Shapiro Erik M, Skrtic Stanko, Sharer Kathryn, Hill Jonathan M, Dunbar Cynthia E, Koretsky Alan P
Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10901-6. doi: 10.1073/pnas.0403918101. Epub 2004 Jul 15.
There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 microm indicated that T(2)* effects can be readily detected from single MPIOs at 50-microm resolution and significant signal effects could be detected at resolutions as low as 200 microm. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging.
磁共振成像(MRI)在分子和细胞成像方面的应用正在迅速增长。这项工作很大程度上依赖于纳米级超小葡聚糖包被氧化铁颗粒的高弛豫率。通常,为了实现高效检测,数百万个葡聚糖包被的超小氧化铁颗粒必须被载入细胞。在此我们表明,单个微米级氧化铁颗粒(MPIO)在体外的琼脂糖样品、培养细胞以及小鼠胚胎中均可通过MRI检测到。研究MRI分辨率以及粒径在0.76至1.63微米之间的颗粒的实验表明,在50微米分辨率下可轻松检测到单个MPIO的T(2)*效应,而在低至200微米的分辨率下也能检测到显著的信号效应。用荧光MPIO标记培养细胞,使得单个细胞中存在单个颗粒。这些单细胞中的单个颗粒可通过MRI和荧光显微镜检测到。最后,在单细胞期小鼠胚胎中注射的单个颗粒在胚胎发育第11.5天可被检测到,这表明即使经过多次细胞分裂,子细胞仍携带单个颗粒。这些结果表明MRI能够检测单个颗粒,并指出单颗粒检测将对细胞成像有用。