Krooshoop, Hendrikus J.G.

ten Haken, Bernard

van de Loosdrecht, Melissa Mathilde

Waanders, Sebastiaan

English

University of Twente Research Information

per offset field interval allow a reliable quantitative measure of theamount of particles. The response is independent of the magne-tization of linear magnetic material (e.g. tissue). In this paper, theprocedure, which patent is pending, is referred to as quantificationprotocol or Diffmag protocol [19].The alternating field excitation causes rotation of the magneticmoments of the nanoparticles. This process includes particlerelaxation mechanisms known as Néel and Brownian relaxation.Néel relaxation is defined as rotation of the magnetic moment ofthe core without physical rotation of the entire particle. InBrownian relaxation the entire particle rotates, which thusincludes rotation of the magnetic moment. Physical rotation ofthe particle is influenced by the volume of the particle and by theviscous drag acting on the particle. The Brownian relaxation timeτB for particles with volume V is defined asτB ¼3VηkBT; ð9Þwith η is the viscosity of the medium surrounding the particle.Néel relaxation is independent of viscosity, but depends ontemperature, size and anisotropy of the core [20].Nonlinearity of the magnetization plays a key role in theDiffmag algorithm. There are two important parameters thatdetermine the sensitivity of the procedure, as is shown in Fig. 2.The Diffmag response is calculated as a function of the offset fieldamplitude for different spherical iron oxide particle sizes using theLangevin model of superparamagnetism, all with identical satura-tion magnetization. For larger offset field amplitudes, the differ-ence in local susceptibility (dM/dH) probed by the alternating fieldis stronger, resulting in a larger Diffmag response. Secondly,magnetic nanoparticles with a large diameter express a strongermagnetization for low fields and magnetization saturates at loweroffset field amplitudes, which together results in a larger Diffmagresponse compared to smaller particles. In addition, the Diffmagresponse of Resovist and Endorem is calculated, based on particlesize distributions obtained from VSM. The larger average particlediameter of Resovist compared to Endorem results in a strongerDiffmag response.The two aspects of particle size and field amplitude have to betaken into account in the design of a system for a specificapplication. Depending on the size of the particles used for atypical application, the signal amplitude gained by increasing theoffset field amplitude is limited. The differential magnetometryprinciple is most sensitive for particles with large core size,allowing a lower offset field amplitude. This is advantageous forclinical applications where magnetic field limits have to beconsidered [21].2.1.3. Measurement of magnetization curveIn an alternative way, the method can be used for characteriza-tion purposes, by measuring the magnetization response to thesmall alternating field for a range of offset field amplitudes. Theoffset field is stepwise increased, while the alternating field isapplied to probe the local susceptibility. The resulting response isthe time derivative of the magnetic moment as a function of offsetfield amplitude. This can be used to reconstruct a (frequencydependent) dm/dH-curve that is equivalent with the point-spread-function (PSF) in x-space MPI [22]. Subsequently, the dm/dH-curvecan be used to determine the magnetization vs. field curve of asample material and the magnetic core size distribution of theparticles in a sample that contribute to the signal.2.2. Experimental setup2.2.1. MagnetometerThe magnetometer is constructed of a set of coils that is placed in ahomemade G10 fiberglass epoxy cryostat with vacuum insulation andFig. 1. The concept of differential magnetometry simulated for monodisperse iron oxide particles with 16 nm diameter (A). The alternating excitation field is applied withintervals with a positive and negative offset field amplitude (B). The colors in each panel correspond with the offset field amplitude. Nonlinear magnetic susceptibility resultsin a reduced alternating magnetization response during periods with offset field (C), which is proportional to the amplitude of inductively measured signal (D). The Diffmagvoltage ΔU specifically represents the contribution from magnetic nanoparticles in a sample.0 5 10 15 20 25 3000.10.20.30.40.5Offset field amplitude [mT]DiffMag d=27 nmd=24 nmd=21 nmd=18 nmd=15 nmd=12 nmResovistEndoremFig. 