MR Agents Research Articles

Characteristics of trauma patients with multidrug-resistant bacteria from an epidemiological, clinical, and microbiological perspective

Trauma, healthcare-associated infections, and antimicrobial resistance are three major public health issues worldwide due to the high probability of patient morbidity and, ultimately, a tragic outcome. In the current study included all patients admitted to The NRI Medical College Hospital, (Mangalagiri, Andhra Pradesh, India) intensive care units between May 1, 2021 and August 31, 2022. Patients with first bacteremia were found to have MRSA, VRE, and carbapenem-resistant Gram-negative bacteria. We included 1528 patients, 302 of whom had trauma and 66 (4.3%) of whom had MR-agent-induced bacteremia. Mechanical ventilation, renal replacement therapy, and surgery were all independent risk factors for MR agent bacteremia. In the trauma cohort, haemodialysis alone was associated with an increased risk of MR agent bacteremia. S. aureus, MRSA (n=27), and K. pneumoniae (n=26) were the two most common isolating agents. The blaKPC gene was found in 83% of the K. pneumoniae strains (while the NDM gene was found in only one). Injuries have no effect on the development of bacteremia caused by MR agents. Certain risk factors appear to be associated with the severity of MR bacteremia cases. 

Fluorescent Probes Based on AIEgen‐Mediated Polyelectrolyte Assemblies for Manipulating Intramolecular Motion and Magnetic Relaxivity

AbstractUniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity‐driven assembling strategy not only restricts the intramolecular motion‐induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation‐induced emission luminogen (AIEgen)‐mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique “soft” inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio‐temporal MRI‐guided high‐efficient PTT.

Fluorescent Probes Based on AIEgen-Mediated Polyelectrolyte Assemblies for Manipulating Intramolecular Motion and Magnetic Relaxivity.

Uniting photothermal therapy (PTT) with magnetic resonance imaging (MRI) holds great potential in nanotheranostics. However, the extensively utilized hydrophobicity-driven assembling strategy not only restricts the intramolecular motion-induced PTT, but also blocks the interactions between MR agents and water. Herein, we report an aggregation-induced emission luminogen (AIEgen)-mediated polyelectrolyte nanoassemblies (APN) strategy, which bestows a unique "soft" inner microenvironment with good water permeability. Femtosecond transient spectra verify that APN well activates intramolecular motion from the twisted intramolecular charge transfer process. This de novo APN strategy uniting synergistically three factors (rotational motion, local motion, and hydration number) brings out high MR relaxivity. For the first time, APN strategy has successfully modulated both intramolecular motion and magnetic relaxivity, achieving fluorescence lifetime imaging of tumor spheroids and spatio-temporal MRI-guided high-efficient PTT.

Mutual promotion of oxidative stress amplification and calcium overload by degradable spatially selective self-cascade catalyst for synergistic tumor therapy

A safe and degradable space-selective multifunctional nanocatalyst-CMFO reaches self-cascade catalysis to mutually promote oxidative stress amplification and calcium overload for synergistic tumor therapy with MRI guide. • A degradable spatially selective theranostic agent-CMFO was successfully prepared. • The CMFO attenuates tumor hypoxia and depletes glutathione to amplify the oxidative stress. • The generated Ca 2+ and ·OH mutually promote intracellular accumulation and lead enhanced therapeutic effect. • CMFO has high biosafety and can be used as a MR agent. The insufficient H 2 O 2, hypoxia and GSH overexpression in tumor microenvironment led to the strong tolerance of cancer cells to various ROS treatments and seriously restrict their therapeutic effect. Hereby, we fabricated a degradable spatially selective multifunctional nanocatalyst-CMFO to synergistically amplify oxidative stress and overload calcium for tumor treatment. The CMFO was constituted by MnFe 2 O 4 nanoparticles as a protective umbrella to coat CaO 2 , which is stable in normal tissues and leads to specific self-cascade catalytic reaction after accumulation in tumor sites. The nano-CaO 2 releases abundant Ca 2+ and sufficient H 2 O 2 , and Mn/Fe ions released from MnFe 2 O 4 catalyze H 2 O 2 into toxic ·OH. MnFe 2 O 4 and H 2 O 2 can also attenuate tumor hypoxia and deplete intracellular reductant-glutathione (GSH), amplifying the oxidative stress and enhancing ROS-related treatment. More importantly, the generated Ca 2+ and ·OH mutually promote their intracellular accumulation by calcium channels and mitochondria, leading enhanced apoptosis of tumor cells. In addition, CMFO can be used as MR agent to identify tumors and monitor the treatment process. Thus, the as-prepared intelligent biodegradable CMFO provides a novel solution for tumor-specific ROS-related treatment and opens a new door for spatially selective self-cascade synergistic therapy.

