Cationic Polyelectrolyte Mediated Synthesis of MnO2‐Based Core–Shell Structures as Activatable MRI Theranostic Platform for Tumor Cell Ablation

Improving nanomaterial imaging contrast is critical for disease diagnosis and treatment monitoring. Designing activatable imaging agents has the extra benefit of improving signal‐to‐background ratios, as well as reporting local environmental cues. MnO₂, sensitive to local pH and redox state, is used to modulate the tumor microenvironment and can serve as a potential activatable magnetic resonance imaging (MRI) agent. However, the intrinsic 2D form may limit their applications in nanomedicine. Here, a novel facile aqueous route to synthesize MnO₂ nanoshells on various core nanomaterials, regardless of their chemical nature and morphology, is reported. Cationic polyelectrolyte is discovered to be the key to obtain a universal method of coatingMnO₂ on nanomaterials. Taking Cu_2−xSe@MnO₂ as an example, a remarkable three times enhanced T₁‐MRI contrast in a tumor reducing environment is demonstrated. Combined with large optical absorbance of inner Cu_2−xSe cores, they can be applied for efficient redox‐activated MRI‐guided photothermal therapy in the NIR‐II window in vitro and in vivo.     

Dextran‐Coated Antiferromagnetic MnO Nanoparticles for a T1‐MRI Contrast Agent with High Colloidal Stability

A simple approach to synthesize carboxymethyl dextran‐coated MnO nanoparticles (CMDex‐MnONPs) with high colloidal stability in physiological saline solutions is described here for potential applications as a magnetic resonance imaging (MRI) T₁ contrast agent. The thermal decomposition methodology is used to produce uniform MnONPs with an average size of around 20 nm, and its hydrophobic surface is modified with CMDex molecules, conferring hydrophilic properties. After CMDex coating, the nanoparticle presents high colloidal stability in concentrations ranging from 10 to 50 μg mL^?1, average hydrodynamic size (Z‐average) of 130 nm, polydispersity degree of ≈12%, and negative surface charge in both simulated body fluid solutions and pure water with zeta‐potential of –20 and –40 mV, respectively. The CMDex‐MnONPs with 20 nm show antiferromagnetic behavior at room temperature, and the magnetic properties are found to be strongly dependent of the nanoparticle size, increasing the contribution of the ferromagnetic Mn₃O₄ phase with decreasing size for nanoparticles about 3 nm. Cytotoxicity evaluation in cancerous and noncancerous cells in the range of 5.0–50.0 μg mL^?1 shows low toxicity for cancerous cells and lack of the same for healthy cells lines. Related to the magnetic properties, CMDex‐MnONP presents significant r₁ relaxivity and low r₂/r₁ relaxivity ratio. The results suggest that these nanoparticles display characteristics for potential applications as an MRI T₁ contrast agent.     

Exclusive T2 MRI contrast enhancement by mesoporous carbon framework encapsulated manganese oxide nanoparticles

Single mode (either T₁ or T₂) contrast agents employed during magnetic resonance imaging owe their advantage over their dual counterparts to the fact that they do not involve any quenching caused by interference between the two modes. The chemistry involving oxides of manganese is highly significant due to their applicability as MRI contrast agents. Manganese oxides are usually known to display a dominant T₁ relaxation enhancement. But, in this work, an engineered structure of manganese oxide (Mn₂O₃) nanoparticles encapsulated within mesoporous carbon frameworks was developed which exhibited dominant T₂ contrast enhancement, through regulation of contact between the magnetic ion and water. Microstructural characterization revealed that the mesoporous carbon frameworks were spherical in shape and the nanoparticles within them had an average size of 40–50 nm. Relaxivity measurement, MRI experiments and cell viability assay convincingly established the system as a new class of biocompatible T₂ based magnetic resonance imaging agent.     

