Vande Velde Greetje, De Langhe Ellen, Poelmans Jennifer, Dresselaers Tom, Lories Rik J, Himmelreich Uwe
From the Departments of *Imaging and Pathology, Biomedical MRI/MoSAIC, †Development and Regeneration, Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven; ‡Division of Rheumatology, University Hospitals Leuven, Belgium.
Invest Radiol. 2014 Nov;49(11):691-8. doi: 10.1097/RLI.0000000000000071.
Bleomycin instillation is frequently used to model lung fibrosis, although the onset and severity of pathology varies highly between mice. This makes non-invasive fibrosis detection and quantification essential to obtain a comprehensive analysis of the disease course and to validate novel therapies. Magnetic resonance imaging (MRI) of lung disease progression and therapy may provide such a sensitive in vivo readout of lung fibrosis, bypassing radiotoxicity concerns (when using micro-CT [μCT]) and elaborate invasive end point measurements (histology). We aimed to optimize and evaluate 3 different lung MRI contrast and acquisition methods to visualize disease onset and progression in the bleomycin-induced mouse model of lung fibrosis using a small-animal MRI scanner. For validation, we compared the MRI results with established μCT and histological measures of lung fibrosis.
Free-breathing bleomycin-instilled and control mice were scanned in vivo with respiration-triggered conventional, ultrashort echo time and self-gated MRI pulse sequences (9.4 T) and μCT at baseline and weekly at days 7, 14, 21, and 28 after bleomycin instillation. After the last imaging time point, the mice were killed and the lungs were isolated for criterion standard histological analysis of lung fibrosis and quantification of lung collagen content for validation of the imaging results. The agreement between quantitative MRI and μCT data and standard measurements was analyzed by linear regression.
All 3 MRI protocols were able to visualize and quantify lung pathology onset and progression in individual bleomycin-instilled mice. In vivo MRI results were in excellent agreement with in vivo μCT and criterion standard histological measures of lung fibrosis. Ultrashort echo time MRI appeared particularly useful for detecting early disease; self-gated MRI, for improved breathing motion handling.
Magnetic resonance imaging sensitively visualizes and quantifies lung fibrosis in vivo, which makes it a noninvasive, translatable, safe, and potentially more versatile alternative to invasive methods or μCT, thereby stimulating pathogenesis and preclinical research.
博来霉素注入常用于建立肺纤维化模型，尽管小鼠之间病理变化的起始和严重程度差异很大。这使得非侵入性纤维化检测和定量对于全面分析疾病进程和验证新疗法至关重要。肺部疾病进展和治疗的磁共振成像（MRI）可能提供这种对肺纤维化敏感的体内读数，避免了辐射毒性问题（使用微型计算机断层扫描[μCT]时）以及复杂的侵入性终点测量（组织学）。我们旨在优化和评估3种不同的肺部MRI对比剂和采集方法，以使用小动物MRI扫描仪在博来霉素诱导的小鼠肺纤维化模型中可视化疾病的起始和进展。为了进行验证，我们将MRI结果与已确立的μCT和肺纤维化组织学测量方法进行了比较。
自由呼吸的注入博来霉素的小鼠和对照小鼠在基线时以及在注入博来霉素后的第7、14、21和28天每周进行一次体内扫描，使用呼吸触发的传统、超短回波时间和自门控MRI脉冲序列（9.4T）以及μCT。在最后一个成像时间点之后，处死小鼠并分离肺部，进行肺纤维化的标准组织学分析和肺胶原含量的定量，以验证成像结果。通过线性回归分析定量MRI与μCT数据和标准测量之间的一致性。
所有3种MRI方案都能够在个体注入博来霉素的小鼠中可视化和定量肺部病理变化的起始和进展。体内MRI结果与体内μCT以及肺纤维化的标准组织学测量结果高度一致。超短回波时间MRI对于检测早期疾病似乎特别有用；自门控MRI则有助于更好地处理呼吸运动。
磁共振成像能够在体内敏感地可视化和定量肺纤维化，这使其成为侵入性方法或μCT的非侵入性、可转化、安全且可能更具通用性的替代方法，从而推动发病机制和临床前研究。
