The Cardiovascular MRI Laboratory

Research Topics

• Toxicity of iron overload in the heart, endocrine glands and liver
• Use of Magnetic Resonance Imaging (MRI) to detect and quantitate iron burden in the heart, liver and endocrine glands
• Mechanisms of vascular damage in sickle cell anemia and other hemoglobin disorders
• Role of the autonomic nervous system in blood flow regulation in hemoglobin disorders

MRI and Iron Overload

The Cardiovascular MRI Laboratory at the Saban Research Institute has pioneered the use of Magnetic Resonance Imaging (MRI) to detect and quantitate tissue iron in patients suffering from iron overload. We were able to eliminate the need for annual liver biopsies in patients with thalassemia, sickle cell disease and other chronic anemia syndromes, integrating our MRI techniques into routine clinical practice. We have also validated MRI estimates in the heart, pancreas, and pituitary gland, allowing us to protect patients from debilitating and sometimes lethal damage to these organs. 
Our MRI tools have also allowed us to study the mechanisms of organ iron uptake, revealing important disparities in iron uptake and clearance rates. Basic investigations in our laboratory have focused on mechanisms in myocardial iron transport, cardiac iron chelation therapy and mechanisms of tissue-iron interaction during MRI acquisition. Future work in this area includes validating our MRI techniques at 3 Tesla, developing international networks to export our technologies to the Middle and Far East.

Abnormal Hemoglobin and Vascular Dysfunction

A second major focus of our laboratory is on the mechanisms of autonomic and vascular dysregulation observed in patients with hemoglobin disorders. We are studying the basic interactions of red cells and blood vessels to understand how abnormal hemoglobins produce vascular dysfunction. We are currently studying how iron overload, ascorbate deficiency and hemolysis impair systemic and pulmonary vascular function. Future work will explore how oxygen saturation and blood viscosity regulate cerebrovascular flow in sickle cell disease (SCD).

Key Findings

1. We were the first to validate MRI measurements of liver iron, eliminating the need for painful liver biopsy in our patients with thalassemia and sickle cell disease.
2. We demonstrated that the novel oral iron chelator, deferasirox, eliminates cardiac iron and protects the heart.
3. We derived fundamental models of iron-proton interactions that accurately predict MRI-iron calibration curves in real patients.
4. We proved that MRI measurements of pancreatic and pituitary iron predict dysfunction of these organs.
5. We demonstrated the flow mediated dilation of the brachial artery predicts pulmonary vascular disease severity in children with sickle cell disease and primary pulmonary hypertension.

Current Funding

1. We are studying the role of transfusional iron overload in promoting vascular damage in patients with sickle cell disease. Our laboratory also receives support from the NFL Charities Foundation to study why athletes with sickle cell trait are at higher risk for muscle damage and death. Novartis GA supports basic and clinical studies of the iron chelator, deferasirox.
2. Current Grants
   • Iron Mediated Vascular Disease in Sickle Cell Disease. 1RC HL099412-01, National Heart Lung and Blood Institute.
   • The Role of Glutamine in Red Cell Oxidative Stress and Viscosity in Subjects with Sickle Cell Trait. NFL Charities 2010 Med Res Grant.
   • TCD with Transfusions Changing to Hydroxyurea (TWiTCH): Sub-study to evaluate prevalence and consequences of hepatic, pancreatic and renal iron overload. 1R01 HL095647-01, National Heart Lung and Blood Institute.
   • Changes in pituitary iron and volume with deferasirox therapy in transfusional iron overload. US29T, Novartis Pharmaceuticals of North America.
   • Evaluation of the effects of vitamin C and deferasirox in iron loaded animals. Novartis GA.