A. Lascialfari

Synthesis of functionalized magnetic nanoparticles (NPs) for biomedical applications represents a current challenge. In this paper we present the synthesis and characterization of water-dispersible sugar-coated iron oxide NPs specifically designed as magnetic fluid hyperthermia heat mediators and negative contrast agents for magnetic resonance imaging. In particular, the influence of the inorganic core size was investigated. To this end, iron oxide NPs with average size in the range of 4-35 nm were prepared by thermal decomposition of molecular precursors and then coated with organic ligands bearing a phosphonate group on one side and rhamnose, mannose, or ribose moieties on the other side. In this way a strong anchorage of the organic ligand on the inorganic surface was simply realized by ligand exchange, due to covalent bonding between the Fe(3+) atom and the phosphonate group. These synthesized nanoobjects can be fully dispersed in water forming colloids that are stable over very long periods. Mannose, ribose, and rhamnose were chosen to test the versatility of the method and also because these carbohydrates, in particular rhamnose, which is a substrate of skin lectin, confer targeting properties to the nanosystems. The magnetic, hyperthermal, and relaxometric properties of all the synthesized samples were investigated. Iron oxide NPs of ca. 16-18 nm were found to represent an efficient bifunctional targeting system for theranostic applications, as they have very good transverse relaxivity (three times larger than the best currently available commercial products) and large heat release upon application of radio frequency (RF) electromagnetic radiation with amplitude and frequency close to the human tolerance limit. The results have been rationalized on the basis of the magnetic properties of the investigated samples.

NMR and magnetization measurements in Li2VOSiO4 and Li2VOGeO4 are reported. The analysis of the susceptibility shows that both compounds are two-dimensional S = 1/2 Heisenberg antiferromagnets on a square lattice with a sizable frustration induced by the competition between the superexchange couplings J1 along the sides of the square and J2 along the diagonal. Li2VOSiO4 undergoes a low-temperature phase transition to a collinear order, as theoretically predicted for J2/J1>0.5. Just above the magnetic transition the degeneracy between the two collinear ground states is lifted by the onset of a structural distortion.

A one-pot, two-step colloidal strategy to prepare bimagnetic hybrid nanocrystals (HNCs), comprising size-tuned fcc FePt and inverse spinel cubic iron oxide domains epitaxially arranged in a heterodimer configuration, is described. The HNCs have been synthesized in a unique surfactant environment by temperature-driven sequential reactions, involving the homogeneous nucleation of FePt seeds and the subsequent heterogeneous growth of iron oxide. This self-regulated mechanism offers high versatility in the control of the geometric features of the resulting heterostructures, circumventing the use of more elaborate seeded growth techniques. It has been found that, as a consequence of the exchange coupling between the two materials, the HNCs exhibit tunable single-phase-like magnetic behavior, distinct from that of their individual components. In addition, the potential of the heterodimers as effective contrast agents for magnetic resonance imaging techniques has been examined.

The magnetic phase diagram of ${\mathrm{La}}_{2\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{CuO}}_{4}$ in the antiferromagnetic regime (x\ensuremath{\le}0.02) has been derived from $^{139}\mathrm{La}$ nuclear quadrupole resonance studies from 4 to 250 K. The data demonstrate freezing of the doped holes' effective spin degrees of freedom below ${\mathit{T}}_{\mathit{f}}$\ensuremath{\approxeq}(815 K)x into a spin-glass-like state which is superimposed on the antiferromagnetic background. These and previous results allow a detailed magnetic phase diagram to be constructed for x\ensuremath{\le}0.05 and reveal a distinct crossover at x\ensuremath{\approxeq}0.02 in the nature of the spin-glass transition.

Novel systems based on suspensions of colloidal magnetic nanoparticles have been investigated as perspective superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI). The nanostructures that we have studied contain surfactant-capped magnetite (Fe3O4) inorganic cores with different controlled sizes, ranging from 5.5 to 12 nm. The as-synthesized nanostructures are passivated by hydrophobic surfactants and thus are fully dispersible in nonpolar media. The magnetic nanocrystals have been transferred into aqueous media by a procedure based on the surface intercalation and coating with an amphiphilic polymer shell. The MRI efficiency in contrasting images, i.e., the NMR relaxivities r1 and r2, have been compared with Endorem and Sinerem, commercial superparamagnetic MRI contrast agents. We found that our nanostructures exhibit r1 and r2 relaxivities comparable to those of commercial CA over the whole frequency range. The MRI efficiency of our samples was related to their microstructural and magnetic properties. The transverse relaxivity r2, leading the contrast in "negative" superparamagnetic agents, was found to improve as the diameter of the inorganic core is increased. The NMR relaxometry profile confirmed the nature of the physical mechanisms inducing the increase of the nuclear relaxation rates at low (magnetic anisotropy) and high (Curie relaxation) fields.

Hyperthermia, though by itself generally non-curative for cancer, can significantly increase the efficacy of radiation therapy, as demonstrated by in vitro, in vivo, and clinical results. Its limited use in the clinic is mainly due to various practical implementation difficulties, the most important being how to adequately heat the tumor, especially deep-seated ones. In this work, we first review the effects of hyperthermia on tissue, the limitations of radiation therapy and the radiobiological rationale for combining the two treatment modalities. Subsequently, we review the theory and evidence for magnetic hyperthermia that is based on magnetic nanoparticles, its advantages compared with other methods of hyperthermia, and how it can be used to overcome the problems associated with traditional techniques of hyperthermia.

For imaging with different modalities, labels, which provide contrast for all modalities, are required. Colloidal nanoparticles composed out of an inorganic core and a polymer shell offer progress in this direction. Both, the core and the polymer shell, can be synthesized to be fluorescent, magnetic, or radioactive. When different cores are combined with different polymer shells, different types of particles for dual imaging can be obtained, as for example, fluorescent cores with radioactive polymer shells. Properties and perspectives of such nanoparticles for multimodal imaging are discussed.

Magnetic nanoparticles (NPs) are increasingly being considered for use in biomedical applications such as biosensors, imaging contrast agents and drug delivery vehicles. In a biological fluid, proteins associate in a preferential manner with NPs. The small sizes and high curvature angles of NPs influence the types and amounts of proteins present on their surfaces. This differential display of proteins bound to the surface of NPs can influence the tissue distribution, cellular uptake and biological effects of NPs. To date, the effects of adsorption of a protein corona (PC) on the magnetic properties of NPs have not been considered, despite the fact that some of their potential applications require their use in human blood. Here, to investigate the effects of a PC (using fetal bovine serum) on the MRI contrast efficiency of superparamagnetic iron oxide NPs (SPIONs), we have synthesized two series of SPIONs with variation in the thickness and functional groups (i.e. surface charges) of the dextran surface coating. We have observed that different physico-chemical characteristics of the dextran coatings on the SPIONs lead to the formation of PCs of different compositions. (1)H relaxometry was used to obtain the longitudinal, r1, and transverse, r2, relaxivities of the SPIONs without and with a PC, as a function of the Larmor frequency. The transverse relaxivity, which determines the efficiency of negative contrast agents (CAs), is very much dependent on the functional group and the surface charge of the SPIONs' coating. The presence of the PC did not alter the relaxivity of plain SPIONs, while it slightly increased the relaxivity of the negatively charged SPIONs and dramatically decreased the relaxivity of the positively charged ones, which was coupled with particle agglomeration in the presence of the proteins. To confirm the effect of the PC on the MRI contrast efficiency, in vitro MRI experiments at ν = 8.5 MHz were performed using a low-field MRI scanner. The MRI contrasts, produced by different samples, were fully in agreement with the relaxometry findings.

We describe an environmentally friendly, top-down approach to the synthesis of Au89Fe11 nanoparticles (NPs). The plasmonic response of the gold moiety and the magnetism of the iron moiety coexist in the Au89Fe11 nanoalloy with strong modification compared to single element NPs, revealing a non-linear surface plasmon resonance dependence on the iron fraction and a transition from paramagnetic to a spin-glass state at low temperature. These nanoalloys are accessible to conjugation with thiolated molecules and they are promising contrast agents for magnetic resonance imaging.

Zinc substitution is often proposed as an efficient strategy to improve the performances of spinel ferrite nanoparticles, particularly related to their application as theranostic agents. In this work, a series of 8 nm spinel ferrite nanoparticles of formula CoxZnyFe3–(x+y)O4 is synthesized by thermal decomposition with the purpose of investigating the role of Zn2+ ions in modifying the structural and magnetic properties. Contrary to most of the literature on this subject, where the sum of Co and Zn is kept constant (x + y = 1), here, the amount of Co is maintained at ca. x = 0.6, corresponding to the maximum of magnetic anisotropy of the Zn-undoped system, whereas the amount of Zn is progressively varied along the series from y = 0.05 to 0.4. This approach allows enlightening the effect of the Zn introduction on the magnetic and crystal structures and, particularly, on magnetic anisotropy, which is deeply investigated by several complementary techniques. A significant increase of the saturation magnetization, MS, upon the Zn content up to y = 0.4 is confirmed only at low temperature, whereas at room temperature, this effect is partially nullified by the weakening of the magnetic exchange coupling constants due to the increasing Zn substitution. Moreover, we demonstrate that the lattice modifications following the Zn introduction are responsible of a strong decrease of the particle magnetic anisotropy. Overall, these effects limit the use of Zn-substituted ferrites in biomedical applications like magnetic resonance imaging and magnetic fluid hyperthermia only to very low amount of Zn, as here confirmed by relaxometric and calorimetric measurements.

A combination of carbon ions/photons irradiation and hyperthermia as a novel therapeutic approach for the in-vitro treatment of pancreatic cancer BxPC3 cells is presented. The radiation doses used are 0–2 Gy for carbon ions and 0–7 Gy for 6 MV photons. Hyperthermia is realized via a standard heating bath, assisted by magnetic fluid hyperthermia (MFH) that utilizes magnetic nanoparticles (MNPs) exposed to an alternating magnetic field of amplitude 19.5 mTesla and frequency 109.8 kHz. Starting from 37 °C, the temperature is gradually increased and the sample is kept at 42 °C for 30 min. For MFH, MNPs with a mean diameter of 19 nm and specific absorption rate of 110 ± 30 W/gFe3o4 coated with a biocompatible ligand to ensure stability in physiological media are used. Irradiation diminishes the clonogenic survival at an extent that depends on the radiation type, and its decrease is amplified both by the MNPs cellular uptake and the hyperthermia protocol. Significant increases in DNA double-strand breaks at 6 h are observed in samples exposed to MNP uptake, treated with 0.75 Gy carbon-ion irradiation and hyperthermia. The proposed experimental protocol, based on the combination of hadron irradiation and hyperthermia, represents a first step towards an innovative clinical option for pancreatic cancer.

We have used $^{139}\mathrm{La}$ nuclear quadrupole resonance (NQR) and positive muon spin rotation (\ensuremath{\mu}SR) measurements to probe the weakly doped antiferromagnetic (AF) region (x0.02) of the ${\mathrm{La}}_{2\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{CuO}}_{4}$ system below the three-dimensional (3D) AF ordering (N\'eel) temperature ${\mathit{T}}_{\mathit{N}}$(x). From these measurements, our previous $^{139}\mathrm{La}$ NQR measurements [F. C. Chou et al., Phys. Rev. Lett. 71, 2323, (1993)], and auxiliary $^{139}\mathrm{La}$ nuclear magnetic resonance (NMR) measurements of single-crystal ${\mathrm{La}}_{2}$${\mathrm{CuO}}_{4}$, we have determined the ${\mathrm{Cu}}^{2+}$ staggered magnetization ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,T) below ${\mathit{T}}_{\mathit{N}}$(x). Above \ensuremath{\sim}30 K, ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,T) at each T is found to be progressively depressed with increasing x (decreasing ${\mathit{T}}_{\mathit{N}}$); the ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,0) at T=0, extrapolated from T>30 K, is found from both the NQR and \ensuremath{\mu}SR measurements to follow the same empirical relation ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,0)/${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(0,0)=(1-x/${\mathit{x}}_{\mathit{c}}$${)}^{\mathit{n}}$ with ${\mathit{x}}_{\mathit{c}}$=0.023 and n=0.236. To model the extrapolated values, we assume that the doped holes are mobile and are situated in 1D ``rivers'' of charge which form walls in the ${\mathrm{CuO}}_{2}$ planes and which separate and uncouple undoped AF domains; an infinite number of these layers are stacked along the c axis.Using linear spin-wave theory and the interplanar and intraplanar ${\mathrm{Cu}}^{2+}$ AF exchange interactions found from neutron-scattering measurements on ${\mathrm{La}}_{2}$${\mathrm{CuO}}_{4}$, we calculated ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,0) for this doped hole and ${\mathrm{Cu}}^{2+}$ spin configuration and find good agreement with the above extrapolated T=0 values. Thus, in the AF region x0.02 of the phase diagram of ${\mathrm{La}}_{2\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{CuO}}_{4}$, these results support the previous hypothesis that microsegregation of the (mobile) doped holes into domain walls occurs above \ensuremath{\sim}30 K, consistent with the phase separation phenomenology of Emery and Kivelson. Below \ensuremath{\sim}30 K, an anomalous increase in ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,T) is observed in ${\mathrm{La}}_{2\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{CuO}}_{4}$, particularly for the larger x values approaching x=0.02, such that ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$(x,T) is nearly independent of x as T\ensuremath{\rightarrow}0 and is therefore about the same as the T\ensuremath{\rightarrow}0 value observed for undoped ${\mathrm{La}}_{2}$${\mathrm{CuO}}_{4}$. We interpret this effect as arising from localization of the doped holes below \ensuremath{\sim}30 K, whereby localized doped holes are much less effective in reducing ${\mathit{M}}^{\mathrm{\ifmmode^\circ\else\textdegree\fi{}}}$ than mobile holes.In support of this hypothesis, we find that the width of the $^{139}\mathrm{La}$ NQR 2${\ensuremath{\nu}}_{\mathit{Q}}$ line in ${\mathrm{La}}_{2\mathrm{\ensuremath{-}}\mathit{x}}$${\mathrm{Sr}}_{\mathit{x}}$${\mathrm{CuO}}_{4}$ is nearly independent of temperature below 4.2 K and increases linearly with x for x0.02. We present new \ensuremath{\mu}SR measurements to support the idea that the effective spin degrees of freedom associated with the localized doped holes undergo a continuous freezing at ${\mathit{T}}_{\mathit{f}}$\ensuremath{\approxeq}(815 K)x, as opposed to a cooperative phase transition, superimposed on the preexisting AF long-range order.

