MRI Imaging Contrast Research Articles

Metal-Organic Framework in Pharmaceutical Drug Delivery.

Metal-organic frameworks (MOFs) are porous, crystalline materials made up of organic ligands and metal ions/metal clusters linked by coordinative bonds. This large family is becoming increasingly popular for drug delivery due to their tuneable porosity, chemical composition, size and shape, and ease of surface functionalization. There has been a growing interest over the last decades in the design of engineered MOFs with controlled sizes for a variety of biomedical applications. Starting with the MOFs classification adapted for drug delivery systems (DDSs) based on the types of constituting metals and ligands. MOFs are appealing drug delivery vehicles because of their substantial drug absorption capacity and slow-release processes, which protect and convey sensitive drug molecules to target areas. Other guest materials have been incorporated into MOFs to create MOF-composite materials, which have added additional functionalities such as externally triggered drug release, improved pharmacokinetics, and diagnostic aids. Magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that increase blood circulation time are examples of synthetically adaptable MOF-composites. By including photosensitizers, which exert lethal effects on cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2), metalorganic frameworks have been employed for photodynamic treatment (PDT) of malignancies among a multitude of nanosized therapies. Importantly, a variety of representative MOF applications are described from the perspectives of pharmaceutics, disease therapy, and advanced drug delivery systems. However, because of their weak conductivity, selectivity, and lack of modification sites, MOF materials' uses in electrochemical biosensing are restricted. MOF-based composites provide excellent electrical conductivity and robust catalytic activity by adding functionalized nanoparticles into MOF structures, which process benefits over single component MOFs.

Cuckoo search constrained gamma masking for MRI image contrast enhancement

Cuckoo search constrained gamma masking for MRI image contrast enhancement

SELF-DEPENDENT ANTITUMOR EFFECTS PRODUCED BY METAL-CONTAINING NANOPARTICLES IN IN VIVO EXPERIMENTS

At present, the scope of research of the medical and biological effects produced by metal-containing nanoparticles (NPs) is very impressive. At the same time, the vast majority of scientific research therein is carried out to cover three main areas: visualization of neoplasms (improvement of image contrast in MRI), targeted delivery of various antitumor factors (cytostatics, vaccines, etc.) and magnetic fluid hyperthermia [1–3]. In the last decade, the fourth area of exploration is forming, associated with the study of the self-dependent effects of metal-containing NPs, which can be considered as a new option in cancer immunotherapy.

Biocompatibility of Bacterial Magnetosomes as MRI Contrast Agent: A Long-Term In Vivo Follow-Up Study.

Derived from magnetotactic bacteria (MTB), magnetosomes consist of magnetite crystals enclosed within a lipid bilayer membrane and are known to possess advantages over artificially synthesized nanoparticles because of the narrow size distribution, uniform morphology, high purity and crystallinity, single magnetic domain, good biocompatibility, and easy surface modification. These unique properties have increasingly attracted researchers to apply bacterial magnetosomes (BMs) in the fields of biology and medicine as MRI imaging contrast agents. Due to the concern of biosafety, a long-term follow-up of the distribution and clearance of BMs after entering the body is necessary. In this study, we tracked changes of BMs in major organs of mice up to 135 days after intravenous injection using a combination of several techniques. We not only confirmed the liver as the well-known targeted organs of BMs, but also found that BMs accumulated in the spleen. Besides, two major elimination paths, as well as the approximate length of time for BMs to be cleared from the mice, were revealed. Together, the results not only confirm that BMs have high biocompatibility, but also provide a long-term in-vivo assessment which may further help to forward the clinical applications of BMs as an MRI contrast agent.