State-of-the-art accounts of hyperpolarized 15N-labeled molecular imaging probes for magnetic resonance spectroscopy and imaging.

Hyperpolarized isotope-labeled agents have significantly advanced nuclear magnetic resonance spectroscopy and imaging (MRS/MRI) of physicochemical activities at molecular levels. An emerging advance in this area is exciting developments of 15N-labeled hyperpolarized MR agents to enable acquisition of highly valuable information that was previously inaccessible and expand the applications of MRS/MRI beyond commonly studied 13C nuclei. This review will present recent developments of these hyperpolarized 15N-labeled molecular imaging probes, ranging from endogenous and drug molecules, and chemical sensors, to various 15N-tagged biomolecules. Through these examples, this review will provide insights into the target selection and probe design rationale and inherent challenges of HP imaging in hopes of facilitating future developments of 15N-based biomedical imaging agents and their applications.

Molecular magnetic resonance imaging of Alpha-v-Beta-3 integrin expression in tumors with ultrasound microbubbles

Microbubbles (MB) are used as ultrasound (US) contrast agents and can be efficiently targeted against markers of angiogenesis and inflammation. Due to their gas core, MB locally alter susceptibilities in magnetic resonance imaging (MRI), but unfortunately, the resulting contrast is low and not sufficient to generate powerful molecular MRI probes. Therefore, we investigated whether a potent molecular MR agent can be generated by encapsulating superparamagnetic iron oxide nanoparticles (SPION) in the polymeric shell of poly (n-butylcyanoacrylate) (PBCA) MB and targeted them against αvβ3 integrins on the angiogenic vasculature of 4T1 murine breast carcinomas. SPION-MB consist of an air core and a multi-layered polymeric shell enabling efficient entrapment of SPION. The mean size of SPION-MB was 1.61 ± 0.32 μm. Biotin-streptavidin coupling was employed to functionalize the SPION-MB with cyclic RGDfK (Arg-Gly-Asp) and RADfK (Arg-Ala-Asp) peptides. Cells incubated with RGD-SPION-MB showed enhanced transverse relaxation rates compared with SPION-MB and blocking αvβ3 integrin receptors with excess free cRGDfK significantly reduced RGD-SPION-MB binding. Due to the fast binding of RGD-SPION-MB in vivo, dynamic susceptibility contrast MRI was employed to track their retention in tumors in real-time. Higher retention of RGD-SPION-MB was observed compared with SPION-MB and RAD-SPION-MB. To corroborate our MRI results, molecular US was performed the following day using the destruction-replenishment method. Both imaging modalities consistently indicated higher retention of RGD-SPION-MB in angiogenic vessels compared with SPION-MB and RAD-SPION-MB. Competitive blocking experiments in mice further confirmed that the binding of RGD-SPION-MB to αvβ3 integrin receptors is specific. Overall, this study demonstrates that RGD-SPION-MB can be employed as molecular MR/US contrast agents and are capable of assessing the αvβ3 integrin expression in the neovasculature of malignant tumors.

