High-performance Magnetic Resonance Imaging Research Articles

One-Pot Fabrication of Kinetically Inert Ultrasmall Manganese(II) Chelate-Backboned Polymer Contrast Agents for High-Performance Magnetic Resonance Imaging.

Traditional macromolecules or nanoscale Mn2+ chelate-based magnetic resonance imaging (MRI) contrast agents (CAs) suffer from complicated and laborious synthesis processes, relatively low kinetic stability and T1 relaxivity, limiting their clinical applications. Herein, we fabricated a series of kinetically inert Mn2+ chelate-backboned polymers, P(MnL-PEG), through a facile and one-pot polymerization process. Particularly, P(MnL-PEG)-3 demonstrates a significantly higher T1 relaxivity of 23.9 Mn mM-1 s-1 at 1.5 T than that of previously reported small molecules and macromolecules or nanoscale Mn2+ chelate-based CAs. Due to its high T1 relaxivity, extended blood circulation, hepatocyte-specific uptake, and kidneys metabolism, P(MnL-PEG)-3 presents significantly enhanced contrast in blood vessel, liver, and kidneys imaging compared to clinical Gd3+-based CAs (Gd-EOB-DTPA and Gd-DOTA) at a dosage of 0.05 mmol Mn/Gd kg-1 BW, and can accurately diagnose orthotopic H22 liver tumors in vivo in animal models. We anticipate that this work will promote the development of clinically relevant MRI CAs.

Carboxylated albumin as a dual-purpose template for fabricating gadolinium oxide nanoprobe with high metal loading and exceptional relaxivity

Biomineralization is a highly efficient approach to synthesizing magnetic resonance imaging (MRI) probes but encounters two limitations: low metal loading and insufficient sensitivity. Herein, based on the Solomon-Bloembergen-Morgan theory and hard and soft acids and bases principle, we proposed the use of fully carboxylated albumin as a dual-purpose template for fabricating gadolinium oxide (BSA-COOH-Gd2O3) nanoprobe with high metal loading and exceptional relaxivity for the first time. The proposed nanoprobe was synthesized using a straightforward one-pot method under mild conditions, exhibiting excellent biocompatibility, good water solubility, high Gd content (6 %), and outstanding relaxivity (41.17 mM-1s−1). In vivo magnetic resonance angiography (MRA) demonstrated that the BSA-COOH-Gd2O3 nanoprobe (0.05 mmol Gd/kg, equivalent to half of the clinical dose) exhibited a sustained and significantly enhanced vascular enhancement effect for at least 2 h with exceptional resolution, enabling clear visualization of vessels as small as 0.3 mm at 3.0 T and 0.13 mm at 9.4 T. Both the severity and location of vascular narrowing can be accurately identified in a carotid artery stenosis model and the tumor can be sensitively detected in a tumor model via the nanoprobe-based MRI. Our study provides an upgraded biomineralization technique for synthesizing high-performance MRI nanoprobes for various applications.

Application of Ultra-High-Field Magnetic Resonance Imaging to the Central Nervous System

The development of high-performance magnetic resonance imaging (MRI) scanners is ongoing. The strength of the magnetic field is the most important factor in the use of this technology. Ultra-high magnetic fields provide many benefits, including high spatial and temporal resolution. In this chapter, we describe the characteristics and images obtained using ultra-high-field MRI.

Fluorinated 1,7-DO2A-Based Iron(II) Complexes as Sensitive 19F MRI Molecular Probes for Visualizing Renal Dysfunction in Living Mice.

Kidney diseases have become an important global health concern due to their high incidence, inefficient diagnosis, and poor prognosis. Devising direct methods, especially imaging means, to assess renal function is the key for better understanding the mechanisms of various kidney diseases and subsequent development of effective treatment. Herein, we developed a fluorinated ferrous chelate-based sensitive probe, 1,7-DO2A-Fe(II)-F18 (Probe 1), for 19F magnetic resonance imaging (MRI). This highly fluorinated probe (containing 18 chemically equivalent 19F atoms with a fluorine content at 35 wt %) achieves a 15-time enhancement in signal intensity compared with the fluorine-containing ligand alone due to the appropriately regulated 19F relaxation times by the ferrous ion, which significantly increases imaging sensitivity and reduces acquisition time. Owing to its high aqueous solubility, biostability, and biocompatibility, this probe could be rapidly cleared by kidneys, which provides a means for monitoring renal dysfunction via 19F MRI. With this probe, we accomplish in vivo imaging of the impaired renal dysfunction caused by various kidney diseases including acute kidney injury, unilateral ureteral obstruction, and renal fibrosis at different stages. Our study illustrates the promising potential of Probe 1 for in vivo real-time visualization of kidney dysfunction, which is beneficial for the study, diagnosis, and even stratification of different kidney diseases. Furthermore, the design strategy of our probe is inspiring for the development of more high-performance 19F MRI probes for monitoring various biological processes.

