Counting cells in motion by quantitative real-time magnetic particle imaging.

Magnetic Particle Imaging (MPI) is an advanced and powerful imaging modality for visualization and quantitative real-time detection of magnetic nanoparticles (MNPs). This opens the possibility of tracking cells in vivo once they have been loaded by MNPs. Imaging modalities such as optical imaging, X-ray computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI) face limitations, from depth of penetration and radiation exposure to resolution and quantification accuracy. MPI addresses these challenges, enabling radiation-free tracking of MNP-loaded cells with precise quantification. However, the real-time tracking of MNP-loaded cells with MPI has not been demonstrated yet. This study establishes real-time quantitative tracking of MNP-loaded cells. Therefore, THP-1 monocytes were loaded with three different MNP systems, including the MPI gold standard Resovist and Synomag. The real-time MPI experiments reveal different MPI resolution behaviors of the three MNP systems after cellular uptake. Real-time quantitative imaging was achieved by time-resolved cell number determination and comparison with the number of inserted cells. About 95% of the inserted cells were successfully tracked in a controlled phantom environment. These results underline the potential of MPI for real-time investigation of cell migration and interaction with tissue in vivo.

Determining the resolution of a tracer for magnetic particle imaging by means of magnetic particle spectroscopy.

Magnetic particle imaging (MPI) is an imaging modality to quantitatively determine the three-dimensional distribution of magnetic nanoparticles (MNPs) administered as a tracer into a biological system. Magnetic particle spectroscopy (MPS) is the zero-dimensional MPI counterpart without spatial coding but with much higher sensitivity. Generally, MPS is employed to qualitatively evaluate the MPI capability of tracer systems from the measured specific harmonic spectra. Here, we investigated the correlation of three characteristic MPS parameters with the achievable MPI resolution from a recently introduced procedure based on a two-voxel-analysis of data taken from the system function acquisition that is mandatory in Lissajous scanning MPI. We evaluated nine different tracer systems and determined their MPI capability and resolution from MPS measurements and compared the results with MPI phantom measurements.

Development of Phantoms for Multimodal Magnetic Resonance Imaging and Magnetic Particle Imaging.

Phantoms are crucial for the development of imaging techniques based on magnetic nanoparticles (MNP). They serve as test objects to simulate application scenarios but are also used for quality assurance and interlaboratory comparisons. Magnetic particle imaging (MPI) is excellent for specifically detecting magnetic nanoparticles (MNP) without any background signals. To obtain information about the surrounding soft tissue, MPI is often used in combination with magnetic resonance imaging (MRI). For such application scenarios, this poses a challenge for phantom fabrication, as they need to accommodate MNP as well as provide MR visibility. Recently, layer-by-layer fabrication of parts using Additive Manufacturing (AM) has emerged as a powerful tool for creating complex and patient-specific phantoms, but these are characterized by poor MR visibility of the AM material. We present the systematic screening of AM materials as candidates for multimodal MRI/MPI imaging. Of all investigated materials, silicone (Dreve, Biotec) exhibited the best properties with sufficient MR-signal performance and the lowest absorption of MNP at the interface of AM materials. With the help of AM and the selection of appropriate materials, we have been able to produce suitable MRI/MPI phantoms.

Cell Tracking by Magnetic Particle Imaging: Methodology for Labeling THP-1 Monocytes with Magnetic Nanoparticles for Cellular Imaging.

