Magnetic Resonance Measurement of Heart and Liver Iron

Summary

Principal Investigator: G M Brittenham
Affiliation: Columbia University
Country: USA
Abstract: The proposed research will integrate radiological, clinical and laboratory efforts in the development and validation of quantitative magnetic resonance methods for the measurement of heart and liver iron. We propose to acquire a fundamental theoretical and physical understanding of the resonance effects of tissue iron as a guide in the development of novel MR techniques that will provide clinically applicable methods for the quantitative measurement of hepatic and cardiac iron. These studies will take advantage of a unique convergence of resources and expertise at Columbia University, including the Hatch MR Research Center, active programs of liver and heart transplantation, the Iron Reference Laboratory, and the SQUID biosusceptometry facility where hundreds of patients with diverse forms of iron overload are seen each year. The proposed research has three specific aims: (1) to investigate systematically in and ex vivo the resonance behavior of ferritin and hemosiderin iron in diverse hepatic and cardiac disorders in patients undergoing organ transplantation, using candidate MR methods including conventional spin- and gradient-echo sequences, spectroscopic techniques, and projection reconstruction-based pulse sequences designed to facilitate capture of short T2* components; and ( 2 ) to examine selected MR methods for measurement of hepatic and cardiac iron in patients with iron overload of diverse severity and etiologies (hereditary hemochromatosis, chronic transfusion for thalassmia major, sickle cell disease, aplastic and other refractory anemia) in conjunction with SQUID biosusceptometry in vivo, magnetic susceptometry ex vivo, ultrastructural and biochemical studies of explant tissue; and (3) to prospectively validate optimized MR measurements of hepatic and cardiac iron concentrations with the results of biochemical analysis of tissue from heart and liver explants in series of adult and pediatric patients with and without disorders affecting iron metabolism. The development of validated, clinically applicable MR methods for the non-invasive measurement of hepatic and cardiac iron would be a major advance in the diagnosis and management of patients with iron overload that would find immediate and widespread diagnostic use both in the U.S. and worldwide.
Funding Period: 2003-09-15 - 2009-06-30
more information: NIH RePORT

Top Publications

  1. pmc MR characterization of hepatic storage iron in transfusional iron overload
    Haiying Tang
    Imaging, Discovery Medicine and Clinical Pharmacology, Bristol Myers Squibb, Princeton, New Jersey, USA
    J Magn Reson Imaging 39:307-16. 2014
  2. pmc Measurement and correction of stimulated echo contamination in T2-based iron quantification
    Christina L Sammet
    Northwestern University, Chicago, IL 60611, USA
    Magn Reson Imaging 31:664-8. 2013
  3. pmc Doppler-defined pulmonary hypertension and the risk of death in children with sickle cell disease followed for a mean of three years
    Margaret T Lee
    Division of Pediatric Hematology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Br J Haematol 146:437-41. 2009
  4. pmc Reduced transverse relaxation rate (RR2) for improved sensitivity in monitoring myocardial iron in thalassemia
    Jerry S Cheung
    Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    J Magn Reson Imaging 33:1510-6. 2011
  5. pmc Rapid monitoring of iron-chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate
    Daniel Kim
    Department of Radiology, Center for Biomedical Imaging, New York University School of Medicine, New York, NY 10016, USA
    NMR Biomed 24:771-7. 2011
  6. pmc Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron
    Ed X Wu
    Department of Electrical and Electronic Engineering, University of Hong Kong, Pokfulam, Hong Kong, China
    Ann N Y Acad Sci 1202:115-22. 2010
  7. pmc Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron
    Jens H Jensen
    Department of Radiology, New York University School of Medicine, Center for Biomedical Imaging, New York, New York 10016 3295, USA
    Magn Reson Med 63:1201-9. 2010
  8. pmc Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation
    Eldad A Hod
    Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Blood 115:4284-92. 2010
  9. pmc Numerical and in vivo validation of fast cine displacement-encoded with stimulated echoes (DENSE) MRI for quantification of regional cardiac function
    Li Feng
    Department of Biomedical Engineering, Polytechnic Institute of New York University, Brooklyn, New York 10016, USA
    Magn Reson Med 62:682-90. 2009
  10. pmc Myocardial T2 quantitation in patients with iron overload at 3 Tesla
    Hua Guo
    Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    J Magn Reson Imaging 30:394-400. 2009

