Relaxivity Values Research Articles

An Optimized Integrin α6-Targeted Magnetic Resonance Probe for Molecular Imaging of Hepatocellular Carcinoma in Mice

IntroductionIntegrin α6 is an attractive diagnostic biomarker for molecular imaging of hepatocellular carcinoma (HCC) as it has an extremely high positive rate (approximately 94%) in clinical early-stage HCC. In this study, based on our previously identified integrin α6-targeted peptide, we developed an optimized integrin α6-targeted magnetic resonance (MR) probe dubbed DOTA(Gd)-ANADYWR for MR imaging of HCC in mice.Materials and MethodsThe longitudinal (R1) relaxivity of DOTA(Gd)-ANADYWR was measured on a 3.0 T MR system . The specific tumor enhancement of the agent was investigated in four distinct mouse models, including subcutaneous, orthotopic, genetically engineered and chemically induced HCC mice.ResultsThe R1 relaxivity value of DOTA(Gd)-ANADYWR is 5.11 mM−1s−1 at 3.0 T, which is similar to that of the nonspecific clinical agent Gadoteridol. DOTA(Gd)-ANADYWR generated superior enhanced MR signal in HCC lesions and provided complementary enhancement MR signals to the clinically available hepatobiliary MR contrast agent gadoxetate disodium (Gd-EOB-DTPA). Importantly, DOTA(Gd)-ANADYWR could efficiently visualize small HCC lesion (approximately 1 mm) which was hardly detected by the clinical Gd-EOB-DTPA.ConclusionThese findings suggest the potential application of this integrin α6-targeted MR probe for the detection of HCC, particularly for small HCC.

Target-Specific Magnetic Resonance Imaging of Human Prostate Adenocarcinoma Using NaDyF4-NaGdF4 Core-Shell Nanoparticles.

We illustrate the development of NaDyF4-NaGdF4 core-shell nanoparticles (NPs) for targeting prostate cancer cells using a preclinical 9.4 T magnetic resonance imaging (MRI) of live animals. The NPs composed of paramagnetic Dy3+ and Gd3+ (T2- and T1-contrast agents, respectively) demonstrate proton relaxivities of r1 = 20.2 mM-1 s-1 and r2 = 32.3 mM-1 s-1 at clinical 3 T and r1 = 9.4 mM-1 s-1 and r2 = 144.7 mM-1 s-1 at preclinical 9.4 T. The corresponding relaxivity values per NP are r1 = 19.4 × 105 mMNP-1 s-1 and r2 = 33.0 × 105 mMNP-1 s-1 at 3 T and r1 = 9.0 × 105 mMNP-1 s-1 and r2 = 147.0 × 105 mMNP-1 s-1 at 9.4 T. In vivo active targeting of human prostate tumors grown in nude mice revealed docking of anti-prostate-specific membrane antigen (PSMA) antibody-tagged NPs at tumor sites post-24 h of their intravenous injection. On the other hand, in vivo passive targeting showed preferential accumulation of NPs at tumor sites only within 2 h of their injection, ascribed to the enhanced permeation and retention effect of the tumor. A biodistribution study employing the harvested organs of mice, post-24 h injection of NPs, quantified active targeting as nearly twice as efficient as passive targeting. These outcomes provide potential opportunities for noninvasive diagnosis using NaDyF4-NaGdF4 core-shell NPs for target-specific MRI.

