Quantitative MRI (QMRI) provides a measure of tissue physical parameters, such as the transverse relaxation time, T2, which characterises decay of excited transverse magnetisation and is used clinically as a biomarker for diagnosing and monitoring of cardiomyopathy. QMRI therefore has the potential for use in clinical diagnosis and prognosis, but quality assurance is needed to ensure the extraction of reliable and accurate quantitative information. In this study, we examine how changes in factors for the MRI scanner set up and model curve fitting parameters impact on output measurements of T2. The model that is chosen to fit the MR data may impact on the output measurement of T2. Additionally, the specific radio-frequency pulse sequence chosen, as well as the various parameters which may be set during the scan set-up, may all have an impact on the output measurement. Longer MRI scan times may allow more precise measurements of T2 but are more difficult to transfer into the clinic. Similarly with model fitting, one is limited by the compute time of fitting individual voxels, and the complexity of the model. With more complex models, there is also the risk of over-fitting and introducing bias to the output estimated T2. In practice, there is a compromise between accuracy (bias) and precision (variance) driven by signal-to-noise considerations. Knowing what compromises can be made without impacting strongly on the output T2 estimate is useful for moving from research into clinical MRI. We use an MRI simulator and digital phantom to systematically investigate the effect of changing individual parameters on the output measured T2 value. We run two full-factorial analysis of variance (ANOVA) sensitivity analyses and show that small changes to factors such as the selected curve fitting method and size of the fitted region of interest (ROI) may have a large impact on the output estimated T2. The factors investigated for the curve fitting sensitivity analysis include the model, fitting method (voxel-wise or fitting a whole ROI at once), the radius and centring of the ROI. For the sensitivity analysis for the simulated MRI scan set up, the factors investigated were the repetition time, frequency and phase encoding steps, slice thickness and flip angle. We find that the factors with the greatest impact on estimated T2 are the fitting method and size of the chosen ROI, and the frequency and phase encodings in the MR sequence. Future work with phantom acquisitions and analysis on clinical systems should take care when adjusting these factors as small changes may have a large impact on the output measurement. Standardised acquisition and analysis protocols are highly recommended.

Treatment planning in magnetic hyperthermia requires a thorough knowledge of specific loss power of magnetic nanoparticles as a function of size and excitation conditions. Moreover, in biological tissues the magnetic nanoparticles can aggregate into clusters, making the evaluation of their heating performance more challenging because of the magnetostatic dipole-dipole interactions. In this paper, we present a comprehensive modelling analysis of 10-40 nm sized spherical magnetite (Fe3O4) nanoparticles, investigating how their heating properties are influenced by magnetic field parameters (peak amplitude and frequency), and by volume concentration and aggregation state. The analysis is performed by means of an in-house micromagnetic numerical model, which solves the Landau-Lifshitz-Gilbert equation under the assumption of single-domain nanoparticles, including thermal effects via a Langevin approach. The obtained results provide insight into how to tune hyperthermia properties by varying magnetic nanoparticle size, under different excitation magnetic fields fulfilling the Hergt-Dutz limit (frequency between 50 kHz and 1 MHz, and peak amplitude between 1 kA m-1 and 50 kA m-1). Special attention is finally paid to the role of volume concentration and aggregation order, putting in evidence the need for models able to account for stochasticity and clustering in spatial distribution, to accurately simulate the contribution of magnetostatic dipole-dipole interactions in real applications.

