Proton Longitudinal Relaxation Research Articles

Optimization of cervical cord synthetic T1-weighted MRI for enhancing clinical application in neurodegenerative spinal cord disorders

Abstract Synthetic MRI offers the advantage of reducing acquisition time and enhancing flexibility through the reconstruction of various contrast weightings from a single set of MRI scans. However, the use of synthetic T1-weighted (synT1-w) MRI can lead to potentially biased measurements of the cross-sectional area (CSA) in the spinal cord when compared to conventionally acquired T1-weighted MRI. This disparity can have implications for comparability and sensitivity of MRI in assessing disease progression or treatment effects in neurodegenerative spinal cord disorders. Thus, this study aimed at improving the accuracy (i.e., difference between synthetic and acquired MRI) of cervical cord CSA measurements (C1-C3 level) based on synT1-w MRI implementing a longitudinal data set acquired from 23 acute spinal cord injury (SCI) patients and 21 healthy controls over 2 years. Moreover, the validity of using synT1-w MRI for tracking cervical cord atrophy following SCI over 2 years was verified. SynT1-w images were reconstructed from quantitative maps of proton density, longitudinal, and effective transverse relaxation rates derived from a multi-parameter mapping protocol. The results showed a minimal bias of -0.31 mm2 (-0.5%) in CSA measurements based on synT1-w compared to acquired MRI. Estimates of atrophy rates and average CSA were comparable between synthetic and acquired MRI. A sample size estimation for detecting treatment effects on CSA atrophy after 2 years following SCI revealed that the required sample size is reduced by 13.5% using synT1-w instead of acquired MRI. This study shows high accuracy of synT1-w MRI and demonstrates its applicability in clinical studies for optimizing long MRI protocols.

Anisotropic longitudinal water proton relaxation in white matter investigated ex vivo in porcine spinal cord with sample rotation

A variation of the longitudinal relaxation time T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} in brain regions that differ in their main fiber direction has been occasionally reported, however, with inconsistent results. Goal of the present study was to clarify such inconsistencies, and the origin of potential T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} orientation dependence, by applying direct sample rotation and comparing the results from different approaches to measure T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document}. A section of fixed porcine spinal cord white matter was investigated at 3 T with variation of the fiber-to-field angle θFB\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ heta_{{{\ ext{FB}}}}$$\\end{document}. The experiments included one-dimensional inversion-recovery, MP2RAGE, and variable flip-angle T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} measurements at 22 °C and 36 °C as well as magnetization-transfer (MT) and diffusion-weighted acquisitions. Depending on the technique, different degrees of T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} anisotropy (between 2 and 10%) were observed as well as different dependencies on θFB\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ heta_{{{\ ext{FB}}}}$$\\end{document} (monotonic variation or T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} maximum at 30–40°). More pronounced anisotropy was obtained with techniques that are more sensitive to MT effects. Furthermore, strong correlations of θFB\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\ heta_{{{\ ext{FB}}}}$$\\end{document}-dependent MT saturation and T1\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$T_{1}$$\\end{document} were found. A comprehensive analysis based on the binary spin-bath model for MT revealed an interplay of several orientation-dependent parameters, including the transverse relaxation times of the macromolecular and the water pool as well as the longitudinal relaxation time of the macromolecular pool.

Multivariate white matter differences links to cognition in individuals with family history of Alzheimer’s disease and APOE4 genetic risk

