Magnetic Resonance Fingerprinting Assessments of Lung Disease

项目总结 慢性肺部疾病，如囊性纤维化、肺气肿、哮喘和特发性肺纤维化 (IPF)，给美国医疗保健系统带来了巨大的负担(总计约1500亿美元)。尽管有各种各样的 病因方面，许多肺部疾病的一个共同特征是反复肺部感染或侮辱导致 导致呼吸功能下降，最终导致死亡。不幸的是，目前可用的临床评估 的肺部疾病要么是侵袭性的(支气管肺泡灌洗[BAL])，要么使患者面临显著的反复 电离辐射剂量(X射线和/或计算机断层扫描[CT])，或提供有限的检测灵敏度 局部肺部疾病(BAL、肺活量测定)。因此，敏感的、非侵入性的和辐射的发展- 免费测量急性肺部感染，以及与慢性肺部疾病相关的生理重构， 特别是在早期阶段，为改善患者的医疗保健提供了承诺。 磁共振成像(MRI)是一种安全、非侵入性的技术，能够提供定量 无X光/CT电离辐射的CF肺疾病的评价例如，多重成像 研究还表明，肺灌注/血管形成减少与慢性肺相关。 疾病和肺功能下降。不幸的是，这些传统的核磁共振技术通常需要 多个信号平均值，以获得可靠的定量评估，因此容易受到 呼吸运动的伪影。目前还没有公认的、广泛可用的肺部核磁共振技术：1)可以 专门检测急性肺部感染的进展/解决；以及2)对呼吸运动具有抵抗力 手工艺品。 CWRU的MRI研究小组开创了一种名为Magic的变革性MRI技术 磁共振指纹图谱(MRF)。22在最初的临床研究(自然2013)中，MRF被证明产生了 导致T1、T2弛豫时间同时产生的动态组织特定信号演化轮廓 只需约10秒即可绘制地图。我们最近已经在临床前实施了这种多参数MRF方法学 核磁共振扫描，并已证明MRF可能抵抗呼吸运动伪影。 本项目的目标是开发和验证超短回声时间(UTE)-MRF评估急性脑出血 肺部疾病小鼠模型中的肺部感染(目标1)和肺灌注(目标2)。我们还将评估 这些技术在纵向监测急性和慢性肺部疾病进展方面的敏感性 遗传性囊性纤维化小鼠模型的建立。这些定量的多参数MRF测量将提供 为未来在小鼠模型中进行机制/治疗研究以及最终转化为研究奠定基础 在患有肺病的患者中。

PROJECT SUMMARY Chronic lung diseases, such as cystic fibrosis (CF), emphysema, asthma, and idiopathic pulmonary fibrosis (IPF), place a significant burden on the U.S. health care system (~$150 billion overall). Despite a variety of etiologies, a common feature of many pulmonary diseases is repeated pulmonary infections or insults leading to declining respiratory function, and ultimately, death. Unfortunately, currently available clinical assessments of lung diseases are either invasive (bronchoalveolar lavage [BAL]), expose patients to significant repeated doses of ionizing radiation (X-ray and/or Computed Tomography [CT]), or offer limited sensitivity to detect regional lung disease (BAL, spirometry). Therefore, the development of sensitive, noninvasive, and radiation- free measures of acute lung infections, as well as physiologic remodeling associated with chronic lung disease, especially at early stages, offers the promise of improved health care for patients. Magnetic Resonance Imaging (MRI) is a safe, non-invasive technique capable of providing quantitative assessments of CF lung disease without the ionizing radiation of Xray/CT. For example, multiple imaging studies have also shown that reduced pulmonary perfusion / vascularization is associated with chronic lung disease and declining pulmonary function. Unfortunately, these conventional MRI techniques typically require multiple signal averages to obtain reliable quantitative assessments and are therefore susceptible to respiratory motion artifacts. There are still no established, widely available lung MRI techniques that: 1) can specifically detect the progression/resolution of acute lung infections; and 2) are resistant to respiratory motion artifacts. The MRI research group at CWRU has pioneered a transformative MRI technology called Magnetic Resonance Fingerprinting (MRF).22 In the initial clinical study (Nature 2013), MRF was shown to generate dynamic tissue-specific signal evolution profiles resulting in simultaneous generation of T1, T2 relaxation time maps in ~10 seconds. We have recently implemented this multi-parametric MRF methodology on preclinical MRI scanners and have demonstrated that MRF may be resistant to respiratory motion artifacts.23 The overall objective of this project is to develop and validate Ultrashort Echo Time (UTE)-MRF assessments of acute lung infection (Aim 1) and pulmonary perfusion (Aim 2) in mouse models of lung disease. We will also evaluate the sensitivity of these techniques to longitudinally monitor acute and chronic lung disease progression in a genetic mouse model of cystic fibrosis. These quantitative multi-parametric MRF measurements will provide the basis for future mechanistic/therapeutic studies in mouse models as well as eventual translation to studies in patients with lung disease.