Bianchi Andrea, Tibiletti Marta, Kjørstad Åsmund, Birk Gerald, Schad Lothar R, Stierstorfer Birgit, Rasche Volker, Stiller Detlef
Boehringer Ingelheim Pharma GmbH & Co. KG, Target Discovery Research, In-Vivo Imaging Laboratory, Biberach an der Riss, Germany.
Core Facility Small Animal MRI, Ulm University, Ulm, Germany.
NMR Biomed. 2015 Nov;28(11):1471-9. doi: 10.1002/nbm.3417. Epub 2015 Sep 24.
Emphysema is a life-threatening pathology that causes irreversible destruction of alveolar walls. In vivo imaging techniques play a fundamental role in the early non-invasive pre-clinical and clinical detection and longitudinal follow-up of this pathology. In the present study, we aimed to evaluate the feasibility of using high resolution radial three-dimensional (3D) zero echo time (ZTE) and 3D ultra-short echo time (UTE) MRI to accurately detect lung pathomorphological changes in a rodent model of emphysema.Porcine pancreas elastase (PPE) was intratracheally administered to the rats to produce the emphysematous changes. 3D ZTE MRI, low and high definition 3D UTE MRI and micro-computed tomography images were acquired 4 weeks after the PPE challenge. Signal-to-noise ratios (SNRs) were measured in PPE-treated and control rats. T2* values were computed from low definition 3D UTE MRI. Histomorphometric measurements were made after euthanizing the animals. Both ZTE and UTE MR images showed a significant decrease in the SNR measured in PPE-treated lungs compared with controls, due to the pathomorphological changes taking place in the challenged lungs. A significant decrease in T2* values in PPE-challenged animals compared with controls was measured using UTE MRI. Histomorphometric measurements showed a significant increase in the mean linear intercept in PPE-treated lungs. UTE yielded significantly higher SNR compared with ZTE (14% and 30% higher in PPE-treated and non-PPE-treated lungs, respectively).This study showed that optimized 3D radial UTE and ZTE MRI can provide lung images of excellent quality, with high isotropic spatial resolution (400 µm) and SNR in parenchymal tissue (>25) and negligible motion artifacts in freely breathing animals. These techniques were shown to be useful non-invasive instruments to accurately and reliably detect the pathomorphological alterations taking place in emphysematous lungs, without incurring the risks of cumulative radiation exposure typical of micro-computed tomography.
肺气肿是一种危及生命的病理状况,会导致肺泡壁的不可逆破坏。体内成像技术在这种病理状况的早期非侵入性临床前和临床检测以及纵向随访中发挥着重要作用。在本研究中,我们旨在评估使用高分辨率径向三维(3D)零回波时间(ZTE)和3D超短回波时间(UTE)磁共振成像(MRI)准确检测肺气肿啮齿动物模型中肺部病理形态学变化的可行性。将猪胰腺弹性蛋白酶(PPE)经气管内注入大鼠以产生肺气肿变化。在PPE激发后4周获取3D ZTE MRI、低分辨率和高分辨率3D UTE MRI以及微型计算机断层扫描图像。在接受PPE治疗的大鼠和对照大鼠中测量信噪比(SNR)。从低分辨率3D UTE MRI计算T2值。在对动物实施安乐死后进行组织形态计量学测量。由于受激发肺部发生的病理形态学变化,ZTE和UTE MR图像均显示,与对照相比,在接受PPE治疗的肺部中测量的SNR显著降低。使用UTE MRI测量发现,与对照相比,接受PPE激发的动物的T2值显著降低。组织形态计量学测量显示,接受PPE治疗的肺部的平均线性截距显著增加。与ZTE相比,UTE产生的SNR显著更高(在接受PPE治疗的肺部和未接受PPE治疗的肺部中分别高出14%和30%)。本研究表明,优化后的3D径向UTE和ZTE MRI能够提供质量优异的肺部图像,具有高各向同性空间分辨率(400 µm)以及实质组织中的高SNR(>25),并且在自由呼吸的动物中运动伪影可忽略不计。这些技术被证明是准确、可靠地检测肺气肿肺部发生的病理形态学改变的有用非侵入性工具,且不会带来微型计算机断层扫描典型的累积辐射暴露风险。