On-board MRI image compression using video encoder for MR-guided radiotherapy.

Magnetic resonance imaging (MRI) is currently used for online target monitoring and plan adaptation in modern image-guided radiotherapy. However, storing a large amount of data accumulated during patient treatment becomes an issue. In this study, the feasibility to compress MRI images accumulated in MR-guided radiotherapy using video encoders was investigated. Two sorting algorithms were employed to reorder the slices in multiple MRI sets for the input sequence of video encoder. Three cropping algorithms were used to auto-segment regions of interest for separate data storage. Four video encoders, motion-JPEG (M-JPEG), MPEG-4 (MP4), Advanced Video Coding (AVC or H.264) and High Efficiency Video Coding (HEVC or H.265) were investigated. The compression performance of video encoders was evaluated by compression ratio and time, while the restoration accuracy of video encoders was evaluated by mean square error (MSE), peak signal-to-noise ratio (PSNR), and video quality matrix (VQM). The performances of all combinations of video encoders, sorting methods, and cropping algorithms were investigated and their effects were statistically analyzed. The compression ratios of MP4, H.264 and H.265 with both sorting methods were improved by 26% and 5%, 42% and 27%, 72% and 43%, respectively, comparing to those of M-JPEG. The slice-prioritized sorting method showed a higher compression ratio than that of the location-prioritized sorting method for MP4 (P=0.00000), H.264 (P=0.00012) and H.265 (P=0.00000), respectively. The compression ratios of H.265 were improved significantly with the applications of morphology algorithm (P=0.01890 and P=0.00530), flood-fill algorithm (P=0.00510 and P=0.00020) and level-set algorithm (P=0.02800 and P=0.00830) for both sorting methods. Among the four video encoders, H.265 showed the best compression ratio and restoration accuracy. The compression ratio and restoration accuracy of video encoders using inter-frame coding (MP4, H.264 and H.265) were higher than that of video encoders using intra-frame coding (M-JPEG). It is feasible to implement video encoders using inter-frame coding for high-performance MRI data storage in MR-guided radiotherapy.

Magnetic Nanoparticle-Based High-Performance Positive and Negative Magnetic Resonance Imaging Contrast Agents.

In recent decades, magnetic nanoparticles (MNPs) have attracted considerable research interest as versatile substances for various biomedical applications, particularly as contrast agents in magnetic resonance imaging (MRI). Depending on their composition and particle size, most MNPs are either paramagnetic or superparamagnetic. The unique, advanced magnetic properties of MNPs, such as appreciable paramagnetic or strong superparamagnetic moments at room temperature, along with their large surface area, easy surface functionalization, and the ability to offer stronger contrast enhancements in MRI, make them superior to molecular MRI contrast agents. As a result, MNPs are promising candidates for various diagnostic and therapeutic applications. They can function as either positive (T1) or negative (T2) MRI contrast agents, producing brighter or darker MR images, respectively. In addition, they can function as dual-modal T1 and T2 MRI contrast agents, producing either brighter or darker MR images, depending on the operational mode. It is essential that the MNPs are grafted with hydrophilic and biocompatible ligands to maintain their nontoxicity and colloidal stability in aqueous media. The colloidal stability of MNPs is critical in order to achieve a high-performance MRI function. Most of the MNP-based MRI contrast agents reported in the literature are still in the developmental stage. With continuous progress being made in the detailed scientific research on them, their use in clinical settings may be realized in the future. In this study, we present an overview of the recent developments in the various types of MNP-based MRI contrast agents and their in vivo applications.

