Kim Bongjune, Yang Jaemoon, Lee Young Han, Kim Myeong-Hoon, Heo Dan, Lee Eugene, Suh Jin-Suck, Haam Seungjoo, Huh Yong-Min
Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul, Republic of Korea.
Department of Radiology, College of Medicine, Yonsei University, Seoul, Republic of Korea; YUHS-KRIBB Medical Convergence Research Institute, Seoul, Republic of Korea.
PLoS One. 2015 May 15;10(5):e0124572. doi: 10.1371/journal.pone.0124572. eCollection 2015.
To obtain compensatory ultra-short echo time (UTE) imaging and T2-weighted (T2W) imaging of Watanabe heritable hyperlipidemic (WHHL) rabbits following dextran-coated magnetic nanocluster (DMNC) injection for the effective in vivo detection of inflammatory vascular wall.
Magnetic nanoparticle was synthesized by thermal decomposition and encapsulated with dextran to prepare DMNC. The contrast enhancement efficiency of DMNC was investigated using UTE (repetition time [TR] = 5.58 and TE = 0.07 ms) and T2W (TR = 4000 and TE = 60 ms) imaging sequences. To confirm the internalization of DMNC into macrophages, DMNC-treated macrophages were visualized by cellular transmission electron microscope (TEM) and magnetic resonance (MR) imaging. WHHL rabbits expressing macrophage-rich plaques were subjected to UTE and T2W imaging before and after intravenous DMNC (120 μmol Fe/kg) treatment. Ex vivo MR imaging of plaques and immunostaining studies were also performed.
Positive and negative contrast enhancement of DMNC solutions with increasing Fe concentrations were observed in UTE and T2W imaging, respectively. The relative signal intensities of the DMNC solution containing 2.9 mM Fe were calculated as 3.53 and 0.99 in UTE and T2W imaging, respectively. DMNC uptake into the macrophage cytoplasm was visualized by electron microscopy. Cellular MR imaging of DMNC-treated macrophages revealed relative signals of 3.00 in UTE imaging and 0.98 in T2W imaging. In vivo MR images revealed significant brightening and darkening of plaque areas in the WHHL rabbit 24 h after DMNC injection in UTE and T2W imaging, respectively. Ex vivo MR imaging results agreed with these in vivo MR imaging results. Histological analysis showed that DMNCs were localized to areas of inflammatory vascular wall.
Using compensatory UTE and T2W imaging in conjunction with DMNC is an effective approach for the noninvasive in vivo imaging of atherosclerotic plaque.
在注射葡聚糖包被的磁性纳米簇（DMNC）后，获取渡边遗传性高脂血症（WHHL）兔的补偿性超短回波时间（UTE）成像和T2加权（T2W）成像，以有效在体内检测炎症性血管壁。
通过热分解合成磁性纳米颗粒，并用葡聚糖包封以制备DMNC。使用UTE（重复时间[TR]=5.58，回波时间[TE]=0.07 ms）和T2W（TR = 4000，TE = 60 ms）成像序列研究DMNC的对比增强效率。为了确认DMNC被巨噬细胞内化，通过细胞透射电子显微镜（TEM）和磁共振（MR）成像观察经DMNC处理的巨噬细胞。对表达富含巨噬细胞斑块的WHHL兔在静脉注射DMNC（120 μmol Fe/kg）治疗前后进行UTE和T2W成像。还进行了斑块的离体MR成像和免疫染色研究。
在UTE和T2W成像中，分别观察到随着铁浓度增加，DMNC溶液出现正性和负性对比增强。在UTE和T2W成像中，含2.9 mM铁的DMNC溶液的相对信号强度分别计算为3.53和0.99。通过电子显微镜观察到DMNC摄取进入巨噬细胞胞质。经DMNC处理的巨噬细胞的细胞MR成像显示在UTE成像中相对信号为3.00，在T2W成像中为0.98。体内MR图像显示，在UTE和T2W成像中，DMNC注射后24小时，WHHL兔斑块区域分别出现明显的变亮和变暗。离体MR成像结果与这些体内MR成像结果一致。组织学分析表明，DMNC定位于炎症性血管壁区域。
将补偿性UTE和T2W成像与DMNC结合使用是一种用于动脉粥样硬化斑块无创体内成像的有效方法。