Magnetic particle imaging (MPI) is a noninvasive tomographic imaging modality for the quantitative visualization of magnetic nanoparticles (MNPs) with high temporal and spatial resolution. The general capability of MPI for cell tracking (e.g., monitoring living cells labeled with MNPs) has successfully been shown. MNPs in cell culture media are often subjected to structural and magnetic changes. In addition to the deteriorating reproducibility, this also complicates the systematic study of the relationship between the MNP properties and their cellular uptake for MPI. Here, we present a method for the preparation of magnetically labeled THP-1 (Tamm-Horsfall Protein-1) monocytes that are used in MPI cell tracking. The method development was performed using two different MPI tracers, which exhibited electrostatic and steric stabilizations, respectively. In the first step, the interaction between the MNPs and cell culture media was investigated and adjusted to ensure high structural and magnetic stability. Furthermore, the influences of the incubation time, MNP concentration used for cellular uptake, and individual preparation steps (e.g., the washing of cells) were systematically investigated. Finally, the success of the developed loading method was demonstrated by the MPI measurements. The presented systematic investigation of the factors that influence the MNP loading of cells will help to develop a reliable and reproducible method for MPI monocyte tracking for the early detection of inflammation in the future.

Tailored Magnetic Multicore Nanoparticles for Use as Blood Pool MPI Tracers.

For the preclinical development of magnetic particle imaging (MPI) in general, and the exploration of possible new clinical applications of MPI in particular, tailored MPI tracers with surface properties optimized for the intended use are needed. Here we present the synthesis of magnetic multicore particles (MCPs) modified with polyethylene glycol (PEG) for use as blood pool MPI tracers. To achieve the stealth effect the carboxylic groups of the parent MCP were activated and coupled with pegylated amines (mPEG-amines) with different PEG-chain lengths from 2 to 20 kDa. The resulting MCP-PEG variants with PEG-chain lengths of 10 kDa (MCP-PEG10K after one pegylation step and MCP-PEG10K2 after a second pegylation step) formed stable dispersions and showed strong evidence of a successful reaction of MCP and MCP-PEG10K with mPEG-amine with 10 kDa, while maintaining their magnetic properties. In rats, the mean blood half-lives, surprisingly, were 2 and 62 min, respectively, and therefore, for MCP-PEG10K2, dramatically extended compared to the parent MCP, presumably due to the higher PEG density on the particle surface, which may lead to a lower phagocytosis rate. Because of their significantly extended blood half-life, MCP-PEG10K2 are very promising as blood pool tracers for future in vivo cardiovascular MPI.

Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy.

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT.

Magnetic separation of iron oxide nanoparticles to improve their application for magnetic particle imaging.

Magnetic particle imaging (MPI) is a promising medical imaging technique for visualizing the three-dimensional distribution of tracer materials, specifically iron oxide nanoparticles (IONP). The optimization of magnetic nanoparticles (MNP) plays an essential role to improve the image resolution and sensitivity of imaging techniques. OBJECTIVE: In this work, the optimization of commercial IONP (EMG 700, Ferrotec) coated with anionic surfactants was carried out using magnetic separation (MS) technique, by a low gradient magnetic separation (LGMS) (<15 T m-1) method, to improve their performance as MPI tracers. APPROACH: The magnetophoretical behavior of the samples in different concentrations ranging from 2 to 120 mmol l-1 was investigated over 24 h of separation. The samples were characterized by dynamic light scattering (DLS), AC susceptibility (ACS), magnetic particle spectroscopy (MPS) and they were imaged in a preclinical MPI scanner, before and after MS. MAIN RESULTS: DLS results showed that by increasing the concentration from 2 to 120 mmol l-1 the hydrodynamic diameter of MNP decrease from 75 to 47 nm and size distribution decrease from 0.19 to 0.11 after 4 min MS. In addition, the MPS results demonstrated the third harmonic amplitude normalized to the iron amount [Formula: see text] and harmonic ratio [Formula: see text] of signal increase from 8.38 to 10.59 Am2 kg-1 (Fe) and 24.21-26.60, respectively. Furthermore, the MPI images of the samples after separation showed higher MPI resolution. SIGNIFICANCE: Therefore, LGMS can be considered as a valuable method to narrow and control the size distribution of MNP for MPI.

Characterization of noise and background signals in a magnetic particle imaging system.