Elastin-specific MRI of extracellular matrix-remodelling following hepatic radiofrequency-ablation in a VX2 liver tumor model

Hepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x − 1.8, R2 = 0.89, p < 0.05) and gadolinium concentrations at inductively coupled mass spectroscopy (ICP-MS, y = 0.04x + 1.2, R2 = 0.95, p < 0.05). Laser-ICP-MS confirmed colocalization of elastin-specific probe with elastic fibers. Following thermal ablation, molecular imaging using an elastin-specific MR probe is feasible and provides a quantifiable biomarker for the assessment of the ablation-induced remodeling of the ECM in the periablational rim.

Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC.ResultsHerein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast.ConclusionsThe results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.

A Multimodal Ca(II) Responsive Near IR-MR Contrast Agent Exhibiting High Cellular Uptake.

Ca(II) ions are critical for the proper function of neurons by contributing to synaptic signaling and regulating neuronal plasticity. Dysregulation of Ca(II) is associated with a number of pathologies that cause neurodegeneration; therefore the ability to monitor Ca(II) intracellularly is an important target for molecular imaging. Contrast-enhanced MR imaging is a promising modality for imaging changes in Ca(II) concentrations.However, the majority of Ca(II) responsive MR agents are limited to the extracellular space or hindered by poor cellular uptake. Here, we describe a new class of multimodal, bioresponsive Ca(II) magnetic resonance agents that are coupled to the NIR probe IR-783. This new design is based on previous generations of our Ca(II) MR agents but overcomes two significant challenges: (1) the presence of the NIR probe dramatically increases cellular uptake of the agent and (2) provides histological validation of the MR signal using NIR fluorescence imaging. IR-783 targets organic anion transporter polypeptides, and we demonstrate that the agents are not toxic in HT-22 or U-87 MG cells up to 20 μM. The cellular uptake of complex 1 was measured to be greater than 16 femtomoles per cell (where ∼1 femtomole/cell is detectable in acquired MR images). Complex 1 is simultaneously detectable by both MR and NIR fluorescence imaging in vitro and is activated (turned on) by intracellular Ca(II) at concentrations between 1 and 10 μM.

Self-Immolative Activation of β-Galactosidase-Responsive Probes for In Vivo MR Imaging in Mouse Models.

Our lab has developed a new series of self-immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β-galactosidase (β-gal). We investigated two molecular architectures to create agents that detect β-gal activity by modulating the coordination of water to GdIII . The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the GdIII ion. This renders the agent ineffective. We show that one agent in particular (6-C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β-gal.

Self‐Immolative Activation of β‐Galactosidase‐Responsive Probes for In Vivo MR Imaging in Mouse Models

AbstractOur lab has developed a new series of self‐immolative MR agents for the rapid detection of enzyme activity in mouse models expressing β‐galactosidase (β‐gal). We investigated two molecular architectures to create agents that detect β‐gal activity by modulating the coordination of water to GdIII. The first is an intermolecular approach, wherein we designed several structural isomers to maximize coordination of endogenous carbonate ions. The second involves an intramolecular mechanism for q modulation. We incorporated a pendant coordinating carboxylate ligand with a 2, 4, 6, or 8 carbon linker to saturate ligand coordination to the GdIII ion. This renders the agent ineffective. We show that one agent in particular (6‐C pendant carboxylate) is an extremely effective MR reporter for the detection of enzyme activity in a mouse model expressing β‐gal.

