Massive Iron Deposit Assessment (MIDAS)

大量铁矿床评估（MIDAS）

• 批准号: 8117515
• 负责人: CLAUDIA M HILLENBRAND
• 金额: $ 37.55万
• 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/8117515
• 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; cost effective; healthy volunteer; image reconstruction; imaging modality; improved; iron chelation therapy; liver biopsy; mortality; prevent; public health relevance; response

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，胃肠道吸收增加的铁或多种输血的严重并发症会影响美国成千上万的人，以及其筛查和治疗的巨大成本。由于人体没有清除铁的生理机制，因此反复输血会导致器官中的铁积聚并导致铁毒性。对铁超负荷的准确评估对于量化过度的铁积累和监测对铁螯合治疗的反应至关重要。磁共振成像（MRI）方法通过其对组织弛豫特性的影响间接测量铁，已用于非侵入性测量肝铁浓度（HIC）。尽管基于MRI的横向松弛速率（R2和R2*）的测量准确地预测了低于15 mg Fe/g的活检证明的HIC，但先前的研究表明，它们的精度限制在15mgfe/g以上的HIC中，并且不准确，并且不准确25mgfe/g。当前的R2*梯度回波（GRE）MR技术偶尔会因非常高的铁超载而失败（HIC〜15-25mgFe/g），并且始终用于大规模的铁超载（HIC> 25mgFe/g），因为R2*是如此之高，以至于MR信号衰减之前可以准确测量MR信号。大规模的铁矿矿床评估（MIDAS）研究旨在通过采用超短回声时间（UTE）成像来改善放松曲线的采样，以扩展基于R2*的基于R2*的HIC测量。 ute缩短了最早的采样时间或回声时间（TE），即r2*测量序列，从而允许检测非常快的信号衰减和较高的R2*拟合精度。 UTE序列达到约505秒的最小TE，从而可以准确地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* - 呼吸序列，以及（2）测试R2* - ute在估计大量铁载荷患者中HIC方面的准确性。将首先实现并集成到MR扫描仪中的多回波呼吸保持R2*-UTE序列。然后，R2* - 脉冲序列将在范围内的R2*值和健康志愿者中进行测试。最后，将大约200名患者用R2*-GRE和R2*-UTE MRI扫描。其中，预计约35名大量铁载后的患者将失败R2*-GRE筛查，并需要临床上指示的肝活检进行铁定量。该队列的研究数据将用于使用HIC进行肝活检作为参考方法来建模R2*-UTE。提出的经过活检的R2* - 急流技术首次用于定量组织中的铁，将提供无创，准确且具有成本效益的活检替代方法，用于在大规模铁的载荷患者中进行HIC定量，并确保适当地剂量对该组的强化铁卸载治疗。这将减少与治疗相关的毒性，这是由于不必要的铁螯合而引起的，并显着改善了患者的护理和生活质量。 公共卫生相关性：肝铁含量（HIC）的准确定量在临床上对于因多次输血而产生大量铁超负荷的患者至关重要，以监测对铁螯合治疗的反应并防止螯合产生的临床毒性。我们提出的R2*ute技术将允许精确测量非常高的HIC值，并且是当前MRI程序和肝活检的无创，具有成本效益且合适的替代品以确定铁超载。该技术将极大地使人们经常需要输血，例如患有血液学疾病的患者，例如镰状细胞疾病和thalassyalasia，以及需要长期监测身体铁的患者，例如癌症的幸存者。