Target-switchable Gd(III)-DOTA/protein cage nanoparticle conjugates with multiple targeting affibody molecules as target selective T1 contrast agents for high-field MRI

Magnetic resonance imaging (MRI) is a non-invasive in vivo imaging tool, providing high enough spatial resolution to obtain both the anatomical and the physiological information of patients. However, MRI generally suffers from relatively low sensitivity often requiring the aid of contrast agents (CA) to enhance the contrast of vessels and/or the tissues of interest from the background. The targeted delivery of diagnostic probes to the specific lesion is a powerful approach for early diagnosis and signal enhancement leading to the effective treatment of various diseases. Here, we established targeting ligand switchable nanoplatforms using lumazine synthase protein cage nanoparticles derived from Aquifex aeolicus (AaLS) by genetically introducing the SpyTag peptide (ST) to the C-terminus of the AaLS subunits to form an ST-displaying AaLS (AaLS-ST). Conversely, multiple targeting ligands were constructed by genetically fusing SpyCatcher protein (SC) to either HER2 or EGFR targeting affibody molecules (SC-HER2Afb or SC-EGFRAfb). Gd(III)-DOTA complexes were chemically attached to the AaLS-ST and the external surface of the Gd(III)-DOTA conjugated AaLS-ST (Gd(III)-DOTA-AaLS-ST) were successfully decorated with either the HER2Afb or the EGFRAfb. The resulting Gd(III)-DOTA-AaLS/HER2Afb and Gd(III)-DOTA-AaLS/EGFR2Afb exhibited high r1 relaxivity values of 57 and 25 mM−1 s−1 at 1.4 and 7 T, respectively, which were 10-fold or higher than those of the clinically used Dotarem. Their target-selective contrast enhancements were confirmed with in vitro cell-based MRI scans and the in vivo MR imaging of tumor-bearing mouse models at 7 T. A target-switchable AaLS-based nanoplatform that was developed in this study might serve as a promising T1 CA developing platform at a high magnetic field to detect various tumor sites in a target-specific manner in future clinical applications.

A Gadolinium(III) Complex Based on the Thymine Nucleobase with Properties Suitable for Magnetic Resonance Imaging.

The paramagnetic gadolinium(III) ion is used as contrast agent in magnetic resonance (MR) imaging to improve the lesion detection and characterization. It generates a signal by changing the relaxivity of protons from associated water molecules and creates a clearer physical distinction between the molecule and the surrounding tissues. New gadolinium-based contrast agents displaying larger relaxivity values and specifically targeted might provide higher resolution and better functional images. We have synthesized the gadolinium(III) complex of formula [Gd(thy)2(H2O)6](ClO4)3·2H2O (1) [thy = 5-methyl-1H-pyrimidine-2,4-dione or thymine], which is the first reported compound based on gadolinium and thymine nucleobase. 1 has been characterized through UV-vis, IR, SEM-EDAX, and single-crystal X-ray diffraction techniques, and its magnetic and relaxometric properties have been investigated by means of SQUID magnetometer and MR imaging phantom studies, respectively. On the basis of its high relaxivity values, this gadolinium(III) complex can be considered a suitable candidate for contrast-enhanced magnetic resonance imaging.

Facile Synthesis of Manganese Tellurite Nanoparticles for Magnetic Resonance Imaging‐Guided Photothermal Therapy

AbstractIn this study, manganese tellurite (MnTeO3) nanoparticles are developed as theranostic agents for magnetic resonance imaging (MRI)‐guided photothermal therapy of tumor. MnTeO3 nanoparticles are synthesized via a simple one‐step method. The as‐synthesized MnTeO3 nanoparticles with uniform size show good biocompatibility. In particular, MnTeO3 nanoparticles exhibit a high photothermal conversion efficiency (η = 26.3%), which is higher than that of gold nanorods. Moreover, MnTeO3 nanoparticles also have high MRI performance. The longitudinal relaxivity (r1) value of MnTeO3 nanoparticles is determined to be 8.08 ± 0.2 mm−1 s−1, which is higher than that of clinically approved T1‐contrast agents Gd‐DTPA (4.49 ± 0.1 mm−1 s−1). The subsequent MnTeO3 nanoparticles‐mediated photothermal therapy displays a highly efficient ablation of tumor cells both in vitro and in vivo with negligible toxicity. It is demonstrated that MnTeO3 nanoparticles can serve as promising theranostic agents with great potentials for MRI‐guided photothermal therapy.

