Feng Xin, Gao Pengli, Li Yabin, Hui Hui, Jiang Jingying, Xie Fei, Tian Jie
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging Institute of Automation, Chinese Academy of Sciences Beijing China.
School of Artificial Intelligence, University of Chinese Academy of Sciences Beijing China.
Bioeng Transl Med. 2023 Nov 29;9(2):e10626. doi: 10.1002/btm2.10626. eCollection 2024 Mar.
Increased pulmonary vascular permeability is a characteristic feature of lung injury. However, there are no established methods that allow the three-dimensional visualization and quantification of pulmonary vascular permeability in vivo. Evans blue extravasation test and total protein test of bronchoalveolar lavage fluid (BALF) are permeability assays commonly used in research settings. However, they lack the ability to identify the spatial and temporal heterogeneity of endothelial barrier disruption, which is typical in lung injuries. Magnetic resonance (MR) and near-infrared (NIR) imaging have been proposed to image pulmonary permeability, but suffer from limited sensitivity and penetration depth, respectively. In this study, we report the first use of magnetic particle imaging (MPI) to assess pulmonary vascular leakage noninvasively in vivo in mice. A dextran-coated superparamagnetic iron oxide (SPIO), synomag®, was employed as the imaging tracer, and pulmonary SPIO extravasation was imaged and quantified to evaluate the vascular leakage. Animal models of acute lung injury and pulmonary fibrosis (PF) were used to validate the proposed method. MPI sensitively detected the SPIO extravasation in both acutely injured and fibrotic lungs in vivo, which was confirmed by ex vivo imaging and Prussian blue staining. Moreover, 3D MPI illustrated the spatial heterogeneity of vascular leakage, which correlated well with CT findings. Based on the in vivo 3D MPI images, we defined the SPIO extravasation index (SEI) to quantify the vascular leakage. A significant increase in SEI was observed in the injured lungs, in consistent with the results obtained via ex vivo permeability assays. Overall, our results demonstrate that 3D quantitative MPI serves as a useful tool to examine pulmonary vascular integrity in vivo, which shows promise for future clinical translation.
肺血管通透性增加是肺损伤的一个特征性表现。然而，目前尚无成熟的方法能够在体内对肺血管通透性进行三维可视化和定量分析。伊文思蓝外渗试验和支气管肺泡灌洗液（BALF）总蛋白检测是研究中常用的通透性检测方法。然而，它们缺乏识别内皮屏障破坏的空间和时间异质性的能力，而这在肺损伤中很典型。磁共振（MR）成像和近红外（NIR）成像已被用于对肺通透性进行成像，但分别存在灵敏度有限和穿透深度受限的问题。在本研究中，我们报告了首次使用磁粒子成像（MPI）在小鼠体内无创评估肺血管渗漏情况。一种葡聚糖包被的超顺磁性氧化铁（SPIO）——synomag®，被用作成像示踪剂，对肺SPIO外渗进行成像和定量分析以评估血管渗漏。使用急性肺损伤和肺纤维化（PF）动物模型对所提出的方法进行验证。MPI在体内灵敏地检测到急性损伤和纤维化肺中的SPIO外渗，这通过离体成像和普鲁士蓝染色得到证实。此外，三维MPI显示了血管渗漏的空间异质性，与CT结果具有良好的相关性。基于体内三维MPI图像，我们定义了SPIO外渗指数（SEI）以量化血管渗漏。在损伤的肺中观察到SEI显著增加，这与通过离体通透性检测获得的结果一致。总体而言，我们的结果表明，三维定量MPI是一种用于在体内检查肺血管完整性的有用工具，具有未来临床转化的潜力。