Alcohol-fixed specimens for high-contrast post-mortem MRI

• Increased contrast between soft tissues in MRI of alcohol-fixed specimens. • Superior contrast in MRI of methanol-fixed murine brain. • High quality MRI images of alcoholic samples by saturation of redundant NMR signals. • Formaldehyde-fixed specimens can be transferred to methanol for better MRI contrast. • Novel contrast in result of interplay of cross-links with coagulation of tissues. MRI of alcohol-fixed mouse specimens, so far unappreciated because of multiple 1 H NMR signals, should be considered as a valuable research strategy due to the possibility of obtaining images with increased contrast between the soft tissues. Moreover, the poor contrast in MRI images of specimens fixed with formaldehyde solutions can be increased by transferring the specimens to a methanol solution. In this work mice fixed with 5%-formaldehyde, 70%-ethanol, 70%-methanol solutions, and also specimen transferred from 5%-formaldehyde to 70%-methanol solution and not fixed specimens were imaged using 9.4 T MRI scanner to obtain T 1 - and T 2 -weighted images as well as T 1 and T 2 maps. For samples containing alcohol saturation of redundant (not of methyl group) 1 H NMR signals, originating from the alcohol and water present in the samples, allowed to obtain high quality MRI images. The optimal distribution of values of T 1 and T 2 was obtained for the methanol-fixed specimen, leading to high-contrast MRI images. Transferring the specimen from formaldehyde to methanol solution resulted in an unfamiliar spatial distributions of T 1 and T 2 of the brain tissues and, consequently, a novel contrast in the MRI images. Presented findings reveal hidden potential of the MRI of wet-fixed specimens.

A Physical Perspective to the Inductive Function of Myelin-A Missing Piece of Neuroscience.

Starting from the inductance in neurons, two physical origins are discussed, which are the coil inductance of myelin and the piezoelectric effect of the cell membrane. The direct evidence of the coil inductance of myelin is the opposite spiraling phenomenon between adjacent myelin sheaths confirmed by previous studies. As for the piezoelectric effect of the cell membrane, which has been well-known in physics, the direct evidence is the mechanical wave accompany with action potential. Therefore, a more complete physical nature of neural signals is provided. In conventional neuroscience, the neural signal is a pure electrical signal. In our new theory, the neural signal is an energy pulse containing electrical, magnetic, and mechanical components. Such a physical understanding of the neural signal and neural systems significantly improve the knowledge of the neurons. On the one hand, we achieve a corrected neural circuit of an inductor-capacitor-capacitor (LCC) form, whose frequency response and electrical characteristics have been validated by previous studies and the modeling fitting of artifacts in our experiments. On the other hand, a number of phenomena observed in neural experiments are explained. In particular, they are the mechanism of magnetic nerve stimulations and ultrasound nerve stimulations, the MRI image contrast issue and Anode Break Excitation. At last, the biological function of myelin is summarized. It is to provide inductance in the process of neural signal, which can enhance the signal speed in peripheral nervous systems and provide frequency modulation function in central nervous systems.

Magnetic Nanomaterials in Chinese Medicine Chemical Composition Analysis and Drug Metabolism and Its Industry Prospect and Development Path Research

The paramagnetism and superparamagnetism of magnetic nanomaterials are very important for in vivo applications. The magnetic particles with paramagnetism or superparamagnetism can redistribute the magnetic particles after the magnetic field is withdrawn, which is widely used for the separation and purification of biomolecules. At the same time, superparamagnetic particles can also be used as MRI imaging contrast agent. Compared with Western medicine, traditional Chinese medicine is different from Western medicine in that it is originated from nature and has thousands of years of clinical efficacy. Therefore, we hope to elaborate the complex mechanism of traditional Chinese medicine through some modern technical means: through the establishment of relevant quality control system, Chinese medicine will be recognized and popularized in the international field. Therefore, this paper discusses the application of magnetic nanomaterials in the chemical composition analysis and drug metabolism of traditional Chinese medicine and its industrial prospect and development path. Firstly, the advantages of magnetic nanomaterials and the shortcomings of chemical composition analysis technology of traditional Chinese medicine are analyzed theoretically. Then, through the experimental simulation, the results show that, under the optimal conditions, the magnetic nanomaterials can be used to analyze the chemical composition of traditional Chinese medicine. The peak current and concentration of THP showed a good linear relationship in the range of 5.2 × 10−8 ∼ 2.1 × 10−5 mol/L, and the detection limit was 1.9 × 10−7 mol/L. Moreover, it showed effective results in repeatability, stability, and interference tests. Therefore, magnetic nanomaterials play an important role in the chemical composition analysis and drug metabolism of traditional Chinese medicine as well as its industrial prospect and development path.

