MRI Quantitation of Tissue Iron in Hematologic Disorders

描述(由申请人提供)： 慢性铁超载会导致组织中铁沉积增加。在长期输血的地中海贫血患者中，外源性铁储存在脾、肝、内分泌器官和心脏中。相反，在遗传性血色沉着症中，铁超载是由于从饮食中过度吸收铁造成的。在这两种疾病中，将铁水平控制在中毒阈值以下是至关重要的。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脏活检。这一过程的侵袭性要求选择创伤较小的替代方法进行多器官铁筛查。 在这里，我们建议实施、验证并应用于地中海贫血患者，这是一种基于MRI的组织铁定量映射技术，重点放在肝脏和心脏，以评估组织铁水平可以准确和重复性测量的假设。该方法基于研究人员实验室开发的GESFIDE成像技术。这种方法可以有效地测量T2‘和T2，即RF可逆和RF不可逆的横向弛豫时间，这两个时间都已知在组织铁水平升高时会缩短。 将致力于实现以下具体目标： 1.我们将在1.5和3T全面开发和实施改进的GESFIDE磁共振铁标测技术，并在人体志愿者身上测试其性能。 2.我们将在地中海贫血小鼠模型的样本上评估该方法的准确性，并将其与化学分析进行比较。 3.在对30名地中海贫血患者的初步研究中，我们将在三年观察期内的三个时间点测量心脏和肝脏中的铁水平，并将结果与肝脏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.在有特殊目的的患者中，我们应该通过磁共振来评估心脏功能，以检验功能受损的严重程度与心脏铁负荷的程度有关的假设。

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.