Chemical synthesis, stability, and characterization of a new albumin-based magnetic nanocarrier containing cobalt ferrite nanoparticles is reported. The BSA–cobalt-based nanocarrier is tested as a theranostic nanomedicine: both diagnostic abilities in vivo and therapeutic hyperthermic effects on standard human tumor cell line (HeLa cells, see image) are investigated.

Abstract A simple and efficient method for synthesizing a range of hybrid nanocomposites based on a core of silica nanospheres (160, 330, and 660 nm in diameter) covered by an outer shell of superparamagnetic nanoparticles, either iron oxide or heterodimeric FePt‐iron oxide nanocrystals, is presented. The magnetic and ultrasound characterization of the resulting nanocomposites shows that they have great potential as contrast agents for dual‐mode imaging purposes, combining magnetic resonance imaging (MRI) and ultrasonography (US).

Controlled assembly of single-crystal, colloidal maghemite nanoparticles is facilitated via a high-temperature polyol-based pathway. Structural characterization shows that size-tunable nanoclusters of 50 and 86 nm diameters (D), with high dispersibility in aqueous media, are composed of ∼13 nm (d) crystallographically oriented nanoparticles. The interaction effects are examined against the increasing volume fraction, φ, of the inorganic magnetic phase that goes from individual colloidal nanoparticles (φ = 0.47) to clusters (φ = 0.72). The frozen-liquid dispersions of the latter exhibit weak ferrimagnetic behaviour at 300 K. Comparative Mössbauer spectroscopic studies imply that intra-cluster interactions come into play. New insight emerges from the clusters' temperature-dependent ac susceptibility that displays two maxima in χ''(T), with strong frequency dispersion. Scaling-law analysis together with the observed memory effects suggests that a superspin-glass state settles-in at TB ∼ 160-200 K, while at lower-temperatures, surface spin-glass freezing is established at Tf ∼ 40-70 K. In such nanoparticle-assembled systems, with increased φ, Monte Carlo simulations corroborate the role of the inter-particle dipolar interactions and that of the constituent nanoparticles' surface spin disorder in the emerging spin-glass dynamics.

We present the magnetic, optical and relaxometric properties of multifunctional Au–Fe3O4 hybrid nanoparticles (HNPs), as possible novel contrast agents (CAs) for magnetic resonance imaging (MRI). The HNPs have been synthesized by wet chemical methods in heterodimer and core–shell geometries and capped with oleylamine. Structural characterization of the samples have been made by X-ray diffraction and transmission electron microscopy, while magnetic properties have been investigated by means of Superconducting Quantum Interference Device-SQUID magnetometry experiments. As required for MRI applications using negative CAs, the samples resulted superparamagnetic at room temperature and well above their blocking temperatures. Optical properties have been investigated by analyzing the optical absorbtion spectra collected in UV–visible region. Relaxometric measurements have been performed on organic suspensions of HNPs and Nuclear Magnetic Resonance (NMR) dispersion curves have been obtained by measuring the longitudinal 1/T1 and transverse 1/T2 relaxation rates of solvent protons in the range 10 kHz/300 MHz at room temperature. NMR relaxivities r1 and r2 have been compared with ENDOREM®, one of the commercial superparamagnetic iron oxide based MRI contrast agents. MRI contrast enhancement efficiencies have been investigated also by examining T2-weighted MR images of suspensions. The experimental results suggest that the nanoparticles' suspensions are good candidates as negative CAs.

The identification of alternative biocompatible magnetic NPs for advanced clinical application is becoming an important need due to raising concerns about iron accumulation in soft issues associated to the administration of superparamagnetic iron oxide nanoparticles (NPs). Here, we report on the performance of previously synthetized iron-doped hydroxyapatite (FeHA) NPs as contrast agent for magnetic resonance imaging (MRI). The MRI contrast abilities of FeHA and Endorem® (dextran coated iron oxide NPs) were assessed by 1H nuclear magnetic resonance relaxometry and their performance in healthy mice was monitored by a 7 Tesla scanner. FeHA applied a higher contrast enhancement, and had a longer endurance in the liver with respect to Endorem® at iron equality. Additionally, a proof of concept of FeHA use as scintigraphy imaging agent for positron emission tomography (PET) and single photon emission computed tomography (SPECT) was given labeling FeHA with 99mTc-MDP by a straightforward surface functionalization process. Scintigraphy/x-ray fused imaging and ex vivo studies confirmed its dominant accumulation in the liver, and secondarily in other organs of the mononuclear phagocyte system. FeHA efficiency as MRI-T2 and PET-SPECT imaging agent combined to its already reported intrinsic biocompatibility qualifies it as a promising material for innovative nanomedical applications.The ability of iron-doped hydroxyapatite nanoaprticles (FeHA) to work in vivo as imaging agents for magnetic resonance (MR) and nuclear imaging is demonstrated. FeHA applied an higher MR contrast in the liver, spleen and kidneys of mice with respect to Endorem®. The successful radiolabeling of FeHA allowed for scintigraphy/X-ray and ex vivo biodistribution studies, confirming MR results and envisioning FeHA application for dual-imaging.

The role of computed tomography (CT) in the diagnosis and characterization of coronavirus disease 2019 (COVID-19) pneumonia has been widely recognized. We evaluated the performance of a software for quantitative analysis of chest CT, the LungQuant system, by comparing its results with independent visual evaluations by a group of 14 clinical experts. The aim of this work is to evaluate the ability of the automated tool to extract quantitative information from lung CT, relevant for the design of a diagnosis support model.LungQuant segments both the lungs and lesions associated with COVID-19 pneumonia (ground-glass opacities and consolidations) and computes derived quantities corresponding to qualitative characteristics used to clinically assess COVID-19 lesions. The comparison was carried out on 120 publicly available CT scans of patients affected by COVID-19 pneumonia. Scans were scored for four qualitative metrics: percentage of lung involvement, type of lesion, and two disease distribution scores. We evaluated the agreement between the LungQuant output and the visual assessments through receiver operating characteristics area under the curve (AUC) analysis and by fitting a nonlinear regression model.Despite the rather large heterogeneity in the qualitative labels assigned by the clinical experts for each metric, we found good agreement on the metrics compared to the LungQuant output. The AUC values obtained for the four qualitative metrics were 0.98, 0.85, 0.90, and 0.81.Visual clinical evaluation could be complemented and supported by computer-aided quantification, whose values match the average evaluation of several independent clinical experts.We conducted a multicenter evaluation of the deep learning-based LungQuant automated software. We translated qualitative assessments into quantifiable metrics to characterize coronavirus disease 2019 (COVID-19) pneumonia lesions. Comparing the software output to the clinical evaluations, results were satisfactory despite heterogeneity of the clinical evaluations. An automatic quantification tool may contribute to improve the clinical workflow of COVID-19 pneumonia.

Measurements of the spin-lattice relaxation rate are reported for muons and protons as a function of temperature for different values of the applied magnetic field in the ${\mathrm{Mn}}_{12}{\mathrm{O}}_{12}$ molecular cluster. Strongly field dependent maxima in the relaxation rate versus temperature are observed below 50 K. The results are explained in terms of thermal fluctuations of the total magnetization of the cluster among the different orientations with respect to the anisotropy axis. The lifetimes of the different $m$ components of the total spin, ${S}_{T}\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}10$, of the molecule are obtained from the experiment and shown to be consistent with the ones expected from a spin-phonon coupling mechanism. No clear evidence for macroscopic quantum tunneling was observed in the field dependence of the proton relaxation rate at low $T$.

Two magnetic molecular clusters containing almost coplanar rings of iron (III) ions with spin S=5/2 have been investigated by $^{1}\mathrm{H}$ NMR and relaxation measurements. The first system, which will be referred to as Fe6, is a molecule of general formula [${\mathrm{NaFe}}_{6}$(${\mathrm{OCH}}_{3}$${)}_{12}$(${\mathrm{C}}_{17}$${\mathrm{O}}_{4}$${\mathrm{H}}_{15}$${)}_{6}$${]}^{+}$${\mathrm{ClO}}_{4}^{\mathrm{\ensuremath{-}}}$ or [${\mathrm{NaFe}}_{6}$(${\mathrm{OCH}}_{3}$${)}_{12}$(${\mathrm{C}}_{15}$${\mathrm{H}}_{11}$${\mathrm{O}}_{2}$${)}_{6}$${]}^{+}$${\mathrm{ClO}}_{4}^{\mathrm{\ensuremath{-}}}$ or [${\mathrm{LiFe}}_{6}$(${\mathrm{OCH}}_{3}$${)}_{12}$(${\mathrm{C}}_{15}$${\mathrm{H}}_{11}$${\mathrm{O}}_{2}$${)}_{6}$${]}^{+}$${\mathrm{ClO}}_{4}^{\mathrm{\ensuremath{-}}}$ while the second type of ring, denoted Fe10, corresponds to the molecule [${\mathrm{Fe}}_{10}$(${\mathrm{OCH}}_{3}$${)}_{20}$(${\mathrm{C}}_{2}$${\mathrm{H}}_{2}$${\mathrm{O}}_{2}$Cl${)}_{10}$]. The $^{1}\mathrm{H}$ NMR linewidth is broadened by the nuclear dipolar interaction and by the dipolar coupling of the protons with the iron (III) paramagnetic moment. It is found that the nuclear spin-lattice relaxation rate, ${\mathrm{T}}_{1}^{\mathrm{\ensuremath{-}}1}$, of the proton is a sensitive probe of the Fe spin dynamics. In both clusters, ${\mathrm{T}}_{1}^{\mathrm{\ensuremath{-}}1}$ decreases with decreasing temperatures from room temperature, goes through a peak just below about 30 K in Fe6 and 10 K in Fe10, and it drops exponentially to very small values at helium temperature. The temperature dependence of the relaxation rate is discussed in terms of the fluctuations of the local spins within the allowed total spin configurations in the framework of the weak collision theory to describe the nuclear relaxation. We use the calculated energy levels for the Fe6 ring based on a Heisenberg Hamiltonian and the value of J obtained from the fit of the magnetic susceptibility to describe semiquantitatively the behavior of ${\mathrm{T}}_{1}^{\mathrm{\ensuremath{-}}1}$ vs T. The exponential drop of ${\mathrm{T}}_{1}^{\mathrm{\ensuremath{-}}1}$ at low temperature is consistent with a nonmagnetic singlet ground state separated by an energy gap from the first excited triplet state. The values obtained for the gap energies are ${\mathrm{E}}_{\mathrm{T}}$/k=12 K for Fe10 and ${\mathrm{E}}_{\mathrm{T}}$/k=38 K for Fe6 which are almost twice as big as the values deduced from susceptibility measurements. At all temperatures the relaxation rate decreases with increasing magnetic field, i.e., NMR resonance frequency. This effect could be related to the long time persistence of the spin correlation functions typical of diffusive modes in low dimensional magnetic systems. It is argued that the data presented are a direct experimental study of spin dynamics in mesoscopic spin rings and should afford a test for exact analytical and/or numerical solutions.

Abstract Spontaneously hypertensive stroke‐prone rats (SHRSP) develop brain abnormalities invariably preceded by the accumulation of acute‐phase proteins in body fluids. This study describes the sequence of pathological events, and in particular the involvement of inflammation, at the onset of brain injury in this animal model. In SHRSP subjected to permissive dietary treatment, the appearance of brain damage and of altered permeability of the blood–brain barrier (BBB) was monitored over time by magnetic resonance imaging (MRI) after intravenous injection of gadolinium. The protein content in cerebrospinal fluid and brain extracts was analyzed by two‐dimensional electrophoresis. Gadolinium diffusion showed impairment of the BBB after 42 ± 3 days from the start of salt loading, simultaneously with the detection of brain abnormalities by MRI. Tissue lesions were initially localized at one or more small foci and then spread throughout the brain in the form of fibrinoid necrosis. This type of lesion is characterized by fibrin deposition, in particular around the vessels; loss of tissue texture; and infiltration of macrophages and lymphocytes. High levels of plasma‐derived proteins of molecular mass up to >130 kDa were detected in the cerebrospinal fluid after MRI had revealed brain abnormalities. Plasma proteins extravasated from brain vessels were immunodetected in tissue homogenates from affected areas. The results obtained in this study provide new insights into the pathogenesis of the spontaneous brain damage in SHRSP and in particular on the involvement of the inflammatory cascade. These studies may be useful in evaluating new pharmacological strategies aimed at preventing/treating brain diseases. © 2004 Wiley‐Liss, Inc.

