MRI Quantitation of Tissue Iron in Hematologic Disorders

描述（由申请人提供）： 慢性铁超负荷导致组织中铁沉积增加。在慢性输血地中海贫血患者中，外源性铁储存在脾脏、肝脏、内分泌器官和心脏中。相比之下，遗传性血色素沉着症由于从饮食中过度吸收铁而发生铁过载。在这两种疾病中，将铁水平控制在毒性阈值以下至关重要。此外，由于血清铁蛋白水平与组织铁水平不平行，因此必须定期进行肝活检。该程序的侵入性要求替代的，创伤较小的方法进行多器官铁筛查。 在这里，我们建议实施，验证和应用于地中海贫血患者，一个基于MRI的定量组织铁映射技术，重点是肝脏和心脏，以评估组织铁水平可以准确和可重复测量的假设。该方法基于研究人员实验室开发的GESFIDE成像技术。该方法允许有效地测量T2'和T2，即RF可逆和RF不可逆的横向弛豫时间，已知两者在升高的组织铁水平下降低。 将努力实现以下具体目标： 1.我们将在1.5 T和3T下全面开发和实施改进的GESFIDE MRI铁标测技术，并在人类志愿者中检查其性能。 2.我们将评估该方法的准确性的一个小鼠模型的地中海贫血的标本相比，化学测定。 3.我们将在30例地中海贫血患者的初步研究中，在三年的观察期内，在三个时间点测量心脏和肝脏中的铁水平，并将结果与肝活检数据以及年龄和性别匹配的对照组的结果进行比较。 4.在特定目标3的患者中，我们将通过MR评价心脏功能，以检验功能受损的严重程度与心脏铁超负荷程度相关的假设。

DESCRIPTION (provided by applicant): Chronic iron overload leads to increased iron deposition in tissues. In chronically-transfused thalassemia patients, exogenous iron is stored in the spleen, liver, endocrine organs and heart. By contrast, in hereditary hemochromatosis iron overload occurs as a result of excessive absorption of iron from the diet. In both diseases, control of iron levels below the toxic threshold is essential. Further, since serum ferritin levels do not parallel tissue iron levels, periodic liver biopsies have to be performed. The invasive nature of this procedure calls for alternative, less traumatic approaches for multi-organ iron screening. Here we propose to implement, validate and apply to patients with thalassemia, a MRI-based quantitative tissue iron mapping technique focusing on the liver and heart, to evaluate the hypothesis that tissue iron levels can be measured accurately and reproducibly. The method is based on the GESFIDE imaging technique developed in the investigators' laboratory. This method allows efficient measurement of T2'and T2, the RF-reversible and RF-irreversible transverse relaxation times, both known to be reduced at elevated tissue iron levels. The following specific aims will be pursued: 1. We shall fully develop and implement improved GESFIDE MRI iron mapping technique at 1.5 and 3T and examine its performance in human volunteers. 2. We shall evaluate the method's accuracy on specimens of a murine model of thalassemia in comparison to chemical assay. 3. We shall, in a pilot study of 30 patients with thalassemia, measure iron levels in the heart and liver at three time points during a three-year observation period and compare the results with liver biopsy data and to results in age- and gender-matched controls. 4. We shall, in the patients of specific aim #3, evaluate cardiac function by MR to test the hypothesis that the severity of impaired function is associated with the degree of cardiac iron overload.