Developing A Novel Coumarone-Phenyl Amide Functionalized [Gd(III)-Pt(IV)] Complex as High T1, T2 Relaxive M-MRI Contrast Agent for Cancer Diagnosis

Pt(IV) cored Gd(III) metal complex as a multimodal MRI contrast agent for cancer diagnosis is reported. The hetero nuclear complex [Pr-(DO3-Ch-Ph-Am-Gd(III))2Pt(II)] is highly soluble in water and stable at room temperature. The complex shows high longitudinal (r1p = 24.43 mM-1 s-1) and transversal (r2p = 38.61 mM-1 s-1) relaxivity values in neat aqueous solution at pH =7 and at 27 oC. The relaxivity value of the complex is greater than the low molecular weight, FDA approved MRI contrast agents. The presence of two water molecules in the first coordination sphere and a replaceable hydrogen atom in the linker enhances the proton relaxation rate and gives a huge relaxivity value. The r2p/r1P ratio of 1.58 confirms that the complex is a T1-weighted contrast agent. The presence of high polar coumarone pendant arm and high rigid acridone moieties in the complex make the complex as better anticancer agent for ovarian cancer. The high polar nature of the coumarone, phenyl amide, acridone moiety will show better binding efficiency with ovarian cancer creating CA125 glycoprotein.

In Vivo Positive Magnetic Resonance Imaging of Brain Cancer (U87MG) Using Folic Acid-Conjugated Polyacrylic Acid-Coated Ultrasmall Manganese Oxide Nanoparticles

Ultrasmall nanoparticles are potential candidates for application as high-performance imaging agents. Herein, we present the synthesis and characterization of folic acid (FA)-conjugated polyacrylic acid (PAA)-coated MnO nanoparticles with an average particle diameter of 2.7 nm. FA conferred cancer-targeting ability, while PAA conferred good colloidal stability and low cellular cytotoxicity on the FA-PAA-coated MnO nanoparticles. Further, the nanoparticles exhibited a high relaxivity (r1) value of 9.3 s−1mM−1 (r2/r1 = 2.2). Their application potential as cancer-targeting T1 magnetic resonance imaging contrast agents was confirmed by their enhanced T1 contrast enhancements at the brain cancer (U87MG) site upon intravenous administration to mice tails.

Folic acid-functionalized gadolinium-loaded phase transition nanodroplets for dual-modal ultrasound/magnetic resonance imaging of hepatocellular carcinoma

Dual-modal molecular imaging by combining two imaging techniques can provide complementary information for early cancer diagnosis and therapeutic monitoring. In the present manuscript, folic acid (FA)-functionalized gadolinium-loaded nanodroplets (NDs) are introduced as dual-modal ultrasound (US)/magnetic resonance (MR) imaging contrast agents. These phase-change contrast agents (PCCAs) with alginate (Alg) stabilizing shell and a liquid perfluorohexane (PFH) core were successfully synthesized via the nano-emulsion method and characterized. In this regard, mouse hepatocellular carcinoma (Hepa1-6) as target cancer cells and mouse fibroblast (L929) as control cells were used. The in vitro and in vivo cytotoxicity assessments indicated that Gd/PFH@Alg and Gd/PFH@Alg-FA nanodroplets are highly biocompatible. Gd-loaded NDs do not induce organ toxicity, and no significant hemolytic activity in human red blood cells is observed. Additionally, nanodroplets exhibited strong ultrasound signal intensities as well as T1-weighted MRI signal enhancement with a high relaxivity value of 6.40 mM−1 s−1, which is significantly higher than that of the clinical Gadovist contrast agent (r1 = 4.01 mM−1 s−1). Cellular uptake of Gd-NDs-FA by Hepa1-6 cancer cells was approximately 2.5-fold higher than that of Gd-NDs after 12 h incubation. Furthermore, in vivo results confirmed that the Gd-NDs-FA bound selectively to cancer cells and were accumulated in the tumor region. In conclusion, Gd/PFH@Alg-FA nanodroplets have great potential as US/MR dual-modal imaging nanoprobes for the early diagnosis of cancer.