For in vivo magnetic hyperthermia tests, which are typically conducted on small animal models, one of the objectives is the design of alternating current (AC) magnetic field applicators able to guarantee an effective activation of magnetic nanoparticles (MNPs). During therapy application, it is critical to optimize heat deposition due to MNPs and minimize side effects in healthy tissues. For an accurate treatment planning, it is required to carefully select the geometry of the applicator coils and their location with respect to the body, as a function of the position and size of the tumour target region. Additionally, one should preliminary estimate the impact of experimental conditions on the MNP heating efficiency and thus on their capability to induce a temperature increase in tissues. Biophysical constraints have also to be taken into account in the choice of AC magnetic field parameters (frequency and amplitude), to avoid eddy current effects as much as possible.In this study, we present realistic simulations of preclinical tests on a mouse model, evaluating thermal response under various experimental conditions. We investigate different field applicator configurations, including helical, Helmholtz and pancake coils, while also analysing the role of the amplitude and frequency of the supply current, as well as of the type and administered dose of MNPs. The temperature increase in tissues, resulting from the heating effects due to AC magnetic field exposure and MNP activation, is calculated by means of in-house finite element models that solve the low-frequency electromagnetic field problem and the bioheat transfer equation. This in silico approach, which is applicable to any type of field applicators and MNPs, has been demonstrated to provide useful insights for the optimization of in vivo experiments, enabling the design of safer and more effective treatments.

Magnetic oxygen-loaded nanodroplets (MOLNDs) are a promising class of nanomaterials dually sensitive to ultrasound and magnetic fields, which can be employed as nanovectors for drug delivery applications, particularly in the field of hypoxic tissue treatment. Previous investigations were primarily focused on the application of these hybrid systems for hyperthermia treatment, exploiting magnetic nanoparticles for heat generation and nanodroplets as carriers and ultrasound contrast agents for treatment progress monitoring. This work places its emphasis on the prospect of obtaining an oxygen delivery system that can be activated by both ultrasound and magnetic fields. To achieve this goal, Fe3O4 nanoparticles were employed to decorate and induce the magnetic vaporization of OLNDs, allowing oxygen release. We present an optimized method for preparing MOLNDs by decorating nanodroplets made of diverse fluorocarbon cores and polymeric coatings. Furthermore, we performed a series of characterizations for better understanding how magnetic decoration can influence the physicochemical properties of OLNDs. Our comprehensive analysis demonstrates the efficacy of magnetic stimulation in promoting oxygen release compared to conventional ultrasound-based methods. We emphasize the critical role of selecting the appropriate fluorocarbon core and polymeric coating to optimize the decoration process and enhance the oxygen release performance of MOLNDs.

The detection of magnetic nanoparticles in a liquid medium and the quantification of their concentration have the potential to improve the efficiency of several relevant applications in different fields, including medicine, environmental remediation, and mechanical engineering. To this end, sensors based on the magneto-impedance effect have attracted much attention due to their high sensitivity to the stray magnetic field generated by magnetic nanoparticles, their simple fabrication process, and their relatively low cost. To improve the sensitivity of these sensors, a multidisciplinary approach is required to study a wide range of soft magnetic materials as sensing elements and to customize the magnetic properties of nanoparticles. The combination of magneto-impedance sensors with ad hoc microfluidic systems favors the design of integrated portable devices with high specificity towards magnetic ferrofluids, allowing the use of very small sample volumes and making measurements faster and more reliable. In this work, a magneto-impedance sensor based on an amorphous Fe73.5Nb3Cu1Si13.5B9 wire as the sensing element is integrated into a customized millifluidic chip. The sensor detects the presence of magnetic nanoparticles in the ferrofluid and distinguishes the different stray fields generated by single-domain superparamagnetic iron oxide nanoparticles or magnetically blocked Co-ferrite nanoparticles.

Unifying quantum theory and general relativity is the holy grail of contemporary physics. Nonetheless, the lack of experimental evidence driving this process led to a plethora of mathematical models with a substantial impossibility of discriminating among them or even establishing if gravity really needs to be quantized or if, vice versa, quantum mechanics must be "gravitized" at some scale. Recently, it has been proposed that the observation of the generation of entanglement by gravitational interaction, could represent a breakthrough demonstrating the quantum nature of gravity. A few experimental proposals have been advanced in this sense, but the extreme technological requirements (e.g., the need for free-falling gravitationally-interacting masses in a quantum superposition state) make their implementation still far ahead. Here we present a feasibility study for a table-top nanodiamond-based interferometer eventually enabling easier and less resource-demanding quantum gravity tests. With respect to the aforementioned proposals, by relying on quantum superpositions of steady massive (mesoscopic) objects our interferometer may allow exploiting just small-range electromagnetic fields (much easier to implement and control) and, at the same time, the re-utilization of the massive quantum probes exploited, inevitably lost in free-falling interferometric schemes.

