Optimizing Tissue Iron Quantification at 3 Tesla

在 3 特斯拉下优化组织铁定量

• 批准号: 8630935
• 负责人: JOHN C WOOD
• 金额: $ 40.98万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8630935
• 关键词: Abdomen; Address; Biological Markers; Biopsy; Blood Transfusion; Calibration; Clinical; Clinical Trials; Complication; Deposition; Detection; Disease; Endocrine; Endocrine Glands; Equilibrium; Fatty acid glycerol esters; Ferritin; Heart; Hemoglobinopathies; Hemosiderin; Hepatic; Hereditary hemochromatosis; Image; Imaging Device; Individual; Iron; Iron Chelation; Iron Overload; Laboratories; Lead; Left; Liver; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measurement; Measures; Mediating; Methods; Metric; Modeling; Monitor; Noise; Organ; Outcome Measure; Pancreas; Pancytopenia; Patients; Performance; Physiologic pulse; Pituitary Gland; Poison; Property; Protocols documentation; Publishing; Recurrence; Relaxation; Research; Risk; Sampling; Scanning; Serological; Serum; Signal Transduction; Spectrum Analysis; Stratification; Suspension substance; Suspensions; Syndrome; System; Techniques; Texture; Thalassemia intermedia; Therapeutic; Time; Tissues; Toxic effect; Training; Validation; Work; clinical risk; improved; insight; iron chelation therapy; liver biopsy; novel; novel strategies; pre-clinical; prevent; primary outcome; public health relevance; response; screening; standard of care; tool; uptake; validation studies

ABSTRACT Iron overload is a surprisingly common clinical complication, resulting from hyperabsorption, as in hereditary hemochromatosis and thalassemia intermedia, or from recurrent blood transfusions in patients with hemoglobinopathies or bone-marrow failure. Iron accumulates silently for years but ultimately poisons the liver, endocrine glands and heart. Our laboratory has pioneered the use of 1.5 Tesla (1.5T) MRI to quantify the iron burden in the heart, liver, pancreas, and pituitary gland, stratifying clinical risk according to the MRI parameters, R2 and R2*. As a result, MRI-derived estimates of liver and heart iron have become the standard of care in hemoglobinopathy centers and are accepted surrogates for clinical trials of iron chelation therapy. To date, iron quantification has been limited to 1.5T magnets; however, newly developed 3 Tesla (3T) magnets potentially offer improved recognition of end-organ toxicity and insight into the size and species of tissue iron deposits, but require new approaches to imaging the high liver iron concentrations (LIC) observed in some patients. Our first specific aim is to cross-calibrate and clinically validate R2 and R2* estimates at 3T. Patients who undergo 1.5T scanning for clinical indications (approximately 4 per week) will be invited to undergo a combined research 3T examination and serologic assessment of endocrine/hepatic function. Patients will be stratified to provide a broad sampling of organ iron burdens and underlying disease states; examinations will be performed for heart, liver, and pancreas assessment (n=100) and for pituitary measurements (n=60). We hypothesize that R2 and R2* at 3T will scale linearly with respect to measurements at 1.5T but at different slopes. We further hypothesize that 3T assessments of organ volume and fat concentration will better discriminate target organ toxicity than iron assessment alone. Our second aim is to develop and validate new imaging tools to overcome current dynamic range limitations of liver iron quantification at 3T and to exploit the improved tissue-characterization produced by high field measurements. Rapid signal loss current prevents measurement of high LIC values at 3T. We will use novel approaches, including ultrashort echo time techniques and coil-localized free induction decay and spin- echo acquisitions, to accurately measure high LIC at 3T. Coil-localized multi-echo spin-echo acquisitions will also be used to measure differential signal decay properties of hemosiderin aggregates and cytosolic ferritin in liver. We postulate that withholding iron chelation therapy for one week will detectably increase the cytosolic ferritin pool in the liver while leaving the hemosiderin pool unchanged; resumption of therapy should reverse the observation. The ability to track changes in liver iron store on such a short-time scale may prove valuable for rapidly evaluating response to therapy as well as for studying the mechanisms and dynamics of hepatic iron uptake and clearance. This work will broaden patient access to noninvasive iron estimation, improve detection of preclinical iron toxicity, and offer new insights in dynamic changes of iron storage pools.

抽象的 铁超负荷是由于超吸附而引起的令人惊讶的常见临床并发症，如 遗传性血色素沉着症和丘脑性中间病，或来自患者的复发性输血 血红蛋白病或骨髓衰竭。铁默默积累了多年，但最终毒害肝脏， 内分泌腺和心脏。我们的实验室率先使用1.5特斯拉（1.5T）MRI来量化铁 心脏，肝脏，胰腺和垂体的负担，根据MRI参数对临床风险进行分层 R2和R2*。结果，MRI衍生的肝脏和心铁的估计已成为护理的标准 血红蛋白病中心，被接受的替代铁螯合疗法。 迄今为止，铁定量限制为1.5T磁铁。但是，新开发了3个特斯拉（3T） 磁铁有可能改善对最终器官毒性的认识，并深入了解大小和物种 组织铁沉积，但需要新的方法来对观察到的高肝铁浓度（LIC）成像 一些患者。我们的第一个具体目的是在3T处进行跨校准和临床验证R2和R2*估计值。 对临床适应症进行1.5T扫描的患者（每周约4个）将被邀请参加 接受3T研究和内分泌功能的血清学评估的联合研究。 将对患者进行分层，以提供器官铁负担和潜在疾病状态的广泛采样； 检查心脏，肝脏和胰腺评估（n = 100）和垂体将进行检查 测量（n = 60）。我们假设在3T处的R2和R2*相对于测量将线性扩展 在1.5t但在不同的斜坡上。我们进一步假设器官体积和脂肪的3T评估 浓度比单独的铁评估更好地区分目标器官的毒性。 我们的第二个目标是开发和验证新的成像工具以克服当前动态范围 3T处肝铁定量的局限 现场测量。快速信号损失电流可阻止在3T时测量高LIC值。我们将使用 新的方法，包括超短回声时间技术和线圈 - 局部自由感应衰减和自旋 - 回声采集，以准确测量3T的高级lic。线圈 - 定位的多回波旋转回波采集将 还用于测量血压素聚集体和胞质铁蛋白的差异信号衰减特性 肝。我们假设预扣铁螯合疗法一周会发现胞质 肝脏中的铁蛋白池，同时离开头皮蛋白池不变；恢复治疗应逆转 观察。在如此短时间内跟踪肝脏铁店变化的能力可能证明很有价值 用于快速评估对治疗的反应以及研究肝铁的机制和动力学 吸收和清除。这项工作将扩大患者获得非侵入性铁估计，改进检测 临床前铁的毒性，并为铁储藏池动态变化提供了新的见解。