Application of [formula omitted]H proton NMR relaxometry to building materials – A review

Since nuclear magnetic resonance with focus on 1H protons is highly sensitive to pore filling fluids, it is nowadays often applied for the investigation of porous media. Mainly in materials research and especially in the field of non-destructive testing in civil engineering it is increasingly used. Scientific questions about and based on NMR meanwhile cover a broad spectrum.To give an overview, we have reviewed various studies dealing with the determination of moisture contents and parameters such as the pore-size distribution, surface relaxivity, porosity, etc. In some papers, the monitoring of moisture transport in connection with degradation processes or admixtures was the main objective. In other papers, NMR was used for pore space analysis or even applied on site to assess the state of conservation of cultural heritage. Building materials that have been investigated in the presented studies are for example cement, concrete, woods, sandstones etc.In this paper, short descriptions and the significant results of the reviewed articles are summarized and their measurement problems and discrepancies are pointed out. A special feature of this review article is the concise tabular compilation of determined T1 and T2 relaxation times, as well as of surface relaxivity values for various materials and components. Finally, relevant aspects are summed up and conclusions about the increasing potential of NMR relaxometry for investigations of porous building materials are drawn, followed by an outlook about future applications and the need for technical development.

Theragnostic Magnetic Core-Shell Nanoparticle as Versatile Nanoplatform for Magnetic Resonance Imaging and Drug Delivery

In this study, magnetic core-shell (MCS) nanoparticles were prepared as theragnostic potential nanoplatforms for simultaneously targeted drug delivery systems for tamoxifen and diagnosis. MCS nanoparticles were prepared in a well-shaped spherical form by the o/w emulsion method and characterized by means of dynamic light scattering (DLS), Scanning electron microscopy (SEM), Nuclear magnetic resonance (NMR), transform infrared (FT-IR) spectroscopy, and vibrating sample magnetometer (VSM). Scanning electron microscopy (SEM) indicated spherical nanostructures' formation with the final average particle size of around 80 nm. The findings proved the superparamagnetic properties of the MCS nanoparticles with relatively high-magnetization values (11.69 emu/g), which indicate that they were sensitive enough to external magnetic fields as a magnetic drug carrier. The nanoparticles showed 8.14% and 52.19% drug loading and encapsulation efficiency, respectively. MCS nanoparticles showed sustained release behavior for 120 h in the phosphate-buffered saline (PBS, pH= 7.4, 5.4) at 37 °C. The ratio between transverse and longitudinal relaxivity (r2/r1) value of the MCS nanoparticles was around 20, indicating their potential as a T2 MRI contrast agent. It can be concluded that the prepared MCS nanoparticles may serve as a promising carrier as an MRI contrast agent and targeted controlled anticancer drug delivery.

Colloidally Stable Monodisperse Fe Nanoparticles as T2 Contrast Agents for High-Field Clinical and Preclinical Magnetic Resonance Imaging

