Vivo Magnetic Resonance Imaging Research Articles

Highly Sensitive Early Diagnosis of Kidney Damage Using Renal Clearable Zwitterion-Coated Ferrite Nanoprobe via Magnetic Resonance Imaging In Vivo.

Iron oxide nanoprobes exhibit substantial potential in magnetic resonance imaging (MRI) of kidney diseases and can eliminate the nephrotoxicity of gadolinium-based contrast agents (GBCAs). Nevertheless, there is an extreme shortage of highly sensitive and renal clearable iron oxide nanoprobes suitable for early kidney damage detection through MRI. Herein, a renal clearable ultra-small ferrite nanoprobe (UMFNPs@ZDS) is proposed for highly sensitive early diagnosis of kidney damage via structural and functional MRI in vivo for the first time. The nanoprobe comprises a ferrite core coated with a zwitterionic layer, and possesses a high T1 relaxivity (12.52 mm-1s-1), a small hydrodynamic size (6.43nm), remarkable water solubility, excellent biocompatibility, and impressive renal clearable ability. In a rat model of unilateral ureteral obstruction (UUO), the nanoprobe-based MRI can not only accurately visualize the locations of renal injury, but also provide comprehensive functional data including peak value, peak time, relative renal function (RRF), and clearance percentage via MRI. The findings prove the immense potential of ferrite nanoprobes as a superior alternative to GBCAs for the early diagnosis of kidney damage.

Near‐Infrared Emission‐Cyanine 5.5 and Doxorubicin Loaded Magnetite Nanoparticles for Dual In Vivo Magnetic Resonance and Biodistribution Imaging

AbstractThe in vivo imaging of the drug distribution during cancer treatment plays an important role in helping physicians and pharmacists to monitor the progress of treatment and improve the effectiveness of therapy. Our goal in this work was to prepare a multifunctional nano drug delivery system that not only co‐loaded iron oxide nanoparticles (Fe3O4 NPs) and Doxorubicin (Dox) but also attached the near‐infrared fluorescent agent Cyanine 5.5 based on poly(lactide)‐tocopheryl polyethylene glycol 1000 succinate (PLA‐TPGS) copolymer. Cyanine 5.5 was attached to the surface Fe3O4 NPs via the NH−CO chemical bond, followed by co‐loading of Dox onto the PLA‐TPGS copolymer by the emulsion solvent evaporation method. The structural, morphological, dimensional, stability, and optical‐magnetic properties of the as‐synthesized nanosystem were fully characterized. From the drug‐released study, the prolonged release of Dox accelerated with increasing acidic conditions (at pH 5.0 and 6.5), while a slow release was observed at pH 7.4. Through the MTT assay, the nanosystem had cellular toxicity against Hep−G2 and HeLa cell lines with low IC50 values of 0.42 and 0.78 μg.mL−1 in terms of Dox concentration, respectively. At a magnetic field of 7 T, this nanosystem also exhibited a high r2/r1 ratio of 164.5 and a strong contrast magnetic resonance (MR) image in the liver. In vivo biodistribution studies revealed that the highest fluorescence intensity achived in the liver after 6 h, and the nanosystem was eliminated from the body after at least 24 h. Collectively, these results demonstrated that the PLA‐TPGS‐Fe3O4‐Cyanine 5.5‐Dox nanosystem is a good candidate for simultaneously increasing contrast for MR and near‐infrared fluorescence imaging.

Redox Properties and in Vivo Magnetic Resonance Imaging of Cyclodextrin-Polynitroxides Contrast Agents.

