Magnetic Resonance Imaging Visualization Research Articles

Polymer capsules modified with iron oxide nanoparticles as an effective platform for MRI visualization and drug delivery

Efficiency of existing (usually toxic) drugs can be increased substantially with the targeted effect on the site of the disease. A potential platform for the targeted drug delivery can be polymer capsules. This will help reduce side effects on the human body and start treatment at the early stages of the disease. Modification of such capsules with the magnetic nanoparticles allows their visualization using magnetic resonance imaging (MRI). In this study the use of polymer microcapsules modified with iron oxide nanoparticles are employed as contrast agents for T2-weighted magnetic resonance (MR) images, the possibility of their implementation as for drug delivery carriers are discussed. For this, two different types of polymer capsules are synthesized. The results on the spin-spin and spin-lattice relaxivities were obtained.

Dual-energy CT as an innovative method for diagnosing fragility fractures of the pelvic ring: a retrospective comparison with MRI as the gold standard.

As the average age of society increases, so does the number of cases of fragility fractures of the pelvis (FFP). Magnetic resonance imaging (MRI) can visualise associated oedema and is thus the gold standard for diagnosing such fractures. MRI, however, is costly, not always available, and involves certain exclusion criteria. Dual-energy computed tomography (DECT) appears to be a promising alternative. It is unclear, however, whether it could be used for diagnosing FFP with similar sensitivity/specificity. The aim of our study was thus to compare conventional CT and DECT with MRI in cases of suspected FFP. A total of 46 patients with suspected FFP underwent MRI, CT and DECT scans. There were three comparison groups for each of these patients: conventional CT image analysis without dual-energy modification (Arm 1), DECT analysis (Arm 2) and MRI as the gold standard (Arm 3). Diagnosis and FFP classification were performed by a radiologist in random order and without clinical information. The sensitivity and specificity of conventional CT and DECT were calculated in comparison with MRI as the reference standard. With 100% sensitivity and specificity, DECT is on par with MRI when it comes to diagnosing fragility fractures of the pelvis and is superior to conventional CT (90.3% sensitivity, 100% specificity). In terms of classification as well, there were no differences between DECT and MRI. On conventional CT, on the other hand, 16 patients were classified differently than they were on MRI. Our study shows DECT to be reliable and superior to conventional CT in terms of oedema detection and specific fracture classification in FFP. DECT thus combines the advantages of conventional CT (good visualisation of bone matter) and MRI (medullary cavity and visualisation of occult fractures).

Contrast Agents Based on Iron Oxide Nanoparticles for Clinical Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is one of the most perspective methods of noninvasive visualization in medicine, and use of contrast agents significantly its potentialities extends. Iron oxide nanoparticles are promising contrast agents, but in fact all the data on their efficiency were obtained in high-field tomographs for experimental animals. We studied the possibility of using magnetic nanoparticles for MRI visualization of rat brain glioblastoma at the most common clinical field 1.5 T The data indicate the efficiency of iron oxide magnetic nanoparticles as contrast agents for 1.5 T MR tomographs.

Non-contrast-enhanced magnetic resonance imaging for visualization and quantification of endovascular aortic prosthesis, their endoleaks and aneurysm sacs at 1.5 T

PurposeAfter an endovascular aortic aneurysm repair (EVAR), a follow-up at 1, 6 and every 12 months is recommended for remainder of the patient's life. The diagnostic standard methods for diagnosing endoleaks and visualization of aneurysms in EVAR-patients are: invasive digital subtraction angiography (DSA), contrast enhanced (CE) computed tomographic angiography (CE-CTA), and magnetic resonance angiography (CE-MRA). These techniques, however, require the use of iodine- or gadolinium-based contrast agents with rare, but possibly life threatening side effects such as renal impairment, thyrotoxicosis and allergic reactions, nephrogenic systemic fibrosis, and cerebral gadolinium deposition. The aim of this prospective study was to compare a non-contrast-enhanced MRI protocol (consist of four MRI methods) with DSA and CE-CTA for visualization and quantification of endovascular aortic prosthesis, their endoleaks and aneurysms. Material and methodsEight patients (mean age 76.8 ± 4.9 years, 63% male), whose thoracic, abdominal, or iliac aneurysms were treated with different endovascular prosthesis and suffered from type I–V endoleaks, were examined on a 1.5 Tesla MR system. Quiescent-interval slice selective MR angiography (QISS-MRA), 4-dimensional (4D)-flow MRI, T1- and T2-mapping, as well as DSA and CE-CTA were used for the visualization and quantification of endoprosthesis, endoleaks, and aneurysms in these patients. ResultsQISS-MRA provided good visualization of endoleaks and comparable quantification of aneurysm size with respect to CE-CTA and DSA. The 4D-flow MRI provided additional information about the wall shear stress, which could not be determined using DSA. In contrast to CE-CTA, T1- and T2-mapping provided detailed information about heterogeneous areas within an aneurysm sac. ConclusionsCompared to DSA and CE-CTA, the proposed MRI methods provide improved anatomical and functional information for various types of endoprostheses and endoleaks. In addition, hemodynamic parameters of the aorta and information on the content of aneurysm sac are provided as well. Within the frame of personalized medicine, the personalized diagnosis enabled by this non-CE MRI protocol is the foundation for a personalized and successful treatment.