2. Calculated response of differential magnetometry for mono-disperse parti-cles with different size for various offset field amplitudes. The response of Resovistand Endorem was based on a bimodal log-normal particle size distribution,determined by VSM. Endorem shows a much smaller response compared toResovist due to the differences in particle size distribution. For larger offset fieldamplitudes and larger particle sizes, the Diffmag response becomes stronger andsaturates finally.M. Visscher et al. / Journal of Magnetism and Magnetic Materials 365 (2014) 31–39 33LAPAROSCOPIC SENTINEL NODE BIOPSYUSING DIFFERENTIAL MAGNETOMETRY Melissa M. van de Loosdrecht*, Sebastiaan Waanders*, Erik Krooshoop*, and Bennie ten Haken*  * Magnetic Detection and Imaging group, Faculty of Science and Technology, University of Twente, Enschede, the Netherlands                                      Correspondence to: m.m.vandeloosdrecht@utwente.nlBACKGROUND PURPOSEOur purpose is to locate superparamagnetic iron oxide nanoparticles (SPIONs) in vivo during laparoscopic surgery (Figure 1), using Differential Magnetometry (DiffMag) [2]. To achieve this, SPIONs are excited at a frequency between 1 and 10 kHz. To enable laparoscopic (minimally invasive) surgery, the diameter of the inserted instrument needs to be 12 mm or less. To limit loss in depth sensitivity, the excitation and detection coils are mechanically seperated [3].When a patient is diagnosed with cancer, it is important to know if the tumor has spread through the body. Sentinel node biopsies are used to determine if the tumor has spread via the lymphatic system [1]. Consequently, patient care will be personalized.RESULTSDISCUSSION CONCLUSIONAcknowledgementsFinancial support by the Netherlands Organization for Scientific Research (NWO), under the research program Magnetic Sensing for Laparoscopy (MagLap) with project number 14322, is gratefully acknowledged.FIGURE 1 A novel laparoscopic probe for sentinel node biopsies. SPIONs are used as a tracer agent. Excitation and detection coils are mechanically separated to increase depth sensitivity.Our next challenge is to enable movement of the detection coils. To achieve this, we will use faster electronics, enabling real time compensation of the excitation signal during DiffMag measurements.Separation of excitation and detection coils is unique and not possible without DiffMag. These first results are promising for sentinel node biopsies, since it is possible to compensate for the excitation field and to measure small quantities of particles.References[1] A. E. Giuliano and A. Gangi, Breast J., vol. 21, no. 1, 2015. [2] S. Waanders et al. Phys. Med. Biol., vol. 61, no. 22, pp. 8120–8134, Nov. 2016. [3] M.M. van de Loosdrecht et al. J. Magn. Magn. Mater., vol. 475, pp 563-569, Apr. 2019 [4] M. Visscher et al. J. Magn. Magn. Mater., vol. 365, pp. 31-39, Sep. 2014.DetectionExcitationTrocarProbeDIFFERENTIAL MAGNETOMETRY ACTIVE COMPENSATION0 10 20Time [ms]-505Detector signal [V]0 10 20Time [ms]-505Detector signal [V]0 10 20Time [ms]-505Detector signal [V]0 10 20Time [ms]-505Detector signal [V]0 10 20Time [ms]-505Detector signal [V]0 10 20Time [ms]-505Detector signal [V]FIGURE 2 The concept of Differential Magnetometry simulated for monodisperse iron oxide particles with 16 nm diameter (A). The alternating excitation field is applied with intervals with a positive and negative offset field amplitude (B). The colors in each panel correspond with the offset field amplitude. Nonlinear magnetic susceptibility results in a reduced alternating magnetization response during periods with offset field (C), which is proportional to the amplitude of inductively measured signal (D). The DiffMag voltage ΔU specifically represents the contribution from magnetic nanoparticles in a sample. The amplitude of the AC field is approximately 1 mT, which is 1000x smaller compared to Magnetic Resonance Imaging and 10x smaller compared to Magnetic Particle Spectroscopy. [4]FIGURE 3 The main challenge after separating excitation and detection coils is a varying mutual inductance between these coils. As a result, the detector signal is hindered by the excitation field. To avoid this, we use active compensation with additional coils. This iterative process is demonstrated in this figure.FIGURE 4 DiffMag measurements using our separate coil setup on SHP-25 particles containing various amounts of iron. 20 DiffMag cycles were acquired with an AC amplitude of 0.5 mT, an AC frequency of 2525 Hz, and a DC offset of 49.8 mT. The distance between the excitation and detection coils in this static setup was 5 cm and the sample was placed directly in front of the detection coils. Air Retractor Water020406080100120140Counts [100 nV]DiffMagAC0 200 400 600Iron content [ g]010203040Counts [100 nV]SHP-25Empty coil0 50 100024FIGURE 5 DiffMag (left) and AC magnetometry (right) measurements using our separate coil setup on SHP-25 particles containing 500 μg iron in air and in proximity to a surgical steel retractor and water. 20 DiffMag cycles were acquired with an AC amplitude of 0.5 mT, an AC frequency of 2525 Hz, and a DC offset of 49.8 mT. The distance between the excitation and detection coils in this static setup was 5 cm and the sample was placed directly in front of the detection coils.

Laparoscopic sentinel node biopsy using differential magnetometry

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Laparoscopic sentinel node biopsy using differential magnetometry

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