Radical polymerization is widely employed for the preparation of advanced materials with controlled properties and responsiveness. Depending on the radical initiator, different stimuli can trigger the beginning of the reaction. This work presents an innovative approach that exploits the heat released by magnetic nanoparticles when they are excited by an alternating current (AC) magnetic field to induce radical polymerizations. In particular, the use of cobalt ferrite (CoFe2O4) nanoparticles is explored for the preparation of polyacrylamide hydrogels, chosen as a model material to demonstrate the strategy. Magnetic and mechanical characterizations reveal that the materials possess properties similar to those of samples prepared by classical thermal polymerization. Indeed, magnetic hyperthermia is a versatile tool for remote temperature control in a localized space that can have different applications. An example is represented by its use for a selective volume polymerization in a thermosensitive environment, overcoming classical problems of both bulk thermal polymerization (e.g., not applicable in delicate environments) and photopolymerization (e.g., poor light penetration). The obtained results pave the way also for production of non-magnetic materials, in which magnetic nanoparticles are first concentrated in a small solution volume (by a permanent magnet) and then exploited to activate the polymerization of the whole material (by an AC magnetic field).

Magnetic hyperthermia is an oncological therapy that exploits magnetic nanoparticles activated by radiofrequency magnetic fields to produce a controlled temperature increase in a diseased tissue. The specific loss power (SLP) of magnetic nanoparticles or the capability to release heat can be improved using surface treatments, which can reduce agglomeration effects, thus impacting on local magnetostatic interactions. In this work, Fe3O4 nanoparticles are synthesized via a coprecipitation reaction and fully characterized in terms of structural, morphological, dimensional, magnetic, and hyperthermia properties (under the Hergt- Dutz limit). Different types of surface coatings are tested, comparing their impact on the heating efficacy and colloidal stability, resulting that sodium citrate leads to a doubling of the SLP with a substantial improvement in dispersion and stability in solution over time; an SLP value of around 170 W/g is obtained in this case for a 100 kHz and 48 kA/m magnetic field.

Preclinical tests on murine models are typically performed to evaluate the therapeutic efficacy of novel magnetic nanoparticles (MNPs) in cancer treatment with magnetic hyperthermia. Here, through in silico experiments, in vivo tests are mimicked on a 30 g mouse and a 500 g rat, with the aim of determining the optimal treatment conditions allowing to reach the therapeutic temperature range (40−45 °C) within tumor regions. Various types of MNPs are considered with very different heating properties in terms of specific loss power, varying their administered dose, as well as the frequency and peak amplitude of the magnetic field. The analysis is performed by means of finite element models that solve the low‐frequency electromagnetic (EM) field problem and the Pennes’ bioheat transfer equation, to calculate the temperature increase in biological tissues due to the combined effects of EM field exposure and MNP activation. The methodology, which can be generalized to any type of MNPs, has permitted to identify the proper doses of MNPs to be administered to the tumor region, as a function of their heating properties and magnetic field parameters, highlighting the conditions that can lead to possible overheating, generation of hot spots or magnetic hyperthermia inefficacy.

While hyperthermia has been shown to induce a variety of cytotoxic and sensitizing effects on cancer tissues, the thermal dose–effect relationship is still not well quantified, and it is still unclear how it can be optimally combined with other treatment modalities. Additionally, it is speculated that different methods of applying hyperthermia, such as water bath heating or electromagnetic energy, may have an effect on the resulting biological mechanisms involved in cell death or in sensitizing tumor cells to other oncological treatments. In order to further quantify and characterize hyperthermia treatments on a cellular level, in vitro experiments shifted towards the use of 3D cell spheroids. These are in fact considered a more representative model of the cell environment when compared to 2D cell cultures. In order to perform radiofrequency (RF)-induced heating in vitro, we have recently developed a dedicated electromagnetic field applicator. In this study, using this applicator, we designed and validated an experimental setup which can heat 3D cell spheroids in a conical polypropylene vial, thus providing a reliable instrument for investigating hyperthermia effects at the cellular scale.

