Quantifying Body Composition and Liver Disease in Children using Free-Breathing MRI and MRE

项目摘要 美国有超过1370万儿童肥胖，所有儿童都有患非酒精性脂肪肝的高风险。 （NAFLD），其可导致纤维化并进展至肝衰竭。NAFLD是最常见的慢性儿科疾病 肝脏疾病和年轻人肝脏移植的头号适应症。准确评估内脏 脂肪组织、肝脂肪和纤维化对于理解、早期诊断和评估 儿童肥胖和NAFLD的新疗法。然而，缺乏适合儿童的技术， 量化内脏脂肪组织和肝脂肪以及纤维化。传统的身体成像技术 组合物涉及辐射并且不测量个体脂肪组织区室。虽然肝 活检是诊断的金标准，该手术具有侵入性，需要麻醉且有并发症。 此外，活检结果可能是非特异性的，并受到采样偏差和解释变异性的影响。 磁共振成像和弹性成像（MRI和MRE）是有前途的非侵入性技术。MRI 量化内脏脂肪组织和肝脏脂肪。MRE定量肝纤维化。MRI和MRE不需要 电离辐射或活检。然而，当前的MRI/MRE技术并不适合大多数儿童和婴儿 因为它需要屏住呼吸来限制腹部运动。在幼儿和婴儿中，屏气并不是 可能即使在能够屏气的儿童中，屏气的不一致性和能力降低也会导致长时间的呼吸困难。 扫描时间、损坏的图像、失败的扫描和不可靠的结果。虽然镇静剂可以促进屏气， 会带来负面的副作用因此，目前的MRI/MRE技术通常将许多儿童排除在外。 为了克服这些限制，研究小组创建了新的自由呼吸（FB）3D径向堆叠MRI 这项技术可以量化儿童和婴儿的内脏脂肪组织和肝脏脂肪。研究小组还 开发了新的2D径向FB-MRE技术来量化儿童肝纤维化。本项目的目标 进一步开发和评估FB-MRI/MRE。研究团队将减少FB-MRI/MRE扫描时间， 保持高图像质量，展示高水平的准确度和精密度，验证FB-MRI/MRE结果 在不能屏气的人群中进行FB-MRI测试。研究小组将利用 同时多切片成像、稀疏约束张量图像重建和自适应成像的创新 导航到：1）开发新的径向FB-MRI/MRE技术，量化内脏脂肪组织和肝脏脂肪 和纤维化的快速扫描时间（1 - 2分钟）和最小的运动伪影，2）测量的准确性和精密度 用于定量这些生物标志物的新FB-MRI/MRE，3）将FB-MRI/MRE生物标志物与肝活检进行比较 在患有肝病的儿童中，以及4）在婴儿中测试新的FB-MRI技术。创新的径向FB- MRI/MRE技术将可靠地量化儿童和婴儿的身体成分和肝脏疾病。反过来， FB-MRI/MRE将改善早期诊断、治疗监测以及对 儿童肥胖、NAFLD和其他肝脏疾病。

PROJECT SUMMARY More than 13.7 million children in the U.S. are obese, and all are at high risk for non-alcoholic fatty liver disease (NAFLD), which can lead to fibrosis and progress to liver failure. NAFLD is the most common chronic pediatric liver disease and number one indication for liver transplant in young adults. Accurate assessments of visceral adipose tissue and hepatic fat and fibrosis are critical to the understanding, early diagnosis, and evaluation of new treatments for pediatric obesity and NAFLD. However, there is a lack of child-appropriate technologies to quantify visceral adipose tissue and hepatic fat and fibrosis. Conventional imaging techniques for body composition involve radiation and do not measure individual adipose tissue compartments. Although liver biopsy is the gold standard for diagnosis, this procedure is invasive, requires anesthesia and has complications. Moreover, biopsy findings can be non-specific and suffer from sampling bias and interpretation variability. Magnetic resonance imaging and elastography (MRI and MRE) are promising non-invasive technologies. MRI quantifies visceral adipose tissue and hepatic fat. MRE quantifies hepatic fibrosis. MRI and MRE do not require ionizing radiation or biopsy. However, current MRI/MRE technology is not appropriate for most children and infants because it requires breath-holding to limit abdominal motion. In young children and infants, breath-holding is not possible. Even in children who can breath-hold, inconsistency and reduced capacity in breath-holding leads to long scan times, corrupted images, failed scans, and unreliable results. Although sedation can facilitate breath-holding, it is associated with negative side effects. As a result, current MRI/MRE technologies typically exclude many children. To overcome these limitations, the research team created new free-breathing (FB) 3D stack-of-radial MRI technology to quantify visceral adipose tissue and hepatic fat in children and infants. The research team has also developed new 2D radial FB-MRE technology to quantify hepatic fibrosis in children. The objectives of this project are to further develop and evaluate FB-MRI/MRE. The research team will reduce FB-MRI/MRE scan times while maintaining high image quality, demonstrate a high level of accuracy and precision, validate FB-MRI/MRE results against biopsy, and test FB-MRI in a population that cannot breath-hold. The research team will leverage innovations in simultaneous multi-slice imaging, sparsity-constrained tensor image reconstruction, and self- navigation to: 1) Develop new radial FB-MRI/MRE technologies that quantify visceral adipose tissue and hepatic fat and fibrosis with rapid scan times (1-2 min) and minimal motion artifacts, 2) Measure the accuracy and precision of the new FB-MRI/MRE for quantifying these biomarkers, 3) Compare the FB-MRI/MRE biomarkers to liver biopsy in children with liver disease, and 4) Test new FB-MRI technology in infants. The innovative radial FB- MRI/MRE technology will reliably quantify body composition and liver disease in children and infants. In turn, FB-MRI/MRE will improve the early diagnosis, treatment monitoring, and understanding and management of pediatric obesity, NAFLD, and other liver diseases.