Susceptibility-weighted imaging at high-performance 0.5T magnetic resonance imaging system: Protocol considerations and experimental results.

The high-performance low-field magnetic resonance imaging (MRI) system, equipped with modern hardware and contemporary imaging capabilities, has garnered interest within the MRI community in recent years. It has also been proven to have unique advantages over high-field MRI in both physical and cost aspects. However, for susceptibility weighted imaging (SWI), the low signal-to-noise ratio and the long echo time inherent at low field hinder the SWI from being applied to clinical applications. This work optimized the imaging protocol to select suitable parameters such as the values of time of echo (TE), repetition time (TR), and the flip angle (FA) of the RF pulse according to the signal simulations for low-field SWI. To improve the signal-to-noise ratio (SNR) performance, averaging multi-echo magnitude images and BM4D phase denoising were proposed. A comparison of the SWI in 0.5T and 1.5T was carried out, demonstrating the capability to identify magnetic susceptibility differences between variable tissues, especially, the blood veins. This would open the possibility to extend SWI applications in the high-performance low field MRI.

Gadolinium-Coated Mesoporous Silica Nanoparticle for Magnetic Resonance Imaging.

Magnetic resonance molecular imaging can provide anatomic, functional and molecular information. However, because of the intrinsically low sensitivity of magnetic resonance imaging (MRI), high-performance MRI contrast agents are required to generate powerful image information for image diagnosis. Herein, we describe a novel T 1 contrast agent with magnetic-imaging properties facilitated by the gadolinium oxide (Gd2O3) doping of mesoporous silica nanoparticles (MSN). The size, morphology, composition, MRI relaxivity (r 1 ), surface area and pore size of these nanoparticles were evaluated following their conjugation with Gd2O3 to produce Gd2O3@MSN. This unique structure led to a significant enhancement in T 1 contrast with longitudinal relaxivity (r 1 ) as high as 51.85 ± 1.38 mM−1s−1. Gd2O3@MSN has a larger T 1 relaxivity than commercial gadolinium diethylene triamine pentaacetate (Gd-DTPA), likely due to the geometrical confinement effect of silica nanoparticles. These results suggest that we could successfully prepare a novel high-performance T 1 contrast agent, which may be a potential candidate for in-vivo MRI.

Fabrication of magnetic nanoprobes for ultrahigh-field magnetic resonance imaging.

Ultrahigh-field magnetic resonance imaging (UHF-MRI) has been attracting tremendous attention in biomedical imaging owing to its high signal-to-noise ratio, superior spatial resolution, and fast imaging speed. However, at UHF-MRI, there is a lack of proper imaging probes that can impart superior imaging sensitivity of disease lesions because conventional contrast agents generally produce pronounced susceptibility artifacts and induce very strong T2 decay effects, thus hindering satisfactory imaging performance. This review focused on the recent development of high-performance nanoprobes that can improve the sensitivity and specificity of UHF-MRI. Firstly, the contrast enhancement mechanism of nanoprobes at UHF-MRI has been elucidated. In particular, the strategies for modulating nanoprobe performance, including size effects, metal alloying and magnetic-dopant effects, surface effects, and stimuli-response regulation, have been comprehensively discussed. Furthermore, we illustrate the remarkable advances in the design of UHF-MRI nanoprobes for medical diagnosis, such as early-stage primary tumor and metastasis imaging, angiography, and dynamic monitoring of biosignaling factors in vivo. Finally, we provide a summary and outlook on the development of cutting-edge UHF-MRI nanoprobes for advanced biomedical imaging.

Conceptual Design of 3-T All HTS MRI Using No-Insulation Winding Technology: Electromagnetic Stress Reinforced Structure

Once the miniaturization of high-performance magnetic resonance imaging (MRI) scanner was accomplished, extremely stringent indexes were needed for the magnetic field, the operational stability and mechanical strength. We adopted “No-insulation (NI) winding technology” to build high-temperature superconducting (HTS) magnets for 3-T grade MRI, in order to achieve these stringent indexes. To realize a compact size of 3-T MRI, the electromagnetic stress of HTS magnet becomes a technical challenge. In this paper, we investigated the construction of an electromagnetic stress reinforced structure for HTS magnets of 3-T MRI. First, the electromagnetic force was estimated, and the distributions of stress and strain induced by electromagnetic force in the winding part of the HTS magnet were reproduced using a finite element analysis. Meanwhile, the influences of the interlayers between sub-coils, shells and blind flanges on the stress property of HTS magnet were evaluated. Based on these results, the material and its consumed volume established the reinforced structure employed of the HTS magnet were also clarified. Finally, the utility of reinforced structure was verified for NI HTS magnets deployed in 3-T MRI.