A Comparative Study of CT and MRI for Evaluating Hepatic Malignant and Focal Nodules Based on ROC Curves

The clinical use of magnetic resonance imaging (MRI) and multiphase enhanced computed tomography (CT) with the contrast media (Gd-EOB-DTPA) for detecting hepatic malignant and focal nodules prior to operation was examined based on the receiver operating characteristic (ROC) curve. This study included 70 patients with malignant and focal liver nodules who underwent MRI and multiphase CT scans before operation. Both scans for each patient were conducted within 1 month. For MRI, the T ₂-weighted image (single shot fast spin echo) and two-dimensional (2-D) and 3-D T ₁-gradient magnetic signals were obtained for all patients before administering the contrast media. The 2-D and 3-D T ₁-gradient magnetic signals were obtained in the same location after delivering the contrast media. For the CT scans, images of artery phase, portal phase, and delayed phase were obtained at a thickness of 5 mm or less after administering contrast similar to MRI. An ROC curve was used (paired-samples T test, P < 0.05) to evaluate the images. When the analysis was based on the ROC curve, MRI showed high values (P < 0.05) for area under curve (AUC), sensitivity, and specificity in terms of detection rates of small lesions (less than 2 cm and more than 2 cm) compared to multidetector computed tomography (MDCT) (for ≤2 cm, MRI: 0.928, 70, 93%, CT: 0.775, 30, 90%; for ≥2 cm, MRI: 0.744, 80%, 84%; CT: 0.692, 40%, 84%). Gd-EOB-DTPA contrast media-enhanced MRI scanner for detecting malignant and focal liver nodules before operation showed the higher detection rate of lesion and classification of lesion as either benign or malignant than multiphase enhanced MDCT when the ROC curve was used for analysis. Based on these results, we believe that analysis based on the ROC curve will provide guidelines for evaluating malignant and focal hepatic lesions prior to operation.     

<Emphasis Type="Italic">T</Emphasis><Subscript>1</Subscript>-<Emphasis Type="Italic">T</Emphasis><Subscript>2</Subscript> correlation analysis of complex foods

The potential of nuclear magnetic resonance two-dimensionalT ₁-T ₂ correlation spectroscopy for quality control in food science is explored for three types of food, namely, egg (white and yolk), cellular tissue (fruit and vegetable) and hydrocolloids (creams and baked products). The complications of cross-relaxation and diffusive exchange are highlighted and various tools for peak assignment are discussed.     

MSE-MRI sequence optimisation for measurement of bi- and tri-exponential T2 relaxation in a phantom and fruit

The transverse relaxation signal from vegetal cells can be described by multi-exponential behaviour, reflecting different water compartments. This multi-exponential relaxation is rarely measured by conventional MRI imaging protocols; mono-exponential relaxation times are measured instead, thus limiting information about of the microstructure and water status in vegetal cells. In this study, an optimised multiple spin echo (MSE) MRI sequence was evaluated for assessment of multi-exponential transverse relaxation in fruit tissues. The sequence was designed for the acquisition of a maximum of 512 echoes. Non-selective refocusing RF pulses were used in combination with balanced crusher gradients for elimination of spurious echoes. The study was performed on a bi-compartmental phantom with known T₂ values and on apple and tomato fruit. T₂ decays measured in the phantom and fruit were analysed using bi- and tri-exponential fits, respectively. The MRI results were compared with low field non-spatially resolved NMR measurements performed on the same samples.     

Continuous-Wave Magnetic Resonance Imaging of Short T2 Materials

There is growing interest in the use of magnetic resonance imaging (MRI) to examine solid materials where the restricted motion of the probed spins leads to broad lines and short T₂ values, rendering many interesting systems invisible to conventional 2DFT pulsed imaging methods. In EPR T₂ seldom exceeds 0.1 μs and continuous-wave methods are adopted for spectroscopy and imaging. In this paper we demonstrate the use of continuous-wave MRI to obtain 2-dimensional images of short T₂ samples. The prototype system can image samples up to 50 mm in diameter by 60 mm long and has been used to image polymers and water penetration in porous media. Typical acquisition times range between 10 and 40 min. Resolution of 1 to 2 mm has been achieved for samples with T₂ values ranging from 38 to 750 μs. There is the possibility of producing image contrast that is determined by the material properties of the sample.     