Socio-Demographic Aspects of Complicated Induced Abortions

Worldwide millions of women seek induced abortion. When successful and complete, it remains secret and if complicated gets highlighted. Hospital data represents a tip of the ice berg. It is an important cause of maternal morbidity and mortality but is preventable. This study was done to have a view to some socio-demographic aspects of induced abortion. This study was conducted from January 2012 to July 2012. Patients admitted with illegal induced abortion (N=50) were included in this study. Patients with spontaneous abortions were excluded. Data was collected using pre-designed data collection sheet and were expressed as actual number and percentage. Age range was 15-45 years with maximum incidence in 25-35 years. Peri-urban &amp; rural area were the maximum habitat. Majority patients and their husbands were illiterate or only had primary level education. Most of them were housewives and majority of their husbands were day laborers or small-business holders. Most of their knowledge about different contraceptives was poor and knowledge of MR services was uncertain or none. 96% of their pregnancies were unwanted. Abortions were induced at local clinic, at own residences or at inducers’ residence. Methods of abortion induction were MR, drugs or herbal agents. Abortions were induced by nurse, respondents herself, ‘dai’ or by midwives; none by physician or well trained personnel. One (2%) patient died due to haemorrhage and sepsis. Rural, illiterate persons of our community with little or poor knowledge of family planning services are at risk of having unwanted pregnancy. And, poor knowledge regarding MR or related facilities, as well as legal restriction provokes them to induce abortions by poorly trained personnel and thereby endangering their lives.&#x0D; TAJ 2018; 31(2): 63-67

Facile synthesis of Silicon quantum dot-Gadolinium: A potential fluorescent/T1-T2 multimodal imaging agent

Highly stable and multifunctional fluorescent quantum dots are particularly attractive in practical applications. Here, a new kind of ultra-small-sized silicon quantum dot-gadolinium (SiQD-Gd) was successfully fabricated by a newly-designed facile hydrothermal growth and chelating method. The obtained SiQD-Gd exhibited outstanding water dispersibility, stability and good fluorescent property with the quantum yield of 11.6%. SiQD-Gd displayed a low cytotoxicity in normal cell lines (HELF, HEK293F) and tumor cell lines (H1299, A549). Meanwhile, SiQD-Gd showed excellent magnetic resonance response with r1 relaxation rate of 10.5 mmol L−1·s−1 and r2 relaxation rate of 47.5 mmol L−1·s−1, which are 2.5 and 7.4 times enhanced comparing to that of the commercial MR agent Magnevist. In vivo studies showed significant contrast enhancement effect of its T1- and T2-weighted MR imaging. In addition, in vivo fluorescent imaging for mice and zebrafish indicated its potential applications in fluorescent tracking. Thus, the excellent multimodal imaging capacity and biocompatibility of SiQD-Gd make it a potential imaging agent for clinic applications.

Hybrid, metal oxide-peptide amphiphile micelles for molecular magnetic resonance imaging of atherosclerosis

BackgroundAtherosclerosis, a major source of cardiovascular disease, is asymptomatic for decades until the activation of thrombosis and the rupture of enlarged plaques, resulting in acute coronary syndromes and sudden cardiac arrest. Magnetic resonance imaging (MRI) is a noninvasive nuclear imaging technique to assess the degree of atherosclerotic plaque with high spatial resolution and excellent soft tissue contrast. However, MRI lacks sensitivity for preventive medicine, which limits the ability to observe the onset of vulnerable plaques. In this study, we engineered hybrid metal oxide-peptide amphiphile micelles (HMO-Ms) that combine an inorganic, magnetic iron oxide or manganese oxide inner core with organic, fibrin-targeting peptide amphiphiles, consisting of the sequence CREKA, for potential MRI imaging of thrombosis on atherosclerotic plaques.ResultsHybrid metal oxide-peptide amphiphile micelles, consisting of an iron oxide (Fe-Ms) or manganese oxide (Mn-Ms) core with CREKA peptides, were self-assembled into 20–30 nm spherical nanoparticles, as confirmed by dynamic light scattering and transmission electron microscopy. These hybrid nanoparticles were found to be biocompatible with human aortic endothelial cells in vitro, and HMO-Ms bound to human clots three to five times more efficiently than its non-targeted counterparts. Relaxivity studies showed ultra-high r2 value of 457 mM−1 s−1 and r1 value of 0.48 mM−1 s−1 for Fe-Ms and Mn-Ms, respectively. In vitro, MR imaging studies demonstrated the targeting capability of CREKA-functionalized hybrid nanoparticles with twofold enhancement of MR signals.ConclusionThis novel hybrid class of MR agents has potential as a non-invasive imaging method that specifically detects thrombosis during the pathogenesis of atherosclerosis.