AbstractBackgroundGrowing evidence suggests Alzheimer’s disease (AD) develops from a complex cascade of events that vary between individuals. Multivariate approaches have the potential to capture the complexity and heterogeneity of pathologies underlying AD in a more holistic manner compared to univariate approaches.MethodThe MRI data of 105 older adults with a family history of AD from the PREVENT‐AD dataset were analysed. Forty six of these individuals had the APOE4‐3 genotype (greater risk of developing AD), while 59 subjects had the APOE3‐3 genotype (normal risk). Diffusion‐weighted imaging and multi‐echo magnetization transfer, proton density and T1‐weighted data were used to compute several WM metrics (Fig1 b‐c). We computed the voxel‐wise Mahalanobis distance (D2) in WM between APOE4‐3 individuals and a reference group (APOE3‐3) (Fig1). D2 is a multivariate measure that combines several MRI metrics, accounting for their covariance, and yielding a score indicative of the degree of abnormality at each WM voxel (Fig2). Associations between WM D2 and cognitive performance were then investigated (Fig3). Independent component analysis (ICA) was performed on spatial dimensions and linear regression analyses were conducted between D2 in ICA components and scores on items of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We then extracted the contribution of each MRI feature to D2 in the regions where significant associations were found.ResultA significant negative association (R = ‐0.36, p = 0.014) was found between D2 in a component corresponding to the splenium of the corpus callosum (CC) and scores on RBANS‐immediate memory (Fig3), indicating a link between a greater degree of WM abnormality and poorer performance. Proton density (MPM_PD) and longitudinal relaxation rate (MPM_R1), potentially indicative of WM loss, contributed most to D2 in this region.ConclusionOur findings suggest that microstructural alterations in the posterior part of the CC may play a role in memory deficit in older adults who are at greater risk of developing AD. This is in line with other studies that showed a link between CC degeneration and memory impairments in early AD stages.1 1. Qiu et al. (2016). Inter‐hemispheric dysconnectivity in AD and aMCI. Sci.Rep.

Multivariate white matter differences links to cognition in individuals with family history of Alzheimer’s disease and APOE4 genetic risk

AbstractBackgroundGrowing evidence suggests Alzheimer’s disease (AD) develops from a complex cascade of events that vary between individuals. Multivariate approaches have the potential to capture the complexity and heterogeneity of pathologies underlying AD in a more holistic manner compared to univariate approaches.MethodThe MRI data of 105 older adults with a family history of AD from the PREVENT‐AD dataset were analysed. Forty six of these individuals had the APOE4‐3 genotype (greater risk of developing AD), while 59 subjects had the APOE3‐3 genotype (normal risk). Diffusion‐weighted imaging and multi‐echo magnetization transfer, proton density and T1‐weighted data were used to compute several WM metrics (Fig1 b‐c). We computed the voxel‐wise Mahalanobis distance (D2) in WM between APOE4‐3 individuals and a reference group (APOE3‐3) (Fig1). D2 is a multivariate measure that combines several MRI metrics, accounting for their covariance, and yielding a score indicative of the degree of abnormality at each WM voxel (Fig2). Associations between WM D2 and cognitive performance were then investigated (Fig3). Independent component analysis (ICA) was performed on spatial dimensions and linear regression analyses were conducted between D2 in ICA components and scores on items of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We then extracted the contribution of each MRI feature to D2 in the regions where significant associations were found.ResultA significant negative association (R = ‐0.36, p = 0.014) was found between D2 in a component corresponding to the splenium of the corpus callosum (CC) and scores on RBANS‐immediate memory (Fig3), indicating a link between a greater degree of WM abnormality and poorer performance. Proton density (MPM_PD) and longitudinal relaxation rate (MPM_R1), potentially indicative of WM loss, contributed most to D2 in this region.ConclusionOur findings suggest that microstructural alterations in the posterior part of the CC may play a role in memory deficit in older adults who are at greater risk of developing AD. This is in line with other studies that showed a link between CC degeneration and memory impairments in early AD stages.1 1. Qiu et al. (2016). Inter‐hemispheric dysconnectivity in AD and aMCI. Sci.Rep.

Water-Soluble Gd(III)-Porphyrin Complexes Capable of Both Photosensitization and Relaxation Enhancement.

With the aim of developing more stable Gd(III)-porphyrin complexes, two types of ligands 1 and 2 with carboxylic acid anchors were synthesized. Due to the N-substituted pyridyl cation attached to the porphyrin core, these porphyrin ligands were highly water-soluble and formed the corresponding Gd(III) chelates, Gd-1 and Gd-2. Gd-1 was sufficiently stable in neutral buffer, presumably due to the preferred conformation of the carboxylate-terminated anchors connected to nitrogen in the meta position of the pyridyl group helping to stabilize Gd(III) complexation by the porphyrin center. 1H NMRD (nuclear magnetic relaxation dispersion) measurements on Gd-1 revealed high longitudinal water proton relaxivity (r1 = 21.2 mM-1 s-1 at 60 MHz and 25 °C), which originates from slow rotational motion resulting from aggregation in aqueous solution. Under visible light irradiation, Gd-1 showed extensive photoinduced DNA cleavage in line with efficient photoinduced singlet oxygen generation. Cell-based assays revealed no significant dark cytotoxicity of Gd-1, while it showed sufficient photocytotoxicity on cancer cell lines under visible light irradiation. These results indicate the potential of this Gd(III)-porphyrin complex (Gd-1) as a core for the development of bifunctional systems acting as an efficient photodynamic therapy photosensitizer (PDT-PS) with magnetic resonance imaging (MRI) detection capabilities.