Features of the low-temperature specific heat in underdoped YBa<Subscript>2</Subscript>Cu<Subscript>3</Subscript>O<Subscript>6 + <Emphasis Type="Italic">x</Emphasis></Subscript> single crystals

The behavior of the low-temperature specific heat C(T) for YBa₂Cu₃O_{6 + x} single crystals with the doping level corresponding to the normal phase has been studied by the relaxation technique at different values of the applied magnetic field. It has been found that the C(T)/T plot exhibits such an anomaly as a steep increase with decreasing temperature from T about 4 K down to T ≤ 2 K (the minimum temperature value accessible in the experiment). The applied magnetic field as high as 9 T inverts this anomaly and leads to a sharp drop in C(T)/T during cooling within the same temperature range. A model involving the Schottky-type centers formulated in this work and the data on spin correlation functions has allowed us to calculate the temperature dependence of the specific heat, which fits the experimental curves quite well.     

Classification of degraded cartilage through multiparametric MRI analysis

MRI analysis of cartilage matrix may play an important role in early detection and development of therapeutic protocols for degenerative joint disease. Correlations between MRI parameters and matrix integrity have been established in many studies, but the substantial overlap in values observed for normal and for degraded cartilage greatly limits the specificity of these analyses. We implemented established multiparametric analysis methods to define data clusters corresponding to control and degraded bovine nasal cartilage in two-, three-, and four-dimensional parameter spaces, and applied these results to discriminant analysis of a validation data set. Analyses were performed using the parameters (T₁, T₂, k_m, ADC), where k_m is the magnetization transfer rate and ADC is the apparent diffusion coefficient. Results were compared to univariate analyses. Multiparametric k-means clustering led to no improvement over univariate analyses, with a maximum sensitivity and specificity in the range of 60–70% for the detection of degradation using T₁, and in the range of 80% sensitivity but only 36% specificity using the parameter pair (T₁, k_m). In contrast, model-based analysis using more general Gaussian clusters resulted in markedly improved classification, with sensitivity and specificity reaching levels of 80–90% using the pair (T₁, k_m). Finally, a fuzzy clustering technique was implemented which may be still more appropriate to the continuum of degradation seen in degenerative cartilage disease. In view of its success in identifying mild cartilage degradation, the formal multiparametric approach implemented here may be applicable to the nondestructive evaluation of other biomaterials using MRI.     

An investigation of the structural aspects of the tomato fruit by means of quantitative nuclear magnetic resonance imaging

In this study, magnetic resonance imaging (MRI) was applied to study the structural aspects of the tomato fruit. The main study was performed on tomatoes (cv. Tradiro) using a 0.2-T electromagnet scanner. Spin-echo images were acquired to visualize the tomato macrostructure. The air bubble content in tissues was evaluated by exploiting susceptibility effects using multiple gradient echo images. The microstructure was further studied by measuring spin–spin (T₂) and spin–lattice (T₁) relaxation time distributions. Nuclear magnetic resonance relaxometry, macro vision imaging and chemical analysis were used as complementary and independent experimental methods in order to emphasize the MRI results. MRI images showed that the air bubble content varied between tissues. The presence of gas was attested by macro vision images. Quantitative imaging showed that T₂ and T₁ maps obtained by MRI reflected the structural differences between tomato tissues and made it possible to distinguish between them. The results indicated that cell size and chemical composition contribute to the relaxation mechanism.     