The evaluation of the biological effects of therapeutic hyperthermia in oncology and the precise quantification of thermal dose, when heating is coupled with radiotherapy or chemotherapy, are active fields of research. The reliable measurement of hyperthermia effects on cells and tissues requires a strong control of the delivered power and of the induced temperature rise. To this aim, we have developed a radiofrequency (RF) electromagnetic applicator operating at 434 MHz, specifically engineered for in vitro tests on 3D cell cultures. The applicator has been designed with the aid of an extensive modelling analysis, which combines electromagnetic and thermal simulations. The heating performance of the built prototype has been validated by means of temperature measurements carried out on tissue-mimicking phantoms and aimed at monitoring both spatial and temporal temperature variations. The experimental results demonstrate the capability of the RF applicator to produce a well-focused heating, with the possibility of modulating the duration of the heating transient and controlling the temperature rise in a specific target region, by simply tuning the effectively supplied power.

This paper aims at studying a sensor concept for possible integration in magnetic field-based lab-on-chip devices that exploit ferromagnetic resonance (FMR) phenomena in magnonic crystals. The focus is on 2D magnetic antidot arrays, i.e., magnetic thin films with periodic non-magnetic inclusions (holes), recently proposed as magnetic field sensor elements operating in the gigahertz (GHz) range. The sensing mechanism is here demonstrated for magnetic nano/microbeads adsorbed on the surface of permalloy (Ni80Fe20) antidot arrays with a rhomboid lattice structure and variable hole size. Through extensive micromagnetic modelling analysis, it is shown that the antidot arrays can be used as both bead traps and high-sensitivity detectors, with performance that can be tuned as a function of bead size and magnetic moment. A key parameter for the detection mechanism is the antidot array hole size, which affects the FMR frequency shifts associated with the interaction between the magnetization configuration in the nanostructured film and the bead stray field. Possible applications of the proposed device concept include magnetic immunoassays, using magnetic nano/microbeads as probes for biomarker detection, and biomaterial manipulation.

• Development and validation of in silico models, as a tool to investigate adverse eddy current effects during magnetic hyperthermia tests on mice and rats and to define safe EM field exposure levels. • Weak eddy current effects observed in mice for a large range of AC magnetic field parameters: maximum temperature increase of 0.25 °C and 0.8 °C in proximity to Hergt-Dutz limit and 4 W/kg SAR threshold, respectively. • Important eddy current effects observed in rats: maximum temperature increase around 7 °C found at the Hergt-Dutz limit, for magnetic fields applied along the body longitudinal axis. • Stronger eddy current effects when the magnetic field is applied transversally: maximum temperature increase around 14 °C found in rats at the Hergt-Dutz limit. • Mitigation of eddy current heating with the introduction of water boluses and the use of applicators targeted to tumour region size and position in the body. Magnetic hyperthermia is an oncological therapy that employs magnetic nanoparticles activated by alternating current (AC) magnetic fields with frequencies between 50 kHz and 1 MHz, to release heat in a diseased tissue and produce a local temperature increase of about 5 °C. To assess the treatment efficacy, in vivo tests on murine models (mice and rats) are typically performed. However, these are often carried out without satisfying the biophysical constraints on the electromagnetic (EM) field exposure, with consequent generation of hot spots and undesirable heating of healthy tissues. Here, we investigate possible adverse eddy current effects, to estimate AC magnetic field parameters (frequency and amplitude) that can potentially guarantee safe animal tests of magnetic hyperthermia. The analysis is performed through in silico modelling by means of finite element simulation tools, specifically developed to study eddy current effects in computational animal models, during magnetic hyperthermia treatments. The numerical tools enable us to locally evaluate the specific absorption rate (SAR) and the produced temperature increase, under different field exposure conditions. The simulation outcomes demonstrate that in mice with weight lower than 30 g the thermal effects induced by AC magnetic fields are very weak, also when slightly overcoming the Hergt-Dutz limit, that is the product of the magnetic field amplitude and frequency should be lower than 5·10 9 A/(m·s). Conversely, we observe significant temperature increases in 500 g rats, amplified when the field is applied transversally to the body longitudinal axis. A strong mitigation of side-effects can be achieved by introducing water boluses or by applying focused fields. The developed physics-based modelling approach has proved to be a useful predictive tool for the optimization of preclinical tests of magnetic hyperthermia, allowing the identification of proper EM field conditions and the design of setups that guarantee safe levels of field exposure during animal treatments. In such contest, the obtained results can be considered as valid indicators to assess reference levels for animal testing of biomedical techniques that involve EM fields, like magnetic hyperthermia, thus complying with the Directive 2010/63/EU on the protection of animals used for scientific purposes.

