This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with thalassemia re often transfusion-dependent, leading to insidious and progressive iron overload. Liver, spleen, bone marrow, heart and endocrine glands are compromised producing inevitable premature cardiac and liver failure in untreated patients. The iron chelator, desfuroxamine, has greatly improved survival and quality of life in these patents, but its requirement for daily subcutaneous infusions leads to significant patient noncompliance. Proper dosing of chelation therapy required monitoring of systemic iron loads. Serologic estimators are not reliable, so liver biopsy remains the cornerstone of therapeutic monitoring. This study proposes to use magnetic resonance imaging (MRI) to estimate liver iron content. MRI has the advantage of being non-invasive, less expensive and can provide information about iron deposition n all body tissues. Recent advances in ultrafast MR techniques, developed for cardiovascular imaging, are expected to yield more sensitive and robust iron estimates than previous approaches. Candidate MR techniques will be validated in thalassemic patients undergoing clinically indicated liver biopsy. While the immediate goal is reduction or elimination of liver biopsies, the long term goal is improved understanding of iron storage and elimination pharmacokinetics in iron overload patients.
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