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

项目总结 美国有超过1370万儿童肥胖，他们都是非酒精性脂肪性肝病的高危人群 (NAFLD)，可导致纤维化和进展为肝功能衰竭。非酒精性脂肪肝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。对内脏的准确评估 脂肪组织和肝脏脂肪和纤维化对于了解、早期诊断和评估 治疗儿童肥胖和非酒精性脂肪肝的新疗法。然而，缺乏适合儿童的技术来 对内脏脂肪组织和肝脏脂肪及纤维化进行量化。传统的人体成像技术 成分涉及辐射，不测量单个脂肪组织隔间。虽然肝脏 活检是诊断的金标准，这一过程是侵入性的，需要麻醉，而且有并发症。 此外，活检结果可能是非特异性的，并受到抽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)是很有前途的非侵入性技术。磁共振成像 量化内脏脂肪组织和肝脏脂肪。MRE对肝纤维化进行量化。MRI和MRE不需要 电离辐射或活组织检查。然而，目前的MRI/MRE技术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的运动。对于幼儿和婴儿来说，屏息不是 有可能。即使在能够屏气的儿童中，屏气不一致和能力降低也会导致长时间 扫描时间、损坏的图像、扫描失败和不可靠的结果。虽然镇静可以促进屏气，但它 与负面副作用有关。因此，目前的MRI/MRE技术通常会将许多儿童排除在外。 为了克服这些限制，研究小组创造了新的自由呼吸(FB)3D放射状核磁共振成像 儿童和婴儿内脏脂肪组织和肝脏脂肪的量化技术。研究小组还 开发了新的2D放射状FB-MRE技术来量化儿童肝纤维化。这个项目的目标是 目的是进一步开发和评价FB-MRI/MRE。研究团队将减少FB-MRI/MRE扫描时间，同时 保持高图像质量，展示高水平的准确性和精密度，验证FB-MRI/MRE结果 针对活检，并在不能屏气的人群中测试FB-MRI。研究小组将利用 在同时多层成像、稀疏约束张量图像重建和自组织成像方面的创新 导航至：1)开发新的放射状FB-MRI/MRE技术，量化内脏脂肪组织和肝脏脂肪 和纤维化，快速扫描时间(1-2分钟)和最少的运动伪影，2)测量 新的FB-MRI/MRE用于量化这些生物标志物，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将提高对该病的早期诊断、治疗监测以及对其的了解和管理 儿童肥胖、非酒精性脂肪肝和其他肝脏疾病。

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.