Massive Iron Deposit Assessment (MIDAS)

大量铁矿床评估（MIDAS）

• 批准号: 7949909
• 负责人: CLAUDIA M HILLENBRAND
• 金额: $ 44.29万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7949909
• 关键词: Affect; Biopsy; Blood Transfusion; Bone Marrow Transplantation; Cancer Survivor; Cardiac; Cessation of life; Clinical; Clinical Management; Complication; Concentration measurement; Data; Deposition; Detection; Diagnosis; Diamond-Blackfan anemia; Dietary Iron; Dose; Drug toxicity; Dysmyelopoietic Syndromes; Endocrine Glands; Ensure; Erythropoiesis; Exposure to; Functional disorder; Goals; Heart; Hemolytic Anemia; Hemorrhage; Hepatic; Image; Imaging Techniques; Individual; Infection; Intestinal Absorption; Iron; Iron Chelation; Iron Overload; Lead; Liver; Magnetic Resonance Imaging; Measurement; Measures; Methods; Modeling; Monitor; Morbidity - disease rate; Multicenter Trials; Organ; Pain; Patient Care; Patient Monitoring; Patients; Physiologic pulse; Physiological; Population; Populations at Risk; Procedures; Property; Quality of life; Regression Analysis; Relaxation; Reporting; Risk; Sampling; Scanning; Screening procedure; Series; Sickle Cell Anemia; Signal Transduction; Spleen; Techniques; Testing; Thalassemia; Therapeutic; Time; Tissues; Toxic effect; Transfusion; Weight; base; chelation; cohort; cost; healthy volunteer; image reconstruction; imaging modality; improved; iron chelation therapy; liver biopsy; mortality; prevent; public health relevance; response; time use

DESCRIPTION (provided by applicant): Iron overload, a severe complication of increased gastrointestinal absorption of iron or multiple blood transfusions, affects hundreds of thousands of individuals in the US and significant costs are associated with its screening and treatment. As the body has no physiologic mechanism for clearing iron, repeated transfusions cause iron accumulation in organs and lead to iron toxicity. Accurate assessment of iron overload is paramount to quantify excessive iron accumulation and to monitor response to iron chelation therapy. Magnetic resonance imaging (MRI) methods, which indirectly measure iron via its effect on tissue relaxation properties, have been used to noninvasively measure hepatic iron concentration (HIC). Although MRI-based measurements of transverse relaxation rates (R2 and R2*) accurately predict biopsy-proven HICs below 15 mg Fe/g, previous studies have shown that their precision is limited for HICs above 15mgFe/g and inaccurate above 25mgFe/g. Current R2* gradient-echo (GRE) MR techniques fail occasionally for very high iron overloads (HIC~15-25mgFe/g) and always for massive iron overloads (HIC>25mgFe/g) because R2* is so high that the MR signal decays before it can be measured accurately. The Massive Iron Deposit Assessment (MIDAS) study aims to extend the clinically useful range of R2*-based HIC measurements by employing ultra short echo time (UTE) imaging to improve sampling of the relaxation curve. UTE shortens the earliest sampling time, or echo time (TE), of the R2*-measurement sequence, allowing detection of very fast signal decay and a higher R2* fit precision. UTE sequences achieve minimum TEs of approximately 505s, enabling accurate quantification of very high iron concentrations. Our goals are to (1) develop, test, and implement a multi-echo R2*-UTE breath hold sequence for HIC quantitation, and (2) test the accuracy of R2*-UTE in estimating HIC in massively iron-overloaded patients. A multi-echo breath hold R2*-UTE sequence will be first implemented and integrated into the MR scanner. Then, the R2*-UTE sequence will be tested in phantoms over a wide range of R2* values and in healthy volunteers. Finally, approximately 200 patients will be scanned with R2*-GRE and R2*-UTE MRI. Of these, about 35 massively iron-overloaded patients are expected to fail the R2*-GRE screen and to require a clinically indicated liver biopsy for iron quantification. Study data of this cohort will be used for modeling R2*-UTE using HIC by liver biopsy as the reference method. The proposed biopsy-calibrated R2*-UTE technique, being used for the first time to quantitate iron in tissues, will provide a noninvasive, accurate, and cost-effective alternative to biopsy for HIC quantification in massively iron-overloaded patients and ensure appropriate dosing of intensive iron unloading treatment to this group. This will reduce treatment-related toxicity arising from unnecessary exposure to iron chelation and significantly improve patients' care and quality of life. PUBLIC HEALTH RELEVANCE: The accurate quantification of hepatic iron content (HIC) is clinically important in patients who develop massive iron overload because of multiple blood transfusions, in order to monitor response to iron chelation therapy and prevent clinical toxicity from chelation. Our proposed R2*-UTE technique will allow accurate measurement of very high HIC values and is a noninvasive, cost-effective, and suitable alternative to current MRI procedures and liver biopsies to determine iron overload. This technique will greatly benefit populations frequently requiring transfusions, such as patients with hematologic conditions like sickle cell disease and thalassemia, as well as those requiring long-term monitoring of body iron, such as survivors of cancer.

