For biomagnetical applications exploiting physical properties of magnetic nanoparticles (MNP), e.g., magnetic hyperthermia, knowledge about the quantitative spatial MNP distribution is crucial, which can be extracted by magnetorelaxometry (MRX) imaging. In this paper, we present quantification, quantitative 1D reconstruction, and quantitative 2D imaging of MNP by exploiting optically pumped magnetometers for MRX. While highlighting the potential of commercially available optically pumped magnetometers (OPM) for MRXI, we discuss current limitations of the used OPM. We show, that with our OPM setup, MNP can be precisely quantified with iron amounts down to ≈6 μg, which can be improved easily. With a 1D-reconstruction setup, point-like and complex MNP phantoms can be reconstructed quantitatively with high precision and accuracy. We show that with our developed 2D MRX imaging setup, which measures 12 cm by 8 cm, point-like MNP distributions with clinically relevant iron concentrations can be reconstructed precisely and accurately. Our 2D setup has the potential to be easily extended to a tomography styled (and thus slice-selective) 3D scanner, by adding a mechanical axis to the phantom.

Magnetic nanoparticles (MNP) offer a large variety of promising applications in medicine thanks to their exciting physical properties, e.g., magnetic hyperthermia and magnetic drug targeting. For these applications, it is crucial to quantify the amount of MNP in their specific binding state. This information can be obtained by means of magnetorelaxometry (MRX), where the relaxation of previously aligned magnetic moments of MNP is measured. Current MRX with optically pumped magnetometers (OPM) is limited by OPM recovery time after the shut-off of the external magnetic field for MNP alignment, therewith preventing the detection of fast relaxing MNP. We present a setup for OPM-MRX measurements using a commercially available pulsed free-precession OPM, where the use of a high power pulsed pump laser in the sensor enables a system recovery time in the microsecond range. Besides, magnetometer raw data processing techniques for Larmor frequency analysis are proposed and compared in this paper. Due to the high bandwidth (≥100 kHz) and high dynamic range of our OPM, a software gradiometer in a compact enclosure allows for unshielded MRX measurements in a laboratory environment. When operated in the MRX mode with non-optimal pumping performance, the OPM shows an unshielded gradiometric noise floor of about 600 fT/cm/Hz for a 2.3 cm baseline. The noise floor is flat up to 1 kHz and increases then linearly with the frequency. We demonstrate that quantitative unshielded MRX measurements of fast relaxing, water suspended MNP is possible with the novel OPM-MRX concept, confirmed by the accurately derived iron amount ratios of MNP samples. The detection limit of the current setup is about 1.37 μg of iron for a liquid BNF-MNP-sample (Bionized NanoFerrite) with a volume of 100 μL.

Objective. Magnetorelaxometry imaging (MRXI) is an experimental imaging technique applicable for noninvasive, qualitative and quantitative imaging of magnetic nanoparticles (MNPs). Accurate reconstructions of nanoparticle distributions are crucial for several novel treatment methods employing MNPs such as magnetic drug targeting or magnetic hyperthermia therapy. Hence, it is desirable to design MRXI setups such that the reconstruction accuracy is maximized for a given set of design parameters. Several attempts exist in literature that focus on the improvement of MRXI and other related linear inverse problems with respect to various figures of merit. However, to date it remains unclear, which approach leads to the largest benefit for the reconstruction accuracy. Thus, the aim of this study is to compare the different figures of merit, thereby determining the most reliable and effective optimization approach for magnetorelaxometry setups. Approach. In the present simulation study, we translate these figures of merit to various cost functions, allowing us to optimize the electromagnetic coil positions and radii of two distinct MRXI setups with an adapted tabu search algorithm. Multiple artificial MNP phantoms are reconstructed employing the optimized setups and the resulting imaging qualities are subsequently compared. Main results. The extensive amount of generated synthetic data unprecedented in previous MRXI studies identifies the condition number as the most reliable indicator for good imaging results. This is the case for both the qualitative as well as the quantitative reconstruction accuracies. Significance. The results of this study show that optimized coil configurations increase the reconstruction quality compared to the state-of-the-art. The insights obtained here can also be extended to other design parameters of MRXI setups, thus enabling more reliable reconstructions of MNP ensembles which will ultimately render the aforementioned treatment methods safer and more efficient.

Spatial quantitative information about magnetic nanoparticle (MNP) distributions is a prerequisite for biomedical applications like magnetic hyperthermia and magnetic drug targeting. This information can be gathered by means of magnetorelaxometry (MRX) imaging, where the relaxation of previously aligned MNP’s magnetic moments is measured by sensitive magnetometers and an inverse problem is solved. To remove or minimize the magnetic shielding in which MRX imaging is carried out today, the knowledge of the influence of background magnetic fields on the MNP’s relaxation is a prerequisite. We show MRX measurements using an intensity-modulated optically pumped magnetometer (OPM) in background magnetic fields of up to $100~\upmu \mbox{T}$ 100 μ T . We show that the relaxation parameters alter or may be intentionally altered significantly by applying static fields parallel or antiparallel to the MNP’s alignment direction. Further, not only the relaxation process of the MNP’s magnetic moments could be measured with OPM, but also their alignment due to the MRX excitation field.

Magnetic nanoparticles (MNPs) are a promising tool in biomedical applications such as cancer therapy and diagnosis, where localization and quantification of MNP distributions are often mandatory. This can be obtained by magnetorelaxometry imaging (MRXI). In this work, the capability of MRXI for quantitative imaging of MNP inside larger volumes such as a human head is investigated. We developed a human head phantom simulating a glioblastoma multiforme (GBM) tumor containing MNP for magnetic hyperthermia treatment. The sensitivity of our MRXI setup for detection of MNP concentrations in the range of 3 to 19 mg/cm3 was studied. The results show the high capability of MRXI to detect MNPs in a human head sized volume. The reconstruction of the MNP distribution, mimicking a GBM tumor of 7 cm3 volume with clinically relevant iron concentration, demonstrates the in vivo feasibility of MRXI in humans.