Quantitative knowledge about the spatial distribution and local environment of magnetic nanoparticles (MNPs) inside an organism is essential for guidance and improvement of biomedical applications such as magnetic hyperthermia and magnetic drug targeting. Magnetorelaxometry (MRX) provides such quantitative information by detecting the magnetic response of MNPs following a fast change in the applied magnetic field.In this article, we review our MRX based procedures that enable both the characterization and the quantitative imaging of MNPs in a biomedical environment.MRX characterization supported the selection of an MNP system with colloidal stability and suitable cellular MNP uptake. Spatially resolved MRX, a procedure employing multi-channel MRX measurements allowed forThese MRX based measurement and analysis procedures have substantially supported the development of MNP based biomedical applications.

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 $600 \mathrm{f}\mathrm{T}/\mathrm{c}\mathrm{m}/\sqrt{\mathrm{Hz}}$ for a $2.3 \mathrm{c}\mathrm{m}$ baseline. The noise floor is flat up to $1 \mathrm{kHz}$ 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$$.

Magnetic nanoparticles can be employed for a broad range of biomedical applications where the knowledge of the distribution of the magnetic nanoparticles is of importance for efficacy, patient's safety, etc. The need exists to have an as accurate as possible quantification of the unknown particles distribution. Magnetorelaxometry (MRX) measurements are able to measure the magnetic induction originating from a certain distribution of magnetically activated nanoparticles. Starting from these measurements it is possible to determine the distribution using a minimum norm estimation technique. This approach is however ill-posed. We sequentially activate the magnetic nanoparticles through the use of excitation coil arrays with the aim to reduce the ill-posedness. This paper presents some advancements in magnetic nanoparticle reconstruction in terms of reconstruction quality using numerical simulations. The results show that inhomogeneous sequential activation is a proper alternative to homogeneous activation with Helmholtz coils since an increase in accuracy with a factor ranging from 1.5 until 2 is obtained. The presented numerical techniques coupled to MRX measurements can be of significant aid so to have more quantitative knowledge of the biodistribution.

Stable posture and body movement in humans is dictated by the precise functioning of the ampulla organs in the semi-circular canals. Statistical analysis of the interrelationship between bony and membranous compartments within the semi-circular canals is dependent on the visualization of soft tissue structures. Thirty-one human inner ears were prepared, post-fixed with osmium tetroxide and decalcified for soft tissue contrast enhancement. High resolution X-ray microtomography images at 15 μm voxel-size were manually segmented. This data served as templates for centerline generation and cross-sectional area extraction. Our estimates demonstrate the variability of individual specimens from averaged centerlines of both bony and membranous labyrinth. Centerline lengths and cross-sectional areas along these lines were identified from segmented data. Using centerlines weighted by the inverse squares of the cross-sectional areas, plane angles could be quantified. The fit planes indicate that the bony labyrinth resembles a Cartesian coordinate system more closely than the membranous labyrinth. A widening in the membranous labyrinth of the lateral semi-circular canal was observed in some of the specimens. Likewise, the cross-sectional areas in the perilymphatic spaces of the lateral canal differed from the other canals. For the first time we could precisely describe the geometry of the human membranous labyrinth based on a large sample size. Awareness of the variations in the canal geometry of the membranous and bony labyrinth would be a helpful reference in designing electrodes for future vestibular prosthesis and simulating fluid dynamics more precisely.