This paper reports the synthesis, characterization and in vivo application of water-soluble supramolecular contrast agents (Mw: 5-5.6 kDa) for MRI obtained from β-cyclodextrin functionalized with different kinds of nitroxide radicals, both with piperidine structure (CD2 and CD3) and with pyrrolidine structure (CD4 and CD5). As to the stability of the radicals in presence of ascorbic acid, CD4 and CD5 have low second order kinetic constants (≤0.05 M-1 s-1 ) compared to CD2 (3.5 M-1 s-1 ) and CD3 (0.73 M-1 s-1 ). Relaxivity (r1 ) measurements on compounds CD3-CD5 were carried out at different magnetic field strength (0.7, 3, 7 and 9.4 T). At 0.7 T, r1 values comprised between 1.5 mM-1 s-1 and 1.9 mM-1 s-1 were found while a significant reduction was observed at higher fields (r1 ≈0.6-0.9 mM-1 s-1 at 9.4 T). Tests in vitro on HEK293 human embryonic kidney cells, L929 mouse fibroblasts and U87 glioblastoma cells indicated that all compounds were non-cytotoxic at concentrations below 1 μmol mL-1 . MRI in vivo was carried out at 9.4 T on glioma-bearing rats using the compounds CD3-CD5. The experiments showed a good lowering of T1 relaxation in tumor with a retention of the contrast for at least 60 mins confirming improved stability also in vivo conditions.

Anatomically Accurate, High-Resolution Modeling of the Human Index Finger Using In Vivo Magnetic Resonance Imaging.

Anatomically accurate models of a human finger can be useful in simulating various disorders. In order to have potential clinical value, such models need to include a large number of tissue types, identified by an experienced professional, and should be versatile enough to be readily tailored to specific pathologies. Magnetic resonance images were acquired at ultrahigh magnetic field (7 T) with a radio-frequency coil specially designed for finger imaging. Segmentation was carried out under the supervision of an experienced radiologist to accurately capture various tissue types (TTs). The final segmented model of the human index finger had a spatial resolution of 0.2 mm and included 6,809,600 voxels. In total, 15 TTs were identified: subcutis, Pacinian corpuscle, nerve, vein, artery, tendon, collateral ligament, volar plate, pulley A4, bone, cartilage, synovial cavity, joint capsule, epidermis and dermis. The model was applied to the conditions of arthritic joint, ruptured tendon and variations in the geometry of a finger. High-resolution magnetic resonance images along with careful segmentation proved useful in the construction of an anatomically accurate model of the human index finger. An example illustrating the utility of the model in biomedical applications is shown. As the model includes a number of tissue types, it may present a solid foundation for future simulations of various musculoskeletal disease processes in human joints.

Hyaluronic Acid-Stabilized Fe3O4 Nanoparticles for Promoting In Vivo Magnetic Resonance Imaging of Tumors.

The use of iron oxide (Fe3O4) nanoparticles as novel contrast agents for magnetic resonance imaging (MRI) has attracted great interest due to their high r 2 relaxivity. However, both poor colloidal stability and lack of effective targeting ability have impeded their further expansion in the clinics. Here, we reported the creation of hyaluronic acid (HA)-stabilized Fe3O4 nanoparticles prepared by a hydrothermal co-precipitation method and followed by electrostatic adsorption of HA onto the nanoparticle surface. The water-soluble HA functions not only as a stabilizer but also as a targeting ligand with high affinity for the CD44 receptor overexpressed in many tumors. The resulting HA-stabilized Fe3O4 nanoparticles have an estimated size of sub-20 nm as observed by transmission electron microscopy (TEM) imaging and exhibited long-term colloidal stability in aqueous solution. We found that the nanoparticles are hemocompatible and cytocompatible under certain concentrations. As verified by quantifying the cellular uptake, the Fe3O4@HA nanoparticles were able to target a model cell line (HeLa cells) overexpressing the CD44 receptor through an active pathway. In addition, we showed that the nanoparticles can be used as effective contrast agents for MRI both in vitro in HeLa cells and in vivo in a xenografted HeLa tumor model in rodents. We believe that our findings shed important light on the use of active targeting ligands to improve the contrast of lesion for tumor-specific MRI in the nano-based diagnosis systems.

In Vivo MRI Tracking of Tumor Vaccination and Antigen Presentation by Dendritic Cells.