Magnetic particle imaging (MPI) is a novel technology, which opens new possibilities for promising biomedical applications. MPI uses magnetic fields to generate a specific response from magnetic nanoparticles (MNPs), to determine their spatial location non-invasively and without using ionizing radiation. One open challenge of MPI is to achieve further improvements in terms of sensitivity to translate the currently preclinical performed research into clinical applications. In this work, we study the noise and background signals of our preclinical MPI system, to identify and characterize disturbing signal contributions. The current limit of detection achieved with our device was determined previously to be20ng of iron. Based on the results presented in this work, we describe possible hardware and software improvements and estimate that the limit of detection could be lowered to about 1-2 ng. Additionally, a long-term analysis of the scanner performance over the last 3 years is presented, which proved to be an easy and effective way to monitor possible changes or damage of hardware components. All the presented results were obtained by analysing empty scanner measurements and the presented methodology can easily be adapted for different scanner types, to compare their performances.

In vivo magnetic particle imaging: angiography of inferior vena cava and aorta in rats using newly developed multicore particles.

Magnetic Particle Imaging (MPI) is a new imaging modality, which maps the distribution of magnetic nanoparticles (MNP) in 3D with high temporal resolution. It thus may be suited for cardiovascular imaging. Its sensitivity and spatial resolution critically depend on the magnetic properties of MNP. Therefore, we used novel multicore nanoparticles (MCP 3) for in-vivo MPI in rats and analyzed dose requirements, sensitivity and detail resolution. 8 rats were examined using a preclinical MPI scanner (Bruker Biospin GmbH, Germany) equipped with a separate receive coil. MCP 3 and Resovist were administered intravenously (i.v.) into the rats' tail veins at doses of 0.1, 0.05 and 0.025 mmol Fe/kg followed by serial MPI acquisition with a temporal resolution of 46 volumes per second. Based on a qualitative visual scoring system MCP 3-MPI images showed a significantly (P ≤ 0.05) higher image quality than Resovist-MPI images. Morphological features such as vessel lumen diameters (DL) of the inferior vena cava (IVC) and abdominal aorta (AA) could be assessed along a 2-cm segment in mesenteric area only after administration of MCP 3 at dosages of 0.1, 0.05 mmol Fe/kg. The mean DL ± SD estimated was 2.7 ± 0.6 mm for IVC and 2.4 ± 0.7 mm for AA. Evaluation of DL of the IVC and AA was not possible in Resovist-MPI images. Our results show, that MCP 3 provide better image quality at a lower dosage than Resovist. MCP 3-MPI with a clinically acceptable dose of 0.05 mmol Fe/kg increased the visibility of vessel lumens compared to Resovist-based MPI towards possible detection of vascular abnormalities such as stenosis or aneurysms, in vivo.

Lissajous scanning magnetic particle imaging as a multifunctional platform for magnetic hyperthermia therapy.

The use of engineered nanoscale magnetic materials in healthcare and biomedical technologies is rapidly growing. Two examples which have recently attracted significant attention are magnetic particle imaging (MPI) for biological monitoring, and magnetic field hyperthermia (MFH) for cancer therapy. Here for the first time, the capability of a Lissajous scanning MPI device to act as a standalone platform to support the application of MFH cancer treatment is presented. The platform is shown to offer functionalities for nanoparticle localization, focused hyperthermia therapy application, and non-invasive tissue thermometry in one device. Combined, these capabilities have the potential to significantly enhance the accuracy, effectiveness and safety of MFH therapy. Measurements of nanoparticle hyperthermia during protracted exposure to the MPI scanner's 3D imaging field sequence revealed spatially focused heating, with a maximum that is significantly enhanced compared with a simple 1-dimensional sinusoidal excitation. The observed spatial heating behavior is qualitatively described based on a phenomenological model considering torques exerted in the Brownian regime. In vitro cell studies using a human acute monocytic leukemia cell line (THP-1) demonstrated strong suppression of both structural integrity and metabolic activity within 24 h following a 40 min MFH treatment actuated within the Lissajous MPI scanner. Furthermore, reconstructed MPI images of the nanoparticles distributed among the cells, and the temperature-sensitivity of the MPI imaging signal obtained during treatment are demonstrated. In summary, combined Lissajous MPI and MFH technologies are presented; demonstrating for the first time their potential for cancer treatment with maximum effectiveness, and minimal collateral damage to surrounding tissues.

