Mitsumori L M, Ricks J L, Rosenfeld M E, Schmiedl U P, Yuan C
Department of Radiology and Pathobiology, University of Washington, Seattle, WA, USA.
Int J Cardiovasc Imaging. 2004 Dec;20(6):561-7. doi: 10.1007/s10554-004-7020-4.
Currently there are no clinically available means of noninvasively detecting early atherosclerotic disease because these lesions are characterized by an accumulation of extracellular lipid and foam cells, but a lack of significant wall thickening or architectural distortion.
We hypothesize that a paramagnetically labeled low density lipoprotein (LDL) could serve as a functional probe to detect sites of abnormal lipid metabolism in the vessel wall that represent sites of early disease.
Isolated LDL was first incubated with manganese-mesoporphyrin, a hydrophobic MR contrast agent (MnMeso). Size exclusion chromatography and absorption mass spectroscopy were performed on the resulting samples to prove that an association between the two occurred. Subsequently, foam cell cultures (n=7) were incubated (10-30 microg/ml for 48 h) with these labeled lipoproteins and the T1 relaxivity of centrifuged pellets of these cells was determined by using an inversion recovery sequence on a 1.5T scanner. These results were compared to control measurements made from foam cell cultures fed unlabeled lipoproteins (n=7).
Measured T1 relaxation times of the cells fed the MnMeso-LDL (443.3 +/- 51.8 ms) was significantly different from the T1 relaxivity obtained from cells fed unlabeled lipoproteins (661.3 +/- 60.9 ms). These findings indicate that the amount of contrast bound to the constructed lipoproteins is sufficient to produce measurable MR signal changes noninvasively.
The study results support the feasibility of future in vivo MR experiments with labeled lipoproteins to assess lipoprotein kinetics in the vessel wall, which will hopefully provide a means of detecting early atherosclerotic disease.
目前尚无临床上可用的非侵入性检测早期动脉粥样硬化疾病的方法，因为这些病变的特征是细胞外脂质和泡沫细胞的积累，但缺乏明显的管壁增厚或结构变形。
我们假设顺磁性标记的低密度脂蛋白（LDL）可作为一种功能性探针，用于检测血管壁中代表早期疾病部位的异常脂质代谢位点。
首先将分离的LDL与锰-中卟啉（一种疏水性磁共振造影剂，MnMeso）一起孵育。对所得样品进行尺寸排阻色谱和吸收质谱分析，以证明两者之间发生了结合。随后，将泡沫细胞培养物（n = 7）与这些标记的脂蛋白一起孵育（10 - 30μg/ml，共48小时），并使用1.5T扫描仪上的反转恢复序列测定这些细胞离心沉淀物的T1弛豫率。将这些结果与用未标记脂蛋白喂养的泡沫细胞培养物（n = 7）的对照测量结果进行比较。
用MnMeso - LDL喂养的细胞测得的T1弛豫时间（443.3±51.8毫秒）与用未标记脂蛋白喂养的细胞获得的T1弛豫率（661.3±60.9毫秒）有显著差异。这些发现表明，与构建的脂蛋白结合的造影剂数量足以产生可测量的非侵入性磁共振信号变化。
研究结果支持未来用标记脂蛋白进行体内磁共振实验以评估血管壁脂蛋白动力学的可行性，这有望提供一种检测早期动脉粥样硬化疾病的方法。