Cancer vaccination using tumor antigen-primed dendritic cells (DCs) was introduced in the clinic some 25 years ago, but the overall outcome has not lived up to initial expectations. In addition to the complexity of the immune response, there are many factors that determine the efficacy of DC therapy. These include accurate administration of DCs in the target tissue site without unwanted cell dispersion/backflow, sufficient numbers of tumor antigen-primed DCs homing to lymph nodes (LNs), and proper timing of immunoadjuvant administration. To address these uncertainties, proton (1H) and fluorine (19F) magnetic resonance imaging (MRI) tracking of ex vivo pre-labeled DCs can now be used to non-invasively determine the accuracy of therapeutic DC injection, initial DC dispersion, systemic DC distribution, and DC migration to and within LNs. Magnetovaccination is an alternative approach that tracks in vivo labeled DCs that simultaneously capture tumor antigen and MR contrast agent in situ, enabling an accurate quantification of antigen presentation to T cells in LNs. The ultimate clinical premise of MRI DC tracking would be to use changes in LN MRI signal as an early imaging biomarker to predict the efficacy of tumor vaccination and anti-tumor response long before treatment outcome becomes apparent, which may aid clinicians with interim treatment management.

Manganese oxide/Metal-Organic Frameworks-Based Nanocomposites for Tumr Micro-environment Sensitive 1H/19F Dual-mode Magnetic Resonance Imaging in Vivo

A pH- and GSH-responsive 1H/19F dual-mode magnetic resonance imaging contrast agent (MRI CA) was constructed by incorporating MnOx into Zr-based MOF nanoparticles (MnOx/UiO-66-F/PPEG NPs) with an organic ligand of tetrafluoro-terephthalic acid (F4PTA). Under a weak acidic tumor micro-environment, MnOx/UiO-66-F/PPEG NPs would collapse to release MnOx and free F4PTA. Due to the released free F4PTA, 19F MRI signal was enhanced. Meanwhile, GSH, which is overexpressed in a tumor micro-environment, reduced MnOx to divalent manganese ions and improved the T1-weighted MR imaging capability. As a proof of concept, MnOx/UiO-66-F/PPEG NPs was favorable for dual 1H/19F MRI with a high signal-to-noise ratio in vivo.

In Vivo MRI Tracking of Mesenchymal Stromal Cells Labeled with Ultrasmall Paramagnetic Iron Oxide Particles after Intramyocardial Transplantation in Patients with Chronic Ischemic Heart Disease.

Background While regenerative stem cell therapy for ischemic heart disease has moved into phase 3 studies, little is still known about retention and migration of cell posttransplantation. In human studies, the ability to track transplanted cells has been limited to labeling with radioisotopes and tracking using nuclear imaging. This method is limited by low resolution and short half-lives of available radioisotopes. Longitudinal tracking using magnetic resonance imaging (MRI) of myocardial injected cells labeled with iron oxide nanoparticles has shown promising results in numerous preclinical studies but has yet to be evaluated in human studies. We aimed to evaluate MRI tracking of mesenchymal stromal cells (MSCs) labeled with ultrasmall paramagnetic iron oxide (USPIO) nanoparticles after intramyocardial transplantation in patients with ischemic heart disease (IHD). Methods Five no-option patients with chronic symptomatic IHD underwent NOGA-guided intramyocardial transplantation of USPIO-labeled MSCs. Serial MRI scans were performed to track labeled cells both visually and using semiautomated T2∗ relaxation time analysis. For safety, we followed symptoms, quality of life, and myocardial function for 6 months. Results USPIO-labeled MSCs were tracked for up to 14 days after transplantation at injection sites both visually and using semiautomated regional T2∗ relaxation time analysis. Labeling of MSCs did not impair long-term safety of treatment. Conclusion This was a first-in-man clinical experience aimed at evaluating the utility of MRI tracking of USPIO-labeled bone marrow-derived autologous MSCs after intramyocardial injection in patients with chronic IHD. The treatment was safe, and cells were detectable at injection sites up to 14 days after transplantation. Further studies are needed to clarify if MSCs migrate out of the injection area into other areas of the myocardium or if injected cells are washed out into the peripheral circulation. The trial is registered with ClinicalTrials.gov NCT03651791.