Rational Constructed Ultra-Small Iron Oxide Nanoprobes Manifesting High Performance for T1-Weighted Magnetic Resonance Imaging of Glioblastoma.

Precise diagnosis and monitoring of cancer depend on the development of advanced technologies for in vivo imaging. Owing to the merits of outstanding spatial resolution and excellent soft-tissue contrast, the application of magnetic resonance imaging (MRI) in biomedicine is of great importance. Herein, Angiopep-2 (ANG), which can simultaneously help to cross the blood-brain barrier and target the glioblastoma cells, was rationally combined with the 3.3 nm-sized ultra-small iron oxide (Fe3O4) to construct high-performance MRI nanoprobes (Fe3O4-ANG NPs) for glioblastoma diagnosis. The in vitro experiments show that the resultant Fe3O4-ANG NPs not only exhibit favorable relaxation properties and colloidal stability, but also have low toxicity and high specificity to glioblastoma cells, which provide critical prerequisites for the in vivo tumor imaging. Furthermore, in vivo imaging results show that the Fe3O4-ANG NPs exhibit good targeting ability toward subcutaneous and orthotopic glioblastoma model, manifesting an obvious contrast enhancement effect on the T1-weighted MR image, which demonstrates promising potential in clinical application.

Dynamically switchable magnetic resonance imaging contrast agents.

Contrast agents can improve the sensitivity and resolution of magnetic resonance imaging (MRI) by accelerating the relaxation times of surrounding water protons. The MRI performances of contrast agents are closely related to their structural characteristics, including size, shape, surface modification, and so on. Recently, dynamically switchable MRI contrast agents that can undergo structural changes and imaging functional activations upon reaching the disease microenvironment have been developed for high performance MRI. This perspective highlights the ingenious design, controllable structural transformation, and tunable imaging property of dynamic MRI contrast agents. Additionally, the current challenges of the dynamic MRI contrast agents for medical diagnosis are discussed. Furthermore, the future integration of high-resolution ultra-high field MRI technology and cutting-edge dynamic MRI contrast agents for non-invasive histopathological level accurate detection of microscopic lesions are commented.

Low-Field Magnetic Resonance Imaging: Its History and Renaissance.

Low-field magnetic resonance imaging (MRI) systems have seen a renaissance recently due to improvements in technology (both hardware and software). Originally, the performance of low-field MRI systems was rated lower than their actual clinical usefulness, and they were viewed as low-cost but poorly performing systems. However, various applications similar to high-field MRI systems (1.5 T and 3 T) have gradually become possible, culminating with high-performance low-field MRI systems and their adaptations now being proposed that have unique advantages over high-field MRI systems in various aspects. This review article describes the physical characteristics of low-field MRI systems and presents both their advantages and disadvantages for clinical use (past to present), along with their cutting-edge clinical applications.

Low-Field Magnetic Resonance Imaging: A New Generation of Breakthrough Technology in Clinical Imaging.

Magnetic resonance imaging (MRI) plays a pivotal role in diagnostic imaging. In today's clinical environment, scanners with field strengths of 1.5 to 3 T are most commonly used. However, recent technological advancements might help to augment the clinical usage and availability of MRI via the introduction of high-performance low-field MRI systems (ranging from ~0.1-0.55 T in current systems). The combination of low field strength and high-performance hardware is characterized by increased flexibility, excellent quality of results, and reduced cost. This review discusses the multifaceted potential advantages of a new generation of high-performance low-field MRI systems and presents the potential impact of such systems in terms of socioeconomic benefits as well as positive effects on patient care.

A design strategy of ultrasmall Gd2O3 nanoparticles for T1 MRI with high performance

Proposing a design strategy of Gd3+ based nanoparticles for high performance magnetic resonance imaging.