Magnetic resonance imaging (MRI) is at the forefront of non-invasive medical imaging techniques. It provides good spatial and temporal resolution that can be further improved by the use of contrast agents (CAs), providing a valuable tool for diagnostic purposes. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are attractive MRI contrast agents due to their negative (T2) contrast enhancement capability and biocompatibility. Clusters of USPIOs with polymer material are of particular interest since they can sustain additional functionalities like drug delivery and targeting. Aiming to establish a relationship between the morphology of the clusters and their efficacy as MRI contrast agents (relaxometric properties), we prepared – using three different maghemite (γ-Fe2O3) USPIO diameters – a series of hybrid copolymer/iron oxide CAs presenting two different geometries (micellar or vesicular). The NMR relaxometry profiles confirmed the nature of the physical mechanisms inducing the increase of nuclear relaxation rates at low (magnetic anisotropy) and high (Curie relaxation) magnetic fields. A heuristic model, first proposed by Roch, Muller, Gillis, and Brooks, allowed the fitting of the whole longitudinal relaxivity r1(ν) profile, for samples with different magnetic core sizes. We show that both types of clusters exhibit transverse relaxivity (r2) values comparable to or higher than those of common contrast agents, over the whole tested frequency range. Moreover, in-depth analysis revealed substantially a linear relationship between r2 and the number of encapsulated USPIOs divided by the diameter of the clusters (NUSPIO/DH), for each USPIO size. The cluster structure (i.e. micelle or vesicle) appeared to have a mild influence on the transverse relaxivity value. Indeed, the r2 value was mainly governed by the individual size of the USPIOs, correlated with both the cluster external diameter and the magnetic material volume fraction.

We report cell endocytosis, drug release, NMR relaxometry and in vitro MRI studies on a novel class of superparamagnetic colloidal nanocrystal clusters (CNCs) with various biocompatible coatings. It is shown that the transverse relaxivity r2, the parameter representing the MRI efficiency in negative contrast agents, for the PVA-coated, PEGF-coated, and crosslinked PEGF-coated CNCs, is high enough to contrast suitably the magnetic resonance images. The same samples have shown a good ability also in drug releasing (particularly the crosslinked PEGF-coated compound), thus finally allowing us to propose this class of compounds for future applications in theranostics.

Magnetic nanoparticles (MNPs) are capable of generate heating power under the influence of alternating magnetic fields (AMF); this behaviour recently opened new scenarios for advanced biomedical applications, mainly as new promising tumor therapies. In this paper we have tested magnetic nanoparticles called magnetosomes (MNs): a class of MNPs naturally produced by magnetotactic bacteria. We extracted MNs from Magnetospirillum gryphiswaldense strain MSR-1 and tested the interaction with cellular elements and anti-neoplastic activity both in vitro and in vivo, with the aim of developing new therapeutic approaches for neoplastic diseases. In vitro experiments performed on Human Colon Carcinoma HT-29 cell cultures demonstrated a strong uptake of MNs with no evident signs of cytotoxicity and revealed three phases in the interaction: adherence, transport and accumulation in Golgi vesicles. In vivo studies were performed on subcutaneous tumors in mice; in this model MNs are administered by direct injection in the tumor volume, then a protocol consisting of three exposures to an AMF rated at 187 kHz and 23kA/m is carried out on alternate days, over a week. Tumors were monitored by Magnetic Resonance Imaging (MRI) to obtain information about MNs distribution and possible tissue modifications induced by hyperthermia. Histological analysis showed fibrous and necrotic areas close to MNs injection sites in mice subjected to a complete thermotherapy protocol. These results, although concerning a specific tumor model, could be useful to further investigate the feasibility and efficacy of protocols based on MFH. Magnetic nanoparticles naturally produced and extracted from bacteria seem to be promising candidates for theranostic applications in cancer therapy.

We present the first comparative investigation of the Nuclear Magnetic Resonance (NMR) relaxivity of a series of nanosized cyano-bridged coordination networks stabilized in aqueous solution. These Ln(3+)/[Fe(CN)6](3-) (Ln = Gd, Tb, Y) and M(2+)/[Fe(CN)6](3-) (M = Ni, Cu, Fe) nanoparticles with sizes ranging from 1.4 to 5.5 nm are stabilized by polyethylene glycols (MW = 400 or 1000), polyethylene glycol functionalized with amine groups (MW = 1500), or by N-acetyl-D-glucosamine. The evaluation of NMR relaxivity allowed estimation of the Magnetic Resonance Imaging (MRI) contrast efficiency of our systems. The results demonstrate that Gd(3+)/[Fe(CN)6](3-) nanoparticles have r1p and r2p relaxivities about four times higher than the values observed in the same conditions for the commercial Contrast Agents (CAs) ProHance or Omniscan, regardless of the stabilizing agent used, while nanoparticles of Prussian blue and its analogues M(2+)/[Fe(CN)6](3-) (M = Ni, Cu, Fe) present relatively modest values. The influence of the chemical composition of the nanoparticles, their crystal structure, spin values of lanthanide and transition metal ions, and stabilizing agent on the relaxivity values are investigated and discussed.

Hydrophilic SPION were decorated with PNA decamers by SH/maleimide clickreaction as potential MRI and hyperthermia agents, and PNA carriers.

In this study, hybrid nanocubes composed of magnetite (Fe3 O4 ) and manganese dioxide (MnO2 ), coated with U-251 MG cell-derived membranes (CM-NCubes) are synthesized. The CM-NCubes demonstrate a concentration-dependent oxygen generation (up to 15%), and, for the first time in the literature, an intracellular increase of temperature (6 °C) due to the exothermic scavenging reaction of hydrogen peroxide (H2 O2 ) is showed. Internalization studies demonstrate that the CM-NCubes are internalized much faster and at a higher extent by the homotypic U-251 MG cell line compared to other cerebral cell lines. The ability of the CM-NCubes to cross an in vitro model of the blood-brain barrier is also assessed. The CM-NCubes show the ability to respond to a static magnet and to accumulate in cells even under flowing conditions. Moreover, it is demonstrated that 500 µg mL-1 of sorafenib-loaded or unloaded CM-NCubes are able to induce cell death by apoptosis in U-251 MG spheroids that are used as a tumor model, after their exposure to an alternating magnetic field (AMF). Finally, it is shown that the combination of sorafenib and AMF induces a higher enzymatic activity of caspase 3 and caspase 9, probably due to an increment in reactive oxygen species by means of hyperthermia.

Targeted radiation therapy (TRT) is a strategy increasingly adopted for the treatment of different types of cancer. The urge for optimization, as stated by the European Council Directive (2013/59/EURATOM), requires the implementation of a personalized dosimetric approach, similar to what already happens in external beam radiation therapy (EBRT). The purpose of this paper is to provide a thorough introduction to the field of personalized dosimetry in TRT, explaining its rationale in the context of optimization and describing the currently available methodologies. After listing the main therapies currently employed, the clinical workflow for the absorbed dose calculation is described, based on works of the most experienced authors in the literature and recent guidelines. Moreover, the widespread software packages for internal dosimetry are presented and critical aspects discussed. Overall, a selection of the most important and recent articles about this topic is provided.

In this perspective article, we present a short selection of some of the most significant case studies on magnetic nanoparticles for potential applications in nanomedicine, mainly magnetic resonance. For almost 10 years, our research activity focused on the comprehension of the physical mechanisms on the basis of the nuclear relaxation of magnetic nanoparticles in the presence of magnetic fields; taking advantage of the insights gathered over this time span, we report on the dependence of the relaxation behaviour on the chemico-physical properties of magnetic nanoparticles and discuss them in full detail. In particular, a critical review is carried out on the correlations between their efficiency as contrast agents in magnetic resonance imaging and the magnetic core of magnetic nanoparticles (mainly iron oxides), their size and shape, and the coating and solvent used for making them biocompatible and well dispersible in physiological media. Finally, the heuristic model proposed by Roch and coworkers is presented, as it was extensively adopted to describe most of the experimental data sets. The large amount of data analyzed allowed us to highlight both the advantages and limitations of the model.

The proton nuclear spin-lattice relaxation rate 1/T1 has been measured as a function of temperature and magnetic field (up to 15 T) in the molecular magnetic ring Fe10. Striking enhancement of 1/T1 is observed around magnetic field values corresponding to a crossing between the ground state and the excited states of the molecule. We propose that this is due to a cross-relaxation effect between the nuclear Zeeman reservoir and the reservoir of the Zeeman levels of the molecule. This effect provides a powerful tool to investigate quantum dynamical phenomena at level crossing.

We investigate the time autocorrelation of the molecular magnetization $M(t)$ for three classes of magnetic molecules (antiferromagnetic rings, grids and nanomagnets), in contact with the phonon heat bath. For all three classes, we find that the exponential decay of the fluctuations of $M(t)$, associated with the irreversible exchange of energy with the heat bath, is characterized by a single characteristic time $\tau (T,B)$ for not too high temperature $T$ and field $B$. This is reflected in a nearly single-lorentzian shape of the spectral density of the fluctuations. We show that such fluctuations are effectively probed by NMR, and that our theory explains the recent phenomenological observation by Baek et al. (PRB70, 134434) that the Larmor-frequency dependence of $1/T_1$ data in a large number of AFM rings fits to a single-lorentzian form.

We have prepared water-soluble gadolinium oxide nanoparticles that show potential as MRI contrast agents. The particles were built into the apoferritin cavity and have an average size of 5 nm. After seven days a loss of 5% of Gd was detected compared with the as-prepared samples; after that the Gd remained constant and stabilized inside the apoferritin, indicating that the apoferritin capsid acts as a Gd store, avoiding metal delivery and consequent toxicity. The NMR longitudinal and transverse relaxivities resulted about 10 and 70 times higher than the ones of clinically approved paramagnetic Gd-chelates, thus indicating the possible route for synthesizing a novel class of MRI contrast agents.

Water-soluble biocompatible rhamnose-coated Fe(3)O(4) nanoparticles of 4.0 nm are obtained by covalent anchorage of rhamnose on the nanoparticles surface via a phosphate linker. These nanoparticles present superparamagnetic behavior and nuclear relaxivities in the same order of magnitude as Endorem that make them potential magnetic resonance imaging (MRI) contrast agents of a second generation, where the saccharides represent also specific ligands able to target lectins on skin cells.

This article presents the first example of ultra-small (3–4 nm) magneto-luminescent cyano-bridged coordination polymer nanoparticles Ln0.333+Gdx3+/[Mo(CN)8]3− (Ln = Eu (x = 0.34), Tb (x = 0.35)) enwrapped by a natural biocompatible polymer chitosan. The aqueous colloidal solutions of these nanoparticles present a luminescence characteristic of the corresponding lanthanides (5D0 → 7F0–4 (Eu3+) or the 5D4 → 7F6–2 (Tb3+)) under UV excitation and a green luminescence of the chitosan shell under excitation in the visible region. Magnetic Resonance Imaging (MRI) efficiency, i.e. the nuclear relaxivity, measurements performed for Ln0.333+Gdx3+/[Mo(CN)8]3−nanoparticles show r1p and r2p relaxivities slightly higher than or comparable to the ones of the commercial paramagnetic compounds Gd-DTPA® or Omniscan® indicating that our samples may potentially be considered as a positive contrast agent for MRI. The in vitro studies performed on these nanoparticles show that they maybe internalized into human cancer and normal cells and well detected by fluorescence at the single cell level. They present high stability even at low pH and lack of cytotoxicity both in human cancer and normal cells.

We report the synthesis, characterization and relaxometric study of ferrofluids based on iron oxide, with potential for use as magnetic resonance imaging (MRI) contrast agents (CAs). The effect of different cost-effective, water-based surface modification approaches which can be easily scaled-up for the large scale synthesis of the ferrofluids has been investigated. Surface modification was achieved by silanization, and/or coating with non-toxic commercial dispersants (a lauric polysorbate and a block copolymer with pigment affinic groups, namely Tween 20 and Disperbyk 190) which were added after or during iron oxide nanoparticle synthesis. It was observed that all the materials synthesized functioned as negative contrast agents at physiological temperature and at frequencies covered by clinical imagers. The relaxometric properties of the magnetic nanoparticles were significantly improved after surface coating with stabilizers compared to the original iron oxide nanoparticles, with particular reference to the silica-coated magnetic nanoparticles. The results indicate that the optimization of the preparation of colloidal magnetic ferrofluids by surface modification is effective in the design of novel contrast agents for MRI by enabling better or more effective interaction between the coated iron oxide nanoparticles and protons present in their aqueous environment.

We investigated the theranostic properties of magnetosomes (MNs) extracted from magnetotactic bacteria, promising for nanomedicine applications. Besides a physico-chemical characterization, their potentiality as mediators for magnetic fluid hyperthermia and contrast agents for magnetic resonance imaging, both in vitro and in vivo, are here singled out. The MNs, constituted by magnetite nanocrystals arranged in chains, show a superparamagnetic behaviour and a clear evidence of Verwey transition, as signature of magnetite presence. The phospholipid membrane provides a good protection against oxidation and the MNs oxidation state is stable over months. Using an alternate magnetic field, the specific absorption rate was measured, resulting among the highest reported in literature. The MRI contrast efficiency was evaluated by means of the acquisition of complete NMRD profiles. The transverse relaxivity resulted as high as the one of a former commercial contrast agent. The MNs were inoculated into an animal model of tumour and their presence was detected by magnetic resonance images two weeks after the injection in the tumour mass.

Recent studies on magnetic nanoparticles (MNPs) used for Magnetic Fluid Hyperthermia treatments have shown that Brownian rotation is suppressed when they are confined within a cell. To investigate this effect we conducted a systematic study of the Specific Absorption Rate (SAR) of colloidal suspensions of MNPs in water and gels at different agarose concentration. SAR measurements were conducted by varying the frequency (f = 110–990 kHz) and amplitude (up to 17 kA/m) of the applied alternating magnetic field (AMF). MNP samples with different diameter (d = 10, 14, and 18 nm) were used. Our results show that Néel relaxation dominates SAR with negligible contribution from Brownian motion for smaller MNPs (d = 10 nm). For the largest MNPs (d = 18 nm) we observed a more significant SAR decrease in gel suspensions as compared to those in solution. In particular, when applying AMFs as the ones used in a clinical setting (16.2 kA/m at f = 110 kHz), we measured SAR value of 67 W/g in solution and 25 W/g in gel. This experimental finding demonstrates that investigation of MNPs properties should be conducted in media with viscosity similar to the one found in mammalian tissues.