Polarons in axial transport in single-layer high-T<Subscript><Emphasis Type="Italic">c</Emphasis></Subscript> superconductors

The temperatureT dependencies ρ(T) of normal state electric resistivitiesρ _c (axial) andρ _ab (in plane) of single-layer high-T _c superconductors show common trends: AsT is raised, the resistivity first drops steeply before it starts rising αT above an apparent semiconductor-to-metal crossoverT _cross . To analyze ρ(T) we plottT/ρ againstT at various dopingsx for bothρ _c andρ _ab .T/ρ is inversely proportional to the traversal time across a potential barrier as an ionic particle drifts in an electric field. We findT/ρ in good agreement with theT dependence of the quantum rate of migrating particles: AsT is raised, a zero-point rate at the lowestT is extended to a nearly flat plateau before a thermally activated branch sets in. We also find evidence for the admixture of 1- & 2-phonon absorptions below the Arrhenius range. These features shape the semiconductor-like branch below T _cross . AboveT _cross a metallic-like branch sets in, its αT character deriving from the field coupling of the migrating particle. Our analysis suggests that metal physics may not suffice if ionic features play a role in transport. We attribute our conclusions to the drift of strong-coupling polarons along Cu−O bonds. These “bond polarons” originate from carrier scattering by double-well potentials associated with the bonds. A bond polaron dissociates to a free hole as it passes onto a neighboring O-O link.     

T1Effects in Sequential Dynamic Susceptibility Contrast Experiments

Residual effects of an initial bolus of gadolinium contrast agent have been previously demonstrated in sequential dynamic susceptibility contrast MR experiments. While these residual effects quickly reach a saturation steady state, their etiology is uncertain, and they can lead to spurious estimates of hemodynamic parameters in activation experiments. The possible influence ofT₁effects is now investigated with experiments in whichT₁weighting is varied as well as with serial regionalT₁measurements. Little evidence for significant residualT₁effects is found, suggesting instead that susceptibility effects underlie these observations. An initial saturation dose of contrast agent minimizes this effect.     

Quantification of cerebral perfusion using the "bookend technique": an evaluation in CNS tumors

We present a method of quantifying cerebral blood volume using dynamic susceptibility contrast. Our approach combines T₂-weighted echo planar imaging (EPI) pulse sequences and reference scans that determine the parenchymal T₁ changes resulting from an injection of a gadolinium chelate. This combined T₂- and T₁-weighted approach (the “bookend” technique) has been shown to be effective in the quantification of gradient-echo (GRE) (T₂*-weighted) perfusion images but has not been applied to spin-echo EPI (SE-EPI) (T₂-weighted) images. The physics related to blood volume measurement based on T₂- and T₂*-weighted EPI sequences is known to be different, and there is a question as to whether the bookend approach is effective with SE-EPI. We have compared the quantitative SE-EPI with GRE-EPI in a series of patients with central nervous system (CNS) tumors. We found that quantitative cerebral blood volume (qCBV) values for SE-EPI and GRE-EPI are in agreement with each other and with historical reference values. A subjective evaluation of image quality showed that image quality in the SE-EPI scans was high and exhibited high interreader agreement. We conclude that measuring qCBV using the bookend technique with SE-EPI images is possible and may be a viable alternative to GRE-EPI in the evaluation of CNS tumors.     

Nonlinear properties and paramagnet-to-ferromagnet transition in Nd<Subscript>0.7</Subscript>Ba<Subscript>0.3</Subscript>MnO<Subscript>3</Subscript> single crystal with metallic ground state

We present the results from studying the magnetic properties (linear and nonlinear susceptibilities and the depolarization of polarized neutrons) of Nd_{1 − x} Ba _x MnO₃ manganite, x = 0.3, with Curie temperature T _C ≈ 140 K and dielectric-to-metal transition temperature T _DM ≈ 129 K. Its critical behavior corresponds to that of an isotropic 3-D ferromagnet at temperatures above T*≈ 144 K, but a strong nonlinear response in weak magnetic fields and depolarization are observed at temperatures below T*. It is shown that this nontraditional behavior is related to the generation of ferromagnetic clusters in the paramagnetic matrix that form a conducting percolative network at temperatures near T _DM.     