Magnetic Resonance Imaging Tracking of Induced Pluripotent Stem Cells-Induced Neural Stem Cells in Traumatic Brain Injury Rats

Abstract INTRODUCTION Induced pluripotent stem cells (iPS cells) are promising cell source for stem cell replacement strategy applied to brain injury caused by traumatic brain injury (TBI) or stroke. Neural stem cell (NSCs), derived from iPS cells could aid the reconstruction of brain tissue and the restoration of brain function. However, how to trace the fate of iPS cells in host brain is still a challenge. METHODS In our study, iPS cells were derived from skin fibroblasts using the 4 classic factors Oct4, Sox2, Myc, and Klf4. Then these iPS cells were induced to differentiate into NSCs, which were incubated with superparamagnetic iron oxides (SPIOs) in Vitro. Next, 30 TBI rat models were prepared and divided into 3 groups (n = 10). One week after brain injury, group A and B rats received NSCs (labeled with SPIOs) implantation, while group C rats received non-labeled NSCs implantation. After cell implantation, all the rats were performed T2*-weighted magnetic resonance imaging (MRI) scan at day 1, and 1 wk to 4 wk, to track NSCs distribution in rats’ brains. One month after cell implantation, all the rats were performed manganese-enhanced MRI (ME-MRI) scan. In group B, diltiazem was infused during the ME-MRI scan period. RESULTS (1) iPS cells were successfully derived from skin fibroblasts using the 4 classic factors Oct4, Sox2, Myc, and Klf4, expressing the typical antigens including SSEA4, Oct4, Sox2, and Nanog. (2) iPS cells were induced to differentiate into NSCs, which could express Nestin and differentiate into neural cells and glia cells. (3) NSCs were incubated with SPIOs overnight, and prussian blue staining showed intra-cellular particles. (4) After cell implantation, T2*-weighted MRI scan showed these implanted NSCs could migrate to the injury area in chronological order. (5) The subsequent ME-MRI scan detected NSCs function, which could be blocked by diltiazem. CONCLUSION In conclusion, using in Vivo MRI tracking technique to trace the fate of iPS cells-induced NSCs in host brain is feasible.

Artifact Induced by a Transponder During In Vivo Magnetic Resonance Imaging on Horse Brain

Magnetic resonance imaging (MRI) is now widely used in equine veterinary practice. However, the mandatory European legislation regarding horse identification imposes the implantation of a transponder within the fatty tissue of the neck cervical ligament. While performing brain MRI for scientific purposes in ponies, we faced artifacts produced by such transponder and reported here this problem. Indeed, pony mares were anesthetized for 2 hours and placed, bedded on their back, in a 3T MRI scanner. A four-element flexible antenna positioned around the head was used. Three MRI sequences were performed on each animal: three-dimensional T1, three-dimensional T2, and two-dimensional T1. The anesthesia allowed the acquisition of MRI for 2 hours. The images for the three MRI sequences for each pony exhibited great quality on all the anterior parts of the brain but began to become distorted posteriorly to the pineal pituitary axis and completely disappeared at the level of the cerebellum. To find the origin of the artifact, the transponder used for the identification of the animal was inserted in an inert gel and imaged in the same conditions as the ponies. The images obtained looked similar to the observed artifact. Our study thus advocates for the further exploration of such kind of artifact when using 3T MRI in brain imaging in horses.

Photoinduced in Vivo Magnetic Resonance Imaging (MRI) with Rapid CO Release from an MnCO-Protein Needle Composite.

Construction of an artificial protein needle (PN), which includes the membrane puncturing needle domain of bacteriophage T4 conjugated to Mn carbonyl (MnCO) complexes, is reported. The responsiveness to visible light of the MnCO complex makes it useful as a photoinduced in vivo magnetic resonance imaging contrast reagent (MRI CR), because the PN carrier has the potential to deliver the MnCO complex into mouse tumors with retention of coordination structure within the in vivo environment. Moreover, the composite has higher relaxivity and longer circulation as an MRI CR than the corresponding MnCO complex. These results demonstrate construction of a responsive in vivo MRI CR by using an artificial metalloprotein.

Homing and Tracking of Iron Oxide Labelled Mesenchymal Stem Cells After Infusion in Traumatic Brain Injury Mice: a Longitudinal In Vivo MRI Study.