Reliability of spinal cord measures based on synthetic T1-weighted MRI derived from multiparametric mapping (MPM)

Short MRI acquisition time, high signal-to-noise ratio, and high reliability are crucial for image quality when scanning healthy volunteers and patients. Cross-sectional cervical cord area (CSA) has been suggested as a marker of neurodegeneration and potential outcome measure in clinical trials and is conventionally measured on T1-weigthed 3D Magnetization Prepared Rapid Acquisition Gradient-Echo (MPRAGE) images. This study aims to reduce the acquisition time for the comprehensive assessment of the spinal cord, which is typically based on MPRAGE for morphometry and multi-parameter mapping (MPM) for microstructure. The MPRAGE is replaced by a synthetic T1-w MRI (synT1-w) estimated from the MPM, in order to measure CSA. SynT1-w images were reconstructed using the MPRAGE signal equation based on quantitative maps of proton density (PD), longitudinal (R1) and effective transverse (R2*) relaxation rates. The reliability of CSA measurements from synT1-w images was determined within a multi-center test-retest study format and validated against acquired MPRAGE scans by assessing the agreement between both methods. The response to pathological changes was tested by longitudinally measuring spinal cord atrophy following spinal cord injury (SCI) for synT1-w and MPRAGE using linear mixed effect models. CSA measurements based on the synT1-w MRI showed high intra-site (Coefficient of variation [CoV]: 1.43% to 2.71%) and inter-site repeatability (CoV: 2.90% to 5.76%), and only a minor deviation of -1.65 mm2 compared to MPRAGE. Crucially, by assessing atrophy rates and by comparing SCI patients with healthy controls longitudinally, differences between synT1-w and MPRAGE were negligible. These results demonstrate that reliable estimates of CSA can be obtained from synT1-w images, thereby reducing scan time significantly.

Engineered Graphene Quantum Dots as a Magnetic Resonance Signal Amplifier for Biomedical Imaging.

The application of magnetic resonance imaging (MRI) nano-contrast agents (nano-CAs) has increasingly attracted scholarly interest owing to their size, surface chemistry, and stability. Herein, a novel T1 nano-CA (Gd(DTPA)-GQDs) was successfully prepared through the functionalization of graphene quantum dots with poly(ethylene glycol) bis(amine) and their subsequent incorporation into Gd-DTPA. Remarkably, the resultant as-prepared nano-CA displayed an exceptionally high longitudinal proton relaxivity (r1) of 10.90 mM-1 s-1 (R2 = 0.998), which was significantly higher than that of commercial Gd-DTPA (4.18 mM-1 s-1, R2 = 0.996). The cytotoxicity studies indicated that the Gd(DTPA)-GQDs were not cytotoxic by themselves. The results of the hemolysis assay and the in vivo safety evaluation demonstrate the outstanding biocompatibility of Gd(DTPA)-GQDs. The in vivo MRI study provides evidence that Gd(DTPA)-GQDs exhibit exceptional performance as T1-CAs. This research constitutes a viable approach for the development of multiple potential nano-CAs with high-performance MR imaging capabilities.

Rational surface modification of gadolinium borate nanoparticles enhancing colloidal stability in physiological media for potential neutron capture therapy and magnetic resonance imaging

Colloidal stability of nanomaterials in physiological media is an indispensable property for their biomedical applications. However, gadolinium borate (GdBO3) nanoparticles that hold promise as a theranostic agent for neutron capture therapy (NCT) and magnetic resonance imaging (MRI) of cancer tend to precipitate in phosphate buffered saline (PBS) owing to formation of insoluble gadolinium phosphate. To address this issue, in this work 10B-enriched GdBO3 nanoparticles were prepared and coated with mesoporous silica (mSiO2) of ~ 40 nm in thickness and subsequently grafted with hydrophilic polyglycerol (PG). The resulting GdBO3 @mSiO2-PG nanoparticles showed excellent colloidal stability in PBS due to the protection of the mSiO2 coating as well as superior dispersibility because of the high hydrophilicity of the PG layer. In vitro experiments revealed that GdBO3 @mSiO2-PG possessed low cytotoxicity and could be taken up by cancer cells in a concentration-dependent manner. In vivo studies indicated that GdBO3 @mSiO2-PG can circulate in mouse body for a considerably long time without obvious acute toxicity. In addition, GdBO3 @mSiO2-PG also showed promise as a T1-weighted MRI contrast agent with a proton longitudinal relaxivity of 0.67 mM−1 s−1. Our results indicate that GdBO3 @mSiO2-PG with enhanced colloidal stability in physiological media could serve as a promising multifunctional agent for cancer theranostics.