Biological Durability, Cytotoxicity and MRI Image Contrast Effects of Chitosan Modified Magnetic Nanoparticles.

In this manuscript, biological durability, cytotoxicity and MRI image contrast effect of chitosan modified magnetic nanoparticles were investigated. The result of durability study shows that the asprepared sample with average size of about 30 nm had a high stability under pH conditions in range of from 2 to 12 and at salt concentration in range of from 0 to 300 mM. The cytotoxicity testing indicates that the obtained Fe₃O₄@CS ferrofluid revealed a low cytotoxicity. After 48 h of test on the line of prostate tumor cells of Sarcoma 180, collected IC50 value was 178.5±22 (μg/ml), 7.5 to 27.9 times less cytotoxicity than that of reported ferromagnetic fluids. MRI data shows that the transverse relaxation rate (r2) of the ferrite nanoparticles was 130.32 (mM-1s-1), 2 and 1.44 times larger than that of the commercial products of Sinerem (AMI-227) and Ferumoxytol products, respectively. Invivo test in rabbit shows that the picture of body parts was clearly observed after the injection of the Fe₃O₄@CS ferrofluid. With these outstanding properties, this magnetic fluid based on the chitosan modified Fe₃O₄ nanoparticles had great potential for enhancing the image contrast in image diagnosis by MRI magnetic resonance imaging technique.

Integration of iron oxide nanoparticles and polyaspartamide biopolymer for MRI image contrast enhancement and an efficient drug-delivery system in cancer therapy

We integrate superparamagnetic iron oxide nanoparticles with polyaspartamide (PA) biopolymer to form a biological construct that functions as a tracking, targeting and drug-delivery system for cancer diagnosis and therapy. Iron oxide nanoparticles with uniformly distributed average spherical diameters of around 10 nm and superparamagnetic characteristics play a key role in increasing the transverse 1/T2 relaxation rate or darkening the T2-weighted MR image for cancer diagnosis using MRI. In in vitro MRI testing on cancer cells, the MR images of samples with the bio-constructshow a much clearer contrast effect than those of controls. The PA biopolymer plays an essential role in enhancing the hydrophilicity and biocompatibility of the bio-construct. In addition, as a multifunctional polymer, PA is conjugated with biotin and doxorubicin (Dox) functional groups to enhance targeting and impairment of cancer cells. In in vivo testing on cancer tumors, injection with the bio-construct decreased the magnitude of cancer tumor volume growth by three times compared with that of uninjected controls. The physicochemical characteristics of the bio-construct and the roles of biotin and Dox functional groups are examined and discussed in detail.

Metal-Organic Framework Composites for Theragnostics and Drug Delivery Applications.

Among a plethora of nano-sized therapeutics, metal-organic frameworks (MOFs) have been some of the most investigated novel materials for, predominantly, cancer drug delivery applications. Due to their large drug uptake capacities and slow-release mechanisms, MOFs are desirable drug delivery vehicles that protect and transport sensitive drug molecules to target sites. The inclusion of other guest materials into MOFs to make MOF-composite materials has added further functionality, from externally triggered drug release to improved pharmacokinetics and diagnostic aids. MOF-composites are synthetically versatile and can include examples such as magnetic nanoparticles in MOFs for MRI image contrast and polymer coatings that improve the blood-circulation time. From synthesis to applications, this review will consider the main developments in MOF-composite chemistry for biomedical applications and demonstrate the potential of these novel agents in nanomedicine. It is concluded that, although vast synthetic progress has been made in the field, it requires now to develop more biomedical expertise with a focus on rational model selection, a major comparative toxicity study, and advanced targeting techniques.