Stem cells transplantation has emerged as a promising alternative therapeutic due to its potency at injury site. The need to monitor and non-invasively track the infused stem cells is a significant challenge in the development of regenerative medicine. Thus, in vivo tracking to monitor infused stem cells is especially vital. In this manuscript, we have described an effective in vitro labelling method of MSCs, a serial in vivo tracking of implanted stem cells at traumatic brain injury (TBI) site through 7T magnetic resonance imaging (MRI). Proper homing of infused MSCs was carried out at different time points using histological analysis and Prussian blue staining. Longitudinal in vivo tracking of infused MSCs were performed up to 21days in different groups through MRI using relaxometry technique. Results demonstrated that MSCs incubated with iron oxide-poly-L-lysine complex (IO-PLL) at a ratio of 50:1.5μg/ml and a time period of 6h was optimised to increase labelling efficiency. T2*-weighted images and relaxation study demonstrated a significant signal loss and effective decrease in transverse relaxation time on day-3 at injury site after systemic transplantation, revealed maximum number of stem cells homing to the lesion area. MRI results further correlate with histological and Prussian blue staining in different time periods. Decrease in negative signal and increase in relaxation times were observed after day-14, may indicate damage tissue replacement with healthy tissue. MSCs tracking with synthesized negative contrast agent represent a great advantage during both in vitro and in vivo analysis. The proposed absolute bias correction based relaxometry analysis could be extrapolated for stem cell tracking and therapies in various neurodegenerative diseases.

Accurate Monitoring of Renal Injury State through in Vivo Magnetic Resonance Imaging with Ferric Coordination Polymer Nanodots.

It is highly challenging to detect the pathophysiology of the diseased kidneys and achieve precise diagnosis because there are few in vivo noninvasive imaging techniques to quantitatively assess kidney dysfunction. This longstanding challenge is normally attributed to the limited molecular contrast agents which can be addressed with renal clearable nanoprobes. In this report, we demonstrate the use of magnetic resonance imaging along with renal clearable ferric coordination polymer nanodots (Fe-CPNDs) for in vivo monitoring the kidney dysfunction effects following drug (daunomycin)-induced kidney injury. After intravenous injection of Fe-CPNDs, the change of the MR signal in the kidney can be precisely correlated with local pathological lesion which is demonstrated by renal anatomic details and biochemical examinations of urine and blood. This finding opens the door to the possibility of noninvasively assessing kidney dysfunction and local injuries.

Zwitterionic Manganese and Gadolinium Metal-Organic Frameworks as Efficient Contrast Agents for in Vivo Magnetic Resonance Imaging.

Two water-stable three-dimensional Mn- and Gd-based metal-organic frameworks (MOFs), {[Mn2(Cmdcp)2(H2O)2]·H2O}n (1) and {[Gd(Cmdcp)(H2O)3](NO3)·3H2O}n (2, H3CmdcpBr = N-(4-carboxy benzyl)-(3,5-dicarboxyl)pyridinium bromide), have been prepared and analyzed. In vitro magnetic resonance imaging indicated that MOFs 1 and 2 possess relaxivity r1 values of 17.50 and 13.46 mM-1·S-1, respectively, which are superior to that of the control Gd-DTPA (r1 = 4.87 mM-1·S-1, DTPA = diethylene triamine pentaacetate). MOFs 1 and 2 also possessed good biocompatibility and low cytotoxicity against a model cell line. In vivo magnetic resonance images of treated Kunming mice indicated that kidneys showed remarkably positive signal enhancement after 15 min with intravenous administration of MOF 1 and the hyperintensity of both kidneys persisted for about 240 min with no obvious tissue damage. MOF 1 is therefore promising in vivo probes for imaging intravascular diseases and renal dysfunction.

Evaluation of high-resolution In Vivo MRI for longitudinal analysis of endochondral fracture healing in mice.