Scientific Experts

  • SUJIT S SHETH
  • Daniel Kim
  • Gary M Brittenham
  • Jens H Jensen
  • Ed X Wu
  • Haiying Tang
  • Truman R Brown
  • Jerry S Cheung
  • Christina L Sammet
  • Kristi Hultman
  • Srirama V Swaminathan
  • Shau Yin Ha
  • Wing Yan Au
  • Hua Guo
  • Li Feng
  • Alvaro Nunez
  • Christina L Tosti
  • Eldad A Hod
  • Pek Lan Khong
  • Margaret T Lee
  • Matthew M Cheung
  • Yin Wu
  • Iris Y Zhou
  • Ning Zhang
  • James C Zimring
  • Phyllis Della-Latta
  • Set A Sokol
  • Richard O Francis
  • Susan Whittier
  • Steven L Spitalnik
  • Daniel Ansaldi
  • Jeanne E Hendrickson
  • Boguslaw S Wojczyk
  • Kevin P Francis
  • Kamila U Szulc
  • Wynnie W M Lam
  • James Babb
  • Queenie Chan
  • Tania Small
  • Kevin C Chan
  • Christina Tosti
  • Leon Axel
  • Muhammad A Khan
  • Erika B Rosenzweig
  • Robert Donnino
  • Robyn J Barst

Detail Information

Publications13

  1. pmc MR characterization of hepatic storage iron in transfusional iron overload
    Haiying Tang
    Imaging, Discovery Medicine and Clinical Pharmacology, Bristol Myers Squibb, Princeton, New Jersey, USA
    J Magn Reson Imaging 39:307-16. 2014
    ..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...
  2. pmc Measurement and correction of stimulated echo contamination in T2-based iron quantification
    Christina L Sammet
    Northwestern University, Chicago, IL 60611, USA
    Magn Reson Imaging 31:664-8. 2013
    ....
  3. pmc Doppler-defined pulmonary hypertension and the risk of death in children with sickle cell disease followed for a mean of three years
    Margaret T Lee
    Division of Pediatric Hematology, Columbia University College of Physicians and Surgeons, New York, NY, USA
    Br J Haematol 146:437-41. 2009
    ..PH may be a manifestation of progressive organ damage from chronic haemolysis and systemic vasculopathy that ultimately leads to early death in adulthood...
  4. pmc Reduced transverse relaxation rate (RR2) for improved sensitivity in monitoring myocardial iron in thalassemia
    Jerry S Cheung
    Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    J Magn Reson Imaging 33:1510-6. 2011
    ....
  5. pmc Rapid monitoring of iron-chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate
    Daniel Kim
    Department of Radiology, Center for Biomedical Imaging, New York University School of Medicine, New York, NY 10016, USA
    NMR Biomed 24:771-7. 2011
    ..Although further studies are needed, myocardial RR(2) may be a promising investigational method for the rapid assessment of the effects of iron-chelating therapy in the heart...
  6. pmc Magnetic resonance assessment of iron overload by separate measurement of tissue ferritin and hemosiderin iron
    Ed X Wu
    Department of Electrical and Electronic Engineering, University of Hong Kong, Pokfulam, Hong Kong, China
    Ann N Y Acad Sci 1202:115-22. 2010
    ..Measurement of tissue ferritin iron is a promising new means to rapidly evaluate the effectiveness of iron-chelating regimens...
  7. pmc Separate MRI quantification of dispersed (ferritin-like) and aggregated (hemosiderin-like) storage iron
    Jens H Jensen
    Department of Radiology, New York University School of Medicine, Center for Biomedical Imaging, New York, New York 10016 3295, USA
    Magn Reson Med 63:1201-9. 2010
    ....
  8. pmc Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation
    Eldad A Hod
    Department of Pathology and Cell Biology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
    Blood 115:4284-92. 2010
    ..Nonetheless, these findings must be confirmed by prospective human studies...
  9. pmc Numerical and in vivo validation of fast cine displacement-encoded with stimulated echoes (DENSE) MRI for quantification of regional cardiac function
    Li Feng
    Department of Biomedical Engineering, Polytechnic Institute of New York University, Brooklyn, New York 10016, USA
    Magn Reson Med 62:682-90. 2009
    ..01 and -0.02). The strain measurements by fast cine DENSE and myocardial tagged MRI were strongly correlated (correlation coefficient = 0.92) and in good agreement (mean difference = 0.01; 95% limits of agreement were 0.07 and -0.04)...
  10. pmc Myocardial T2 quantitation in patients with iron overload at 3 Tesla
    Hua Guo
    Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
    J Magn Reson Imaging 30:394-400. 2009
    ..To investigate the feasibility of measuring myocardial T2 at 3 Tesla for assessment of tissue iron in thalassemia major and other iron overloaded patients...
  11. pmc Breathhold multiecho fast spin-echo pulse sequence for accurate R2 measurement in the heart and liver
    Daniel Kim
    Department of Radiology, New York University School of Medicine, New York, NY 10016, USA
    Magn Reson Med 62:300-6. 2009
    ..99) and in excellent agreement (mean difference [CPMG - FSE] = 0.10 s(-1); 95% limits of agreement were 1.98 and -1.78 s(-1)) between the two pulse sequences...
  12. ncbi Methods for noninvasive measurement of tissue iron in Cooley's anemia
    Sujit Sheth
    Department of Pediatrics, Columbia University College of Physicians and Surgeons, Harkness Pavilion, Room HP5, 180 Fort Washington Avenue, New York, NY 10032, USA
    Ann N Y Acad Sci 1054:358-72. 2005
    ....