Computed tomography and magnetic resonance imaging in the diagnosis of the small and large intestine strictures in Crohn’s disease. Radiological semiotics and assessment of the inflammation activity

Rationale: Crohn's disease is characterized by continuous severe course, and in a half of the patients is associated with formation of strictures that are difcult to treat and signifcantly decrease quality of life. Difculties during the differentiation between inflammation-related and fbrostenotic strictures and divergent approaches to their treatment in patients with Crohn's disease indicate the need in precise diagnostics and systematization of the radiological semiotics of strictures.Aim: To propose radiological semiotics of the small and large intestine strictures based on the results of multiaxial computed tomography (MACT) and magnetic resonance imaging (MRI).Materials and methods: MACT and MRI visualization was performed in 40 patients with a stenotic type of Crohn's disease.Results: The radiological signs of the strictures were classifed into two main groups: intestinal and extra-intestinal. They were systematized according to nine criteria, such as character of formation, etiology, number, inflammation grade, extension, shape, and location, presence of ileus and presence of other complications. The inflammation activity in the intestinal wall was evaluated during the postcontrast assessment: active inflammation in the arterial phase (at 25 seconds after administration of the contrast agent), chronic inflammation in the delayed phase (at 10 minutes). The MRI results were cross-checked with those of MACT. At the precontrast stage, MRI was more informative as per the width of the intestinal lumen, whereas MACT was preferential in the diagnosis of fat infltration of the intestinal wall. Post-contrast MACT and MRI were diagnostically equivalent. The most indicative for active inflammation were diffuse weighed MRI images, arterial phase MACT and MRI, whereas chronic inflammation and wall fbrosis were better diagnosed at the delayed phase (at 10 minutes) of MACT and MRI. Both methods (MACT and MRI) could not differentiate between the submucous and muscular layers of the intestinal wall. Mixed type of inflammation was seen in the walls of intestinal strictures: chronic inflammation dominated in the intermediate, most extensive part of a stricture and remained stable during the dynamic follow-up, whereas active inflammation was found in the marginal parts of the strictures, which were most susceptible to changes during the follow-up.Conclusion: Based on a set of certain signs obtained by radiological visualization, we propose a registry for stricture assessment based on evaluation of the inflammation activity.

“Magnus nano-bullets” as T1/T2 based dual-modal for in vitro and in vivo MRI visualization

Tissue specific T1/T2 dual contrast abilities for magnetic resonance imaging (MRI) have great significance in initial detection of cancer lesions. Herein, we developed a novel kind of Magnus nano-bullets (Mn-DTPA-F-MSNs) distinguished by magnetic (Fe3O4-NPs) head combined with mesoporous (SiO2) persist body, respectively. Subsequently, modify mesoporous SiO2 group and finally loaded with Mn2+. These Magnus nano-bullets have relaxivity value (r1 = 5.12 mM−1 s−1) and relaxivity value (r2 = 265.32 mM−1 s−1); they were > 2 folds in comparison to control at 3.0 T. Meanwhile, Magnus nano-bullets also offered significant enhancements for the detection of Glutathione (GSH), a biomarker that has been showed a redox responsive T1-weighted MRI effect in vitro and in vivo evaluations with good biocompatibility. Therefore, our finding endorses that Magnus nano-bullets offer a “smart” and tremendous strategy for greater GSH responsive T1/T2 dual MRI image probes for future biomedical applications.