<h2>Abstract</h2><h3>Purpose</h3> To develop a phantom for methodological radiomic investigation on Magnetic Resonance (MR) images of female patients affected by pelvic cancer. <h3>Methods</h3> A pelvis-shaped container was filled with a MnCl₂ solution reproducing the relaxation times (T₁, T₂) of muscle surrounding pelvic malignancies. Inserts simulating multi-textured lesions were embedded in the phantom. The relaxation times of muscle and tumour were measured on an MR scanner on healthy volunteers and patients; T₁ and T₂ of MnCl₂ solutions were evaluated with a relaxometer to find the concentrations providing a match to <i>in vivo</i> relaxation times. Radiomic features were extracted from the phantom inserts and the patients' lesions. Their repeatability was assessed by multiple measurements. <h3>Results</h3> Muscle T₁ and T₂ were 1128 (806–1378) and 51 (40–65) ms, respectively. The phantom reproduced <i>in vivo</i> values within 13% (T₁) and 12% (T₂). T₁ and T₂ of tumour tissue were 1637 (1396–2121) and 94 (79–101) ms, respectively. The phantom insert best mimicking the tumour agreed within 7% (T₁) and 24% (T₂) with <i>in vivo</i> values. Out of 1034 features, 75% (95%) had interclass correlation coefficient greater than 0.9 on T₁ (T₂)-weighted images, reducing to 33% (25%) if the phantom was repositioned. The most repeatable features on phantom showed values in agreement with the features extracted from patients' lesions. <h3>Conclusions</h3> We developed an MR phantom with inserts mimicking both relaxation times and texture of pelvic tumours. As exemplified with repeatability assessment, such phantom is useful to investigate features robustness and optimise the radiomic workflow on pelvic MR images.

Abstract Deep gray matter nuclei are the synaptic relays, responsible to route signals between specific brain areas. Dentate nuclei (DNs) represent the main output channel of the cerebellum and yet are often unexplored especially in humans. We developed a multimodal MRI approach to identify DNs topography on the basis of their connectivity as well as their microstructural features. Based on results, we defined DN parcellations deputed to motor and to higher‐order functions in humans in vivo. Whole‐brain probabilistic tractography was performed on 25 healthy subjects from the Human Connectome Project to infer DN parcellations based on their connectivity with either the cerebral or the cerebellar cortex, in turn. A third DN atlas was created inputting microstructural diffusion‐derived metrics in an unsupervised fuzzy c‐means classification algorithm. All analyses were performed in native space, with probability atlas maps generated in standard space. Cerebellar lobule‐specific connectivity identified one motor parcellation, accounting for about 30% of the DN volume, and two non‐motor parcellations, one cognitive and one sensory, which occupied the remaining volume. The other two approaches provided overlapping results in terms of geometrical distribution with those identified with cerebellar lobule‐specific connectivity, although with some differences in volumes. A gender effect was observed with respect to motor areas and higher‐order function representations. This is the first study that indicates that more than half of the DN volumes is involved in non‐motor functions and that connectivity‐based and microstructure‐based atlases provide complementary information. These results represent a step‐ahead for the interpretation of pathological conditions involving cerebro‐cerebellar circuits.

Abstract Background We investigated to what extent tube voltage, scanner model, and reconstruction algorithm affect radiomic feature reproducibility in a single-institution retrospective database of computed tomography images of non-small-cell lung cancer patients. Methods This study was approved by the Institutional Review Board (UID 2412). Images of 103 patients were considered, being acquired on either among two scanners, at 100 or 120 kVp. For each patient, images were reconstructed with six iterative blending levels, and 1414 features were extracted from each reconstruction. At univariate analysis, Wilcoxon-Mann-Whitney test was applied to evaluate feature differences within scanners and voltages, whereas the impact of the reconstruction was established with the overall concordance correlation coefficient (OCCC). A multivariable mixed model was also applied to investigate the independent contribution of each acquisition/reconstruction parameter. Univariate and multivariable analyses were combined to analyse feature behaviour. Results Scanner model and voltage did not affect features significantly. The reconstruction blending level showed a significant impact at both univariate analysis (154/1414 features yielding an OCCC &lt; 0.85) and multivariable analysis, with most features (1042/1414) revealing a systematic trend with the blending level (multiple comparisons adjusted p &lt; 0.05). Reproducibility increased in association to image processing with smooth filters, nonetheless specific investigation in relation to clinical endpoints should be performed to ensure that textural information is not removed. Conclusions Combining univariate and multivariable models is allowed to identify features for which corrections may be applied to reduce the trend with the algorithm and increase reproducibility. Subsequent clustering may be applied to eliminate residual redundancy.

X-ray magnetic-circular-dichroism (XMCD) spectra on the molecular superparamagnets $[{\mathrm{Mn}}_{12}{\mathrm{O}}_{12}{(\mathrm{C}\mathrm{H}}_{3}{\mathrm{C}\mathrm{O}\mathrm{O})}_{16}{(\mathrm{H}}_{2}{\mathrm{O})}_{24}]\ensuremath{\cdot}{2\mathrm{C}\mathrm{H}}_{3}{\mathrm{COOH}\mathrm{\ensuremath{\cdot}}4\mathrm{H}}_{2}\mathrm{O}$ (in short Mn12) and $[{\mathrm{Fe}}_{8}{\mathrm{O}}_{2}{(\mathrm{OH})}_{12}{(\mathrm{tacn})}_{6}{]\mathrm{Br}}_{2}{\mathrm{\ensuremath{\cdot}}9\mathrm{H}}_{2}\mathrm{O}$ (in short Fe8) are presented. The XMCD measurements have been performed at the ${\mathrm{M}\mathrm{n}\ensuremath{-}\mathrm{L}}_{\mathrm{I}\mathrm{I}\mathrm{I},\mathrm{I}\mathrm{I}}$ edges in the Mn12 compound and at the ${\mathrm{F}\mathrm{e}\ensuremath{-}\mathrm{L}}_{\mathrm{I}\mathrm{I}\mathrm{I},\mathrm{I}\mathrm{I}}$ edges in the Fe8 compound. For Fe8 the typical two-peak structure of Fe(III) compounds is found. For Mn12 and Fe8, from the dichroic signals a very low or negligible $〈{L}_{z}〉$ was obtained: to the best of our knowledge, this is the first direct experimental evidence of the quenching of the angular momentum by the crystal field in these systems. Quantitative analysis of the dichroic spectra for Fe8 yielded $〈{L}_{z}〉/〈{S}_{z}〉=0.02(1).$

The NMR spectra of $^{19}\mathrm{F}$ and $^{53}\mathrm{Cr}$ have been obtained at low temperatures in a heterometallic substituted antiferromagnetic (AF) ring Cr7Cd with an $S=3/2$ ground state and compared with the spectra in a homometallic Cr8 AF ring with an $S=0$ ground state. From the analysis of the spectra one can derive directly model independent values of the staggered nonuniform distribution of the local moment in the heterometallic ring Cr7Cd. The experimental values are found to be in excellent agreement with the theoretical values calculated on the basis of an effective spin Hamiltonian which includes crystal field effects.

Novel systems based on colloidal magnetic nanocrystals (NCs), potentially useful as superparamagnetic (SP) contrast agents for magnetic resonance imaging (MRI) have been investigated. The NCs we have studied comprise organic-capped single-crystalline maghemite (γ-Fe2O3) cores possessing controlled sizes and shapes. We have comparatively examined spherical and tetrapod-like NCs, the latter being branched particles possessing four arms which depart out at tetrahedral angles from a central point. The as-synthesized NCs are passivated by hydrophobic surfactant molecules and thus are fully dispersible in nonpolar media only. The NCs have been made soluble in aqueous solution by applying a procedure based on the surface intercalation and coating with an amphiphilic polymer shell. NMR relaxivities R1 and R2 were compared with ENDOREM®, one of the standard commercial SP-MRI contrast agent. We found that the spherical NCs exhibit R1 and R2 relaxivities slightly lower than those of ENDOREM®, over the whole frequency range; on the contrary, tetrapods show relaxivities about one order of magnitude lower. The physical origin of such difference in relaxivities between tetrapod- and spheres-based nanostructures is under investigation and it is possibly related to different sources of the magnetic anisotropy.

Novel systems to be employed as superparamagnetic contrast agents (CA) for magnetic resonance imaging (MRI) have been synthesized. These compounds are composed of an iron oxide magnetic core coated by polyethylenimine (PEI) or carboxylated polyethylenimine (PEI-COOH). The aim of the present work was to prepare and study new nanostructured systems (with better or at least comparable relaxivities, R1 and R2, with respect to the commercial ones) with controlled, almost monodisperse average dimensions and shape, as candidates for molecular targeting. By means of atomic force microscopy (AFM) measurements we determined the average diameter, of the order of 200 nm, and the shape of the particles. The superparamagnetic behavior was assessed by SQUID measurements. From X-ray data the estimated average diameters of the magnetic cores were found to be ∼5.8 nm for PEI-COOH60 and ∼20 nm for the compound named PEI25. By NMR-dispersion (NMRD), we found that PEI-COOH60 presents R1 and R2 relaxivities slightly lower than Endorem®. The experimental results suggest that these novel compounds can be used as MRI CA.

Low-temperature specific heat, magnetic susceptibility, and zero-field muon spin resonance ($\ensuremath{\mu}\mathrm{SR}$) measurements have been performed in the quasi-one-dimensional molecular helimagnetic compound $\mathrm{Gd}(hfac{)}_{3}\mathrm{NITEt}$. The specific heat presents two anomalies at ${T}_{0}=2.19\ifmmode\pm\else\textpm\fi{}0.02\text{ }\text{ }\mathrm{K}$ and ${T}_{N}=1.88\ifmmode\pm\else\textpm\fi{}0.02\text{ }\text{ }\mathrm{K}$, which both disappear upon the application of a weak magnetic field. Conversely, magnetic susceptibility and $\ensuremath{\mu}\mathrm{SR}$ data show the divergence of two-spin correlation functions only at ${T}_{N}=1.88\ifmmode\pm\else\textpm\fi{}0.02\text{ }\text{ }\mathrm{K}$. These results suggest an experimental validation of Villain's conjecture of a two-step magnetic ordering in quasi-one-dimensional $XY$ helimagnets; i.e., the paramagnetic phase and the helical spin solid phase are separated by a chiral spin liquid phase, where translational invariance is broken without violation of rotational invariance.

¹H-NMR relaxometric experiments over an extended frequency range show that ferrimagnetic colloidal nanoclusters exhibit enhanced transverse relaxivity, <italic>r</italic>₂.

The spin dynamics of Mn spins in the dodecanuclear manganese cluster of formula $[{\mathrm{Mn}}_{12}{\mathrm{O}}_{12}{(\mathrm{C}\mathrm{H}}_{3}{\mathrm{C}\mathrm{O}\mathrm{O})}_{16}{(\mathrm{H}}_{2}{\mathrm{O})}_{4}{]\mathrm{\ensuremath{\cdot}}2\mathrm{C}\mathrm{H}}_{3}{\ensuremath{-}\mathrm{C}\mathrm{O}\mathrm{O}\mathrm{H}\mathrm{\ensuremath{\cdot}}4\mathrm{H}}_{2}\mathrm{O}({\mathrm{Mn}}_{12})$ has been investigated by ${}^{1}\mathrm{H}\mathrm{}\mathrm{NMR}$ and muon spin-lattice relaxation rate ${1/T}_{1}$ as a function of temperature (10--400 K) and external magnetic field (0--9.4 T). At room temperature, the proton ${1/T}_{1}$ depends on the measuring frequency. The results can be interpreted in terms of a slow decay of the Mn electronic-spin autocorrelation function, a feature characteristic of the almost zero dimensionality of the system. As the temperature is lowered, ${1/T}_{1}$ displays a critical enhancement that can be related to the slowing down of the local spin fluctuations as the cluster approaches the condensation into the total spin $S=10$ ground-state configuration. It is found that the application of an external magnetic field greatly depresses the enhancement of ${1/T}_{1}$ an effect that could be related to the superparamagnetic behavior of the ${\mathrm{Mn}}_{12}$ molecule.

Heat capacity (C), magnetic torque, and proton NMR relaxation rate (1/T(1)) measurements were performed on Fe6:Li single crystals in order to study the crossings between S = 0 and S = 1 and between S = 1 and S = 2 magnetic states of the molecular rings, at magnetic fields B(c1) = 11.7 T and B(c2) = 22.4 T, respectively. C vs B data at 0.78 K show that the energy gap between two states remains finite at B(c)'s (Delta(1)/k(B) = 0.86 K and Delta(2)/k(B) = 2.36 K) thus proving that levels repel each other. The large Delta(1) value may also explain the anomalously large width of the peak in 1/T(1) vs B, around B(c1). This anticrossing, unexpected in a centrosymmetric system, requires a revision of the Hamiltonian.