描述（由申请人提供）：铁超载是胃肠道吸收铁增加或多次输血的严重并发症，影响着美国数十万人，其筛查和治疗费用高昂。由于人体没有清除铁的生理机制，反复输血会导致铁在器官中积聚并导致铁中毒。准确评估铁过载对于量化过量铁积累和监测铁螯合疗法的反应至关重要。磁共振成像 (MRI) 方法通过铁对组织松弛特性的影响来间接测量铁，已用于无创测量肝铁浓度 (HIC)。尽管基于 MRI 的横向弛豫率测量（R2 和 R2*）可以准确预测经活检证实的低于 15 mg Fe/g 的 HIC，但之前的研究表明，其精度对于高于 15 mgFe/g 的 HIC 是有限的，而对于高于 25 mgFe/g 的 HIC 则不准确。目前的 R2* 梯度回波 (GRE) MR 技术偶尔会在极高铁过载 (HIC~15-25mgFe/g) 时失败，而在大量铁过载 (HIC>25mgFe/g) 时总是会失败，因为 R2* 太高，导致 MR 信号在准确测量之前就衰减了。大规模铁沉积评估 (MIDAS) 研究旨在通过采用超短回波时间 (UTE) 成像来改进弛豫曲线的采样，从而扩展基于 R2* 的 HIC 测量的临床有用范围。 UTE 缩短了 R2* 测量序列的最早采样时间或回波时间 (TE)，从而可以检测非常快的信号衰减和更高的 R2* 拟合精度。 UTE 序列可实现约 505 秒的最小 TE，从而能够准确定量非常高的铁浓度。我们的目标是 (1) 开发、测试和实施用于 HIC 定量的多回波 R2*-UTE 屏气序列，以及 (2) 测试 R2*-UTE 在估计大量铁超载患者的 HIC 方面的准确性。首先将实施多回波屏气 R2*-UTE 序列并将其集成到 MR 扫描仪中。然后，R2*-UTE 序列将在人体模型中和健康志愿者中进行大范围 R2* 值的测试。最后，大约 200 名患者将接受 R2*-GRE 和 R2*-UTE MRI 扫描。其中，大约 35 名严重铁超载的患者预计无法通过 R2*-GRE 筛查，需要进行临床指示的肝活检以进行铁定量。该队列的研究数据将用于以肝活检 HIC 作为参考方法来建模 R2*-UTE。拟议的活检校准 R2*-UTE 技术首次用于定量组织中的铁，将为大量铁超载患者的 HIC 定量提供一种无创、准确且经济高效的活检替代方案，并确保对该组患者进行适当剂量的强化铁卸载治疗。这将减少因不必要地接触铁螯合剂而产生的与治疗相关的毒性，并显着改善患者的护理和生活质量。 公众健康相关性：肝铁含量 (HIC) 的准确定量对于因多次输血而出现大量铁超负荷的患者具有重要的临床意义，可以监测铁螯合疗法的反应并预防螯合引起的临床毒性。我们提出的 R2*-UTE 技术将允许精确测量非常高的 HIC 值，并且是一种无创、经济高效且适合替代当前 MRI 程序和肝活检以确定铁过载的方法。这项技术将极大地惠及经常需要输血的人群，例如患有镰状细胞病和地中海贫血等血液疾病的患者，以及需要长期监测体内铁的患者，例如癌症幸存者。