Phenols as Diamagnetic T2 -Exchange Magnetic Resonance Imaging Contrast Agents.

Although T2 -exchange (T2ex ) NMR phenomena have been known for decades, there has been a resurgence of interest to develop T2ex MRI contrast agents. One indispensable advantage of T2ex MR agents is the possibility of using non-toxic and/or bio-compatible diamagnetic compounds with intermediate exchangeable protons. Herein a library of phenol-based compounds is screened and their T2ex contrast (exchange relaxivity, r2ex ) at 9.4 T determined. The T2ex contrast of phenol protons allows direct detection by MRI at a millimolar concentration level. The effect of chemical modification of the phenol on the T2ex MRI contrast through modulation of exchange rate and chemical shift was also studied and provides a guideline for use of endogenous and exogenous phenols for T2ex MRI contrast. As a proof-of-principle application, phenol T2ex contrast can be used to detect enzyme activity in a tyrosinase-catalyzed catechol oxidation reaction.

A unique nanogel-based platform for enhanced dual mode tumor MR/CT imaging.

We develop a convenient approach to loading both gold nanoparticles (AuNPs) and gadolinium (Gd) within alginate nanogels (AG NGs) for enhanced tumor dual-modal MR/CT imaging applications. In this study, polyethyleneimine (PEI) partially modified with polyethylene glycol (PEG) was used to entrap AuNPs and load gadolinium via chelation. The formed PEI-Au-Gd NPs were used as a crosslinker to crosslink AG NGs with activated carboxyl groups obtained through a double emulsion process. The formed hybrid NGs (AG/PEI-Au-Gd NGs) having a size of 83 ± 21 nm exhibit excellent colloidal stability in aqueous solution and good cytocompatibility in the studied concentration range. In particular, the AG/PEI-Au-Gd NGs exhibit a higher r1 relaxivity (9.16 mM-1 s-1) than acetylated PEI-Au-Gd NPs (PEI.Ac-Au-Gd NPs) and a clinical MR contrast agent and a greater X-ray attenuation performance than conventional iodinated CT contrast agents (e.g., Omnipaque), and they can be more significantly taken up by cancer cells than PEI.Ac-Au-Gd NPs. Furthermore, the AG/PEI-Au-Gd NGs enable effective dual mode MR/CT imaging of cancer cells in vitro as well as a subcutaneous tumor model in vivo. Strikingly, the AG/PEI-Au-Gd NGs exhibit a much better dual-modal MR/CT imaging performance than PEI.Ac-Au-Gd NPs and clinical CT or MR agents in in vivo tumor imaging. The developed AG/PEI-Au-Gd NGs with good biosafety confirmed by histological examinations may be potentially employed as an efficient contrast agent for enhanced dual-modal MR/CT imaging applications.

Nanocrystals of Zn(Fe)O-based diluted magnetic semi-conductor as potential luminescent and magnetic bimodal bioimaging probes

Nanocrystals of Zn(Fe)O-based diluted magnetic semi-conductor (nanoDMS) have been prepared by forced hydrolysis in polyol medium, using zinc and iron salts, and coated with carboxymethylpullulan (CMP). TEM studies revealed that CMP-nanoDMS are spherical, with average diameters on the order of 20 nm. Hydrodynamic diameters of about 75 nm were found in a physiological medium. NanoDMS were superparamagnetic at body temperature, and exhibited high saturation magnetization values (3.25 emu g−1). In aqueous suspensions, the colloids revealed high transverse proton relaxivities (T2) with an r2 value of 203 mM−1 s−1 (300 K, 1.41 T). Visible photoluminescent properties were evidenced with an excitation wavelength of 366 nm. No evidence of cell toxicity was found for human endothelial cells incubated with CMP-nanoDMS, at concentrations up to 100 μg mL−1 and for 48 h. No modification to the cytoskeleton was found up to 6 days of exposure. These hybrid nanomaterials could be considered as novel potential MR and luminescent bioimaging agents.