We present new and refined data for the magnetic field $(H)$ and temperature $(T)$ dependence of the proton spin-lattice relaxation rate $(1∕{T}_{1})$ in antiferromagnetic molecular rings as well as a new explicit scaling formula that accurately reproduces our data. The key ingredients of our formulation are (1) a reduced relaxation rate, $R(H,T)=(1∕{T}_{1})∕(T\ensuremath{\chi}(T))$, given by $R(H,T)=A{\ensuremath{\omega}}_{c}(T)∕({\ensuremath{\omega}}_{c}^{2}(T)+{\ensuremath{\omega}}_{N}^{2})$, where $\ensuremath{\chi}={(\ensuremath{\partial}M∕\ensuremath{\partial}H)}_{T}$ is the differential susceptibility, $A$ is a fitting constant, and ${\ensuremath{\omega}}_{N}$ is the proton Larmor frequency, and (2) a temperature-dependent correlation frequency ${\ensuremath{\omega}}_{c}(T)$ which at low $T$ is given by ${\ensuremath{\omega}}_{c}(T)\ensuremath{\propto}{T}^{\ensuremath{\alpha}}$, that we identify as a lifetime broadening of the energy levels of the exchange-coupled paramagnetic spins due to spin-acoustic phonon coupling. The main consequences are (1) $R(H,T)$ has a local maximum for fixed $H$ and variable $T$ that is proportional to $1∕H$; the maximum occurs at the temperature ${T}_{0}(H)$ for which ${\ensuremath{\omega}}_{c}(T)={\ensuremath{\omega}}_{N}$; (2) for low $T$ a scaling formula applies, $R(H,T)∕R(H,{T}_{0}(H))=2{t}^{\ensuremath{\alpha}}∕(1+{t}^{2\ensuremath{\alpha}})$, where $t\ensuremath{\equiv}T∕{T}_{0}(H)$. Both results are confirmed by our experimental data for the choice $\ensuremath{\alpha}=3.5\ifmmode\pm\else\textpm\fi{}0.5$.

Three isostructural cyanido-bridged heptanuclear complexes, [{CuII(saldmen)(H2O)}6{MIII(CN)6}](ClO4)3·8H2O (M = FeIII2; CoIII, 3; CrIII4), have been obtained by reacting the dinuclear copper(II) complex, [Cu2(saldmen)2(μ-H2O)(H2O)2](ClO4)2·2H2O 1, with K3[Co(CN)6], K4[Fe(CN)6], and K3[Cr(CN)6], respectively (Hsaldmen is the Schiff base resulting from the condensation of salicylaldehyde with N,N-dimethylethylenediamine). A unique octameric water cluster, with bicyclo[2,2,2]octane-like structure, is sandwiched between the heptanuclear cations in 2, 3 and 4. The cryomagnetic investigations of compounds 2 and 4 reveal ferromagnetic couplings of the central FeIII or CrIII ions with the CuII ions (JCuFe = +0.87 cm−1, JCuCr = +30.4 cm−1). The intramolecular Cu⋯Cu exchange interaction in 3, across the diamagnetic cobalt(III) ion, is −0.3 cm−1. The solid-state 1H-NMR spectra of compounds 2 and 3 have been investigated.

A new approach to the synthesis of multifunctional nanoparticles was developed by using covalent anchoring of cyano-bridged coordination polymer Ni2+/[Fe(CN)6]3− to the surface of two-photon dye-doped mesoporous silica nanoparticles. The obtained hybrid nanoparticles were studied by infrared (IR) spectroscopy, nitrogen adsorption (BET), X-ray diffraction, transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), luminescence, and magnetic analysis. The synthesis leads to homogeneously dispersed uni-shaped nanoparticles of around 100 nm in length that are coated with cyano-bridged metallic coordination polymer nanoparticles. These hybrid nanoparticles combine effective two-photon excited fluorescence, porosity, high transverse nuclear relaxivity values (i.e. the magnetic resonance imaging efficiency) and superparamagnetic properties.

Several studies suggest that the plasma membrane is composed of micro-domains of saturated lipids that segregate together to form lipid rafts. Lipid rafts have been operationally defined as cholesterol- and sphingolipid-enriched membrane micro-domains resistant to solubilization by non-ionic detergents at low temperatures. Here we report a biophysical approach aimed at investigating lipid rafts of MDA-MB-231 human breast cancer cells by coupling an atomic force microscopy (AFM) study to biochemical assays namely Western blotting and high performance thin layer chromatography. Lipid rafts were purified by ultracentrifugation on discontinuous sucrose gradient using extraction with Triton X-100. Biochemical analyses proved that the fractions isolated at the 5% and 30% sucrose interface (fractions 5 and 6) have a higher content of cholesterol, sphingomyelin and flotillin-1 with respect to the other purified fractions. Tapping mode AFM imaging of fraction 5 showed membrane patches whose height corresponds to the one awaited for a single lipid bilayer as well as the presence of micro-domains with lateral dimensions in the order of a few hundreds of nanometers. In addition, an AFM study using specific antibodies suggests the presence, in these micro-domains, of a characteristic marker of lipid rafts, the protein flotillin-1.

A series of maghemite/polymer composite ferrofluids with variable magnetic core size, which show a good efficiency as MRI contrast agents, are presented. These ferrofluids are biocompatible and can be proposed as possible platforms for multifunctional biomedical applications, as they contain anchoring groups for biofunctionalization, can incorporate fluorescent dyes, and have shown low cellular toxicity. The magnetic properties of the ferrofluids have been determined by means of magnetization and ac susceptibility measurements as a function of temperature and frequency. The NMR dispersion profiles show that the low frequency behavior of the longitudinal relaxivity r(1) is well described by the heuristic model of (1)H nuclear relaxation induced by superparamagnetic nanoparticles proposed by Roch and co-workers. The contrast efficiency parameter, i.e., the nuclear transverse relaxivity r(2), for samples with d > 10 nm assumes values comparable with or better than the ones of commercial samples, the best results obtained in particles with the biggest magnetic core, d = 15 nm. The contrast efficiency results are confirmed by in vitro MRI experiments at ν = 8.5 MHz, thus allowing us to propose a set of optimal microstructural parameters for multifunctional ferrofluids to be used in MRI medical diagnosis.

An experimental 1H NMR relaxometry investigation on iron oxide nanoparticles with different magnetic core size and coated with PolyAcrylic Acid (PAA), is presented. A full structural, morphodimensional and magnetic characterization of the nanoparticles has been performed by means of X-ray diffraction, Dynamic Light Scattering, Transmission Electron Microscopy, Atomic Force Microscopy and SQUID DC magnetometry. The application of a heuristic model for the field dependence of the NMR relaxivity curves allowed us to evaluate the distance of minimum approach of the solvent molecules from the magnetic centers, and to conclude that the local correlation times, namely the Neél time τN and the diffusion time τD related to the magnetization reversal and to the diffusion process respectively, depend strongly on the core size. A preliminary evaluation of their r2 efficiency as Magnetic Resonance Imaging (MRI) contrast agents is also performed by means of a universal scaling law model. The results of our experimental investigation should allow to tailor the physical properties of the nanoparticles for obtaining systems with a resultant contrast efficiency optimized for the in-vivo application of MRI at pre-clinical and clinical level.

Superparamagnetic iron oxide particles find their main application as contrast agents for cellular and molecular magnetic resonance imaging. The contrast they bring is due to the shortening of the transverse relaxation time T 2 of water protons. In order to understand their influence on proton relaxation, different theoretical relaxation models have been developed, each of them presenting a certain validity domain, which depends on the particle characteristics and proton dynamics. The validation of these models is crucial since they allow for predicting the ideal particle characteristics for obtaining the best contrast but also because the fitting of T 1 experimental data by the theory constitutes an interesting tool for the characterization of the nanoparticles. In this work, T 2 of suspensions of iron oxide particles in different solvents and at different temperatures, corresponding to different proton diffusion properties, were measured and were compared to the three main theoretical models (the motional averaging regime, the static dephasing regime, and the partial refocusing model) with good qualitative agreement. However, a real quantitative agreement was not observed, probably because of the complexity of these nanoparticulate systems. The Roch theory, developed in the motional averaging regime (MAR), was also successfully used to fit T 1 nuclear magnetic relaxation dispersion (NMRD) profiles, even outside the MAR validity range, and provided a good estimate of the particle size. On the other hand, the simultaneous fitting of T 1 and T 2 NMRD profiles by the theory was impossible, and this occurrence constitutes a clear limitation of the Roch model. Finally, the theory was shown to satisfactorily fit the deuterium T 1 NMRD profile of superparamagnetic particle suspensions in heavy water.

We investigated the flexibility of high-temperature thermal decomposition synthesis to design magnetic nanoparticles (NPs) with engineered properties. We prepared spinel iron oxide particles with the desired composition (Fe <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> and CoFe <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> ) and a well-controlled average size (5-8 nm) by tuning the synthesis procedure. The substitution of Fe by Co produces a dramatic increase of the magnetocrystalline anisotropy: for 5 nm particles, the anisotropy constant increased from ~3.9×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> to ~7.5×10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sup> J/m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> . The magnetocrystalline anisotropy has shown a major effect on the magnetic behavior of highly crystalline particles, except for the smallest iron oxide sample, where the surface anisotropy plays a dominant role. The presence of surfactant (oleic acid) on the NPs surface prevents direct exchange coupling among them, whereas the dipolar interaction was predominant, with an estimated temperature-equivalent energy in the range of 4-60 K.

Purpose To investigate the repeatability and reproducibility of radiomic features extracted from MR images and provide a workflow to identify robust features. Methods T 2 ‐weighted images of a pelvic phantom were acquired on three scanners of two manufacturers and two magnetic field strengths. The repeatability and reproducibility of features were assessed by the intraclass correlation coefficient and the concordance correlation coefficient, respectively, and by the within‐subject coefficient of variation, considering repeated acquisitions with and without phantom repositioning, and with different scanner and acquisition parameters. The features showing intraclass correlation coefficient or concordance correlation coefficient &gt;0.9 were selected, and their dependence on shape information (Spearman’s ρ &gt; 0.8) analyzed. They were classified for their ability to distinguish textures, after shuffling voxel intensities of images. Results From 944 two‐dimensional features, 79.9% to 96.4% showed excellent repeatability in fixed position across all scanners. A much lower range (11.2% to 85.4%) was obtained after phantom repositioning. Three‐dimensional extraction did not improve repeatability performance. Excellent reproducibility between scanners was observed in 4.6% to 15.6% of the features, at fixed imaging parameters. In addition, 82.4% to 94.9% of the features showed excellent agreement when extracted from images acquired with echo times 5 ms apart, but decreased with increasing echo‐time intervals, and 90.7% of the features exhibited excellent reproducibility for changes in pulse repetition time. Of nonshape features, 2.0% was identified as providing only shape information. Conclusion We showed that radiomic features are affected by MRI protocols and propose a general workflow to identify repeatable, reproducible, and informative radiomic features to ensure robustness of clinical studies.

We present an investigation of the effects on BxPC3 pancreatic cancer cells of proton therapy combined with hyperthermia, assisted by magnetic fluid hyperthermia performed with the use of magnetic nanoparticles. The cells’ response to the combined treatment has been evaluated by means of the clonogenic survival assay and the estimation of DNA Double Strand Breaks (DSBs). The Reactive Oxygen Species (ROS) production, the tumor cell invasion and the cell cycle variations have also been studied. The experimental results have shown that the combination of proton therapy, MNPs administration and hyperthermia gives a clonogenic survival that is much smaller than the single irradiation treatment at all doses, thus suggesting a new effective combined therapy for the pancreatic tumor. Importantly, the effect of the therapies used here is synergistic. Moreover, after proton irradiation, the hyperthermia treatment was able to increase the number of DSBs, even though just at 6 h after the treatment. Noticeably, the magnetic nanoparticles’ presence induces radiosensitization effects, and hyperthermia increases the production of ROS, which contributes to cytotoxic cellular effects and to a wide variety of lesions including DNA damage. The present study indicates a new way for clinical translation of combined therapies, also in the vision of an increasing number of hospitals that will use the proton therapy technique in the near future for different kinds of radio-resistant cancers.

Superconduting quantum interference device magnetization measurements in oriented powders of ${\mathrm{Y}}_{1\ensuremath{-}x}{\mathrm{Ca}}_{x}{\mathrm{Ba}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{y},$ with x ranging from $0$ to $0.2,$ for $y\ensuremath{\approx}6.1$ and 6.97, are performed in order to study the doping dependence of the fluctuating diamagnetism above the superconducting transition temperature ${T}_{c}.$ While for optimally doped compounds the diamagnetic susceptibility and the magnetization curves $\ensuremath{-}{M}_{\mathrm{fl}}(T=\mathrm{const})$ vs H are rather well justified on the basis of an anisotropic Ginzburg-Landau (GL) functional, in underdoped and overdoped regimes an anomalous diamagnetism is observed, with a large enhancement with respect to the GL scenario. Furthermore, the shape of magnetization curves differs strongly from the one derived in that scheme. The anomalies are discussed in terms of phase fluctuations of the order parameter in a layered system of vortices and with the assumption of charge inhomogeneities inducing local, non-percolating, superconducting regions with ${T}_{c}^{(\mathrm{loc})}$ higher than the resistive transition temperature ${T}_{c}.$ The susceptibility displays an activated temperature behavior, a marked characteristic of the vortex-antivortex description, while the history-dependent magnetization, with relaxation after zero-field cooling, is consistent with the hypothesis of superconducting droplets in the normal state. Thus the theoretical picture consistently accounts for most experimental findings.

The static and dynamic properties of the single-chain molecular magnet [Co(hfac)$_2$NITPhOMe] are investigated in the framework of the Ising model with Glauber dynamics, in order to take into account both the effect of an applied magnetic field and a finite size of the chains. For static fields of moderate intensity and short chain lengths, the approximation of a mono-exponential decay of the magnetization fluctuations is found to be valid at low temperatures; for strong fields and long chains, a multi-exponential decay should rather be assumed. The effect of an oscillating magnetic field, with intensity much smaller than that of the static one, is included in the theory in order to obtain the dynamic susceptibility $\chi(\omega)$. We find that, for an open chain with $N$ spins, $\chi(\omega)$ can be written as a weighted sum of $N$ frequency contributions, with a sum rule relating the frequency weights to the static susceptibility of the chain. Very good agreement is found between the theoretical dynamic susceptibility and the ac susceptibility measured in moderate static fields ($H_{\rm dc}\le 2$ kOe), where the approximation of a single dominating frequency turns out to be valid. For static fields in this range, new data for the relaxation time, $\tau$ versus $H_{\rm dc}$, of the magnetization of CoPhOMe at low temperature are also well reproduced by theory, provided that finite-size effects are included.