Distinct Coordination Chemistry of Fe(III)-Based MRI Probes.

Contrast agents are used in approximately 40% of all magnetic resonance imaging (MRI) procedures to improve the quality of the images based on the distribution and dynamic clearance of the agent. To date, all clinically approved contrast agents are Gd(III) coordination complexes that serve to shorten the longitudinal (T1) and transverse (T2) proton relaxation times of water. Recent interest in replacing Gd with biologically relevant metal ions such as Mn or Fe has led to increased interest in the aqueous coordination chemistry of their complexes. In this Account, we focus on high-spin Fe(III) complexes that have been recently reported as MRI contrast agents or probes in our laboratory.The highly Lewis acidic Fe(III) center has distinct coordination chemistry in aqueous solutions, facilitating alternative strategies in the design of MRI probes. To illustrate this, we describe different classes of Fe(III) MRI probes with a focus on macrocyclic complexes and multinuclear complexes such as self-assembled metal organic polyhedra (MOP). Our initial efforts focused on macrocyclic complexes of Fe(III) in order to tune spin and oxidation states with the goal of stabilizing high-spin Fe(III) in reducing biological environments. Our probes feature six-coordinate Fe(III) complexes of 1,4,7-triazacyclononane with hydroxypropyl, phosphonate, or carboxylate pendant groups to produce Fe(III) complexes that shorten proton T1 times predominantly from second-sphere or outer-sphere interactions at neutral pH. Analogues with pentadentate macrocyclic ligands have an inner-sphere water that does not exchange rapidly on the NMR time scale, yet these complexes are effective relaxation agents. Fe(III) macrocyclic complexes in this class can be modified to modulate their biodistribution and pharmacokinetic clearance in mice. The goal of these studies is for the Fe(III) agents to clear as extracellular fluid agents and produce profiles similar to those of Gd agents. Finally, studies of multimeric Fe(III) complexes are of interest to produce probes that give large proton relaxivity. In this approach the two Fe(III) centers are connected through aryl linkers as demonstrated for several macrocyclic complexes. Even more tightly connected Fe(III) centers are produced in a Fe(III) self-assembled cage with relaxivity of 21 mM-1 s-1 at 4.7 T, 37 °C in the presence of serum albumin to which it is tightly bound. This cage enhances contrast of the vasculature as a blood pool agent and accumulates in tumors. Finally, we present our perspectives on the further development of Fe(III) complexes for various applications in MRI.

NMR relaxation time investigation of highly diluted aqueous solutions of silica-lactose

The aim of the present investigation was to replicate a study published by Demangeat in 2010 in the Journal of Molecular Liquids. We measured 20 MHz longitudinal (T1) and transverse (T2) proton relaxation of H2O in highly diluted silica-lactose (Sil/Lac) solutions in 0.15 M LiCl in water (Sil/Lac C6–C24, range 10−7 M–10−47 M). The samples were prepared by repetitive succussion and centesimal dilution under rigorously controlled laboratory conditions. Lactose solutions in 0.15 M LiCl in water (Lac C6–C24) were identically and simultaneously treated, as controls. Neither for lactose (Lac) nor for Sil/Lac solutions did T1 and T2 relaxation parameters show a significant correlation with increasing dilution level. A cross-correlation analysis of T1 and T2 revealed a significant negative correlation for both Sil/Lac and LiCl samples, which changed to positive after placing the tubes for 10 min in boiling water. These results diverge from those obtained in the study of Demangeat. In our investigation, the process of potentisation (repetitive succussion and dilution) seems to be responsible for the modifications of proton relaxation times, irrespective of the presence of silica. We hypothesise that succussion intensity during dilution is a crucial factor that needs to be investigated in more detail in future investigations.

Experimental Protocols for MRI Mapping of Renal T1.

