Low-Cost, Noninvasive Liver Iron Measurements in African American Iron Overload

非洲裔美国人铁超载的低成本、无创肝铁测量

• 批准号: 8000450
• 负责人: William F Avrin
• 金额: $ 10万
• 依托单位: INDEPENDENT SCHOLAR--AVRIN, WILLIAM F.
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-10 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8000450
• 关键词: Address; Affect; African American; American; Blood Transfusion; Books; Cardiac; Cardiomyopathies; Caring; Case Study; Caucasians; Caucasoid Race; Cells; Characteristics; Chronic; Clinical Management; Clinical Research; Clinics and Hospitals; Collaborations; Cost Analysis; Deposition; Devices; Diabetes Mellitus; Dialysis procedure; Disease; Dysmyelopoietic Syndromes; Engineering; Ferritin; Genetic; Goals; Hand; Health; Heart Diseases; Helium; Hematologic Neoplasms; Hematological Disease; Hemochromatosis; Hemodialysis; Hereditary hemochromatosis; Inflammation; Insulin Resistance; Iron; Iron Metabolism Disorders; Iron Overload; Italy; Kidney Diseases; Knowledge; Liquid substance; Liver; Liver diseases; Magnetic Resonance Imaging; Magnetism; Marketing; Measurement; Measures; Medical; Medical Device; Metabolic syndrome; Methods; Modeling; Monitor; Mutation; Patients; Phase; Population Sizes; Population Study; Predisposition; Prevalence; Production; Radiology Specialty; Research; Research Design; Research Personnel; Resolution; Risk; Science; Serum; Sickle Cell Anemia; Small Business Technology Transfer Research; Squid; System; Technology; Temperature; Temperature Sense; Testing; Thalassemia; Tissues; Transferrin; Transfusion; Universities; Visit; Work; alpha-Thalassemia; clinically relevant; cost; cost effective; design; health care delivery; improved; iron metabolism; liver biopsy; magnetic field; medically underserved population; metal transporting protein 1; novel diagnostics; patient population; phase 2 study; programs; prototype; public health relevance; quantum; research study; response; statistics; tool

DESCRIPTION (provided by applicant): This STTR program will test the utility of a low-cost device for noninvasive liver iron measurements, by using the device to determine the prevalence of iron overload in African Americans. African American iron overload is both an under-studied health issue in a medically underserved population, and an example of the wider problem of mild to moderate iron overload in conditions such as liver disease and metabolic syndrome. In all of these settings, the prevalence, causes and effects of excess iron are poorly understood, in part because existing methods of measuring iron stores are unreliable (serum ferritin), invasive (liver biopsy), or expensive and inconvenient (magnetic resonance imaging). The new device offers a new way to measure iron stores. This room-temperature magnetic susceptometer uses inexpensive technology to detect the magnetic-field response of iron in the liver. It can potentially make liver iron measurements in any hospital clinic, for a fifth of the cost of MRI. Recent tests show that new system is well correlated (r=0.93) with existing susceptometers that use Super- conducting QUantum Interference Devices (SQUIDs), in patients with transfusional iron overload. However, to benefit the largest numbers of patients, the new device needs to measure not only the severely elevated liver iron caused by chronic blood transfusions, but the milder iron elevations characteristic of metabolic syndrome, liver disease and African American iron overload. This program aims to achieve that improved accuracy, and demonstrate the low-cost susceptometer's usefulness as a tool to study iron overload. Phase I has three specific aims: 1. Improve susceptometer's accuracy by more effectively correcting for tissue overlying the liver. 2. Validate accuracy by determining measurement variability in subjects with normal iron stores. 3. Design Phase II study investigating prevalence, effects and causes of African American iron overload. Phase II will (a) further improve measurement accuracy as needed, (b) compare liver iron in normal subjects and patients whose serum ferritin and transferrin saturation indicate increased risk of iron overload, and (c) examine associations of elevated liver iron with health effects including liver damage, cardiomyopathy and diabetes, as well as genetic changes affecting iron metabolism. This project, in collaboration with Victor Gordeuk of Howard University, will put the new iron measurement system in the hands of an established iron-overload research program. It will both improve our understanding of iron overload in African Americans, and show that an inexpensive device can measure the mild to moderate iron overloads found in diseases that affect millions of patients. This broader capability may open up a $300M/year market for noninvasive measurements of iron stores. This project thus advances both medical science and medical device technology. PUBLIC HEALTH RELEVANCE: This program will illuminate the poorly understood health problem of iron overload, or accumulation of excess iron, in African Americans. It will also give clinicians and medical researchers an affordable, accurate, non-invasive way to measure iron overload in many other settings, such as sickle-cell disease, liver disease, metabolic syndrome, blood disorders such as myelodysplastic syndrome, and dialysis for kidney disease. This new diagnostic tool, and the improved medical knowledge that it makes possible, will benefit millions of patients.

描述（由申请人提供）：该STTR项目将通过使用低成本设备确定非裔美国人铁过载的患病率，测试该设备用于无创肝脏铁测量的实用性。非裔美国人的铁超载既是一个未充分研究的健康问题，在医疗服务不足的人口，和一个例子，更广泛的问题，轻度至中度铁超载的条件，如肝脏疾病和代谢综合征。在所有这些情况下，对过量铁的患病率、原因和影响知之甚少，部分原因是现有的测量铁储存的方法不可靠（血清铁蛋白）、侵入性（肝活检）或昂贵且不方便（磁共振成像）。新设备提供了一种测量铁储存的新方法。这种室温磁共振仪使用廉价的技术来检测铁在肝脏中的磁场响应。它可以在任何医院诊所进行肝脏铁测量，成本仅为MRI的五分之一。最近的测试表明，新系统与使用超导量子干涉装置（SQUID）的现有心率计在输血性铁过载患者中具有良好的相关性（r=0.93）。然而，为了使最大数量的患者受益，新设备不仅需要测量由慢性输血引起的严重升高的肝脏铁，而且还需要测量代谢综合征，肝脏疾病和非裔美国人铁过载的轻度铁升高。该计划旨在提高准确性，并证明低成本电纳计作为研究铁超载的工具的有用性。第一阶段有三个具体目标：1.通过更有效地校正覆盖肝脏的组织来提高血糖仪的准确性。 2.通过测定正常铁储备受试者的测量变异性来确定准确性。 3.设计II期研究调查非裔美国人铁超载的患病率，影响和原因。第二阶段将（a）根据需要进一步提高测量准确性，（B）比较正常受试者和血清铁蛋白和转铁蛋白饱和度表明铁过载风险增加的患者的肝脏铁，以及（c）检查肝脏铁升高与健康影响（包括肝损伤、心肌病和糖尿病）以及影响铁代谢的遗传变化的关联。该项目与霍华德大学的维克托戈多克合作，将把新的铁测量系统交给一个已建立的铁过载研究计划。它将提高我们对非裔美国人铁过载的理解，并表明一种廉价的设备可以测量影响数百万患者的疾病中发现的轻度至中度铁过载。这种更广泛的能力可能会为铁储存的非侵入性测量开辟3亿美元/年的市场。因此，该项目推动了医学科学和医疗器械技术的发展。 公共卫生关系：该计划将阐明在非裔美国人中，铁过载或过量铁积累的健康问题。它还将为临床医生和医学研究人员提供一种负担得起的，准确的，非侵入性的方法来测量许多其他环境中的铁过载，如镰状细胞病，肝病，代谢综合征，血液疾病，如骨髓增生异常综合征和肾脏疾病透析。这种新的诊断工具，以及它所带来的医学知识的改进，将使数百万患者受益。