Iron nanoparticles (Fe NPs) produce negative contrast in magnetic resonance imaging (MRI) by shortening the transverse relaxation time (T2) of water protons at tissue sites. The high sensitivity of Fe toward oxidation under ambient conditions has challenged and impeded the development of stable Fe NPs for bioapplications compared to iron oxide nanoparticles (IONPs). This article demonstrates the synthesis of three batches of fairly monodisperse (size dispersion, <10%), colloidal Fe NPs with inorganic core diameters of 15.2, 12.0, and 8.8 nm. The 15.2 nm Fe NPs show high stability against oxidation, beyond 5 months, when dispersed in chloroform and deionized water. Upon dispersion in deionized water, these NPs gradually develop an amorphous iron oxide shell. On the contrary, upon transfer into water, the smaller Fe NPs oxidize to amorphous iron oxide eventually. The 15.2 nm Fe NPs exhibit much stronger shortening of the T2 relaxation time compared to the 12.0 and 8.8 nm Fe NPs at both high-field clinical 3 T and preclinical 9.4 T. The transverse relaxivity (r2) values of the 15.2 nm Fe NPs, based on per Fe ion concentration, were determined to be 167.9 mM–1 s–1 at 3 T and 236.4 mM–1 s–1 (higher than similarly sized IONPs) at 9.4 T. The respective r2/r1 ratios of 280 and 788 are high for a T2 contrast agent, although comprehensive MRI data for Fe NPs are not available in the literature for direct comparison. Fe NPs are promising MRI contrast agents for medical imaging.

TEA-assistant synthesis of MOF-74 nanorods for drug delivery and in-vitro magnetic resonance imaging

Zn-MOF-74 nanorods with uniform diameters of about 200 nm were successfully prepared by a triethylamine (TEA) assistant solvothermal method. The effects of TEA on the sizes and morphologies of nanoscale particles were investigated. Guided by this method, bimetallic ZnxMn1-x-MOF-74s were facilely prepared to endow the nanomaterial with magnetic resonance imaging (MRI) ability. Nanoscale Zn0.7Mn0.3-MOF-74 were successfully produced with homogenous Mn dispersion. Magnetic resonance relaxivity studies using clinical MRI equipment proved that Zn0.7Mn0.3-MOF-74 nanoparticles show a satisfactory r1 relaxivity value of 6.5 mM−1 s−1. The saturated DOX loading capacity of Zn0.7Mn0.3-MOF-74 nanocarriers was evaluated to 113 mg g−1. After chitosan (CS) coating, cytotoxicity experiments showed that [email protected]0.7Mn0.3[email protected] nanocomposites featured adequate biotolerability and no interference with cellular metabolism. These results indicated great potential of the bimetallic ZnMn-MOF-74s as new biomedical materials integrating cellular drug delivery with MR imaging applications.

Potential of a sonochemical approach to generate MRI-PPT theranostic agents for breast cancer.

The production of nanomaterials integrating diagnostic and therapeutic roles within one nanoplatform is important for medical applications. Such theranostics nanoplatforms could provide information on imaging, accurate diagnosis and, at the same time, could eradicate cancer cells. Fe3O4@Au core@shell nanoparticles (Fe3O4@AuNPs) have gained broad attention due to their unique innovations in magnetic resonance imaging (MRI) and photothermal therapy (PTT). Seed-mediated growth procedures were used to produce the Fe3O4@AuNPs. In these processes, complicated surface modifications, resulted in unsatisfactory properties. This work used the ability of the sonochemical approach to synthesize highly efficient theranostics agent Fe3O4@AuNPs with a size of approximately 22 nm in 5 min. The inner core of Fe3O4 acts as an MRI agent, whereas the photothermal effect stands accomplished by near-infrared absorption of the gold shell (Au shell), which results in the eradication of cancer cells. We have shown that Fe3O4@AuNPs have great biocompatibility and no major cytotoxicity has been identified. Relaxivity value (r2) of synthesized Fe3O4@Au NPs, measured at 233 mM-1s-1, is significantly higher than those reported previously. The as-synthesized NPs have shown substantial photothermal ablation ability on MCF-7 in vitro under near-infrared laser irradiation. Consequently, Fe3O4@AuNPs synthesized in this study have great potential as an ideal candidate for MR imaging and PTT.

Optimizing the relaxivity at high fields: systematic variation of the rotational dynamics in polynuclear Gd-complexes based on the AAZTA ligand

A homogeneous series of polynuclear Gd-complexes (n = 1–8) based on a stable and bis-hydrated [Gd(AAZTA)]− chelate shows high relaxivity values at high fields (1.5–7 T), per Gd, particularly pronounced for the more rigid and compact members.

