Beijing Institute of Radiation Medicine, Beijing, China.
Department of Neurology, Henry Ford Health System, Detroit, Michigan.
NMR Biomed. 2020 May;33(5):e4256. doi: 10.1002/nbm.4256. Epub 2020 Feb 11.
Imaging brain microvasculature is important in cerebrovascular diseases. However, there is still a lack of non-invasive, non-radiation, and whole-body imaging techniques to investigate them. The aim of this study is to develop an ultra-small superparamagnetic iron oxide (USPIO) enhanced susceptibility weighted imaging (SWI) method for imaging micro-vasculature in both animal (~10 μm in rat) and human brain. We hypothesized that the USPIO-SWI technique could improve the detection sensitivity of the diameter of small subpixel vessels 10-fold compared with conventional MRI methods. Computer simulations were first performed with a double-cylinder digital model to investigate the theoretical basis for this hypothesis. The theoretical results were verified using in vitro phantom studies and in vivo rat MRI studies (n = 6) with corresponding ex vivo histological examinations. Additionally, in vivo human studies (n = 3) were carried out to demonstrate the translational power of the USPIO-SWI method. By directly comparing the small vessel diameters of an in vivo rat using USPIO-SWI with the small vessel diameters of the corresponding histological slide using laser scanning confocal microscopy, 13.3-fold and 19.9-fold increases in SWI apparent diameter were obtained with 5.6 mg Fe/kg and 16.8 mg Fe/kg ferumoxytol, respectively. The USPIO-SWI method exhibited its excellent ability to detect small vessels down to about 10 μm diameter in rat brain. The in vivo human study unveiled hidden arterioles and venules and demonstrated its potential in clinical practice. Theoretical modeling simulations and in vitro phantom studies also confirmed a more than 10-fold increase in the USPIO-SWI apparent diameter compared with the actual small vessel diameter size. It is feasible to use SWI blooming effects induced by USPIO to detect small vessels (down to 10 μm in diameter for rat brain), well beyond the spatial resolution limit of conventional MRI methods. The USPIO-SWI method demonstrates higher potential in cerebrovascular disease investigations.
脑微血管成像在脑血管疾病中至关重要。然而，目前仍缺乏非侵入性、非放射性且可全身成像的技术来进行研究。本研究旨在开发一种超小超顺磁性氧化铁（USPIO）增强磁敏感加权成像（SWI）技术，以在动物（大鼠中约 10μm）和人脑内成像微血管。我们假设 USPIO-SWI 技术可将小亚像素血管直径的检测灵敏度与传统 MRI 方法相比提高 10 倍。首先通过双圆柱数字模型进行计算机模拟，以研究该假设的理论基础。通过体外体模研究和体内大鼠 MRI 研究（n=6）以及相应的离体组织学检查来验证理论结果。此外，还进行了体内人体研究（n=3），以证明 USPIO-SWI 方法的转化能力。通过直接比较使用 USPIO-SWI 的活体大鼠的小血管直径和使用激光共聚焦显微镜的相应组织学载玻片的小血管直径，分别使用 5.6mgFe/kg 和 16.8mgFe/kg 的 ferumoxytol 获得 SWI 表观直径增加了 13.3 倍和 19.9 倍。USPIO-SWI 方法表现出良好的检测大鼠脑中小至约 10μm 直径的小血管的能力。体内人体研究揭示了隐藏的动静脉，并展示了其在临床实践中的潜力。理论建模模拟和体外体模研究也证实，与实际小血管直径相比，USPIO-SWI 的表观直径增加了 10 倍以上。使用 USPIO 诱导的 SWI 晕影效应来检测小血管（大鼠脑中小至 10μm）是可行的，远远超过了传统 MRI 方法的空间分辨率极限。USPIO-SWI 方法在脑血管病研究中具有更高的潜力。