Mice are extensively used for experimental bone-healing studies. However, there are few established nondestructive in vivo techniques for longitudinal fracture-healing analysis in mice, including in vivo micro-computed tomography (μCT) and radiography. Importantly, none of the established methods can discriminate between non-mineralized fibrous tissue and cartilage in the soft fracture callus. Therefore, the objective was to establish high-resolution in vivo magnetic resonance imaging (MRI) for the longitudinal assessment of soft callus formation during bone healing in mice. C57BL/6J mice received a femur osteotomy stabilized using an external fixator and were randomly assigned to five groups. Group 1 mice were scanned three times longitudinally during fracture healing using an optimized MRI scanning protocol to establish an algorithm to characterize the different fracture-callus tissues. Mice of groups 2–4 were scanned once on day 10, 14 or 21, respectively, euthanized after scanning and their femurs subjected to ex vivo μCT and histomorphometric analysis to compare the data assessed by MRI with μCT and histology. Control group 5 mice were not scanned. After 28 days, mice of groups 1 and 5 were euthanized and the fracture-healing outcome was evaluated by bending-test, μCT and histology to determine whether the repeated anesthesia, handling and the MRI measurements themselves influenced fracture healing. The callus-tissue values determined by MRI were mostly comparable to those obtained by μCT and histomorphometric analysis. However, at time points characterized by small relative bone or cartilage areas, MRI measurements were weakly comparable to histomorphometric data, possibly due to the inferior spatial resolution. Importantly, at the early and intermediate phases of healing, cartilage and fibrous-tissue values obtained by MRI were highly accurate. Furthermore, repeated anesthesia, handling and MRI scans did not impact bone healing. Therefore, we demonstrated the feasibility of high-resolution in vivo MRI for longitudinal assessment of soft callus formation during murine endochondral fracture healing.

Using Multi-fluorinated Bile Acids and In Vivo Magnetic Resonance Imaging to Measure Bile Acid Transport.

Along with their traditional role as detergents that facilitate fat absorption, emerging literature indicates that bile acids are potent signaling molecules that affect multiple organs; they modulate gut motility and hormone production, and alter vascular tone, glucose metabolism, lipid metabolism, and energy utilization. Changes in fecal bile acids may alter the gut microbiome and promote colon pathology including cholerrheic diarrhea and colon cancer. Key regulators of fecal bile acid composition are the small intestinal Apical Sodium-dependent Bile Acid Transporter (ASBT) and fibroblast growth factor-19 (FGF19). Reduced expression and function of ASBT decreases intestinal bile acid up-take. Moreover, in vitro data suggest that some FDA-approved drugs inhibit ASBT function. Deficient FGF19 release increases hepatic bile acid synthesis and release into the intestines to levels that overwhelm ASBT. Either ASBT dysfunction or FGF19 deficiency increases fecal bile acids and may cause chronic diarrhea and promote colon neoplasia. Regrettably, tools to measure bile acid malabsorption and the actions of drugs on bile acid transport in vivo are limited. To understand the complex actions of bile acids, techniques are required that permit simultaneous monitoring of bile acids in the gut and metabolic tissues. This led us to conceive an innovative method to measure bile acid transport in live animals using a combination of proton (1H) and fluorine (19F) magnetic resonance imaging (MRI). Novel tracers for fluorine (19F)-based live animal MRI were created and tested, both in vitro and in vivo. Strengths of this approach include the lack of exposure to ionizing radiation and translational potential for clinical research and practice.

In Vivo Magnetic Resonance Imaging and Microwave Thermotherapy of Cancer Using Novel Chitosan Microcapsules.

Herein, we develop a novel integrated strategy for the preparation of theranostic chitosan microcapsules by encapsulating ion liquids (ILs) and Fe3O4 nanoparticles. The as-prepared chitosan/Fe3O4@IL microcapsules exhibit not only significant heating efficacy in vitro under microwave (MW) irradiation but also obvious enhancement of T2-weighted magnetic resonance (MR) imaging, besides the excellent biocompatibility in physiological environments. The chitosan/Fe3O4@IL microcapsules show ideal temperature rise and therapeutic efficiency when applied to microwave thermal therapy in vivo. Complete tumor elimination is realizing after MW irradiation at an ultralow power density (1.8 W/cm2), while neither the MW group nor the chitosan microcapsule group has significant influence on the tumor development. The applicability of the chitosan/Fe3O4@IL microcapsules as an efficient contrast agent for MR imaging is proved in vivo. Moreover, the result of in vivo systematic toxicity shows that chitosan/Fe3O4@IL microcapsules have no acute fatal toxicity. Our study presents an interesting type of multifunctional platform developed by chitosan microcapsule promising for imaging-guided MW thermotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-016-1536-0) contains supplementary material, which is available to authorized users.

MoS2-Gd Chelate Magnetic Nanomaterials with Core-Shell Structure Used as Contrast Agents in in Vivo Magnetic Resonance Imaging.

