Massive Iron Deposit Assessment (MIDAS)

大量铁矿床评估（MIDAS）

• 批准号: 8462599
• 负责人: CLAUDIA M HILLENBRAND
• 金额: $ 31.41万
• 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 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8462599
• 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; 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; screening

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.

描述（由申请人提供）：铁超载是一种由胃肠道铁吸收增加或多次输血引起的严重并发症，在美国影响着数十万人，其筛查和治疗需要大量费用。由于机体没有清除铁的生理机制，反复输铁会导致铁在器官内积聚，导致铁中毒。铁超载的准确评估是至关重要的定量过量铁积累和监测反应铁螯合治疗。磁共振成像（MRI）方法通过铁对组织松弛特性的影响间接测量铁，已被用于无创测量肝铁浓度（HIC）。尽管基于mri的横向弛豫率（R2和R2*）测量准确预测活检证实的HICs低于15mgFe/g，但先前的研究表明，其精度对HICs高于15mgFe/g有限，高于25mgFe/g则不准确。目前的R2*梯度回波（GRE） MR技术偶尔会对非常高的铁过载（HIC~15-25mgFe/g）失败，并且总是对大量铁过载（HIC>25mgFe/g）失败，因为R2*太高了，MR信号在可以准确测量之前就衰减了。大规模铁矿床评估（MIDAS）研究旨在通过采用超短回波时间（UTE）成像来改善松弛曲线的采样，扩大基于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），允许检测非常快的信号衰减和更高的R2*拟合精度。UTE序列的最小te值约为505s，能够准确定量非常高的铁浓度。我们的目标是：(1)开发、测试和实现用于HIC定量的多回波R2*-UTE屏气序列，以及(2)测试R2*-UTE在估计大量铁负荷患者HIC时的准确性。多回声屏气R2*-UTE序列将首先实现并集成到MR扫描仪中。然后，R2*-UTE序列将在大范围R2*值的幻影和健康志愿者中进行测试。最后，约200名患者将接受R2*-GRE和R2*-UTE MRI扫描。其中，约35例重度铁超载患者预计无法通过R2*-GRE筛查，需要临床指示的肝活检进行铁定量。本队列的研究数据将以肝活检HIC为参考方法建立R2*-UTE模型。提出的活检校准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法，并确保对该组患者进行适当剂量的强化铁卸载治疗。这将减少因不必要接触铁螯合而引起的治疗相关毒性，并显著改善患者的护理和生活质量。

项目成果

Quantitative Susceptibility Mapping Using a Multispectral Autoregressive Moving Average Model to Assess Hepatic Iron Overload.

• DOI: 10.1002/jmri.27584
• 发表时间: 2021-09
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Tipirneni-Sajja, Aaryani;Loeffler, Ralf B.;Hankins, Jane S.;Morin, Cara;Hillenbrand, Claudia M.
• 通讯作者: Hillenbrand, Claudia M.

Quantitative ultrashort echo time imaging for assessment of massive iron overload at 1.5 and 3 Tesla.

• DOI: 10.1002/mrm.26592
• 发表时间: 2017-11
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Krafft AJ;Loeffler RB;Song R;Tipirneni-Sajja A;McCarville MB;Robson MD;Hankins JS;Hillenbrand CM
• 通讯作者: Hillenbrand CM

Automated vessel exclusion technique for quantitative assessment of hepatic iron overload by R2*-MRI.

通过 R2*-MRI 定量评估肝铁过载的自动血管排除技术。

• DOI: 10.1002/jmri.25880
• 发表时间: 2018
• 期刊: Journal of magnetic resonance imaging : JMRI
• 作者: Tipirneni-Sajja,Aaryani;Song,Ruitian;McCarville,MBeth;Loeffler,RalfB;Hankins,JaneS;Hillenbrand,ClaudiaM
• 通讯作者: Hillenbrand,ClaudiaM

Fast quantitative parameter maps without fitting: Integration yields accurate mono-exponential signal decay rates.

• DOI: 10.1002/mrm.26964
• 发表时间: 2018-06
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Song R;Loeffler RB;Holtrop JL;McCarville MB;Hankins JS;Hillenbrand CM
• 通讯作者: Hillenbrand CM

Simultaneous field and R2 mapping to quantify liver iron content using autoregressive moving average modeling.

• DOI: 10.1002/jmri.23545
• 发表时间: 2012-05
• 期刊: JOURNAL OF MAGNETIC RESONANCE IMAGING
• 影响因子: 4.4
• 作者: Taylor, Brian A.;Loeffler, Ralf B.;Song, Ruitian;McCarville, M. Beth;Hankins, Jane S.;Hillenbrand, Claudia M.
• 通讯作者: Hillenbrand, Claudia M.