Aptamer modified nanoprobe for multimodal fluorescence/magnetic resonance imaging of human ovarian cancer cells

A multifunctional-aptamer (APT) nanoprobe, TOV6 APT-superparamagnetic iron oxide nanoparticle-carbon dots (APT-SPION-CDs), for fluorescence and magnetic resonance targeted imaging (FI/MRI) of human ovarian cancer cells (OVCAR-3) is introduced. The SPION-CDs were synthesized and conjugated with TOV6 APT recognizing the stress-induced phosphoprotein 1 (STIP1) overexpressed on OVCAR-3 cells. The capability of the nanoprobe as a contrast agent for MRI and simultaneously as a fluorescent probe for fluorescence microscopy was studied. TOV6 APTs were adsorbed on SPION-CDs and were confirmed with Fourier transform infrared spectrometer. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed higher cytotoxic effects for APT-SPION-CDs compared to SPION-CDs on STIP1-negative HeLa cells. But on OVCAR-3, as STIP1-positive cells, the cytotoxic effect was negligible. The fluorescence microscopic images confirmed that APT-SPION-CDs specifically targeted ovarian cancer cells due to the tumor-targeting effect of TOV6 APT. High spin–spin relaxivity value (r2 = 308.5 mM−1 s−1) and the signal enhancement in T2-weighted MRIs confirmed the capability of the nanoprobe as a T2-based contrast agent. In vitro cellular uptake and signal enhancement of this multimodal FI/MRI nanoprobe demonstrated the potential application of APT-SPION-CDs as a contrast agent for MRI and as a fluorescent probe for fluorescence microscopic imaging.

Iron (III)-Quercetin Complex: Synthesis, Physicochemical Characterization, and MRI Cell Tracking toward Potential Applications in Regenerative Medicine.

In cell therapy, contrast agents T1 and T2 are both needed for the labeling and tracking of transplanted stem cells over extended periods of time through magnetic resonance imaging (MRI). Importantly, the metal-quercetin complex via coordination chemistry has been studied extensively for biomedical applications, such as anticancer therapies and imaging probes. Herein, we report on the synthesis, characterization, and labeling of the iron (III)-quercetin complex, “IronQ,” in circulating proangiogenic cells (CACs) and also explore tracking via the use of a clinical 1.5 Tesla (T) MRI scanner. Moreover, IronQ had a paramagnetic T1 positive contrast agent property with a saturation magnetization of 0.155 emu/g at 1.0 T and longitudinal relaxivity (r1) values of 2.29 and 3.70 mM−1s−1 at 1.5 T for water and human plasma, respectively. Surprisingly, IronQ was able to promote CAC growth in conventional cell culture systems without the addition of specific growth factors. Increasing dosages of IronQ from 0 to 200 μg/mL led to higher CAC uptake, and maximum labeling time was achieved in 10 days. The accumulated IronQ in CACs was measured by two methodologies, an inductively coupled plasma optical emission spectrometry (ICP-EOS) and T1-weighted MRI. In our research, we confirmed that IronQ has excellent dual functions with the use of an imaging probe for MRI. IronQ can also act as a stimulating agent by favoring circulating proangiogenic cell differentiation. Optimistically, IronQ is considered beneficial for alternative labeling and in the tracking of circulation proangiogenic cells and/or other stem cells in applications of cell therapy through noninvasive magnetic resonance imaging in both preclinical and clinical settings.

Gd(AAZTA)]- Derivatives with n-Alkyl Acid Side Chains Show Improved Properties for Their Application as MRI Contrast Agents*.