Well calibrated core–shell multifunctional nanoparticles for biomedical applications were synthesized by a multistep soft chemistry route. The core is composed of Gd(OH)CO3·H2O spheres prepared via a urea-based homogeneous precipitation technique, while the shell is a homogeneous thin silica layer embedded with the fluorescent dye rhodamine B (RhB) prepared via a modified Stöber process. The hybrid core–shell nanoparticles show a paramagnetic behavior with a specific saturation magnetization of 2.8 emu g−1. The nuclear magnetic resonance relaxation measurements reveal that these systems could be used as T1 and T2 magnetic resonance imaging (MRI) contrast agents. Also, the resulting core–shell nanoparticles are fluorescent due to the presence of RhB entrapped inside the silica shell. When incubated with the human cervical carcinoma (HeLa) cells the core–shell composite particles exhibit bright intracellular fluorescence, indicating their capability for optical imaging in biology. Furthermore, the incorporation of organic dyes inside the silica matrix yields outstanding advantages such as significantly improved photostability of the dye and reduced cytotoxicity due to the protection of biocompatible silica shell. These features demonstrate that the magnetofluorescent core–shell nanoparticles prepared in our work have the potential to serve as a versatile imaging tool for smart detection or diagnosis in future biomedical engineering.

A detailed experimental investigation of the effects giving rise to the magnetic energy level structure in the vicinity of the level crossing (LC) at low temperature is reported for the open antiferromagnetic molecular ring Cr8Zn. The study is conducted by means of thermodynamic techniques (torque magnetometry, magnetization and specific heat measurements) and microscopic techniques (nuclear magnetic resonance line width, nuclear spin lattice, and spin-spin relaxation measurements). The experimental results are shown to be in excellent agreement with theoretical calculations based on a minimal spin model Hamiltonian, which includes a Dzyaloshinskii-Moriya interaction. The first ground state level crossing at μ0Hc1 = 2.15 T is found to be an almost true LC while the second LC at μ0Hc2 = 6.95 T has an anti-crossing gap of Δ12 = 0.19 K. In addition, both NMR and specific heat measurements show the presence of a level anti-crossing between excited states at μ0H = 4.5 T as predicted by the theory. In all cases, the fit of the experimental data is improved by introducing a distribution of the isotropic exchange couplings (J), i.e., using a J strain model. The peaks at the first and second LCs in the nuclear spin-lattice relaxation rate are dominated by inelastic scattering and a value of Γ ∼ 10(10) rad/s is inferred for the life time broadening of the excited state of the open ring, due to spin phonon interaction. A loss of NMR signal (wipe-out effect) is observed for the first time at LC and is explained by the enhancement of the spin-spin relaxation rate due to the inelastic scattering.

Magnetic nanoparticles are promising systems for biomedical applications and in particular for Magnetic Fluid Hyperthermia, a promising therapy that utilizes the heat released by such systems to damage tumor cells. We present an experimental study of the physical properties that influences the capability of heat release, i.e. the Specific Loss Power, SLP, of three biocompatible ferrofluid samples having a magnetic core of maghemite with different core diameter d= 10.2, 14.6 and 19.7 nm. The SLP was measured as a function of frequency f and intensity of the applied alternating magnetic field H, and it turned out to depend on the core diameter, as expected. The results allowed us to highlight experimentally that the physical mechanism responsible for the heating is size-dependent and to establish, at applied constant frequency, the phenomenological functional relationship SLP=cH^x, with 2<x<3 for all samples. The x-value depends on sample size and field frequency/ intensity, here chosen in the typical range of operating magnetic hyperthermia devices. For the smallest sample, the effective relaxation time Teff=19.5 ns obtained from SLP data is in agreement with the value estimated from magnetization data, thus confirming the validity of the Linear Response Theory model for this system at properly chosen field intensity and frequency.

We investigate the magnetic properties and the phonon-induced relaxation dynamics of the first regular ${\mathrm{Cr}}_{9}$ antiferromagnetic (AF) ring, which represents a prototype frustrated AF ring. Geometrical frustration in ${\mathrm{Cr}}_{9}$ yields an energy spectrum with twofold degenerate low-lying levels and a low-spin ground state. The electronic relaxation dynamics is probed by ${}^{1}\mathrm{H}$-NMR through the temperature dependence of the spin-lattice relaxation rate $1/{T}_{1}$. We develop a microscopic model that reproduces $1/{T}_{1}(T)$ curves, taking also into account the wipeout effect. By interpreting these measurements we determine the spin-phonon coupling strength and we investigate the decay of the cluster magnetization due to the spin-phonon interaction. We find that at very low temperatures, the relaxation is characterized by a single dominating Arrhenius-type relaxation process, whereas several relevant processes emerge at higher temperatures. In addition, we calculate the temperature and magnetic field dependence of level lifetimes.

High aspect-ratio elongated nanoparticles with suitable porosity present partially controlled chemico-physical properties to obtain good heating/contrast efficiency for biomedical applications.

Cognitive impairment affects about 50% of multiple sclerosis (MS) patients, but the mechanisms underlying this remain unclear. The default mode network (DMN) has been linked with cognition, but in MS its role is still poorly understood. Moreover, within an extended DMN network including the cerebellum (CBL-DMN), the contribution of cortico-cerebellar connectivity to MS cognitive performance remains unexplored. The present study investigated associations of DMN and CBL-DMN structural connectivity with cognitive processing speed in MS, in both cognitively impaired (CIMS) and cognitively preserved (CPMS) MS patients. 68 MS patients and 22 healthy controls (HCs) completed a symbol digit modalities test (SDMT) and had 3T brain magnetic resonance imaging (MRI) scans that included a diffusion weighted imaging protocol. DMN and CBL-DMN tracts were reconstructed with probabilistic tractography. These networks (DMN and CBL-DMN) and the cortico-cerebellar tracts alone were modeled using a graph theoretical approach with fractional anisotropy (FA) as the weighting factor. Brain parenchymal fraction (BPF) was also calculated. In CIMS SDMT scores strongly correlated with the FA-weighted global efficiency (GE) of the network [GE(CBL-DMN): ρ = 0.87, R2 = 0.76, p < 0.001; GE(DMN): ρ = 0.82, R2 = 0.67, p < 0.001; GE(CBL): ρ = 0.80, R2 = 0.64, p < 0.001]. In CPMS the correlation between these measures was significantly lower [GE(CBL-DMN): ρ = 0.51, R2 = 0.26, p < 0.001; GE(DMN): ρ = 0.48, R2 = 0.23, p = 0.001; GE(CBL): ρ = 0.52, R2 = 0.27, p < 0.001] and SDMT scores correlated most with BPF (ρ = 0.57, R2 = 0.33, p < 0.001). In a multivariable regression model where SDMT was the independent variable, FA-weighted GE was the only significant explanatory variable in CIMS, while in CPMS BPF and expanded disability status scale were significant. No significant correlation was found in HC between SDMT scores, MRI or network measures. DMN structural GE is related to cognitive performance in MS, and results of CBL-DMN suggest that the cerebellum structural connectivity to the DMN plays an important role in information processing speed decline.

The magnetic molecular cluster $[{\mathrm{Fe}}_{8}({\mathrm{N}}_{3}{\mathrm{C}}_{6}{\mathrm{H}}_{15}{)}_{6}{\mathrm{O}}_{2}(\mathrm{OH}{)}_{12}{]}^{8+}[{\mathrm{Br}}_{8}\ensuremath{\cdot}9{\mathrm{H}}_{2}\mathrm{O}{]}^{8\ensuremath{-}},$ in short Fe8, has been investigated at low temperature by ${}^{1}\mathrm{H}$-NMR and relaxation measurements. Some measurements of ${}^{2}\mathrm{D}$-NMR in partially deuterated Fe8 clusters will also be reported. Upon decreasing temperature the NMR spectra display a very broad and structured signal which is the result of the internal local fields at the proton sites due to the local moments of the Fe(III) ions in the total $S=10$ magnetic ground state. The proton and deuteron NMR spectra have been analyzed and the different resonance peaks have been attributed to the different proton groups in the molecule. The simulation of the spectra by using a dipolar hyperfine field and the accepted model for the orientation of the Fe(III) local moments do not agree with the experiments even when the magnitude of the local Fe(III) moments is allowed to vary. It is concluded that a positive contact hyperfine interaction of the same order of magnitude as the dipolar interaction is present for all proton sites except the water molecules. The temperature and magnetic field dependence of the nuclear spin-lattice relaxation rate is ascribed to the fluctuations of the local Fe(III) moments, which follow rigidly the fluctuations of the total ground state magnetization of the nanomagnet. By using a simple model already utilized for the Mn12 cluster, we derive the value of the spin phonon coupling constant which determines the lifetime broadening of the different magnetic quantum number m substates of the $S=10$ ground state. It is shown that the lifetime broadening decreases rapidly on lowering the temperature. When the lifetime becomes longer than the reciprocal of the frequency shift of the proton lines a structure emerges in the NMR spectrum reflecting the ``frozen'' local moment configuration.

Magnetization and ${}^{63}\mathrm{Cu}$ nuclear magnetic resonance-nuclear quadrupole resonance relaxation measurements are used to study the superconducting fluctuations in ${\mathrm{YBa}}_{2}{\mathrm{Cu}}_{3}{\mathrm{O}}_{6+x}$ (YBCO) oriented powders. In optimally doped YBCO the fluctuating negative magnetization ${M}_{\mathrm{fl}}(H,T)$ is rather well described by an anisotropic Ginzburg-Landau (GL) functional and the curves ${M}_{\mathrm{fl}}/\sqrt{H}$ cross at ${T}_{c}.$ In underdoped YBCO, instead, over a wide temperature range an anomalous diamagnetism is observed, stronger than in the optimally doped compound by about an order of magnitude. The field and temperature dependence of ${M}_{\mathrm{fl}}$ cannot be described either by an anisotropic GL functional or on the basis of scaling arguments. The anomalous diamagnetism is more pronounced in samples with a defined order in the Cu(1)O chains. The ${}^{63}\mathrm{Cu}(2)$ relaxation rate shows little, if any, field dependence in the vicinity of the transition temperature ${T}_{c}(H=0).$ It is argued how the results in the underdoped compounds can be accounted for by the presence of charge inhomogeneities, favored by chains ordering.

High-resolution isothermal magnetization curves above the transition temperature ${T}_{c}$ in a single crystal of superconducting underdoped cuprate ${\mathrm{La}}_{1.9}{\mathrm{Sr}}_{0.1}{\mathrm{CuO}}_{4}$ ${(T}_{c}=26\mathrm{K})$ are reported. For magnetic field $H&gt;~1\mathrm{kOe}$ the diamagnetic magnetization is rather well described by the Ginzburg-Landau theory in finite fields, as observed in previous works. On the contrary, in the low-field range and for T within ${T}_{c}+2\mathrm{K},$ evidence is given for precursor diamagnetism of different character, with magnetization curves displaying an upturn in the field dependence and magnetic-history dependent effects below $T\ensuremath{\simeq}27\mathrm{K}.$ These findings are the magnetic counterpart of the observation by scanning superconducting quantum interference device microscopy of regions precursor of bulk superconductivity. The interpretation of the experimental data in terms of phase fluctuations of local order parameter is shown to account for most of the aspects of the precursor diamagnetism, which appears to be a general phenomenon in cuprates.

Zero- and longitudinal-field muon-spin-rotation $(\ensuremath{\mu}\mathrm{SR})$ and $^{1}\mathrm{H}$ NMR measurements on the $S=\frac{1}{2}$ molecular nanomagnet ${\mathrm{K}}_{6}[{\mathrm{V}}_{15}^{IV}{\mathrm{As}}_{6}{\mathrm{O}}_{42}({\mathrm{H}}_{2}\mathrm{O})]∙8{\mathrm{H}}_{2}\mathrm{O}$ are presented. In LF experiments, the muon asymmetry $P(t)$ was fitted by the sum of three different exponential components with fixed weights. The different muon relaxation rates ${\ensuremath{\lambda}}_{i}$ $(i=1,2,3)$ and the low-field $H=0.23\phantom{\rule{0.3em}{0ex}}\mathrm{T}$ $^{1}\mathrm{H}$ NMR spin-lattice relaxation rate $1∕{T}_{1}$ show a similar behavior for $T&gt;50\phantom{\rule{0.3em}{0ex}}\mathrm{K}$: starting from room temperature they increase as the temperature is decreased. The increase of ${\ensuremath{\lambda}}_{i}$ and $1∕{T}_{1}$ can be attributed to the ``condensation'' of the system toward the lowest-lying energy levels. The gap $\ensuremath{\Delta}\ensuremath{\sim}550\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ between the first and second $S=\frac{3}{2}$ excited states was determined experimentally. For $T&lt;2\phantom{\rule{0.3em}{0ex}}\mathrm{K}$, the muon relaxation rates ${\ensuremath{\lambda}}_{i}$ stay constant, independently of the field value $H\ensuremath{\leqslant}0.15\phantom{\rule{0.3em}{0ex}}\mathrm{T}$. The behavior for $T&lt;2\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ strongly suggests that, at low $T$, the spin fluctuations are not thermally driven but rather originate from quasielastic intramolecular or intermolecular magnetic interactions. We suggest that the very-low-temperature relaxation rates could be driven by energy exchanges between two almost degenerate $S=\frac{1}{2}$ ground states and/or by quantum effects.