The development and plasticity of axons and dendrites in mammalian neurons may depend on the presence and phosphorylation state of cytoskeletal proteins, including certain microtubule-associated proteins. One of these proteins, microtubule-associated protein 1B, is modified by different protein kinases, which give rise to two major types of phosphorylated isoforms. The distribution of these isoforms in cultured hippocampal neurons has been studied using antibodies to specific phosphorylation-sensitive epitopes. Mode I-phosphorylated MAP1B is largely restricted to developing axonal processes, particularly at their distal regions including their growth cones where no mode I-dephosphorylated MAP1B is present. Axonal maturation is accompanied by dephosphorylation of MAP1B at mode I sites. Thus, mode I-phosphorylated MAP1B may be a marker for axonal growth. In contrast, mode II-phosphorylated MAP1B is abundant in the axonal and somatodendritic compartments, and no increased dephosphorylation occurs during maturation. These results are compatible with a role for the mode I phosphorylation of M AP1B (which might be catalysed by proline-directed protein kinases) in supporting a rapid axonal-specific growth mechanism and a more general role for the mode II phosphorylation of MAP1B (which seems to be catalysed by casein kinase II) in controlling axonal and dendritic growth and remodeling.

This set of data complements the published article "Experimental and Modelling Analysis of the Hyperthermia Properties of Iron Oxide Nanocubes" published on Nanomaterials https://doi.org/10.3390/nano11092179 Ferrero, R.; Barrera, G.; Celegato, F.; Vicentini, M.; Sözeri, H.; Yıldız, N.; Atila Dinçer, C.; Coïsson, M.; Manzin, A.; Tiberto, P. Experimental and Modelling Analysis of the Hyperthermia Properties of Iron Oxide Nanocubes. Nanomaterials 2021, 11, 2179. https://doi.org/10.3390/nano11092179

The ability of magnetic nanoparticles (MNPs) to transform electromagnetic energy into heat is widely exploited in well-known thermal cancer therapies, such as magnetic hyperthermia, which proves useful in enhancing the radio- and chemo-sensitivity of human tumor cells. Since the heat release is ruled by the complex magnetic behavior of MNPs, a careful investigation is needed to understand the role of their intrinsic (composition, size and shape) and collective (aggregation state) properties. Here, the influence of geometrical parameters and aggregation on the specific loss power (SLP) is analyzed through in-depth structural, morphological, magnetic and thermometric characterizations supported by micromagnetic and heat transfer simulations. To this aim, different samples of cubic Fe3O4 NPs with an average size between 15 nm and 160 nm are prepared via hydrothermal route. For the analyzed samples, the magnetic behavior and heating properties result to be basically determined by the magnetic single- or multi-domain configuration and by the competition between magnetocrystalline and shape anisotropies. This is clarified by micromagnetic simulations, which enable us to also elucidate the role of magnetostatic interactions associated with locally strong aggregation.