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

描述（由申请人提供）： 该项目将验证新的高转变温度（高Tc;在77 ° K下工作，由液氮冷却）超导磁流变仪作为监测需要长期红细胞输血患者铁过载的最有效临床手段。输血性铁超负荷是一种罕见病，发生在需要定期输血以治疗各种难治性贫血的患者中，这些难治性贫血本身就是罕见病，包括镰状细胞病、重型地中海贫血（库利氏贫血）、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疾病。在美国，输血性铁过载的贫血患者人数估计不到50，000人。如果不进行铁螯合治疗，这些患者体内可能会积累致命量的铁。用能够螯合铁并允许其从体内排泄的螯合剂治疗提供了一种管理输血铁过载的方法，其可以延长存活并避免或改善铁诱导的器官损伤。患者的最佳管理需要仔细监测体内铁，以防止铁诱导的毒性，同时避免过量螯合剂给药的不良反应。 低转变温度（低Tc;在4 K下工作，由液氦冷却）超导量子干涉仪（SQUID）超导测量法最初是作为一种临床方法开发的，用于定量肝脏铁储备。磁测量的安全性、简便性、快速性和舒适性使得频繁的系列研究在技术上可行，并且实际上为患者所接受。最近，一系列技术突破和仪器创新已经取得，使得在液氦中在4 <$K下工作的低Tc温度计的元件的替换、重新设计和改进成为可能，其中部件能够在液氮中在77 <$K下工作。 拟定的II期临床研究旨在检验以下假设：使用新型高Tc流速仪测量肝脏铁储备在临床上上级所有其他可用方法，并提供FDA批准医疗器械所需的基本数据。该项目有三个具体目标：（1）用接受肝移植的成人和儿童患者的肝组织和临床肝活检组织的生化分析结果校准高Tc流速计;（2）以高效率为目标，Tc流速计，以及成人和儿童患者肝外植体和临床指征肝活检组织的生化分析结果;和（3）前瞻性地比较通过高Tc流速计测量的肝铁浓度与（i）从肝磁共振成像（MRI）弛豫速率（R2，R2*，信号强度比）得到的估计值，（ii）血清铁蛋白的测定，和（iii）组织病理学检查，使用肝贮存铁浓度的生化分析作为参考标准。

DESCRIPTION (provided by applicant): This project will validate the 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. Low-transition-temperature (low-Tc; operating at 4¿K, cooled by liquid helium) superconducting quantum interference device (SQUID) susceptometry was originally developed 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, a series of technological breakthroughs and instrumental innovations have been made 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 the 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.