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

4.4.6其他项目信息组成部分：项目概要/摘要 该项目将验证我们新的高转变温度（高Tc;在77 ° K下工作，由液体冷却） 氮）超导磁流变仪作为监测铁的最有效的临床手段 需要长期输注红细胞的患者超负荷。输血铁超载是一个孤儿 在需要定期输血以治疗各种难治性疾病的患者中发生的疾病 贫血本身就是孤儿疾病，包括镰状细胞病、重型地中海贫血（库利氏贫血）、 贫血）、Diamond-Blackfan贫血、再生障碍性贫血、纯红细胞再生障碍性贫血、发育不良和骨髓增生异常 紊乱在美国，据估计，输血铁超负荷的贫血患者人数 低于50，000。如果没有铁螯合疗法，潜在的致命量的铁积累在这些 患者用能够螯合铁并允许其从组织中排泄的螯合剂处理， 身体提供了一种管理输血铁过载的方法，可以延长生存期，避免或 改善铁引起的器官损伤。患者的最佳管理需要仔细监测身体状况 铁，以防止铁诱导的毒性，同时避免过量螯合剂给药的副作用。 我们的实验室最初开发了低转变温度（低Tc;在4 ° K下工作，通过液体冷却 氦）超导量子干涉仪（SQUID）作为临床方法 肝脏铁储备的定量。磁测量的安全性、简便性、快速性和舒适性 使频繁的系列研究在技术上可行，并为患者实际接受。最近我们 取得了一系列技术突破和仪器创新， 更换、重新设计和改进在4 º K液体中工作的低Tc温度计的元件 氦，其组件能够在液氮中在77 ° K下工作。 拟定的II期临床研究旨在检验以下假设： 商店与我们的新的高Tc体温计是临床优于所有其他可用的方法，并提供上级 FDA批准医疗器械所需的基本数据。拟议的项目有三个具体目标： (1)用来自肝移植物的组织的生化分析结果校准高Tc流速计， 接受肝移植和有临床指征的肝活检的成人和儿科患者;以及 (2)用肝脏组织的生化分析结果前瞻性验证高Tc流速计 来自成人和儿科患者以及来自有临床指征的肝活检的外植体;以及 (3)前瞻性比较高Tc流速计测量肝脏铁浓度与（i） 从肝脏磁共振成像（MRI）弛豫速率（R2，R2*，信号强度）导出的估计 比率），（ii）血清铁蛋白测定，和（iii）组织病理学检查，使用 生化分析肝脏储存铁浓度作为参考标准。

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.