Ex vivo magnetic particle imaging of vascular inflammation in abdominal aortic aneurysm in a murine model.

Abdominal aortic aneurysms (AAAs) are currently one of the leading causes of death in developed countries. Inflammation is crucial in the disease progression, having a substantial impact on various determinants in AAAs development. Magnetic particle imaging (MPI) is an innovative imaging modality, enabling the highly sensitive detection of magnetic nanoparticles (MNPs), suitable as surrogate marker for molecular targeting of vascular inflammation. For this study, Apolipoprotein E-deficient-mice underwent surgical implantation of osmotic minipumps with constant Angiotensin II infusion. After 3 and 4 weeks respectively, in-vivo-magnetic resonance imaging (MRI), ex-vivo-MPI and ex-vivo-magnetic particle spectroscopy (MPS) were performed. The results were validated by histological analysis, immunohistology and laser ablation-inductively coupled plasma-mass spectrometry. MR-angiography enabled the visualization of aneurysmal development and dilatation in the experimental group. A close correlation (R = 0.87) with histological area assessment was measured. Ex-vivo-MPS revealed abundant iron deposits in AAA samples and ex-vivo histopathology measurements were in good agreement (R = 0.76). Ex-vivo-MPI and MPS results correlated greatly (R = 0.99). CD68-immunohistology stain and Perls'-Prussian-Blue-stain confirmed the colocalization of macrophages and MNPs. This study demonstrates the feasibility of ex-vivo-MPI for detecting inflammation in AAA. The quantitative ability for mapping MNPs establishes MPI as a promising tool for monitoring inflammatory progression in AAA in an experimental setting.

Cellular uptake of magnetic nanoparticles imaged and quantified by magnetic particle imaging.

Magnetic particle imaging (MPI) is a non-invasive, non-ionizing imaging technique for the visualization and quantification of magnetic nanoparticles (MNPs). The technique is especially suitable for cell imaging as it offers zero background contribution from the surrounding tissue, high sensitivity, and good spatial and temporal resolutions. Previous studies have demonstrated that the dynamic magnetic behaviour of MNPs changes during cellular binding and internalization. In this study, we demonstrate how this information is encoded in the MPI imaging signal. Through MPI imaging we are able to discriminate between free and cell-bound MNPs in reconstructed images. This technique was used to image and quantify the changes that occur in-vitro when free MNPs come into contact with cells and undergo cellular-uptake over time. The quantitative MPI results were verified by colorimetric measurements of the iron content. The results showed a mean relative difference between the MPI results and the reference method of 23.8% for the quantification of cell-bound MNPs. With this technique, the uptake of MNPs in cells can be imaged and quantified directly from the first MNP cell contact, providing information on the dynamics of cellular uptake.

Continuously manufactured single-core iron oxide nanoparticles for cancer theranostics as valuable contribution in translational research.

Micromixer technology was used to manufacture magnetic single core iron oxide nanoparticles that combine imaging as well as therapeutic functions. In a continuous, scalable and highly controllable manner, synthesis with biocompatible educts via an aqueous synthesis route was performed. Size control by varying relevant process parameters e.g. temperature was confirmed by transmission electron microscopy measurements of experimental series demonstrating the exceptional size control and homogeneity. Furthermore, analytical centrifugation evidenced the stably dispersed state of the single core nanoparticles in aqueous media. Size controlled production of single-core iron oxide nanoparticles was used to design optimized nanoparticles with a core diameter of about 30 nm, showing high signal amplitudes in Magnetic Particle Imaging (MPI) as a promising MPI tracer material. Moreover, therapeutic potential of these particles in magnetic fluid hyperthermia was evaluated and specific absorption rates (SAR values) up to 1 kW per g(Fe) were obtained, which exceed the comparable SAR value of Resovist® by more than a factor of three. Relaxometry measurements clearly confirmed the capacity of these single-core magnetic nanoparticles to generate significant T 2-weighted magnetic resonance imaging (MRI) contrast that potentially allows multimodal imaging for monitoring the particles in vivo in a theranostic application scenario. Finally, first cell viability and apoptosis tests on endothelial cells did not show any cytotoxicity certifying a good biocompatibility of the iron oxide nanoparticles. This microtechnological approach provides reproducible, scalable single core iron oxide nanoparticles as highly performing tracers for MPI diagnosis as well as efficient heat generators for hyperthermia therapy. These preliminary results contribute to translational research in image guided cancer therapy - a further step from basic research to future medicine.