Treatment of oral cancer using magnetized paclitaxel

N,N’-Bis(salicylidene)ethylenediamine iron (Fe(Salen)) is an anti-cancer agent with intrinsic magnetic property. Here, we covalently linked Fe(Salen) to paclitaxel (PTX), a widely used anti-cancer drug, to obtain a magnetized paclitaxel conjugate (M-PTX), which exhibited magnetic characteristics for magnet-guided drug delivery and MRI visualization. M-PTX increased apoptosis and G2/M arrest of cultured human oral cancer cell lines in the same manner as PTX. Furthermore, marked contrast intensity was obtained in magnetic resonance imaging (MRI) of M-PTX. In a mouse oral cancer model, a permanent magnet placed on the body surface adjacent to the tumor resulted in distinct accumulation of M-PTX, and the anti-cancer effect was greater than that of M-PTX without the magnet. We believe that this strategy may improve future cancer chemotherapy by providing conventional anti-cancer drugs with novel functionalities such as magnet-guided drug delivery or MRI-based visualization/quantitation of drug distribution.

Peculiarities of the Rice Statistical Distribution: Mathematical Substantiation

The Rice statistical distribution has recently become a subject of increasing scientific interest due to its wide applicability in various fields of science and technology, such as the magnetic-resonance visualization and ultrasound diagnostics in medicine, the radio and radar signals’ analysis and processing, the optical measurements, etc. The common feature of the tasks that are adequately described by the Rician statistical model consists in the fact that the value to be measured and analyzed is an amplitude, or an envelope of the output signal which is composed as a sum of the initially determined informative component and a random noise component being formed by many independent normally-distributed summands. The efficient reconstruction of the Rician signal’s informative component against the noise background is shown to be achieved only on the basis of joint determination of both a priori unknown Rician parameters. The Rice statistical distribution possesses some peculiarities that allow solving rather complicated tasks connected with the stochastic data processing. The paper considers the issues of the strict mathematical substantiations of the Rice distribution properties that are meaningful for its efficient application, namely: the Rician likelihood function features and the stable character of the Rice distribution. There are provided the rigorous proofs of the mentioned properties.

7T MRI Visualization of Cortical Lesions in Adolescents and Young Adults with Pediatric-Onset Multiple Sclerosis.

Cortical pathology in multiple sclerosis (MS) has been associated with prolonged and progressive disease. 7T magnetic resonance imaging (MRI) provides enhanced visualization of cortical lesions (CLs). Hence, we conducted a pilot study to explore whether CLs occur early in MS, as evidenced by pediatric-onset patients. A total of 8 pediatric-onset MS patients were imaged using 7T MRI. CLs were annotated on T1-weighted magnetization-prepared rapid acquisition of gradient echoes images as leukocortical (LC), intracortical, or subpial. Total CLs, age at onset, age at scan, disease duration, total relapses, and Expanded Disability Status Scale (EDSS) score were recorded. A median of 120 (range: 48-144) CLs was identified in 8 MS patients (3 female, all with relapsing remitting MS, mean age at scan 21 years ± 3.5 SD, mean age of disease onset 15 years ± 2.3 SD, mean disease duration 5.3 years ± 3.4 SD, median EDSS 2.0). Nearly all the lesions identified were LC. Many CLs are detectable using 7T MRI in patients with pediatric-onset MS despite relatively brief disease duration, absence of progressive disease, and very limited physical disability-supporting early cortical involvement in MS.

Magnetic Enhancement of Stem Cell–Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood–Brain Barrier

Focused ultrasound (FUS)-mediated blood–brain barrier disruption (BBBD) can enable even large therapeutics such as stem cells to enter the brain from the bloodstream. However, the efficiency is relatively low. Our previous study showed that human neural progenitor cells (hNPCs) loaded with superparamagnetic iron oxide nanoparticles (SPIONs) in culture were attracted by an external magnetic field. In vivo, enhanced brain retention was observed near a magnet mounted on the skull in a rat model of traumatic brain injury, where BBBD also occurs. The goal of the current study was to determine whether magnetic attraction of SPION-loaded hNPCs would also enhance their retention in the brain after FUS-mediated BBBD. A small animal magnetic resonance imaging (MRI)-guided FUS system operating at 1.5 MHz was used to treat rats (∼120 g) without tissue damage or hemorrhage. Evidence of successful BBBD was validated with both radiologic enhancement of gadolinium on postsonication TI MRI and whole brain section visualization of Evans blue dye. The procedure was then combined with the application of a powerful magnet to the head directly after intravenous injection of the hNPCs. Validation of cells within the brain was performed by staining with Perls’ Prussian blue for iron and by immunohistochemistry with a human-specific antigen. By injecting equal numbers of iron oxide (SPIONs) and noniron oxide nanoparticles–loaded hNPCs, each labeled with a different fluorophore, we found significantly greater numbers of SPIONs-loaded cells retained in the brain at the site of BBBD as compared to noniron loaded cells. This result was most pronounced in regions of the brain closest to the skull (dorsal cortex) in proximity to the magnet surface. A more powerful magnet and a Halbach magnetic array resulted in more effective retention of SPION-labeled cells in even deeper brain regions such as the striatum and ventral cortex. There, up to 90% of hNPCs observed contained SPIONs compared to 60% to 70% with the less powerful magnet. Fewer cells were observed at 24 h posttreatment compared to 2 h (primarily in the dorsal cortex). These results demonstrate that magnetic attraction can substantially enhance the retention of stem cells after FUS-mediated BBBD. This procedure could provide a safer and less invasive approach for delivering stem cells to the brain, compared to direct intracranial injections, substantially reducing the risk of bleeding and infection.