Amphiphilic Core–Shell Nanocomposite Particles for Enhanced Magnetic Resonance Imaging

A scalable synthesis of magnetic core–shell nanocomposite particles, acting as a novel class of magnetic resonance (MR) contrast agents, has been developed. Each nanocomposite particle consists of a biocompatible chitosan shell and a poly(methyl methacrylate) (PMMA) core where multiple aggregated γ‐Fe₂O₃ nanoparticles are confined within the hydrophobic core. Properties of the nanocomposite particles including their chemical structure, particle size, size distribution, and morphology, as well as crystallinity of the magnetic nanoparticles and magnetic properties were systematically characterized. Their potential application as an MR contrast agent has been evaluated. Results show that the nanocomposite particles have good stability in biological media and very low cytotoxicity in both L929 mouse fibroblasts (normal cells) and HeLa cells (cervical cancer cells). They also exhibited excellent MR imaging performance with a T₂ relaxivity of up to 364 mM_Fe^?1 s^?1. An in vivo MR test performed on a naked mouse bearing breast tumor indicates that the nanocomposite particles can localize in both normal liver and tumor tissues. These results suggest that the magnetic core–shell nanocomposite particles are an efficient, inexpensive and safe T₂‐weighted MR contrast agent for both liver and tumor MR imaging in cancer therapy.     

Magnetocaloric effect in the Sm<Subscript>0.55</Subscript>Sr<Subscript>0.45</Subscript>MnO<Subscript>3</Subscript> manganite

The magnetocaloric effect ΔT has been studied by a direct method in two samples of the manganite Sm_0.55Sr_0.45MnO₃, namely, a single crystal (sample A) and a ceramic sample (sample C). The temperature dependences of the ΔT effect of both samples exhibit a maximum at T _max = 143.3 K for the sample A and T _max = 143 K for the sample C. In these maxima, the values of the ΔT effect are 0.8 and 0.4 K in the magnetic field H = 14.2 kOe for the samples A and C, respectively. In addition, the ΔT(T) curve of the sample A has a minimum at T _min = 120 K, in which ΔT = −0.1 K. The maximum value of the ΔT effect increases with an increase in the magnetic field H in the range of magnetic fields up to 14.2 kOe, and the rate of this increase at H > 8 kOe is higher than that at H < 8 kOe. These features of the ΔT effect are explained by the presence of ferromagnetic and antiferromagnetic A- and CE-type clusters in the samples.     

Deriving new soft tissue contrasts from conventional MR images using deep learning

Versatile soft tissue contrast in magnetic resonance imaging is a unique advantage of the imaging modality. However, the versatility is not fully exploited. In this study, we propose a deep learning-based strategy to derive more soft tissue contrasts from conventional MR images obtained in standard clinical MRI. Two types of experiments are performed. First, MR images corresponding to different pulse sequences are predicted from one or more images already acquired. As an example, we predict T_1ρ weighted knee image from T₂ weighted image and/or T₁ weighted image. Furthermore, we estimate images corresponding to alternative imaging parameter values. In a representative case, variable flip angle images are predicted from a single T₁ weighted image, whose accuracy is further validated in quantitative T₁ map subsequently derived. To accomplish these tasks, images are retrospectively collected from 56 subjects, and self-attention convolutional neural network models are trained using 1104 knee images from 46 subjects and tested using 240 images from 10 other subjects. High accuracy has been achieved in resultant qualitative images as well as quantitative T₁ maps. The proposed deep learning method can be broadly applied to obtain more versatile soft tissue contrasts without additional scans or used to normalize MR data that were inconsistently acquired for quantitative analysis.     