Targeted MR Imaging Adopting T1-Weighted Ultra-Small Iron Oxide Nanoparticles for Early Hepatocellular Carcinoma: An in vitro and in vivo Study.

Objective The purpose of this study was to produce an arginylglycylaspartic acid (RGD) peptide-modified ultra-small superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) for targeted magnetic resonance (MR) imaging of hepatocellular carcinoma (HCC) cells and verify its utility as a T1 positive MRI imaging contrast agent in vitroand in vivo.Methods The carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD nanoparticles to form a novel target contrast agent Fe3O4-PEG-RGD NPs. The specificity of Fe3O4-PEG-RGD to bind RGD receptor was investigated in vitro by HepG2 cellular uptake and cell MR imaging, and in vivo by MR imaging of subcutaneous HepG2 tumors of nude mice.Results The formed Fe3O4-PEG-RGD NPs displayed good biocompatibility, and the ultrahigh r1 relaxivity was 1.37 mM -1S -1. The synthesized Fe3O4-PEG-RGD NPs were demonstrated spherical-like with an approximate diameter of 2.7 nm in similar size. The targeting effect to HepG2 cells was confirmed by in vitro cellular uptake and cell MR imaging. The in vivo MR imaging of nude mice demonstrated that the MR signal intensity enhancement of HepG2 tumor in Fe3O4-PEG-RGD NPs treated mice was significantly higher than in mice treated with non-targeted Fe3O4-mPEG NPs at the same post-administration time point. Conclusion The results indicate that the Fe3O4-PEG-RGD particles have potential utility as T1 positive contrast agent in targeted MR imaging.

Magnetic field distribution modulation of intrathecal delivered ketorolac iron-oxide nanoparticle conjugates produce excellent analgesia for chronic inflammatory pain

BackgroundNanoparticles have become one of the most promising among the potential materials used for biomedical applications. However, few researchers have focused on their effects on analgesia. Despite the fact that various nanoparticles have been evaluated for drug delivery and MRI imaging contrast enhancement in clinical settings, no reports have investigated the in vivo synergy of ketorolac iron-oxide nanoparticle conjugates to improve the analgesic effect.MethodsKetorolac conjugated magnetic iron oxide nanoparticles (Keto-SPIO) were synthesized via two-stage additions of protective agents and chemical co-precipitation. ICR mice were used to develop inflammatory pain models induced by Complete Freund’s adjuvant (CFA) injection in the hind paw. Different magnet field strengths and polarities were applied to the spinal cord after injecting Keto-SPIO into the theca space. Analgesia behavior was evaluated with the up-down method via von Frey microfilament measurement. Spinal cord tissues were harvested at the end analgesia time point upon induction of the inflammatory pain. The presence of the two cyclooxygenases (COX) in the spinal cord was examined via Western blotting to quantify the changes after intra-thecal Keto-SPIO administration.ResultsIntrathecal Keto-SPIO administration demonstrated a magnetic field-dependent analgesia effect in CFA pain model with a significant reduction in COX expression.ConclusionsOur results indicated that intrathecal administration of the Keto-SPIO combined magnet field modulated delivery significantly promoted an analgesia effect with suppression of COX in the mice inflammatory pain model.

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast.

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

Targeted Molecular Imaging of Cancer Cells Using MS2-Based 129Xe NMR

We have synthesized targeted, selective, and highly sensitive (129)Xe NMR nanoscale biosensors using a spherical MS2 viral capsid, Cryptophane A molecules, and DNA aptamers. The biosensors showed strong binding specificity toward targeted lymphoma cells (Ramos line). Hyperpolarized (129)Xe NMR signal contrast and hyper-CEST (129)Xe MRI image contrast indicated its promise as highly sensitive hyperpolarized (129)Xe NMR nanoscale biosensor for future applications in cancer detection in vivo.

Azoimidazole functionalized Ni-porphyrins for molecular spin switching and light responsive MRI contrast agents

Azo-N-methylimidazole functionalized Ni(ii)porphyrins were rationally designed and synthesized and their performance as molecular spin switches was investigated. They perform intramolecular light-driven coordination-induced spin state switching (LD-CISSS) in the presence of water and therefore are an important step towards spin switches for medicinal applications, particularly functional MRI contrast agents.