Herein, the synthesis and an extensive characterization of two novel Gd(AAZTA) (AAZTA=6-amino-6-methylperhydro-1,4-diazepine tetra acetic acid) derivatives functionalized with short (C2 and C4 ) n-alkyl acid functions are reported. The carboxylate functionality is the site for further conjugations for the design of more specific contrast agents (CAs). Interestingly, it has been found that the synthesized complexes display enhanced properties for use as MRI contrast agents on their own. The stability constants determined by using potentiometric titration and UV/Vis spectrophotometry were slightly higher than the one reported for the parent Gd(AAZTA) complex. This observation might be accounted for by the larger sigma-electron donation of the acyl substituents with respect to the one provided by the methyl group in the parent complex. As far as concerns the kinetic stability, transmetallation experiments with endogenous ions (e.g. Cu2+ ) implied that the Gd3+ ions present in these Gd(AAZTA) derivatives show somewhat smaller susceptibility to chemical exchange towards these ions at 25 °C, close to the physiological condition. The 1 H NMR spectra of the complexes with EuIII and YbIII displayed a set of signals consistent with half the number of methylene protons present on each ligand. The number of resonances was invariant over a large range of temperatures, suggesting the occurrence of a fast interconversion between structural isomers. The relaxivity values (298 K, 20 MHz) were consistent with q=2 being equal to 8.8 mm-1 s-1 for the C2 derivative and 9.4 mm-1 s-1 for the C4 one, that is, sensibly larger than the one reported for Gd(AAZTA) (7.1 mm-1 s-1 ). Variable-temperature (VT)-T2 17 O NMR measurements showed, for both complexes, the presence of two populations of coordinated water molecules, one in fast and one in slow exchange with the bulk water. As the high-resolution 1 H NMR spectra of the analogs with EuIII and YbIII did not show the occurrence of distinct isomers (as frequently observed in other macrocyclic lanthanide(III)-containing complexes), we surmised the presence of two fast-interconverting isomers in solution. The analysis of the 17 O NMR VT-T2 profiles versus temperature allowed their relative molar fraction to be established as 35 % for the isomer with the fast exchanging water and 65 % for the isomer with the water molecules in slower exchange. Finally, 1 H NMRD profiles over an extended range of applied magnetic field strengths have been satisfactory fitted on the basis of the occurrence of the two interconverting species.

MR Imaging of Peripheral Nerves Using Targeted Application of Contrast Agents: An Experimental Proof-of-Concept Study.

Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a nerve's capacity for axonal transport, it may be visualized by targeted application of a contrast agent and assessing the distribution through radiological imaging, thus revealing a nerve's continuity. This concept has not been explored, however, may potentially guide the treatment of peripheral nerve injuries. In this experimental proof-of-concept study, we tested imaging through MRI after administering gadolinium-based contrast agents which were then retrogradely transported.Methods: We synthesized MRI contrast agents consisting of paramagnetic agents and various axonal transport facilitators (HSA-DTPA-Gd, chitosan-DTPA-Gd or PLA/HSA-DTPA-Gd). First, we measured their relaxivity values in vitro to assess their radiological suitability. Subsequently, the sciatic nerve of 24 rats was cut and labeled with one of the contrast agents to achieve retrograde distribution along the nerve. One week after surgery, the spinal cords and sciatic nerves were harvested to visualize the distribution of the respective contrast agent using 7T MRI. In vivo MRI measurements were performed using 9.4 T MRI on the 1st, 3rd, and the 7th day after surgery. Following radiological imaging, the concentration of gadolinium in the harvested samples was analyzed using inductively coupled mass spectrometry (ICP-MS).Results: All contrast agents demonstrated high relaxivity values, varying between 12.1 and 116.0 mM−1s−1. HSA-DTPA-Gd and PLA/HSA-DTPA-Gd application resulted in signal enhancement in the vertebral canal and in the sciatic nerve in ex vivo MRI. In vivo measurements revealed significant signal enhancement in the sciatic nerve on the 3rd and 7th day after HSA-DTPA-Gd and chitosan-DTPA-Gd (p < 0.05) application. Chemical evaluation showed high gadolinium concentration in the sciatic nerve for HSA-DTPA-Gd (5.218 ± 0.860 ng/mg) and chitosan-DTPA-Gd (4.291 ± 1.290 ng/mg).Discussion: In this study a novel imaging approach for the evaluation of a peripheral nerve's integrity was implemented. The findings provide radiological and chemical evidence of successful contrast agent uptake along the sciatic nerve and its distribution within the spinal canal in rats. This novel concept may assist in the diagnostic process of peripheral nerve injuries in the future.

