# The Applications of Magnetic Particle Imaging: From Cell to Body
## 4 Applications of MPI
### Cell Tracking  
Among the earliest applications of MPI was to use SPIONs to track cells, which is similar to MRI [60; 61; 62; 63; 64]. MPI has unique advantages in cell tracing. First, it has high sensitivity and resolution that enable the device to detect as few as 200 labeled cells [8]. In addition, a currently used imaging tracer is superparamagnetic nanoparticles, which are relatively small and can be easily uptaken by cells. Moreover, there are safe, biocompatible magnetic nanoparticle tracers--Feraheme--approved by the Food and Drug Administration (FDA) for clinical use. In addition, since MPI has high tissue penetration and no background noise, these characteristics make it suitable for in vivo cell tracking [42].  
For example, [PERSON]'s research team at Stanford University researched on MPI applications from in vitro to in vivo [3]. In this study, they designed a ferroferric oxide nanoparticle wrapped in a semiconductor polymer as an MPI tracer. This tracer had excellent performance in MPI scanning. Its MPI signal intensity is three times that of the commercial MPI imaging tracer VivoTrax and seven times that of the MRI tracer Feraheme. The semiconductor polymer coating material allowed the nanoparticles to be fluorescently imaged, thus enabling multimodal imaging, including MPI, MRI, and fluorescence imaging. The research team coincubated these superparamagnetic particles with the human cervical cancer cell line HeLa and then used MPI, MRI, and fluorescence imaging to scan the cells. The results showed that MPI had a better signal-to-noise ratio, and the intensity of the MPI signal was linearly related to the number of cells. In addition, MPI could detect a minimum of 250 labeled cells according to the imaging results. To investigate the application of MPI in vivo, researchers injected labeled HeLa cells into the abdomens of mice by subcutaneous injection. They then scanned the mice using MPI, MRI, and fluorescence imaging. According to the results, MPI could effectively track the labeled cancer cells injected into mice. In addition, because MPI directly imaged the particles rather than surrounding tissues, its penetration depth was not limited. Therefore, whether the device was scanning the mouse from the front or the back, the MPI signals had a high signal-to-noise ratio and contrast. The research team also conducted a long-term imaging study on mice, which showed that MPI signals could still be detected 10 to 20 days after the injection of cancer cells labeled with the particles. In addition, the signal was reduced by less than 20%, which demonstrated that MPI could achieve long-term cell tracking.  
There are also other studies on the application of MPI in cell tracing. For example, [PERSON] et al. of the University of California, Berkeley, used Resovist to label human mesenchymal stem cells (hMSCs). They then performed long-term tracking of the distribution of labeled stem cells that were injected into mice through the tail vein [42]. [PERSON] et al. of Stanford University used superparamagnetic particles to label exosomes released either by hypoxic tumor cells or by normal tumor cells. They used MPI to trace those labeled exosomes and showed that the exosomes released by hypoxic cancer cells were taken up more readily by hypoxic cancer cells. The exosomes released by hypoxic cancer cells can thus deliver drugs more effectively to the hypoxic area of the tumor [45].  
Another example is the work of [PERSON]'s group from the Chinese Academy of Sciences and co-author (Figure 1) [40]. They designed a specialized tracer tailored to MPI physics theory by controlling the size and shape of the particle. This tracer had high saturation magnetization and provided high sensitivity and high resolution in MPI. It performed remarkably well in the labeling and tracking of stem cells compared to the commercialized tracer VivoTrax. The tracer also achieved the real-time and long-term tracking of stem cells in vivo.  
Figure 1: \(Cont.\)