Cardiac MRI (T2,T2*) Predicts Cardiac Iron in the Gerbil Model of Iron Cardiomyopathy.

Introduction: Transfusional therapy for thalassemia major and sickle cell disease can lead to iron deposition and damage to the heart, liver, and endocrine organs. Iron causes the MRI parameters T1, T2, and T2* to shorten in these organs, creating a potential mechanism for iron quantitation. Validation of liver MRI has been achieved by studying patients undergoing clinically indicated liver biopsy. However, because of the danger and variability of cardiac biopsy, cardiac MRI studies have relied upon “clinical” validation, i.e., the association between low cardiac T2* and cardiac function. In this study, we demonstrate that iron produces similar T1, T2, and T2* changes in the heart and liver, using a gerbil iron overload model.

Methods: Twelve gerbils underwent iron dextran loading (200 mg/kg/week) from 2–14 weeks; 5 age-matched controls were studied as well. Animals had in-vivo assessment of cardiac T2* as well as hepatic T2 and T2* using a General Electric 1.5 T CVi system with custom isofluorane anesthesia delivery system, imaging enclosure, coil and pulse sequences. Liver and heart were harvested following imaging, weighed, and portions collected for histology and quantitative iron (Mayo Metals Laboratory, Rochester, MN). Ex-vivo cardiac and liver T1 and T2 measurements were performed on fresh specimens (< 30 minutes post-sacrifice) using a Bruker minispectrometer.

Results: Control animals had minimal detectable iron at baseline and did not accumulate iron in the liver or the heart over the 14-week study interval. Chemically-assayed heart iron concentration increased 0.078 mg/g(wet wt)/wk (r²=0.98) and iron content 0.022 mg/wk (r²=0.92) by linear regression analysis. Similarly, assayed liver iron concentration increased 1.15 mg/g(wet wt)/week (r²=0.93) over a 10 week interval and liver iron content increased 3.82 mg/wk (r²=0.96).

Liver iron deposition was prominent in both sinusoidal cells and hepatocytes. Interstitial fibrosis was mild and there was no necrosis. Cardiac iron deposition was predominantly endomysial, generally sparing the myocytes themselves. Interstitial fibrosis was prominent, originating from areas of high iron concentration. No myocyte necrosis was observed, however myocyte hypertrophy was evident at high iron concentrations.

Cardiac and liver R2* (1/T2*), R2 (1/T2), and R1 (1/T1) rose linearly with tissue iron concentration (r² averaged 0.94 [0.74 to 0.98]. The slope of these parameter with respect to iron was15–29% steeper in heart than in liver, although these differences reached statistical significance only for R2. Systematic differences in wet-to-dry weight ratio between heart and liver (5.07 vs 3.82) antagonized this effect, however, such that calibrations were similar on a dry-weight basis.

Conclusion: Cardiac iron is the primary determinant of cardiac MRI relaxivity. Calibration curves were similar between heart and liver on a dry weight basis. Extrapolation of liver calibration curves to heart may be a rationale approximation in humans where direct tissue validation is difficult and dangerous. Regardless of systematic differences in absolute calibration, these data support prior claims that cardiac R2 and R2* measurements reflect cardiac iron concentration