The long-term objective of this proposal is to develop in vivo magnetic resonance (MR) techniques for a reliable non-invasive assessment of iron stores in patients with iron overload due to chronic transfusion therapy for diseases such as thalassemia, sickle cell disease and other blood disorders.
The specific aims of the project are: 1a) to study the T2 of liver tissue under iron overload conditions in vivo and correlate with biopsy determined iron level; 1b) to measure T2 of cardiac tissue from autopsied human hearts and an iron overload gerbil model in vitro and correlate with a chemically determined iron level; 2) to assess a new, non-invasive magnetic susceptibility measurement technique, """"""""the contact reference method,"""""""" that will be applicable for outer myocardium; (3) to develop a non-invasive susceptibility measurement technique for the liver using blood vessel signal as internal reference. An accurate assessment of body iron stores plays a central role in the management of chronically-transfused patients. Current body iron assessment methods are limited to liver biopsy or superconducting quantum interference device (SQUID) susceptometry, but neither is convenient for routine use, and there is no non-invasive technique to evaluate the heart. The focus of this application centers on developing techniques for the liver examination, and characterizing MR properties of heart tissue under iron overload conditions. A spectroscopy sequence with minimum TE 1.5 ms will be used to measure the liver T2 in a 3x3x3 cm3 volume in 30 patients, and correlate the results with biopsy determine iron level; In vitro T2 of 108 specimens from 9 human autopsy hearts and 192 specimens from 48 gerbil hearts will be measured and correlated with the tissue iron level. The magnetic susceptibility of the same human autopsy hearts and gerbil hearts will be evaluated by a contact reference technique: the resonant frequency differences across the interface of tissue and saline reference, obtained by using 3-dimensional gradient echo imaging, will be used to qualify the tissue susceptibility. Finally, an in vivo liver susceptibility measurement technique will be developed: sequential 2-dimensional navigator echo imaging will be used to measure frequency offset, the magnetic susceptibility of the liver will be obtained. For each aim, statistical analysis using linear regression will be done to assess the reliability of iron level predicted by the MR technique.
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