Improving the sensitivity of T1 contrast-enhanced MRI and sensitive diagnosing tumors with ultralow doses of MnO octahedrons.

Rationale: Sensitive and accurate imaging of cancer is essential for early diagnosis and appropriate treatment. For generally employed magnetic resonance imaging (MRI) in clinic, comprehending how to enhance the contrast effect of T1 imaging is crucial for improving the sensitivity of cancer diagnosis. However, there is no study ever to reveal the clear mechanism of how to enhance the effect of T1 imaging and accurate relationships of influencing factors. Herein, this study aims to figure out key factors that affect the sensitivity of T1 contrast-enhanced MRI (CE-MRI), thereby to realize sensitive detection of tumors with low dose of CAs.Methods: Manganese oxide (MnO) nanoparticles (NPs) with various sizes and shapes were prepared by thermal decomposition. Factors impacting T1 CE-MRI were investigated from geometric volume, surface area, crystal face to r2/r1 ratio. T1 CE-MR imaging of liver, hepatic and subcutaneous tumors were conducted with MnO NPs of different shapes.Results: The surface area and occupancy rate of manganese ions have positive impacts on the sensitivity of T1 CE-MRI, while volume and r2/r1 ratio have negative effects. MnO octahedrons have a high r1 value of 20.07 mM-1s-1 and exhibit an excellent enhanced effect in liver T1 imaging. ZDS coating facilitates tumor accumulation and cellular uptake, hepatic and subcutaneous tumors could be detected with MnO octahedrons at an ultralow dose of 0.4 mg [Mn]/kg, about 1/10 of clinical dose.Conclusions: This work is the first quantitative study of key factors affecting the sensitivity of T1 CE-MRI of MnO nanoparticles, which can serve as a guidance for rational design of high-performance positive MRI contrast agents. Moreover, these MnO octahedrons can detect hepatic and subcutaneous tumors with an ultralow dose, hold great potential for sensitive and accurate diagnosis of cancer with lower cost, less dosages and side effects in clinic.

Lanthanide-Activated Nanoparticles: A Toolbox for Bioimaging, Therapeutics, and Neuromodulation.

Owing to their unique features, the past decade has witnessed rapid developments of lanthanide-activated nanoparticles for biological applications. These include highly tunable upconverting and downshifting photoluminescence when illuminated in deep tissue, excellent photostability against blinking and bleaching effects, biocompatibility through versatile surface modification, and ease of achieving multifunctionality, as well as satisfactory signal output. These attributes make lanthanide-doped nanoparticles an ideal toolbox for advanced bioimaging and next-generation therapeutics.The interest in lanthanide-doped nanoparticles for biomedical research arises from their unique optical properties in response to deep-tissue-penetrable light sources. Upon near-infrared irradiation, these nanoparticles with properly doped emitters display photon upconversion with large anti-Stokes shifts and broad-spectrum tunability from the ultraviolet to the visible. It is also possible to achieve orthogonal photoluminescence with variations in wavelength and lifetime. Coupled with surface ligands, dyes, biomolecules, or other types of functional nanomaterials, lanthanide-doped nanoparticles offer new opportunities for applications in bioimaging, advanced oncotherapy, and neuromodulation. Given the possibility of locating downshifting luminescence at "biological transmission windows", exquisite design of lanthanide-doped nanoparticles also enables deep-tissue imaging with high spatial resolution. In addition, these nanoparticles can respond to high-energy photons, such as X-rays, to trigger nonradioactive and radiative pathways, making it possible to develop high-sensitivity X-ray detectors. Precise control of paramagnetic lanthanide ions in nanocrystal lattices also provides advanced materials for high-performance magnetic resonance imaging in medical diagnostics and biomedical research. Full consideration of fundamental attributes of lanthanide-doped nanoparticles will facilitate the design of multifunctional and sensitive probes and improve diagnostic and therapeutic outcomes.In this Account, we categorize various lanthanide-activation strategies into three modes: near-infrared excitation, X-ray irradiation, and magnetic field stimulation. We introduce energy manipulations in upconverting, downshifting, and persistence luminescence in spectral and time domains and discuss how they can be applied in biological practices. We assess general design principles for lanthanide-activated nanosystems with multiple modalities of bioimaging, oncotherapy, and neuromodulation. We also review the current state-of-the-art in the field of lanthanide-based theranostic nanoplatforms, with particular emphasis on energy conversion and nano-/biointerfacing as well as emerging bioapplications. In this context, we also highlight recent advances in controlling optical properties of nanoplatforms for single- or multimodal bioimaging, stimulus-responsive phototherapy, and optogenetics. Finally, we discuss future opportunities and challenges of this exciting research field.

