High-Tc susceptometer to monitor transfusional iron overload (NSR device)

4.4.6其他项目信息组件：项目摘要/摘要 该项目将验证我们新的高温转变温度(高温；工作在77K，由液体冷却 临床上最有效的铁监测手段--超导磁化率计 需要慢性红细胞输注的患者超负荷。输血铁超载是一个孤儿 一种在需要定期输血治疗各种难治性疾病的患者中发展起来的疾病 贫血本身是孤儿疾病，包括镰状细胞病、重型地中海贫血(库利氏病 贫血)、钻石-黑粉贫血、再生障碍性贫血、纯红细胞再生障碍性贫血、发育不良和骨髓发育不良 精神错乱。在美国，输血铁超载的贫血患者的数量估计为 少于50,000。如果没有铁螯合疗法，这些体内可能积累了致命数量的铁。 病人。用一种能够隔离铁并允许其从体内排泄出来的螯合剂进行治疗 Body提供了一种管理输血铁超载的方法，可以延长生存时间并避免 改善铁引起的器官损伤。对病人的最佳管理需要对身体的仔细监测 铁，以防止铁诱导的毒性，同时避免过量使用螯合剂的不良影响。 我们的实验室最初开发了低转变温度(Low-Tc；在4K下工作，由液体冷却) 超导量子干涉仪(SQUID)灵敏度测量作为一种临床方法 肝脏铁储备量的测定。磁性测量的安全性、易用性、快速性和舒适性具有 使频繁、连续的检查在技术上可行，并在实践中为患者所接受。最近，我们 取得了一系列技术突破和工具创新，使之成为可能 更换、重新设计和改进在4K液体中工作的低T_c磁感仪的元件 氦，其成分能够在77K的液氮中发挥作用。 拟议的第二阶段临床研究旨在测试一种假设，即肝铁的测量 使用我们新的高TC磁感仪的商店在临床上优于所有其他可用的方法和供应 FDA批准该医疗器械所需的基本数据。拟议的项目有三个具体目标： (1)用肝组织生化分析结果校准高T_c磁感仪。 接受肝移植的成人和儿童患者以及来自临床指征的肝活检；以及 (2)用肝组织生化分析结果对高T_c磁感仪进行前瞻性验证 来自成人和儿童患者以及临床显示的肝活检的外植体；以及 (3)前瞻性比较高T_c磁感仪测量肝铁浓度与(I)。 从肝脏磁共振成像(MRI)弛豫率(R2，R2*，信号强度)得出的估计 比率)，(Ii)血清铁蛋白的测定，以及(Iii)组织病理学检查，使用 以生化分析中肝脏储藏铁浓度为参考标准。

4.4.6 Other Project Information Component: Project Summary/Abstract This project will validate our new high-transition-temperature (high-Tc; operating at 77¿K, cooled by liquid nitrogen) superconducting magnetic susceptometer as the most clinically effective means for monitoring iron overload in patients who require chronic red blood cell transfusion. Transfusional iron overload is an orphan disease that develops in patients who require regular blood transfusions for treatment of a variety of refractory anemias that are themselves orphan disorders, including sickle-cell disease, thalassemia major (Cooley's anemia), Diamond-Blackfan anemia, aplastic anemia, pure red cell aplasia, hypoplastic and myelodysplastic disorders. In the United States, the number of anemic patients with transfusional iron overload is estimated to be less than 50,000. Without iron-chelating therapy, potentially lethal amounts of iron accumulate in these patients. Treatment with a chelating agent capable of sequestering iron and permitting its excretion from the body provides a means of managing transfusional iron overload that can prolong survival and avert or ameliorate iron-induced organ damage. Optimal management of patients requires careful monitoring of body iron to prevent iron-induced toxicity while avoiding adverse effects of excessive chelator administration. Our laboratories originally developed low-transition-temperature (low-Tc; operating at 4¿K, cooled by liquid helium) superconducting quantum interference device (SQUID) susceptometry as a clinical method for quantitation of hepatic iron stores. The safety, ease, rapidity and comfort of magnetic measurements have made frequent, serial investigations technically feasible and practically acceptable to patients. Recently, we have made a series of technological breakthroughs and instrumental innovations that have made possible replacement, redesign and refinement of the elements of the low-Tc susceptometer, operating at 4¿K in liquid helium, with components able to function at 77¿K in liquid nitrogen. The proposed Phase 2 clinical studies are designed to test the hypothesis that measurements of hepatic iron stores with our new high-Tc susceptometer are clinically superior to all other available methods and to supply essential data needed for FDA approval of the medical device. The proposed project has three specific aims: (1) to calibrate the high-Tc susceptometer with results of biochemical analysis of tissue from liver explants from adult and pediatric patients undergoing liver transplantation and from clinically indicated liver biopsy; and (2) to prospectively validate the high-Tc susceptometer with results of biochemical analysis of tissue from liver explants from adult and pediatric patients and from clinically indicated liver biopsy; and (3) to prospectively compare measurements of hepatic iron concentration by the high-Tc susceptometer with (i) estimates derived from liver magnetic resonance imaging (MRI) relaxation rates (R2, R2*, signal intensity ratios), (ii) with determinations of serum ferritin, and (iii) with histopathological examination, using biochemical analysis of liver storage iron concentrations as the reference standard.