Massive Iron Deposit Assessment (MIDAS)

描述(申请人提供)：铁超载是一种严重的并发症，胃肠道对铁的吸收增加或多次输血，在美国影响数十万人，与其筛查和治疗相关的巨额费用。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，导致铁中毒。准确的铁负荷评估对于量化过量的铁蓄积和监测铁螯合治疗的反应至关重要。磁共振成像(MRI)方法通过铁对组织松弛特性的影响间接测量铁，已被用于非侵入性测量肝脏铁浓度(HIC)。尽管基于MRI的横向弛豫速率测量(R2和R2*)可以准确预测活检证实的HICs低于15mgFe/g，但先前的研究表明，其精度对于高于15mgFe/g的HICs是有限的，超过25mgFe/g是不准确的。目前的R2*梯度回波(GRE)磁共振技术偶尔会在非常高的铁超载(HIC~15-25mgFe/g)和大规模铁超载(HIC&GT；25mgFe/g)时失效，因为R2*太高，MR信号在可以被准确测量之前就会衰减。大规模铁矿床评估(MIDAS)研究旨在通过使用超短回波时间(UTE)成像来改进弛豫曲线的采样，从而扩大基于R2*的HIC测量的临床应用范围。UTE缩短了R2*测量序列的最早采样时间或回波时间(TE)，允许检测到非常快的信号衰减和更高的R2*拟合精度。UTE序列的最小TES约为505s，能够准确量化非常高的铁浓度。我们的目标是(1)开发、测试和实施用于HIC定量的多回声R2*-UTE屏气序列，以及(2)测试R2*-UTE在评估重度铁超负荷患者HIC方面的准确性。将首先实施多回声屏气R2*-UTE序列并将其集成到MR扫描仪中。然后，R2*-UTE序列将在各种R2*值范围内的模体和健康志愿者身上进行测试。最后，大约200名患者将接受R2*-GRE和R2*-UTE MRI扫描。在这些患者中，大约35名铁负荷过高的患者预计不能通过R2*-GRE筛查，并需要临床指示的肝脏活检以进行铁的定量。该队列的研究数据将被用于以肝活检HIC为参考方法建立R2*-UTE模型。拟议的活检校准R2*-UTE技术首次用于定量组织中的铁，将为大规模铁超载患者的HIC定量提供一种无创、准确和成本效益高的活检替代方法，并确保对这一群体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络合物而产生的治疗相关毒性，并显著改善患者的护理和生活质量。

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.