MPI Phantom Study with A High-Performing Multicore Tracer Made by Coprecipitation.

Magnetic particle imaging (MPI) is a new imaging technique that detects the spatial distribution of magnetic nanoparticles (MNP) with the option of high temporal resolution. MPI relies on particular MNP as tracers with tailored characteristics for improvement of sensitivity and image resolution. For this reason, we developed optimized multicore particles (MCP 3) made by coprecipitation via synthesis of green rust and subsequent oxidation to iron oxide cores consisting of a magnetite/maghemite mixed phase. MCP 3 shows high saturation magnetization close to that of bulk maghemite and provides excellent magnetic particle spectroscopy properties which are superior to Resovist® and any other up to now published MPI tracers made by coprecipitation. To evaluate the MPI characteristics of MCP 3 two kinds of tube phantoms were prepared and investigated to assess sensitivity, spatial resolution, artifact severity, and selectivity. Resovist® was used as standard of comparison. For image reconstruction, the regularization factor was optimized, and the resulting images were investigated in terms of quantifying of volumes and iron content. Our results demonstrate the superiority of MCP 3 over Resovist® for all investigated MPI characteristics and suggest that MCP 3 is promising for future experimental in vivo studies.

Improved sensitivity and limit-of-detection using a receive-only coil in magnetic particle imaging.

Magnetic particle imaging (MPI) is an imaging modality capable of quantitatively determining the 3D distribution of a magnetic nanoparticle (MNP) ensemble. In this work, we present a method for reducing the MNP limit of detection by employing a new receive-only coil (Rx-coil) for signal acquisition. The new signal detector is designed to improve the sensitivity and thus quality of reconstructed images. We present characterization measurements conducted with the prototype Rx-coil installed in a preclinical MPI scanner. The gradiometric design of the Rx-coil attenuates the unwanted signal contributions arising from the excitation field, leading to a 17 dB lower background level compared to the conventional dual-purpose coil (TxRx-coil), which is crucial for detecting low amounts of MNP. Network analyzer measurements of the frequency-dependent coil sensitivity, as well as spectral analysis of recorded MPI data demonstrate an overall increase of the coil sensitivity of about +12 dB for the Rx-coil. Comparisons of the sensitivity distributions revealed no significant degradations in terms of homogeneity for the Rx-coil compared to the TxRx-coil in an imaging volume of 6 × 3 × 3 cm3. Finally, the limit of detection was determined experimentally for each coil type using a serial dilution of MNPs, resulting in values of 133 ng of iron for the conventional TxRx-coil and 20 ng for the new Rx-coil, using an acquisition time of 2 s. A linear relationship between the reconstructed signal intensities and the iron mass in the samples was observed with coefficients of determination (R2) of above 99% in the range of the limit of detection to 3 103ng(Fe). These results open the way for improved image quality and faster acquisition time in pre-clinical MPI scanners.

Optimization of Iron Oxide Tracer Synthesis for Magnetic Particle Imaging.