The water proton longitudinal relaxation time, T1, is a common and useful MR parameter in nephrology research. Here we provide three step-by-step T1-mapping protocols suitable for different types of nephrology research. Firstly, we provide a single-slice 2D saturation recovery protocol suitable for studies of global pathology, where whole-kidney coverage is unnecessary. Secondly, we provide an inversion recovery type imaging protocol that may be optimized for specific kidney disease applications. Finally, we also provide imaging protocol for small animal kidney imaging in a clinical scanner.This chapter is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers. This analysis protocol chapter is complemented by two separate chapters describing the basic concept and experimental procedure.

Molecular mobility changes after high-temperature, short-time pasteurization: An extended time-domain nuclear magnetic resonance screening of ewe milk

This study presents an extensive investigation on the effect of pasteurization on raw whole ewe milk. Milk samples have been analyzed, throughout lactation (from February to July), by time-domain nuclear magnetic resonance (TD-NMR), collecting the characteristic TD-NMR relaxation parameters, proton longitudinal and transverse relaxation times (1H T1 and T2). Collected data aim at integrating previous NMR works, mainly focusing on dairy model systems (casein and whey proteins solutions and gels, reconstituted skim milk) and cheese, with specific reference to the effect of heat treatments. Whole ewe milk, from a single flock (Sarda sheep breed), was daily analyzed both as untreated (raw) and heat treated with a laboratory-scaled high-temperature, short-time treatment (72°C for 15 and 20 s). Moreover, molecular dynamics in milk were investigated by TD-NMR in different periods of lactation for the first time. As a consequence of high-temperature short-time treatment, 1H T1 and T2 consistently shifted to lower values with respect to raw counterparts. Statistical analysis indicated a significant decrease of T2 in treated samples, to an extent dependent on the heat treatment duration. A subset of dedicated experiments demonstrated that the observed T2 shift is largely ascribable to protein molecular rearrangements and, to a lesser extent, to the interaction of fat globules with proteins or other nonfat components (or both). In light of the crucial importance of detecting the application of a heat treatment to milk, the results reported here suggest TD-NMR relaxation parameters were able to describe heat-induced changes in molecular dynamics and interactions of milk components in a water-rich environment. The use of TD-NMR can be considered a potential suitable technique for quality control and assurance practices in the dairy industry. Upon statistical validation of methods, the application of TD-NMR in the dairy industry would take advantage of its low cost, reliability, and robustness.

Gd(DOTA)-grafted submicronic polysaccharide-based particles functionalized with fucoidan as potential MR contrast agent able to target human activated platelets

Early detection of thrombotic events remains a big medical challenge. Dextran-based submicronic particles bearing Gd(DOTA) groups and functionalized with fucoidan have been produced via a simple and green water-in-oil emulsification/co-crosslinking process. Their capacity to bind to human activated platelets was evidenced in vitro as well as their cytocompatibility with human endothelial cells. The presence of Gd(DOTA) moieties was confirmed by elemental analysis and total reflection X-ray fluorescence (TRXF) spectrometry. Detailed characterization of particles was performed in terms of size distribution, morphology, and relaxation rates. In particular, longitudinal and transversal proton relaxivities were respectively 1.7 and 5.0 times higher than those of DOTAREM. This study highlights their potential as an MRI diagnostic platform for atherothrombosis.

Silicon nanoparticles with iron impurities for multifunctional applications

Crystalline silicon (Si) nanoparticles (NPs) doped with iron (Fe) in the range from 0.02 to 2.5 at.% were prepared by plasma-ablative synthesis and were investigated by means of the transmission electron microscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), infrared spectroscopy and nuclear magnetic resonance relaxometry. While the nanocrystal size in Si:Fe NPs did not depend significantly on Fe content, the hydrodynamic diameter of NPs in aqueous suspensions increases from 50 to 180[Formula: see text]nm. Both the transverse and longitudinal proton relaxation time were found to decrease in the prepared suspensions of Si:Fe NPs. Maximal shortening of the transverse relaxion was observed for Si:Fe NPs with 0.2 at.% of Fe and the relaxation rate was almost linearly proportional to the NP concentration. Both these findings and in vivo tests indicate that Si:Fe NPs are promising for biomedical applications in magnetic resonance imaging (MRI) and therapy of cancer.

Recent Advances of Bioresponsive Nano-Sized Contrast Agents for Ultra-High-Field Magnetic Resonance Imaging.