Despite their frequent usages as contrast agents for in vivo MRI imaging, paramagnetic molecules continue to suffer from low resolution, physicochemical instability, and high toxicity. Herein, we present a molybdenum disulfide and gadolinium complex, as an alternative core-shell magnetic nanomaterial that exhibits enhanced paramagnetic property; 4.5-times longer water proton spin-lattice relaxation time (T1) when compared to commercial gadolinium contrast agents; as well as lowered toxicity, extended blood circulation time, increased stability, and desirable excretion characteristic. Transmission electron microscopy (TEM) revealed smooth core-shell nanoparticles 100 nm in size with a shell width of approximately 10 nm. These findings suggest that the synthesized nanomaterial possesses high potential as a positive contrast agent for the enhancement of MRI imaging.

In Vivo Magnetic Resonance Imaging of Small Interfering RNA Nanodelivery to Pancreatic Islets.

Pancreatic islet transplantation is a promising therapeutic approach for type 1 diabetes.However, recent advances in islet transplantation are limited by significant graft loss after transplantation. Multiple immunological and nonimmunological factors contribute to this loss. Novel therapies that could target the core reasons for the islet graft loss are desperately needed. Small interfering RNA can be used to inhibit the expression of virtually any gene with single-nucleotide specificity including genes responsible for islet damage. Applying adequate delivery of siRNA molecules to pancreatic islets prior to transplantation holds a great potential for improving the survival of islet grafts. Noninvasive imaging provides means for monitoring the survival of transplanted islets in real time. Here, we summarize the approach that has been developed to deliver siRNA to pancreatic islets in conjunction with tracking of the graft outcome by in vivo magnetic resonance imaging (MRI). We synthesize a nano-sized theranostic agent consisting of magnetic nanoparticles (MN), a reporter for MRI, labeled with Cy5.5 dye for near-infrared fluorescence (NIRF) imaging, and conjugated to siRNA molecule targeting genes that are harmful to islet grafts. Pre-labeling of islets by MN-Cy5.5-siRNA allowed us to monitor the survival of transplanted islet grafts by MRI and NIRF imaging and resulted in efficient silencing of the target genes in vivo. This novel approach combines a therapeutic effect provided by RNA interference technology with in vivo MR imaging and is expected to significantly improve the outcome of islet transplantation in patients with type 1 diabetes.

In Vivo Magnetic Resonance Imaging Evaluation of Porous Tantalum Interbody Fusion Devices in a Porcine Spinal Arthrodesis Model.

Animal experimental study. To investigate the use of magnetic resonance (MR) imaging in the assessment of lumbar interbody fusion using porous tantalum implants in a porcine spinal fusion model. Porous tantalum has been used successfully as a spinal interbody fusion device. However, to our knowledge, there has been no consensus on the optimal technique for evaluating spinal fusion when using porous tantalum implants. Twelve 12-week-old female Danish Landrace pigs underwent 3 levels of anterior lumbar interbody fusion at L2-3, L4-5 and L6-7. One level was fused using a solid porous tantalum cage with pedicle screw fixation. The other 2 levels were fused using a hollow porous tantalum ring packed with autograft and stabilized anteriorly with staples. Six months postoperatively, T1-weighted, T2-weighted, and gadolinium-DTPA contrast-enhanced MRI were obtained on a GE 1.5-T unit. After sacrifice, conventional radiograph and histological examination were carried out. Eleven pigs went through the experiment without complications. On all the MR sequences, there were significant higher signal intensity bands at the vertebrae-implant interface of nonfused segments compared with that of fused segments and the vertebral bone and implants themselves (P < 0.001). There was an agreement between histological findings of fibrous tissues surrounding the implants and the high signal intensity band on T1- and T2-weighted MR images respectively (sensitivity 69.6% and 56.5%, specificity 90.7% and 95.3%), both of which were superior to conventional radiograph images (sensitivity 52.2%, specificity 97.7%), especially the T1-weighted MR images. MR imaging could be an effective and noninvasive way to determine the fusion status of tantalum metal implants. Compared with T2-weighted MR imaging and conventional radiograph, T1-weighted spin-echo MR imaging is more sensitive and specific in detecting nonunion via the lucency between the vertebral body and tantalum metal device. N/A.