We present the magnetic properties and the 1H nuclear magnetic resonance dispersion profiles of Mn-ferrites-based compounds, as possible novel contrast agents (CAs) for magnetic resonance imaging (MRI). The samples consist of nanoparticles (NPs) with the magnetic core made of Mn1+xFe2−xO4, obtained by the rapid decomposition of metalcarbonyl into a hot solvent containing an oxidizer and a coordinating surfactant; by this procedure, monodisperse capped NPs with different sizes have been obtained. We have performed structural and morphological investigation by x-ray powder diffraction and transmission electron microscopy techniques and SQUID magnetometry experiments to investigate the magnetic behaviour of the samples. As required for MRI applications using negative CAs, the samples are superparamagnetic at room temperature, having blocking temperatures in the range 14–80 K. The longitudinal r1 and transverse r2 nuclear relaxivities appear to vary strongly with the magnetic core size, their values being comparable to commercial compounds in the high-frequency range ν > 100 MHz. The experimental results suggest that our samples are suitable for high-frequency MRI imagers in general and in particular for the 3 T clinical imager, as indeed suggested by a recent report (Tromsdorf et al 2007 Nanoletters 7 2422).

Superconducting fluctuations (SFs) in SmFeAsO${}_{0.8}$F${}_{0.2}$ (characterized by superconducting transition temperature ${T}_{c}\ensuremath{\simeq}52.3$ K) are investigated by means of isothermal high-resolution dc magnetization measurements. The diamagnetic response above ${T}_{c}$ to magnetic fields up to 1 T is similar to that previously reported for underdoped cuprate superconductors and justified in terms of metastable superconducting islands of nonzero order parameter lacking long-range coherence because of strong phase fluctuations. In the high-field regime ($H\ensuremath{\gtrsim}1.5$ T) scaling arguments predicted on the basis of the Ginzburg-Landau theory for conventional SFs are confirmed, at variance with what is observed in the low-field regime. This fact shows that two different phenomena are simultaneously present in the fluctuating diamagnetism, namely the phase SFs of novel character and the conventional SFs. High magnetic fields ($1.5$ T $\ensuremath{\lesssim}H\ensuremath{\ll}{H}_{c2}$) are found to suppress the former while leaving unaltered the latter.

Three-component nanocomposites, constituted by a superparamagnetic iron oxide core coated with a polymeric surfactant bearing tightly bound Re(CO)3 moieties, were prepared and fully characterized. The water soluble and biocompatible surfactant was a linear poly(amidoamine) copolymer (PAA), containing cysteamine pendants in the minority part (ISA23SH), able to coordinate Re(CO)3 fragments. For the synthesis of the nanocomposites two methods were compared, involving either (i) peptization of bare magnetite nanoparticles by interaction with the preformed ISA23SH-Re(CO)3 complex, or (ii) "one-pot" synthesis of iron oxide nanoparticles in the presence of the ISA23SH copolymer, followed by complexation of Re to the SPIO@ISA23SH nanocomposite. Full characterization by TEM, DLS, TGA, SQUID, and relaxometry showed that the second method gave better results. The magnetic cores had a roundish shape, with low dispersion (mean diameter ca. 6 nm) and a tendency to form larger aggregates (detected both by TEM and DLS), arising from multiple interactions of the polymeric coils. Aggregation did not affect the stability of the nano-suspension, found to be stable for many months without precipitate formation. The SPIO@PAA-Re nanoparticles (NPs) showed superparamagnetic behaviour and nuclear relaxivities similar or superior to commercial MRI contrast agents (CAs), which make them promising as MRI "negative" CAs. The possibility to encapsulate (186/188)Re isotopes (γ and β emitters) gives these novel NPs the potential to behave as bimodal nanostructures devoted to theranostic applications.

We report a systematic experimental study of the evolution of the magnetic and relaxometric properties as a function of metal (Co, Ni) doping in iron oxide nanoparticles. A set of five samples, having the same size and ranging from stoichiometric cobalt ferrite (CoFe2O4) to stoichiometric nickel ferrite (NiFe2O4) with intermediate doping steps, was ad hoc synthesized. Using both DC and AC susceptibility measurements, the evolution of the magnetic anisotropy depending on the doping is qualitatively discussed. In particular, we observed that the height of the magnetic anisotropy barrier is directly proportional to the amount of Co, while the Ni has an opposite effect. By Nuclear Magnetic Resonance Dispersion (NMR-D) experiments, the experimental longitudinal r1 and transverse r2 relaxivity profiles were obtained, and the heuristic theory of Roch et al. was used to analyze the data of both r1 and, for the first time, r2. While the experimental and fitting results obtained from r1 profiles were satisfying and confirmed the anisotropy trend, the model applied to r2 hardly explains the experimental findings.

High-density nanoarchitectures, endowed with simultaneous fluorescence and contrast properties for MRI and TEM imaging, have been obtained using a simple self-assembling strategy based on supramolecular interactions between non-doped fluorescent organic nanoparticles (FON) and superparamagnetic nanoparticles. In this way, a high-payload core-shell structure [email protected] has been obtained, protecting the hydrophobic fluorophores from the surroundings as well as from emission quenching by the shell of magnetic nanoparticles. Compared to isolated nanoparticles, maghemite nanoparticles self-assembled as an external shell create large inhomogeneous magnetic field, which causes enhanced transverse relaxivity and exacerbated MRI contrast. The magnetic load of the resulting nanoassemblies is evaluated using magnetic sedimentation and more originally electrospray mass spectrometry. The role of the stabilizing agents (citrate versus polyacrylate anions) revealed to be crucial regarding the cohesion of the resulting high-performance magneto-fluorescent nanoassemblies, which questions their use after cell internalization as nanocarriers or imaging agents for reliable correlative light and electron microcopy.

In the retrospective-prospective multi-center "Blue Sky Radiomics" study (NCT04364776), we plan to test a pre-defined radiomic signature in a series of stage III unresectable NSCLC patients undergoing chemoradiotherapy and maintenance immunotherapy. As a necessary preliminary step, we explore the influence of different image-acquisition parameters on radiomic features' reproducibility and apply methods for harmonization.We identified the primary lung tumor on two computed tomography (CT) series for each patient, acquired before and after chemoradiation with i.v. contrast medium and with different scanners. Tumor segmentation was performed by two oncological imaging specialists (thoracic radiologist and radio-oncologist) using the Oncentra Masterplan® software. We extracted 42 radiomic features from the specific ROIs (LIFEx). To assess the impact of different acquisition parameters on features extraction, we used the Combat tool with nonparametric adjustment and the longitudinal version (LongComBat).We defined 14 CT acquisition protocols for the harmonization process. Before harmonization, 76% of the features were significantly influenced by these protocols. After, all extracted features resulted in being independent of the acquisition parameters. In contrast, 5% of the LongComBat harmonized features still depended on acquisition protocols.We reduced the impact of different CT acquisition protocols on radiomic features extraction in a group of patients enrolled in a radiomic study on stage III NSCLC. The harmonization process appears essential for the quality of radiomic data and for their reproducibility. ClinicalTrials.gov Identifier: NCT04364776, First Posted:April 28, 2020, Actual Study Start Date: April 15, 2020, https://clinicaltrials.gov/ct2/show/NCT04364776 .

We investigated the effect of different organic coatings on the 1H-NMR relaxation properties of ultra-small iron-oxide-based magnetic nanoparticles. The first set of nanoparticles, with a magnetic core diameter ds1 = 4.4 ± 0.7 nm, was coated with polyacrylic acid (PAA) and dimercaptosuccinic acid (DMSA), while the second set, ds2 = 8.9 ± 0.9 nm, was coated with aminopropylphosphonic acid (APPA) and DMSA. At fixed core diameters but different coatings, magnetization measurements revealed a similar behavior as a function of temperature and field. On the other hand, the 1H-NMR longitudinal r1 nuclear relaxivity in the frequency range ν = 10 kHz ÷ 300 MHz displayed, for the smallest particles (diameter ds1), an intensity and a frequency behavior dependent on the kind of coating, thus indicating different electronic spin dynamics. Conversely, no differences were found in the r1 relaxivity of the biggest particles (ds2) when the coating was changed. It is concluded that, when the surface to volume ratio, i.e., the surface to bulk spins ratio, increases (smallest nanoparticles), the spin dynamics change significantly, possibly due to the contribution of surface spin dynamics/topology.

In a recent article, Konwar et al. [ Langmuir 2022, 38, 11087-11098.] reported a new relationship between the structure of clusters of superparamagnetic nanoparticles and the proton nuclear magnetic resonance transverse relaxation they induce. In this comment, we would like to express reservations concerning the adequacy of the new relaxation model proposed in this work.

Control over temperature in space and time is of utmost importance in many contexts, including photothermal therapies, where a good temperature monitoring and control is expected to improve their clinical outcome. One of the most promising techniques involves the use of magnetic resonance imaging, exploring the temperature change of proton relaxometric properties or exploring the temperature change of contrast agents. In real applications, the use of contrast agents for thermometry is much better justified if thermometry comes as an added value of a photothermal agent. Here we show iron selenide nanoparticles (NPs) that are able to work simultaneously as efficient near infrared photothermal and thermometry agents embedded in cellular models at concentrations where their toxicity is low. The simultaneous heat generation and temperature mapping around these NPs allow the control over the depth achieved by the therapy and detection and control of hot spots that would be otherwise overlooked, for instance.

Introduction The aim of this study was to develop an AI-based algorithm for the identification, segmentation, and classification of chronic rhinosinusitis (CRS) with and without nasal polyposis using the Lund-McKay Score.

Einleitung Ziel dieser Studie war die Entwicklung eines KI-Basierten Algorithmus zur Identifizierung, Segmentierung und Klassifizierung der chronischen Rhinosinusitis (CRS) mit und ohne Polyposis nasi mit Hilfe des Lund-McKay-Scores.

We report a detailed $^{1}\mathrm{H}$ NMR study on the spin dynamics of single molecule magnets as a function of temperature and external magnetic field. A gradual loss of the $^{1}\mathrm{H}$ NMR signal intensity (wipeout effect) is observed on decreasing the temperature for all the investigated ferromagnetic clusters. This effect is accompanied by a simultaneous enhancement of the spin-spin and spin-lattice relaxation rate ${T}_{2}^{\ensuremath{-}1}$ and ${T}_{1}^{\ensuremath{-}1}$, respectively. The complications entered in the interpretation of the signal loss by the wipeout effect are overcome, and the information about the spin dynamics is retrieved, by implementing a simple and intuitive model that captures the main physical characteristics of the problem and reveals a universal behavior of the spin dynamics for all the clusters. According to our analysis the origin of the wipeout effect as well as the enhancement of the relaxation rates ${T}_{1}^{\ensuremath{-}1}$ and ${T}_{2}^{\ensuremath{-}1}$ in the FM clusters is related to a decrease of the lifetime broadening parameter of the magnetic energy levels, down to the range of the $^{1}\mathrm{H}$ Larmor frequency. The temperature dependence of the lifetime broadening can be described at intermediate temperatures by a power law dependence on $T$ similar to that observed in antifferomagnetic rings [S. H. Baek et al., Phys. Rev. B 70, 134434 (2004)].

High-resolution superconducting quantum interference device isothermal magnetization measurements in Al-doped Sm-based superconducting cuprates are presented, at the aim to analyze the properties of the underdoped, pseudogapped phase in regards of the superconducting fluctuations (SF) above ${T}_{\text{c}}$. In the optimally doped compound, the SF are well described by the conventional Ginzburg-Landau (GL) free-energy functional for three-dimensional anisotropic systems. On the contrary, in the underdoped compounds, obtained by Al for in-chain Cu substitution at constant oxygen content, dramatic differences are detected. The isothermal curves ${M}_{\text{dia}}$ above ${T}_{\text{c}}$ show an upturn field ${H}_{\text{up}}$, where $|{M}_{\text{dia}}|$ starts to decrease on increasing field. ${H}_{\text{up}}$ is found to increase on increasing temperature. The experimental data on the field dependence of the diamagnetic magnetization above ${T}_{\text{c}}$ can be justified by transforming the GL-Lawrence-Doniach functional into the one for a layered system of vortices with frozen amplitude of the order parameter but with strong phase fluctuations. It is argued that this behavior is characteristic of the underdoped phase of the cuprates, thus providing insights on the pseudogapped phase as accompanied by fluctuations in the phase of order parameter.

We investigate the phonon-induced relaxation dynamics in the Fe${}_{7}$ magnetic molecule, which is made of two Fe${}^{3+}$ triangles bridged together by a central Fe${}^{3+}$ ion. The competition between different antiferromagnetic exchange interactions leads to a low-spin ground state multiplet with a complex pattern of low-lying excited levels. We theoretically investigate the decay of the time correlation function of molecular observables, such as the cluster magnetization, due to the spin-phonon interaction. We find that more than one time contributes to the decay of the molecular magnetization. The relaxation dynamics is probed by measurements of the nuclear spin-lattice relaxation rate $1/{T}_{1}$. The interpretation of these measurements allows the determination of the magnetoelastic coupling strength and to set the scale factor of the relaxation dynamics time scales. In our theoretical interpretation of $1/{T}_{1}$ data we also take into account the wipeout effect at low temperatures.

Colloidal magnetic nanoparticles (MNPs) based on a nearly monodisperse iron oxide core and capped by oleic acid have been used as model systems for investigating the superparamagnetic spin dynamics by means of magnetometry measurements and nuclear magnetic resonance (1H NMR) relaxometry. The key magnetic properties (saturation magnetization, coercive field, and frequency dependent "blocking" temperature) of MNPs with different core size (3.5 nm, 8.5 nm, and 17.5 nm), shape (spherical and cubic), and dispersant (hexane and water-based formulation) have been determined. 1H NMR dispersion profiles obtained by measuring the r1 (longitudinal) and r2 (transverse) nuclear relaxivities in the frequency range 0.01-60 MHz confirmed that in all samples the physical mechanisms that drive the nuclear relaxation are the Néel reversal at low temperature and the Curie relaxation at high frequency. The magnetization reversal time at room temperature extracted from the fitting of NMR data falls in the typical range of superparamagnetic systems (10-9-10-10 s). Furthermore, from the distance of minimum approach we could conclude that water molecules do not arrive in close vicinity of the magnetic core. Our findings contribute to elucidate the local spin dynamics mechanisms in colloidal superparamagnetic nanoparticles which are useful in biomedical application as, e.g., contrast agents for magnetic resonance imaging.