Multi-Stimuli-Responsive DOX Released from Magnetosome for Tumor Synergistic Theranostics.

BackgroundTo improve responses to tumor microenvironments for achieving a better therapeutic outcome in combination cancer therapy, poly(ε-caprolactone)-SS-poly(methacrylic acid) diblock copolymer (PCL-SS-PMAA) with a disulfide linkage between the hydrophobic and hydrophilic junctions was synthesized.Materials and MethodsRepeating units of PCL and PMAA in PCL-SS-PMAA were controlled and formulated into polymersomes (PSPps). Truncated octahedral Fe3O4 nanoparticles (IONPs) were synthesized and encapsulated to produce IONPs-PSPps NPs and doxorubicin (DOX) was further loaded to produce IONPs-PSPps@DOX NPs for theranostic applications.ResultsIONPs-PSPps NPs remained a superparamagnetic property with a saturation magnetization value of 85 emu⋅gFe3O4−1 and a relaxivity value of 180 mM−1⋅s−1. Upon exposure to an alternating magnetic field (AMF), IONPs-PSPps NPs increased temperature from 25°C to 54°C within 15 min. Among test groups, the cell apoptosis was greatest in the group exposed to IONPs-PSPps@DOX NPs with AMF and magnet assistance. In vivo T2-weighted magnetic resonance images of A549 tumor-bearing mice also showed highest contrast and greatest tumor suppression in the tumor with AMF and magnet assistance.ConclusionIONPs-PSPps@DOX NPs are a potential theranostic agent having multifaceted applications involving magnetic targeting, MRI diagnosis, hyperthermia and chemotherapy.

A new method to determine surface relaxivity of tight sandstone cores based on LF-NMR and high-speed centrifugation measurements

Low-field nuclear magnetic resonance (LF-NMR) T2 spectrum commonly is converted into pore size distribution (PSD) with accurate calculation of surface relaxivity. Currently, the surface relaxivity for unconventional cores is determined indirectly using average pore radius (ARS) method or surface-to-volume ratio (SVR) method. The ARS method is time consuming, and inevitably it causes permanent damage to core samples because of the injection of mercury. In this study, we proposed a new method, the pseudo T2 cut-off (PTC) method, instead of the ARS method to calculate the surface relaxivity of tight sandstone core samples by correlating a PTC value with the corresponding pore radius. First, we performed LF-NMR and high-speed centrifugation (HSC) measurements on four tight sandstone core samples to determine surface relaxivity using the PTC method. Then, we compared the calculated surface relaxivity using the new method with that determined using the ARS and SVR methods. Then, we converted the T2 spectrum into PSD using appropriate surface relaxivity. Finally, we obtained residual oil distribution. The results showed that we had established an exponential correlation between the PTC value and surface relaxivity. Ultimate surface relaxivity values for tight sandstone core samples were 5.85, 2.98, 4.66, and 2.17 μm/s. The values of ρARS and ρPTC were close but generally larger than that of ρSVR. We still observed a linear correlation between illite content and different surface relaxivity. Moreover, we obtained PSD in mesopores and macropores by jointly using ρPTC (or ρARS) and ρSVR. After centrifugation, the residual oil (62.94 wt%) was mainly distributed in the micropores (~20 wt%) and mesopores (~35 wt%). This study provided a nondestructive method to determine the surface relaxivity of tight sandstone cores and provided information for residual oil distribution.