The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based synthesis of multicore superparamagnetic iron oxide nanoparticles stabilized with dextran (MC-SPIONs). We also demonstrate the preparation of single core superparamagnetic iron oxide nanoparticles in organic media, subsequently coated with a poly(ethylene glycol) gallic acid polymer and phase transferred to water (SC-SPIONs). Our aim was to obtain long-term stable particles in aqueous media with high MPI performance. We found that the amplitude of the third harmonic measured by magnetic particle spectroscopy (MPS) at 10 mT is 2.3- and 5.8-fold higher than Resovist for the MC-SPIONs and SC-SPIONs, respectively, revealing excellent MPI potential as compared to other reported MPI tracer particle preparations. We show that the reconstructed MPI images of phantoms using optimized multicore and specifically single-core particles are superior to that of commercially available Resovist, which we utilize as a reference standard, as predicted by MPS.

Novel magnetic multicore nanoparticles designed for MPI and other biomedical applications: From synthesis to first in vivo studies.

Synthesis of novel magnetic multicore particles (MCP) in the nano range, involves alkaline precipitation of iron(II) chloride in the presence of atmospheric oxygen. This step yields green rust, which is oxidized to obtain magnetic nanoparticles, which probably consist of a magnetite/maghemite mixed-phase. Final growth and annealing at 90°C in the presence of a large excess of carboxymethyl dextran gives MCP very promising magnetic properties for magnetic particle imaging (MPI), an emerging medical imaging modality, and magnetic resonance imaging (MRI). The magnetic nanoparticles are biocompatible and thus potential candidates for future biomedical applications such as cardiovascular imaging, sentinel lymph node mapping in cancer patients, and stem cell tracking. The new MCP that we introduce here have three times higher magnetic particle spectroscopy performance at lower and middle harmonics and five times higher MPS signal strength at higher harmonics compared with Resovist®. In addition, the new MCP have also an improved in vivo MPI performance compared to Resovist®, and we here report the first in vivo MPI investigation of this new generation of magnetic nanoparticles.

A reference dataset for verifying numerical electrophysiological heart models.

BACKGROUND: The evaluation, verification and comparison of different numerical heart models are difficult without a commonly available database that could be utilized as a reference. Our aim was to compile an exemplary dataset. METHODS: The following methods were employed: Magnetic Resonance Imaging (MRI) of heart and torso, Body Surface Potential Maps (BSPM) and MagnetoCardioGraphy (MCG) maps. The latter were recorded simultaneously from the same individuals a few hours after the MRI sessions. RESULTS: A training dataset is made publicly available; datasets for blind testing will remain undisclosed. CONCLUSIONS: While the MRI data may provide a common input that can be applied to different numerical heart models, the verification and comparison of different models can be performed by comparing the measured biosignals with forward calculated signals from the models.

Ultra-wideband sensors for improved magnetic resonance imaging, cardiovascular monitoring and tumour diagnostics.

The specific advantages of ultra-wideband electromagnetic remote sensing (UWB radar) make it a particularly attractive technique for biomedical applications. We partially review our activities in utilizing this novel approach for the benefit of high and ultra-high field magnetic resonance imaging (MRI) and other applications, e.g., for intensive care medicine and biomedical research. We could show that our approach is beneficial for applications like motion tracking for high resolution brain imaging due to the non-contact acquisition of involuntary head motions with high spatial resolution, navigation for cardiac MRI due to our interpretation of the detected physiological mechanical contraction of the heart muscle and for MR safety, since we have investigated the influence of high static magnetic fields on myocardial mechanics. From our findings we could conclude, that UWB radar can serve as a navigator technique for high and ultra-high field magnetic resonance imaging and can be beneficial preserving the high resolution capability of this imaging modality. Furthermore it can potentially be used to support standard ECG analysis by complementary information where sole ECG analysis fails. Further analytical investigations have proven the feasibility of this method for intracranial displacements detection and the rendition of a tumour's contrast agent based perfusion dynamic. Beside these analytical approaches we have carried out FDTD simulations of a complex arrangement mimicking the illumination of a human torso model incorporating the geometry of the antennas applied.

Pseudo current density maps of electrophysiological heart, nerve or brain function and their physical basis.

BACKGROUND: In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular. METHODS: The physical basis of these intuitive maps is clarified by means of analytically solvable problems. RESULTS: Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method. CONCLUSION: Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.