The ultra-high-field magnetic resonance imaging (MRI) nowadays has been receiving enormous attention in both biomaterial research and clinical diagnosis. MRI contrast agents are generally comprising of T1-weighted and T2-weighted contrast agent types, where T1-weighted contrast agents show positive contrast enhancement with brighter images by decreasing the proton's longitudinal relaxation times and T2-weighted contrast agents show negative contrast enhancement with darker images by decreasing the proton's transverse relaxation times. To meet the incredible demand of MRI, ultra-high-field T2 MRI is gradually attracting the attention of research and medical needs owing to its high resolution and high accuracy for detection. It is anticipated that high field MRI contrast agents can achieve high performance in MRI imaging, where parameters of chemical composition, molecular structure and size of varied contrast agents show contrasted influence in each specific diagnostic test. This review firstly presents the recent advances of nanoparticle contrast agents for MRI. Moreover, multimodal molecular imaging with MRI for better monitoring is discussed during biological process. To fasten the process of developing better contrast agents, deep learning of artificial intelligent (AI) can be well-integrated into optimizing the crucial parameters of nanoparticle contrast agents and achieving high resolution MRI prior to the clinical applications. Finally, prospects and challenges are summarized.

In vivo assessment of tumour associated macrophages in murine melanoma obtained by low-field relaxometry in the presence of iron oxide particles

Tumour-associated macrophages (TAM) are forced by cancer cells to adopt an anti-inflammatory phenotype and secrete factors to promote tumour invasion thus being responsible for poor patient outcome. The aim of this study is to develop a clinically applicable, non-invasive method to obtain a quantitative TAM detection in tumour tissue. The method is based on longitudinal proton relaxation rate (R1) measurements at low field (0.01–1 MHz) to assess the localization of ferumoxytol (clinical approved iron oxide particles) in TAM present in melanoma tumours, where R1 = 1/T1. R1 at low magnetic fields appears highly dependent on the intra or extra cellular localization of the nanoparticles thus allowing an unambiguous TAM quantification. R1 profiles were acquired on a Fast Field-Cycling relaxometer equipped with a 40 mm wide bore magnet and an 11 mm solenoid detection coil placed around the anatomical region of interest. The R1 values measured 3 h and 24 h after the injection were significantly different. At 24 h R1 exhibited a behavior similar to “in vitro” ferumoxytol-labelled J774A.1 macrophages whereas at 3 h, when the ferumoxytol distribution was extracellular, R1 exhibited higher values similar to that of free ferumoxytol in solution. This finding clearly indicated the intracellular localization of ferumoxytol at 24 h, as confirmed by histological analysis (Pearls and CD68 assays). This information could be hardly achievable from measurements at a single magnetic field and opens new horizons for cell tracking applications using FFC-MRI.

Quantification of brain proton longitudinal relaxation (T1 ) in lithium-treated and lithium-naïve patients with bipolar disorder in comparison to healthy controls.

BackgroundProton longitudinal relaxation (T1) is a quantitative MRI‐derived tissue parameter sensitive to myelin, macromolecular, iron and water content. There is some evidence to suggest that cortical T1 is elevated in bipolar disorder and that lithium administration reduces cortical T1. However, T1 has not yet been quantified in separate groups containing lithium‐treated patients, lithium‐naïve patients, and matched healthy controls.MethodsEuthymic patients with bipolar disorder receiving lithium (n = 18, BDL) and those on other medications but naïve to lithium (n = 20, BDC) underwent quantitative T1 mapping alongside healthy controls (n = 18, HC). T1 was compared between groups within the cortex, white matter and subcortical structures using regions of interest (ROI) derived from the Desikan‐Killiany atlas. Effect sizes for each ROI were computed for BDC vs BDL groups and Bipolar Disorder vs HC groups.ResultsNo significant differences in T1 were identified between BDL and BDC groups when corrected for multiple comparisons. Patients with bipolar disorder had significantly higher mean T1 in a range of ROIs compared to healthy controls, including bilateral motor, somatosensory and superior temporal regions, subcortical structures and white matter.ConclusionsThe higher T1 values observed in the patients with bipolar disorder may reflect abnormal tissue microstructure. Whilst the precise mechanism remains unknown, these findings may have a basis in differences in myelination, macromolecular content, iron and water content between patients and controls.