Superhydrophilic fluorinated polymer and nanogel for high-performance 19F magnetic resonance imaging

19F magnetic resonance imaging (19F MRI), a kind of non-invasive and non-radioactive diagnostic technique with no endogenous background signals, opens up new research avenues for accurate molecular imaging studies. However, 19F MRI is manily limited by the performance of contrast agents. Here, for the first time, we presented the zwitterionic fluorinated polymer and nanogel as new types of superhydrophilic, sensitive and ultra-stable 19F MRI contrast agents. The superhydrophilicity of carboxybetaine zwitterionic structure completely overcame the hydrophobic aggregation-induced signal attenuation associated with amphiphilic fluorinated polymer-based nanoprobes. In addition, the superhydrophilic contrast agent exhibited distinct advantages, including high 19F-content (19.1 wt%), superior resistance to protein adsorption, constant MR properties and 19F MRS-based quantitative determination in complex biological fluids, and intense 19F MRI signals in the whole-body images after intravenous injection. In combination with angiogenesis targeting ligand, the superhydrophilic contrast agent was applied for the unambiguous detection of tumor. Importantly, computational algorithm was established for the directly quantitative determination of bioavailability and tumor-to-whole body ratio (TBR) from the in vivo19F MRI dataset, providing real-time information with non-invasive manner. Finally, crosslinked nanogels were developed with significantly prolonged systemic circulation, of which intense 19F MRI signals nonspecifically distributed in the aortaventralis and blood-rich organs, instead of being trapped steadily in liver as with the state-of-the-art superhydrophobic perfluocarbon nanoemulsions. Overall, this kind of superhydrophilic, zwitterionic fluorinated polymer and nanogel could be defined as a new generation of high-performance 19F MRI contrast agents, which hold great potential for image-based unambiguous disease detection and computational quantification.

Recombinant Silk Hydrogel as a Novel Dermal Filler Component: Preclinical Safety and Efficacy Studies of a New Class of Tissue Fillers.

Hyaluronic acid-based tissue fillers are commonly utilized in reconstructive surgery as well as for aesthetic augmentation. A new type of recombinant silk-based tissue filler might pose a beneficial alternative for surgeons and patients. The aim of this study was to compare injectability, reshaping, tolerability, and postimplantation behavior of dermal filler preparations containing recombinant silk hydrogel with a commercially available hyaluronic acid filler in 2 different animal models. Recombinant silk hydrogel as standalone preparation or as a mixture with commercial stabilized hyaluronic acid was tested in rodent and porcine animal models. The preparations were analyzed in detail and administered subdermally followed by clinical, volumetric, and histological monitoring of the subdermal depots over several months. Applicability, dosing, and tissue distribution of the filler preparations were facilitated in the presence of silk hydrogel. No clinical complications attributable to tissue filler application were recorded. State-of-the art methods, such as high-performance magnetic resonance imaging, were applied successfully to monitor the volumetric development of the filler depots in live animals. The preclinical data demonstrate the basic suitability of recombinant silk hydrogel as safe and convenient tissue filler ingredient. Due to its shear thinning properties, recombinant silk hydrogel has the potential for less painful application, comfortable aesthetic reshaping immediately after administration, and negligible postoperative discomfort.

Harnessing Surface Plasmons for Magnetic Resonance Imaging Applications

Metamaterials have great potential to control near-field electromagnetic response at will. Lately metamaterial-based devices have been used to manipulate the rf magnetic field in magnetic resonance imaging (MRI) via Fabry-Perot resonances or subdiffraction lenses. This work shows that a negative-permeability metamaterial incorporated into an MRI setup supports magnetic surface plasmons, allowing local boosting of the magnetic field and an improved signal-to-noise ratio. These results could pave the way for high-performance MRI systems.