Optimizing Tissue Iron Quantification at 3 Tesla

在 3 特斯拉下优化组织铁定量

• 批准号: 8915144
• 负责人: JOHN C WOOD
• 金额: $ 39.43万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8915144
• 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; Health; 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; 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; response; screening; standard of care; tool; uptake; validation studies

DESCRIPTION (provided by applicant): 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 fo 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.

描述（由申请人提供）：铁超负荷是由于遗传性血糖症和丘脑中性疾病中介导的高吸附而引起的令人惊讶的常见临床并发症，或者是血红蛋白或骨骼衰竭患者的复发性输血。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 tesla（1.5t）MRI来量化心脏，肝脏，胰腺和垂体中的铁负担，并根据MRI参数R2和R2*对临床风险进行分层。结果，MRI衍生的肝脏和心铁的估计已成为血红蛋白病中心的护理标准，并被接受以替代铁螯合治疗的临床试验。 迄今为止，铁定量限制为1.5T磁铁。然而，新开发的3台特斯拉（3T）磁铁可能会改善对末端器官毒性的识别，并洞悉组织铁矿沉积物的大小和物种，但需要新的方法来对某些患者观察到高肝铁浓度（LIC）。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）将被邀请接受研究3T检查和内分泌/肝功能的血清学评估。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）以及垂体测量值（n = 60）将进行检查。我们假设在3T处的R2和R2*将相对于1.5T但在不同斜率下的测量值线性扩展。我们进一步假设，与单独的铁评估相比，对器官体积和脂肪浓度的3T评估将更好地区分目标器官的毒性。 我们的第二个目的是开发和验证新的成像工具，以克服3T时肝铁定量的当前动态范围限制，并利用高场测量产生的改进的组织特征。快速信号损失电流可阻止在3T时测量高LIC值。我们将使用新颖的方法，包括超短回声时间技术以及线圈定位的自由感应衰减和自旋 - 回声采集，以准确测量3T的高LIC。线圈定位的多回声旋转回波采集也将用于测量肝中血压素聚集体和胞质铁蛋白的差异信号衰减特性。我们假设一周的预扣铁螯合疗法可以发现肝脏中的胞质铁蛋白库，同时使血压素池保持不变。恢复治疗应扭转观察结果。在如此短时间内跟踪肝铁储存的变化的能力对于快速评估对治疗的反应以及研究肝铁摄取和清除的机制和动力学可能是有价值的。这项工作将扩大患者获得非侵入性铁估计的机会，改善临床前铁毒性的检测，并为铁储存池动态变化提供新的见解。