This work reports some effects that aging time of the used catalyst (Fe/MgO) has on the produced N-doped carbon nanotubes. In particular, the catalyst age affects the synthesized nanomaterials with respect to morphology, surface composition and electrocatalytic behavior towards the electrochemical oxygen reduction.

Tumor recurrence after the incomplete removal of a tumor mass inside brain tissue is the main reason that scientists are working to identify new strategies in brain oncologic therapy. In particular, in the treatment of the most malignant astrocytic tumor glioblastoma, the use of magnetic nanoparticles seems to be one of the most promising keys in overcoming this problem, namely by means of magnetic fluid hyperthermia (MFH) treatment. However, the major unknown issue related to the use of nanoparticles is their toxicological behavior when they are in contact with biological tissues. In the present study, we investigated the interaction of glioblastoma and other tumor cell lines with superparamagnetic iron-oxide nanoparticles covalently coated with a rhamnose derivative, using proper cytotoxic assays. In the present study, we focused our attention on different strategies of toxicity evaluation comparing different cytotoxicological approaches in order to identify the biological damages induced by the nanoparticles. The data show an intensive internalization process of rhamnose-coated iron oxide nanoparticles by the cells, suggesting that rhamnose moiety is a promising biocompatible coating in favoring cells' uptake. With regards to cytotoxicity, a 35% cell death at a maximum concentration, mainly as a result of mitochondrial damages, was found. This cytotoxic behavior, along with the high uptake ability, could facilitate the use of these rhamnose-coated iron-oxide nanoparticles for future MFH therapeutic treatments.

Muon Spin Rotation is employed to investigate the spin dynamics of ferritin proteins isolated from the brain of an Alzheimer's disease (AD) patient and of a healthy control, using a sample of horse-spleen ferritin as a reference. A model based on the N\'eel theory of superparamagnetism is developed in order to interpret the spin relaxation rate of the muons stopped by the core of the protein. Using this model, our preliminary observations show that ferritins from the healthy control are filled with a mineral compatible with ferrihydrite, while ferritins from the AD patient contain a crystalline phase with a larger magnetocrystalline anisotropy, possibly compatible with magnetite or maghemite.

Abstract Purpose This study aims at exploiting artificial intelligence (AI) for the identification, segmentation and quantification of COVID-19 pulmonary lesions. The limited data availability and the annotation quality are relevant factors in training AI-methods. We investigated the effects of using multiple datasets, heterogeneously populated and annotated according to different criteria. Methods We developed an automated analysis pipeline, the LungQuant system, based on a cascade of two U-nets. The first one (U-net $$_1$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow /> <mml:mn>1</mml:mn> </mml:msub> </mml:math> ) is devoted to the identification of the lung parenchyma; the second one (U-net $$_2$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msub> <mml:mrow /> <mml:mn>2</mml:mn> </mml:msub> </mml:math> ) acts on a bounding box enclosing the segmented lungs to identify the areas affected by COVID-19 lesions. Different public datasets were used to train the U-nets and to evaluate their segmentation performances, which have been quantified in terms of the Dice Similarity Coefficients. The accuracy in predicting the CT-Severity Score (CT-SS) of the LungQuant system has been also evaluated. Results Both the volumetric DSC (vDSC) and the accuracy showed a dependency on the annotation quality of the released data samples. On an independent dataset (COVID-19-CT-Seg), both the vDSC and the surface DSC (sDSC) were measured between the masks predicted by LungQuant system and the reference ones. The vDSC (sDSC) values of 0.95±0.01 and 0.66±0.13 (0.95±0.02 and 0.76±0.18, with 5 mm tolerance) were obtained for the segmentation of lungs and COVID-19 lesions, respectively. The system achieved an accuracy of 90% in CT-SS identification on this benchmark dataset. Conclusion We analysed the impact of using data samples with different annotation criteria in training an AI-based quantification system for pulmonary involvement in COVID-19 pneumonia. In terms of vDSC measures, the U-net segmentation strongly depends on the quality of the lesion annotations. Nevertheless, the CT-SS can be accurately predicted on independent test sets, demonstrating the satisfactory generalization ability of the LungQuant .

Tuning the fundamental properties of iron oxide magnetic nanoparticles (MNPs) according to the required biomedical application is an unsolved challenge, as the MNPs' properties are affected by their composition, their size, the synthesis process, and so on. In this work, we studied the effect of zinc and manganese doping on the magnetic and structural properties of MNPs synthesized by the microwave-assisted polyol process, using diethylene glycol (DEG) and tetraethylene glycol (TEG) as polyols. The detailed morpho-structural and magnetic characterization showed a correspondence between the higher amounts of Mn and smaller crystal sizes of the MNPs. Such size reduction was compensated by an increase in the global magnetic moment so that it resulted in an increase of the saturation magnetization. Saturation magnetization MS values up to 91.5 emu/g and NMR transverse relaxivities r2 of 294 s-1mM-1 were obtained for Zn and Mn- doped ferrites having diameters around 10 nm, whereas Zn ferrites with diameters around 15 nm reached values of MS∼ 97.2 emu/g and of r2∼ 467 s-1mM-1, respectively. Both kinds of nanoparticles were synthesized by a simple, reproducible, and more sustainable method that makes them very interesting for diagnostic applications as MRI contrast agents.

Proton spin-lattice relaxation (NSLR) measurements have been performed in two molecular copper magnetic rings containing 6 and 8 spins (S=1/2), respectively, in an almost coplanar arrangement in order to probe the spin dynamics of the spins in the ring. The NSLR results obtained in the Cu6 and Cu8 rings as a function of temperature and of applied magnetic field are compared with previous results of NSLR of H1 in the iron(III) rings Fe6 and Fe10 (S=5/2). At room temperature, common features are found in the spin dynamics while at low temperature, when correlation effects become important, important differences are observed in the rings depending on the kind of coupling between magnetic spins (ferromagnetic or antiferromagnetic) and on the spin value S.

${}^{1}\mathrm{H}$ nuclear magnetic resonance (NMR) measurements have been carried out in ${\mathrm{Mn}}_{12}{\mathrm{O}}_{12}$-acetate clusters at low temperature in order to investigate microscopically the static and dynamic magnetic properties of the molecule in its high-spin $S=10$ ground state. Below liquid helium temperature it is found that the local hyperfine fields at the proton sites are static as expected for the very slow superparamagnetic relaxation of ${\mathrm{Mn}}_{12}{\mathrm{O}}_{12}$ at low temperature. The magnitude and distribution of the hyperfine fields can be reproduced to a good approximation by considering only the dipolar interaction of protons with the local Mn magnetic moments and by assigning the magnitude and orientation of the local moments of the different ${\mathrm{Mn}}^{3+}$ and ${\mathrm{Mn}}^{4+}$ ions according to an accepted coupling scheme for the total $S=10$ ground state. The relaxation time of the macroscopic magnetization of the cluster was measured by monitoring the change of the intensity of the ${}^{1}\mathrm{H}\ensuremath{-}\mathrm{NMR}$ shifted lines following inversion of the applied magnetic field. This is possible because the sudden change of the field orientation changes the sign of the shift of the NMR lines in the proton spectrum. Although important differences are noticed, the relaxation time of the magnetization as measured indirectly by the ${}^{1}\mathrm{H}\ensuremath{-}\mathrm{NMR}$ method is comparable to the one obtained directly with a superconducting quantum interference device magnetometer. In particular we could reproduce the minima in the relaxation time as a function of magnetic field at the fields for level crossing, minima which are considered to be a signature of the quantum tunneling of the magnetization.

We present a novel method to measure the relaxation rate $W$ of the magnetization of $\mathrm{Mn}{}_{12}\mathrm{O}{}_{12}$-acetate (Mn12) magnetic molecular cluster in its $S\phantom{\rule{0ex}{0ex}}=\phantom{\rule{0ex}{0ex}}10$ ground state at low $T$. It is based on the observation of an exponential growth in time of the proton NMR signal during the thermal equilibration of the magnetization of the molecules. We can explain the novel effect with a simple model which relates the intensity of the proton echo signal to the microscopic reversal of the magnetization of each individual Mn12 molecule during the equilibration process. The method should find wide application in the study of magnetic molecular clusters in off-equilibrium conditions.

High resolution SQUID magnetization measurements in lead nanoparticles are used to study the fluctuating diamagnetism in zero-dimensional condition, namely for particle size d lesser than the coherence length. The diamagnetic magnetization Mdia (H, T= const) as a function of the field H at constant temperature is reported in the critical region and compared with the behaviour in the temperature range where the first-order fluctuation correction is expected to hold. The magnetization curves are analysed in the framework of exact fluctuation theories based on the Ginzburg-Landau functional for the coherence length much greater than d. The role of the upturn field Hup where Mdia reverses the field dependence is discussed and its relevance for the study of the fluctuating diamagnetism, particularly in the critical region where the first-order fluctuation correction breaks down, is pointed out. The size and temperature dependence of Hup is theoretically derived and compared to the experimental data. The relevance and the magnetization curves for non-evanescent field and of the upturn field for the study of the fluctuating diamagnetism above the superconducting transition temperature is emphasized.

We present a comparison of the results obtained in the antiferromagnetic (AFM) homometallic ring ${\text{Cr}}_{8}$ with the results in three heterometallic rings with a Cr ion replaced by Cd, Ni, and Fe ions, i.e., ${\text{Cr}}_{7}\text{Cd}$, ${\text{Cr}}_{7}\text{Ni}$, and ${\text{Cr}}_{7}\text{Fe}$, respectively. The experimental results include magnetic susceptibility, $^{1}\text{H}$ nuclear-magnetic-resonance (NMR) spectra, spin-spin and spin-lattice relaxation rates data, collected in the temperature range $1.65&lt;T&lt;300\text{ }\text{K}$ at two applied magnetic fields. The data include both new results and previously published data. The static magnetic properties derived from susceptibility and $^{1}\text{H}$ NMR linewidth can be analyzed in a simple way in terms of the properties of the individual ions constituting the ring and their nearest-neighbor antiferromagnetic exchange coupling. The nuclear-spin-lattice relaxation rate at low temperature can be described phenomenologically by a model, which assumes a single-correlation time for the relaxation of the magnetization, as used previously for homometallic AFM rings. The correlation frequencies obtained from the fit of the data, increase by as much as two orders of magnitude in the ${\text{Cr}}_{7}\text{Ni}$ and ${\text{Cr}}_{7}\text{Fe}$ rings with respect to the homometallic ring ${\text{Cr}}_{8}$ and the diamagnetically substituted ${\text{Cr}}_{7}\text{Cd}$ ring. This result can be explained qualitatively in terms of a change in spin-phonon coupling due to the enhancement of crystal-field effects in the heterometallic rings. For a more quantitative analysis one should take into account the multi-Lorentzian behavior of the spin-spin correlation function for which detailed theoretical calculations are required. At temperatures higher than the magnetic exchange energy $J/{k}_{B}$, the mechanism for nuclear-spin-lattice relaxation changes since the fluctuations of the moments of the magnetic ions become weakly correlated. We find a fluctuation frequency much higher in the heterometallic rings as a result of the perturbation introduced by the substituted magnetic ion.

We present (53)Cr-NMR spectra collected at low temperature in a single crystal of the heterometallic antiferromagnetic (AF) ring Cr(7)Ni in the S = 1/2 ground state with the aim of establishing the distribution of the local electronic moment in the ring. Due to the poor S/N we observed only one signal which is ascribed to three almost equivalent (53)Cr nuclei in the ring. The calculated spin density in Cr(7)Ni in the ground state, with the applied magnetic field both parallel and perpendicular to the plane of the ring, turns out to be AF staggered with the greatest component of the local spin <s> for the Cr(3+) ions next to the Ni(2+) ion. The (53)Cr-NMR frequency was found to be in good agreement with the local spin density calculated theoretically by assuming a core polarization field of H(cp) = - 11 T/μ(B) for both orientations, close to the value found previously in Cr(7)Cd. The observed orientation dependence of the local spin moments is well reproduced by the theoretical calculation and evidences the importance of single-ion and dipolar anisotropies.

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) were synthesized and coated with pseudopolyrotaxanes (PPRs) and proposed as a novel hybrid nanostructure for medical imaging and drug delivery. PPRs were prepared by addition of α-cyclodextrin rings to functionalized polyethylene glycol (PEG) chain with hydrophobic triazine end-groups. Non-covalent interactions between SPIONs and PPRs led to the assembly of SPIONs@PRs hybrid nanomaterials. Measurements of the (1)H Nuclear Magnetic Resonance (NMR) relaxation times T(1) and T(2) allowed us to determine the NMR dispersion profiles. Comparison between our SPIONs@PRs hybrid nano-compound and the commercial SPION compound, Endorem, showed a higher transverse relaxivity for SPIONs@PRs. In vitro MRI experiments showed that our SPIONs@PRs produces better negative contrast compared to Endorem and can be considered as a novel MRI contrast agent.

The creation of novel engineered multimodal nanoparticles (NPs) is a key focus in bionanotechnology and can lead to deep understanding of biological processes at the molecular level. Here, we present a multi-component system made of gold-coupled core–shell SPIONs, as a new nanoprobe with signal enhancement in surface Raman spectroscopy, due to its jagged-shaped gold shell coating.