Published online before print July 18, 2005, doi: 10.1161/CIRCULATIONAHA.104.504415
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(Circulation. 2005;112:535-543.)
© 2005 American Heart Association, Inc.
Heart Failure |
Cardiac Iron Determines Cardiac T2*, T2, and T1 in the Gerbil Model of Iron Cardiomyopathy
From the Divisions of Pediatric Cardiology (J.C.W.), Pediatric Hematology (T.D.C.), and Pediatric Radiology (M.O.-D., M.A., M.D.N., H.P., R.M.), Departments of Pediatrics and Radiology, Children’s Hospital Los Angeles, Los Angeles, Calif; and Novartis Pharma (H.N.), AG, Basel, Switzerland.
Correspondence to Dr John Wood, Division of Cardiology, Mail stop 34, Children’s Hospital of Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027. E-mail jwood{at}chla.usc.edu
Received September 2, 2004; revision received March 28, 2005; accepted April 18, 2005.
Background— 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, which creates a potential mechanism for iron quantification. However, because of the danger and variability of cardiac biopsy, tissue validation of cardiac iron estimates by MRI has not been performed. 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 and Results— Twelve gerbils underwent iron dextran loading (200 mg · kg–1 · wk–1) from 2 to 14 weeks; 5 age-matched controls were studied as well. Animals had in vivo assessment of cardiac T2* and hepatic T2 and T2* and postmortem assessment of cardiac and hepatic T1 and T2. Relaxation measurements were performed in a clinical 1.5-T magnet and a 60-MHz nuclear magnetic resonance relaxometer. Cardiac and liver iron concentrations rose linearly with administered dose. Cardiac 1/T2*, 1/T2, and 1/T1 rose linearly with cardiac iron concentration. Liver 1/T2*, 1/T2, and 1/T1 also rose linearly, proportional to hepatic iron concentration. Liver and heart calibrations were similar on a dry-weight basis.
Conclusions— MRI measurements of cardiac T2 and T2* can be used to quantify cardiac iron. The similarity of liver and cardiac iron calibration curves in the gerbil suggests that extrapolation of human liver calibration curves to heart may be a rational approximation in humans.
CLINICAL PERSPECTIVE
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