Chemical exchange saturation transfer MRI using intermolecular double-quantum coherences with multiple refocusing pulses

Chemical exchange saturation transfer (CEST) provides a new type of image contrast in MRI. Due to the intrinsically low CEST effect, new and improved experimental techniques are required to achieve reliable and quantitative CEST images. In the present work, we proposed a novel and more sensitive CEST acquisition approach, based on the intermolecular double-quantum coherence with a module of multiple refocusing pulses (iDQC-MRP). Experiments were performed on creatine and egg white phantoms using a Varian 7T animal MRI scanner. The iDQC-MRP CEST technique showed a substantial enhancement in CEST and nuclear Overhauser enhancement (NOE) signal intensities, compared to the standard single-quantum coherence approach. In addition, the iDQC-MRP approach increased the signal-to-noise ratio of acquired saturation images, compared to the conventional iDQC approach. The new iDQC-MRP CEST sequence provides a promising way for exploiting in vivo CEST and NOE imaging applications.

Comparison of X-ray CT and MRI of watercore disorder of different apple cultivars

Watercore is an internal disorder that appears as water-soaked, glassy regions near the core in apples. Fast and non-destructive solutions for sensing watercore would be readily accepted in the postharvest industry. X-ray CT and MRI were compared as potential imaging technologies for detecting this particular disorder. After matching the 3D datasets of X-ray CT and MRI, the images that were obtained on identical fruit were compared quantitatively. Both MRI and CT were able to detect watercore, however the contrast in MRI images was superior. High-resolution micro-CT images showed the microstructural changes in watercore fruit: the intercellular spaces of the affected apple tissue are filled with water. This explained the higher density that is detected here by the X-rays and the higher water content in the MRI. Mean and variance of the frequency distribution of MRI and X-ray CT intensity appeared to be a parameter that allows the identification of healthy apples from affected fruit. Automatic image processing based on thresholding the images resulted in comparable watercore classification accuracy of up to 89% for X-ray CT and 79% for MRI data, despite the better contrast in the MRI images.

MRI of articular cartilage at microscopic resolution

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T1, T2 and T1ρ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative.

Phospholipid micelle encapsulated gadolinium oxide nanoparticles for imaging and gene delivery.

We encapsulated gadolinium oxide (Gd2O3) nanoparticles within phospholipid micelles as a novel low cytotoxic T1-weighted MRI imaging contrast agent (MGdNPs) that can also deliver small molecules such as DNA plasmids. MGdNPs show relatively good MRI relaxivity values, negligible cytotoxicity, excellent cellular uptake and expression of DNA plasmids in vivo. Biodistribution studies in mice show that intranasal and intraperitoneal administration of MGdNPs can effectively target specific organs.

Antitumor effects of the combination of magnetohydrodynamic thermochemotherapy and magnetic resonance tomography

Fe3O4 nanoparticles were coated with a layer of citric acid, forming coordination bonds between citrate ions and iron ions. The resulting aqueous citrate ferrite colloid was used as a T2-weighted MRI negative contrasting agent. Sequential i.v. doses of citrate ferrite and Magnevist led to increases in MRI image contrast for 40 h and brightness for 30 min; scanning using a Bruker Biospec BC 70/30 USR biospectrotomograph yielded enhanced MRI images. This enhancement of MRI images was used to monitor oncogenesis during magnetohydrodynamic thermochemotherapy (MT) of mammary adenocarcinoma Ca 755 in female C57Bl/6j mice. Dextran ferrite colloid containing cyclophosphamide was tested as a magnetically directed antitumor agent using MT. Treatment of non-infiltrating tumors of volume ≈ 30 mm3 with six sessions of MT each lasting 30 min at 46°C led to 40% tumor regression and 300% increases in survival time. Treatment of infiltrating tumors of volume ≈ 300 mm3 in the same conditions yielded a 200% increase in survival time.