MRI Method for In Vivo Iron Quantification

描述(由申请人提供)： 这项研究的总体目标是开发一种新的磁共振成像(MRI)技术来量化体内铁的储存。体内铁水平升高可发展为多种疾病，包括遗传性血色素沉着症、重型地中海贫血、骨髓发育不良和镰状细胞性贫血。体内过量的铁或“铁超载”可能是有毒的，并可能导致各种由铁引起的并发症，如糖尿病、肝硬变和心脏病。在诊断和管理铁超载时，量化体内的铁过量是很重要的。临床上普遍使用的两种方法--肝脏活检和血清铁蛋白测定--存在明显的缺陷。肝活检是有创的，对于有肝硬变的肝脏可能不准确，而血清铁蛋白水平与总铁的相关性较差。这项研究将开发一种基于铁对磁共振信号衰减的影响的铁的量化方法。这项研究将优化和验证肝脏组织的技术，因为肝脏铁浓度被认为是铁超载的最佳单一指标。MRI对铁超载进行量化的一个主要优势是，这种方法是完全非侵入性的，可以在治疗期间频繁监测铁水平。所提出的方法与以前使用MRI进行铁定量的尝试显著不同，因为测量的是两个独立的MRI量，而不是一个。这是获得高准确度的关键，因为肝脏中的铁以两种形式存在，铁蛋白铁和含铁血黄素铁，这两种形式以显著不同的方式影响MRI信号衰减。我们的研究将分为两个阶段。首先，我们将使用由悬浮铁颗粒的凝胶组成的组织模型(体模)来开发和测试必要的MRI脉冲序列。其次，该方法将应用于150名铁超载患者。作为验证，MRI的预测将与目前临床黄金标准--肝脏针吸活检的结果相关联。我们还将把核磁共振数据与用鱿鱼生物检验法获得的铁的测量结果进行比较。

DESCRIPTION (provided by applicant): The broad goal of the research is to develop a new magnetic resonance imaging (MRI) technique for quantifying body iron stores. Elevated body iron levels can develop in a variety of disorders, including hereditary hemochromatosis, thalassemia major, myelodysplasia, and sickle cell anemia. Excess body iron or "iron overload" can be toxic and may lead to a variety of iron-induced complications, such as diabetes, cirrhosis, and heart disease. In diagnosing and managing iron overload, it is important to quantify body iron excess. The two generally available clinical methods for doing this, liver biopsy and blood serum ferritin measurement, suffer from significant shortcomings. Liver biopsy is invasive and may be inaccurate for liver with cirrhosis, while the serum ferritin level correlates poorly with total body iron. The research would develop a method for iron quantification based on the effect of iron on MRI signal decay. The research would optimize and validate the technique for liver tissue, since liver iron concentration is considered the best single indicator of iron overload. A major advantage of MRI quantification of iron overload is that this method is completely non-invasive, which allows the frequent monitoring of iron levels during therapy. The proposed approach differs markedly from prior attempts to use MRI for iron quantification, in that two independent MRI quantities, rather than one, are measured. This is critical for obtaining a high accuracy, as iron in the liver comes in two forms, ferritin iron and hemosiderin iron, which affect MRI signal decay in significantly different ways. Our research will be divided into two stages. First, we will develop and test the necessary MRI pulse sequences using a tissue model (phantom) consisting of a gel with suspended iron particles. Second the method will be applied to 150 iron overload patients. As validation, the MRI predictions will be correlated to results of needle biopsy of the liver, the current clinical gold standard. We will also compare the MRI data to iron measurements obtained with SQUID biosusceptometry.