Quantitative "Hot Spot" Imaging of Transplanted Stem Cells using Superparamagnetic Tracers and Magnetic Particle Imaging (MPI).
Quantitative "Hot Spot" Imaging of Transplanted Stem Cells using Superparamagnetic Tracers and Magnetic Particle Imaging (MPI).
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DOI：
10.18383/j.tom.2015.00172
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Rahmer J
中科院分区：
文献类型：
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作者：
Bulte JW;Walczak P;Janowski M;Krishnan KM;Arami H;Halkola A;Gleich B;Rahmer J
干细胞的磁性标记使其能够通过磁共振成像（MRI）进行无创检测。实际上，大多数MRI研究仅限于局部植入的可视化，因为其他来源的内源性低强度对比使全身（全身）细胞分布的解释复杂化。此外，MRI细胞跟踪本质上是固有的非定量。我们在此报告磁粒子成像（MPI）作为一种新的断层扫描技术的无创性的“热点”成像和定量的干细胞使用超顺磁性氧化铁（SPIO）示踪剂的潜力。代表小和大细胞体的神经和间充质干细胞用3种不同的SPIO示踪剂制剂标记，包括先前已用于临床MRI细胞跟踪研究的2种制剂（Feridex和Resovist）。磁性粒子光谱测量表明MPI信号和铁含量的自由粒子在均匀的溶液和标记的细胞在很宽的浓度范围内的内化和聚集的颗粒之间的线性相关性。总体MPI信号范围为1 × 10−3至3 × 10−4 Am 2/g Fe，相当于每个细胞2 × 10−14至1 × 10−15 Am 2，表明可以用MPI定量细胞数量，类似于在核医学中使用放射性示踪剂或在19 F MRI中使用氟示踪剂。当将SPIO标记的细胞移植到小鼠脑中时，它们可以在约5 × 104个细胞的检测阈值下容易地被MPI检测到，MPI/MRI重叠显示低信号MRI区域与MPI热点之间的良好一致性。100 000与50 000个植入细胞的组织MPI信号比计算值为2.08。因此，MPI可以潜在地进一步开发用于定量和易于解释的基于示踪剂的非侵入性细胞成像，优选地使用MRI作为辅助解剖成像方式。
Magnetic labeling of stem cells enables their noninvasive detection by magnetic resonance imaging (MRI). In practical terms, most MRI studies have been limited to the visualization of local engraftment because other sources of endogenous hypointense contrast complicate the interpretation of systemic (whole-body) cell distribution. In addition, MRI cell tracking is inherently nonquantitative in nature. We report herein on the potential of magnetic particle imaging (MPI) as a novel tomographic technique for noninvasive “hot-spot” imaging and quantification of stem cells using superparamagnetic iron oxide (SPIO) tracers. Neural and mesenchymal stem cells, representing small and larger cell bodies, were labeled with 3 different SPIO tracer formulations, including 2 preparations (Feridex and Resovist) that have previously been used in clinical MRI cell-tracking studies. Magnetic particle spectroscopy measurements demonstrated a linear correlation between MPI signal and iron content for both free particles in homogeneous solution and for internalized and aggregated particles in labeled cells over a wide range of concentrations. The overall MPI signal ranged from 1 × 10−3 to 3 × 10−4 Am2/g Fe, which was equivalent to 2 × 10−14 to 1 × 10−15 Am2 per cell, indicating that cell numbers can be quantified with MPI analogous to the use of radiotracers in nuclear medicine or fluorine tracers in 19F MRI. When SPIO-labeled cells were transplanted in the mouse brain, they could be readily detected by MPI at a detection threshold of about 5 × 104 cells, with MPI/MRI overlays showing an excellent agreement between the hypointense MRI areas and MPI hot spots. The calculated tissue MPI signal ratio for 100 000 vs 50 000 implanted cells was 2.08. Hence, MPI can potentially be further developed for quantitative and easy-to-interpret, tracer-based noninvasive cell imaging, preferably with MRI as an adjunct anatomical imaging modality.