Sentinel lymph node biopsy has become a staple tool in the diagnosis of breast cancer. By replacing the morbidity-plagued axillary node clearance with removing only those nodes most likely to contain metastases, it has greatly improved the quality of life of many breast cancer patients. However, due to the use of ionizing radiation emitted by the technetium-based tracer material, the current sentinel lymph node biopsy has serious drawbacks. Most urgently, the reliance on radioisotopes limits the application of this procedure to small parts of the developed world, and it imposes restrictions on patient planning and hospital logistics. Magnetic alternatives have been tested in recent years, but all have their own drawbacks, mostly related to interference from metallic instruments and electromagnetic noise coming from the human body. In this paper, we demonstrate an alternative approach that utilizes the unique nonlinear magnetic properties of superparamagnetic iron oxide nanoparticles to eliminate the drawbacks of both the traditional gamma-radiation centered approach and the novel magnetic techniques pioneered by others. Contrary to many other nonlinear magnetic approaches however, field amplitudes are limited to 5 mT, which enables handheld operation without additional cooling. We show that excellent mass sensitivity can be obtained without the need for external re-balancing of the probe to negate any influences from the human body. Additionally, we show how this approach can be used to suppress artefacts resulting from the presence of metallic instruments, which are a significant dealbreaker when using conventional magnetometry-based approaches.
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.
a b s t r a c tThe increasing interest for local detection of magnetic nanoparticles (MNPs) during clinical interventions requires the development of suitable probes that unambiguously detect the MNPs at a depth of several centimeters in the body. The present study quantitatively evaluates the limitations of a conventional magnetometry method using a sinusoidal alternating field. This method is limited by the variability of the magnetic susceptibility of the surrounding diamagnetic tissue. Two different sensors are evaluated in a theoretical model of MNP detection in a tissue volume. For a coil that completely encloses the sample volume, the MNPs can be detected if the total mass contributing to the signal is larger than 4.1 10 7 × − times the tissue mass. For a handheld surface coil, intended to search for the MNPs in a larger tissue volume, an amount of 1 μg of iron oxide cannot be detected by sensors with a diameter larger than 15 mm. To detect a spot with MNPs at 5 cm depth in tissue, it should contain at least 325 μg iron oxide.Therefore, for high-sensitive clinical MNP detection in surgical interventions, techniques with increased specificity for the nonlinear magnetic properties of MNPs are indispensable.
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