Synthesis,characterization, and in vitro biological evaluation of highly stable diversely functionalized superparamagnetic iron oxide nanoparticles

In this article, we report the design and synthesis of a series of well-dispersed superparamagnetic iron oxide nanoparticles (SPIONs) using chitosan as a surface modifying agent to develop a potential T ₂ contrast probe for magnetic resonance imaging (MRI). The amine, carboxyl, hydroxyl, and thiol functionalities were introduced on chitosan-coated magnetic probe via simple reactions with small reactive organic molecules to afford a series of biofunctionalized nanoparticles. Physico-chemical characterizations of these functionalized nanoparticles were performed by TEM, XRD, DLS, FTIR, and VSM. The colloidal stability of these functionalized iron oxide nanoparticles was investigated in presence of phosphate buffer saline, high salt concentrations and different cell media for 1 week. MRI analysis of human cervical carcinoma (HeLa) cell lines treated with nanoparticles elucidated that the amine-functionalized nanoparticles exhibited higher amount of signal darkening and lower T ₂ relaxation in comparison to the others. The cellular internalization efficacy of these functionalized SPIONs was also investigated with HeLa cancer cell line by magnetically activated cell sorting (MACS) and fluorescence microscopy and results established selectively higher internalization efficacy of amine-functionalized nanoparticles to cancer cells. These positive attributes demonstrated that these nanoconjugates can be used as a promising platform for further in vitro and in vivo biological evaluations.     

Separation of Anisotropy and Exchange Broadening Using N CSA–N–H Dipole–Dipole Relaxation Cross-Correlation Experiments

Based on the measurement of cross-correlation rates between ¹⁵N CSA and ¹⁵N–¹H dipole–dipole relaxation we propose a procedure for separating exchange contributions to transverse relaxation rates (R₂ = 1/T₂) from effects caused by anisotropic rotational diffusion of the protein molecule. This approach determines the influence of anisotropy and chemical exchange processes independently and therefore circumvents difficulties associated with the currently standard use of T₁/T₂ ratios to determine the rotational diffusion tensor. We find from computer simulations that, in the presence of even small amounts of internal flexibility, fitting T₁/T₂ ratios tends to underestimate the anisotropy of overall tumbling. An additional problem exists when the N–H bond vector directions are not distributed homogeneously over the surface of a unit sphere, such as in helix bundles or β-sheets. Such a case was found in segment 4 of the gelation factor (ABP 120), an F-actin cross-linking protein, in which the diffusion tensor cannot be calculated from T₁/T₂ ratios. The ¹⁵N CSA tensor of the residues for this β-sheet protein was found to vary even within secondary structure elements. The use of a common value for the whole protein molecule therefore might be an oversimplification. Using our approach it is immediately apparent that no exchange broadening exists for segment 4 although strongly reduced T₂ relaxation times for several residues could be mistaken as indications for exchange processes.     

Facile Synthesis of Gd(OH)3‐Doped Fe3O4 Nanoparticles for Dual‐Mode T1‐ and T2‐Weighted Magnetic Resonance Imaging Applications

The facile hydrothermal synthesis of polyethyleneimine (PEI)‐coated iron oxide (Fe₃O₄) nanoparticles (NPs) doped with Gd(OH)₃ (Fe₃O₄‐Gd(OH)₃‐PEI NPs) for dual mode T₁‐ and T₂‐weighted magnetic resonance (MR) imaging applications is reported. In this approach, Fe₃O₄‐Gd(OH)₃‐PEI NPs are synthesized via a hydrothermal method in the presence of branched PEI and Gd(III) ions. The PEI coating onto the particle surfaces enables further modification of poly(ethylene glycol) (PEG) in order to render the particles with good water dispersibility and improved biocompatibility. The formed Fe₃O₄‐Gd(OH)₃‐PEI‐PEG NPs have a Gd/Fe molar ratio of 0.25:1 and a mean particle size of 14.4 nm and display a relatively high r₂ (151.37 × 10^?3m ^?1 s^?1) and r₁ (5.63 × 10^?3m ^?1 s^?1) relaxivity, affording their uses as a unique contrast agent for T₁‐ and T₂‐weighted MR imaging of rat livers after mesenteric vein injection of the particles and the mouse liver after intravenous injection of the particles, respectively. The developed Fe₃O₄‐Gd(OH)₃‐PEI‐PEG NPs may hold great promise to be used as a contrast agent for dual mode T₁‐ and T₂‐weighted self‐confirmation MR imaging of different biological systems.