Bulte J W M, Walczak P, Janowski M, Krishnan K M, Arami H, Halkola A, Gleich B, Rahmer J
Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research and Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Chemical & Biomolecular Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Dept. of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Russell H. Morgan Dept. of Radiology and Radiological Science, Division of MR Research and Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Tomography. 2015 Dec;1(2):91-97. doi: 10.18383/j.tom.2015.00172.
Magnetic labeling of stem cells enables their non-invasive detection by magnetic resonance imaging (MRI). Practically, most MRI studies have been limited to visualization of local engraftment as other sources of endogenous hypointense contrast complicate the interpretation of systemic (whole body) cell distribution. In addition, MRI cell tracking is inherently non-quantitative in nature. We report here on the potential of magnetic particle imaging (MPI) as a novel tomographic technique for non-invasive 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 three different SPIO tracer formulations, including two preparations that have previously been used in clinical MRI cell tracking studies (Feridex® and Resovist®). Magnetic particle spectroscopy (MPS) measurements demonstrated a linear correlation between MPI signal and iron content, for both homogeneous solutions of free particles in solution and for internalized and aggregated particles in labeled cells over a wide range of concentrations. The overall MP signal ranged from 1×10 - 3×10 Am/g Fe, which was equivalent to 2×10 - 1×10 Am per cell, indicating that cell numbers can be quantified with MPI analogous to the use of radiotracers in nuclear medicine or fluorine tracers in F MRI. When SPIO-labeled cells were transplanted in mouse brain, they could be readily detected by MPI at a detection threshold of about 5×10 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 has potential to be further developed for quantitative and easy-to-interpret, tracer-based non-invasive imaging of cells, preferably with MRI as an adjunct anatomical imaging modality.
干细胞的磁性标记能够通过磁共振成像（MRI）对其进行非侵入性检测。实际上，大多数MRI研究仅限于局部植入的可视化，因为内源性低信号对比的其他来源会使全身（整体）细胞分布的解释变得复杂。此外，MRI细胞追踪本质上是非定量的。我们在此报告磁性粒子成像（MPI）作为一种新型断层扫描技术的潜力，该技术可使用超顺磁性氧化铁（SPIO）示踪剂对干细胞进行非侵入性热点成像和定量分析。代表小细胞体和大细胞体的神经干细胞和间充质干细胞用三种不同的SPIO示踪剂制剂进行标记，其中包括两种先前已用于临床MRI细胞追踪研究的制剂（Feridex®和Resovist®）。磁性粒子光谱（MPS）测量表明，在很宽的浓度范围内，对于溶液中游离颗粒的均匀溶液以及标记细胞中内化和聚集的颗粒，MPI信号与铁含量之间存在线性相关性。总的MP信号范围为1×10 - 3×10 Am/g Fe，相当于每个细胞2×10 - 1×10 Am，这表明细胞数量可以用MPI进行定量，类似于在核医学中使用放射性示踪剂或在功能磁共振成像中使用氟示踪剂。当将SPIO标记的细胞移植到小鼠脑中时，通过MPI可以很容易地在约5×10个细胞的检测阈值下检测到它们，MPI/MRI叠加显示低信号MRI区域与MPI热点之间具有极好的一致性。计算得出，植入100,000个细胞与50,000个细胞时的组织MPI信号比为2.08。因此，MPI有潜力进一步开发用于基于示踪剂的细胞定量且易于解释的非侵入性成像，最好将MRI作为辅助解剖成像方式。
