Superparamagnetic iron oxide nanoparticles (SPIONs) are used as a tracer material in sentinel node biopsies. The latter is a procedure to analyze if cancer cells have spread to lymph nodes, helping to personalize patient care. To predict SPION behavior in vivo, it is important to analyze their magnetic properties in biological environments. The superparamagnetic quantifier (SPaQ) is a new device to measure the dynamic magnetization curve of SPIONs. The magnetization curve was measured for two types of SPIONs: Resovist and SHP-25. We used three techniques: Vibrating Sample Magnetometry (VSM), Magnetic Particle Spectroscopy (MPS), and our new SPaQ. Furthermore, AC susceptibility (ACS) measurements were performed as part of the evaluation of the three techniques. SPaQ and VSM results were found to be similar. Measurement results were nearly identical in both directions, indicating minor hysteresis. However, in MPS measurements, a clear hysteresis loop was observed. Furthermore, the ACS measurements showed a pronounced Brownian maximum, indicating an optimal response for an AC frequency below 10 kHz for both particle systems. Both the SPaQ and MPS were found to be superior to VSM since measurements are faster, can be performed at room temperature, and are particularly sensitive to particle dynamics. The main difference between the SPaQ and MPS lies in the excitation sequence. The SPaQ combines an alternating magnetic field that has a low amplitude with a gradual DC offset, whereas MPS uses only an alternating field that has a large amplitude. In conclusion, both the SPaQ and MPS are highly suited to improve understanding SPION behavior, which will lead to the radical improvement of sentinel node biopsy accuracy.
Purpose
Sentinel lymph node biopsy is a routine procedure for nodal staging in penile cancer. Most commonly, this procedure is guided by radioactive tracers, providing various forms of preoperative and intraoperative guidance. This is further extended with fluorescence imaging using hybrid radioactive–fluorescence tracers. Alternatively, a magnetic-based approach has become available using superparamagnetic iron-oxide nanoparticles (SPIONs). This study investigates a novel freehand magnetic particle imaging and navigation modality (fhMPI) for intraoperative localization, along with a hybrid approach, combining magnetic and fluorescence guidance.
Materials and methods
The fhMPI set-up was built with a surgical navigation device, optical tracking system and magnetometer probe. A dedicated reconstruction software based on a look-up-table method was used to reconstruct a superficial 3D volume of the SPION distribution in tissue. For fluorescence guidance, indocyanine green (ICG) was added to the SPIONs. The fhMPI modality was characterized in phantoms, ex vivo human skin and in vivo porcine surgery.
Results
Phantom and human skin explants illustrated that the current fhMPI modality had a sensitivity of 2.2 × 10–2 mg/mL SPIONs, a resolving power of at least 7 mm and a depth penetration up to 1.5 cm. Evaluation during porcine surgery showed that fhMPI allowed for an augmented reality image overlay of the tracer distribution in tissue, as well as 3D virtual navigation. Besides, using the hybrid approach, fluorescence imaging provided a visual confirmation of localized nodes.
Conclusion
fhMPI is feasible in vivo, providing 3D imaging and navigation for magnetic nanoparticles in the operating room, expanding the guidance possibilities during magnetic sentinel lymph node procedures. Furthermore, the integration of ICG provides the ability to visually refine and confirm correct localization. Further clinical evaluation should verify these findings in human patients as well.
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