Riboflavin carrier protein-targeted fluorescent USPIO for the assessment of vascular metabolism in tumors

Riboflavin (Rf) and its metabolic analogs flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential for normal cellular growth and function. Their intracellular transport is regulated by the riboflavin carrier protein (RCP), which has been shown to be over-expressed by metabolically active cancer cells. Therefore, FAD-decorated ultrasmall superparamagnetic iron oxide nanoparticles (FAD USPIO) were developed as the first carrier-protein-targeted molecular MR agents for visualizing tumor metabolism. FAD USPIO were synthesized using an adsorptive, fluorescent and non-polymeric coating method, and their physicochemical properties were characterized using TEM, SEM, FTIR, MRI and fluorescence spectroscopy. In vitro analyses showed the biocompatibility of FAD USPIO, and confirmed that they were strongly and specifically taken up by cancer (LnCap) and endothelial (HUVEC) cells. In vivo molecular MRI together with subsequent histological validation finally demonstrated that FAD USPIO efficiently accumulate in tumors and tumor blood vessels, indicating that RCP-targeted diagnostic nanoparticles are interesting new materials for the assessment of vascular metabolism in tumors.

Quasi-Cubic Magnetite/Silica Core-Shell Nanoparticles as Enhanced MRI Contrast Agents for Cancer Imaging

Development of magnetic resonance imaging (MRI) contrast agents that can be readily applied for imaging of biological tissues under clinical settings is a challenging task. This is predominantly due to the expectation of an ideal MR agent being able to be synthesized in large quantities, possessing longer shelf life, reasonable biocompatibility, tolerance against its aggregation in biological fluids, and high relaxivity, resulting in better contrast during biological imaging. Although a repertoire of reports address various aforementioned issues, the previously reported results are far from optimal, which necessitates further efforts in this area. In this study, we demonstrate facile large-scale synthesis of sub-100 nm quasi-cubic magnetite and magnetite/silica core-shell (Mag@SiO2) nanoparticles and their applicability as a biocompatible T2 contrast agent for MRI of biological tissues. Our study suggests that silica-coated magnetite nanoparticles reported in this study can potentially act as improved MR contrast agents by addressing a number of aforementioned issues, including longer shelf life and stability in biological fluids. Additionally, our in vitro and in vivo studies clearly demonstrate the importance of silica coating towards improved applicability of T2 contrast agents for cancer imaging.

Glycans in Magnetic Resonance Imaging: Determinants of Relaxivity to Smart Agents, and Potential Applications in Biomedicine

Carbohydrate chemistry and glycobiology have become a "hot" subject. These extensive, complex structures serve essential roles in cell surface phenomena, but we are only beginning to understand what some of these functions are; any advances in the development of synthetic and/or analytical tools for glycobiology are extremely useful for our understanding of the roles of carbohydrates in biology, and as biomarkers of physiological/pathological states. This review provides an outlook of the potential of carbohydrate chemistry/biology in magnetic resonance imaging (MRI), a major important and prominent technique in diagnostic clinical medicine and biomedical research. During the last 30 years, MRI has developed from an intriguing research project to an essential diagnostic method in the clinic. Although MRI contrast in endogenous tissues provides excellent sensitivity for detecting subtle changes in anatomy and function, MRI still has poor specificity for attributing image contrast to specific biological processes. To overcome this limitation, MRI methods are being developed that induce changes in MR image contrast in response to molecular compositions and functions that serve as early biomarkers of pathologies. Carbohydrates with their intriguing chemistry, not only can provide structures for novel MRI probes for imaging specific biological processes, but can themselves provide novel targets/biomarkers. For example, the glycan structure can simply provide a molecular scaffold for modulating the physicochemical properties of the imaging contrast agent, or can be used for the design of novel MR agents with the ability to disclose relevant physiological or pathological cellular events.