magnetic Resonance Imaging Quantification of Liver Iron

“…MRI particles may have round, cylindrical, or irregular shapes 84 . These features (particle size, distribution, loading factor, and shape) may vary between individual patients, between patient groups, or in response to different chelating agents 11, 85 . They are thought to affect the relationship between LIC and R 2 relaxation values 10, 11, 71, 84, 86, 87 and, because they cannot be determined non-invasively, introduce unavoidable error in R 2 -based LIC estimation.…”

Liver MRI is more precise than liver biopsy for assessing total body iron balance: a comparison of MRI relaxometry with simulated liver biopsy results

“…R2* measurements lack static refocusing that occurs at larger iron scales [29], causing R2* values to be larger than R2 but retain linearity with iron burden [30,31]. As a result, R2* measurements are much less sensitive than R2 measurements to acute changes in tissue iron distribution [28,30,32] or proton mobility [25,32], responding primarily to total tissue magnetic susceptibility. In this trial, all patients were placed on a novel agent, and some were also under-dosed for the first 24 weeks, producing disequilibrium in the length scale of tissue iron [32].…”

“…As a result, R2* measurements are much less sensitive than R2 measurements to acute changes in tissue iron distribution [28,30,32] or proton mobility [25,32], responding primarily to total tissue magnetic susceptibility. In this trial, all patients were placed on a novel agent, and some were also under-dosed for the first 24 weeks, producing disequilibrium in the length scale of tissue iron [32]. While 12 week observation intervals are not typically performed in clinical practice, rapid dose adjustment may be desirable in high-risk situations or in dose-finding clinical trials.…”

Quantitative analysis and modelling of hepatic iron stores using stereology and spatial statistics

“…Not only might this information be helpful for understanding responses to different iron chelating agents but also it is essential for understanding the water proton–iron interactions that occur during MRI imaging. MRI is gaining clinical acceptance as a non‐invasive tool to monitor hepatic iron stores, but the calibration curves depend upon patterns of iron distribution within tissues (Wood, 2007; Wood et al ., 2008). Accurate knowledge of iron microscale will enable us to simulate realistic synthetic MRI signals, including predicted inter‐patient variability.…”

“…Liver biopsy provides an ideal model system to study the organization of iron deposits because it is routinely obtained for clinical purposes. Knowledge of tissue iron distribution appears to be relevant to iron chelation therapy because iron chelating agents interact differently in different tissues (Glickstein et al , 2005; Wood et al , 2008).…”