D‐Glucuronic Acid‐Coated Ultrasmall Paramagnetic Ln2O3 (Ln = Tb, Dy, and Ho) Nanoparticles: Magnetic Properties, Water Proton Relaxivities, and Fluorescence Properties

Many of the lanthanide‐based nanoparticles are valuable in magnetic resonance imaging (MRI) because they have excellent magnetic properties that make them suitable for MRI contrast agents, while some of them have additional optical properties and thus can serve as fluorescence imaging (FI) agents as well. Herein, we synthesized d‐glucuronic acid‐coated ultrasmall Ln2O3 (Ln = Tb, Dy, and Ho) nanoparticles with average diameters of ∼ 2 nm. All the nanoparticles showed unsaturated but appreciable magnetization of ∼ 4 emu/g at an applied field of 1.8 T at room temperature, and consequently, high transverse water proton relaxivities (r2) of ∼ 7 s–1 mm–1 at 1.5 T, ∼ 35 s–1 mm–1 at 3.0 T, and ∼ 55 s–1 mm–1 at 9.4 T with negligible longitudinal water proton relaxivities (r1), thus being eligible for use as T2 MRI contrast agents at high MR fields. In addition, d‐glucuronic acid‐coated ultrasmall Tb2O3 nanoparticles exhibited fluorescence in the green region, useful for dual‐modal imaging.

Gadolinium vanadate nanocrystals as carriers of α-emitters (225Ac, 227Th) and contrast agents

Gadolinium vanadate (GdVO4) core and core + 2 shell nanocrystals (NCs) were evaluated for in vitro retention of 225Ac, 227Th, and their first decay daughters, 221Fr and 223Ra, respectively. GdVO4 NCs with a tetragonal crystal system (zircon-type) and spherical morphology were obtained by precipitation of GdCl3 and Na3VO4 using sodium citrate as a complexing agent. The growth of two nonradioactive GdVO4 shells on both Gd(225Ac)VO4 and Gd(227Th)VO4 core NCs was demonstrated by an increase of 0.7 nm and 2 nm in the crystallite size, respectively. The maximum leakage of 225Ac was 15% and 2.4% from core and core + 2 shells, whereas the leakage of 227Th was 3% and 1.5%, respectively. The presence of two nonradioactive GdVO4 shells increased the retention of 221Fr and 223Ra by 20% and 15% with respect to core NCs. Furthermore, a longitudinal proton relaxivity, r1 = 0.9289 s−1 mM−1, confirmed their potential application as contrast agents for magnetic resonance imaging. In summary, GdVO4 NCs show promising capabilities as radionuclide carriers with partial retention of decay daughters and as contrast agents for theranostic applications.

Size-tunable MRI-visible nitroxide-based magnetic mixed micelles: preparation, stability, and theranostic application

Metal-free magnetic mixed micelles (mean diameter: 16 nm) composed of biocompatible surfactant Tween 80 and hydrophobic pyrrolidine-N-oxyl radical were prepared by mixing them in phosphate-buffered saline. The magnetic mixed micelles were characterized by dynamic light scattering and small angle neutron scattering measurements. The stability of the micelles is found to depend on the length of alkyl side chain in the nitroxide compounds and degree of unsaturation in the hydrophobic chain in the surfactant. The size of the mixed micelle can be tuned by changing the molar ratio of Tween 80 and nitroxyl radical. In view of theranostic application of the micelle, the cytotoxicity and stability in a physiological environment was investigated; the mixed micelle exhibited no cytotoxicity, high colloidal stability and high resistance towards reduction by large excess ascorbic acid. The in vitro and in vivo magnetic resonance imaging (MRI) revealed sufficient contrast enhancement in the proton longitudinal relaxation time (T1) weighted images. In addition, hydrophobic fluorophores and an anticancer drug are stably encapsulated in the mixed micelles and showed fluorescence (FL) upon reduction by ascorbic acid and cytotoxicity to cancer cells, respectively. For example, the paclitaxel-loaded mixed micelles efficiently suppressed cancer cell growth. Furthermore, they were found to give higher MRI contrast (higher r1 value) in vitro than the micelles without paclitaxel. The magnetic mixed micelles presented here are promising theranostic agents in nanomedicine due to their high biocompatibility and high resistivity towards reduction as well as functioning as a drug carrier in therapy and MR or FL imaging probe in diagnosis.