Lanthanide Complexes in Molecular Magnetic Resonance Imaging and Theranostics.

Lanthanide complexes have attracted much attention in the biomedical field, and today various imaging applications make use of their versatile magnetic and luminescence properties. In this minireview, we give insight into the mechanistic aspects that allow modulation of the relaxation or chemical exchange saturation transfer (CEST) features, and thus the magnetic resonance imaging (MRI) efficiency of paramagnetic lanthanide chelates in order to create agents that are capable of providing an MRI response as a function of a specific biomarker. We focus on the detection of neurotransmitters, enzymatic activities, and amyloid peptides. We also describe two selected theranostic strategies: 1) a novel approach directed at monitoring drug release from liponanoparticles and 2) molecular or nanoparticle probes for the MRI visualization of photosensitizer delivery in photodynamic therapy.

Theranostic Nanoparticles for MRI-Guided Thermochemotherapy: “Tight” Clustering of Magnetic Nanoparticles Boosts Relaxivity and Heat-Generation Power

Magnetic-resonance-imaging (MRI)-guided magnetic thermochemotherapy is a potentially invasive technique combining diagnosis and treatment. It requires the development of multifunctional nanoparticles with (1) biocompatibility, (2) high relaxivity, (3) high heat-generation power, (4) controlled drug release, and (5) tumor targeting. Here, we show the synthesis of such multifunctional nanoparticles ("Core-Shells") and the feasibility of MRI-guided magnetic thermochemotherapy using the synthesized nanoparticles. "Tight" iron-oxide nanoparticle clustering to zero interparticle distance within the Core-Shells boosts the relaxivity and heat-generation power while maintaining biocompatibility. The initial Core-Shell drug release occurs in response to an alternating magnetic field (AMF) and continues gradually after removal of the AMF. Thus, a single Core-Shell dose realizes continuous chemotherapy over a period of days or weeks. The Core-Shells accumulate in abdomen tumors, facilitating MRI visualization. Subsequent AMF application induces heat generation and drug release within the tumors, inhibiting their growth. Core-Shell magnetic thermochemotherapy exhibits significantly higher therapeutic efficacy than both magnetic hyperthermia and chemotherapy alone. More importantly, there are minimal side effects. The findings of this study introduce new perspectives regarding the development of materials for MRI, magnetic hyperthermia, and drug delivery systems. Both conventional and novel iron-oxide-based materials may render theranostics (i.e., techniques fusing diagnosis and treatment) feasible.

Myelin-targeted, texaphyrin-based multimodal imaging agent for magnetic resonance and optical imaging.

Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin-specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin-specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin-specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin-specific histological stain, into texaphyrins coordinated to GdIII . These new complexes demonstrated absorption of visible light, emission of near-IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section- and en block-staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin. Copyright © 2016 John Wiley & Sons, Ltd.

In vivo MRI visualization of U87 glioblastoma development dynamics in the model of orthotopic xenotransplantation to the SCID mouse

Glioblastoma is an extremely aggressive type of brain tumor. The average life span of patients with this diagnosis is 9–12 months. The development of adequate experimental models is required for the search of efficient approaches for the therapy and diagnostics of this disease. In this study, we used a number of magnetic resonance imaging (MRI) methods for describing the growth dynamics and cell morphology of U87 glioblastoma orthotopically xenotransplanted into mice of the immunodeficient SCID line. A comparison of the visualization efficiency of the developing tumor by means of T1- and T2-weighted images (obtained using an ultra-high field Bruker BioSpec (11.7 T) tomograph) demonstrated that T1-weighted images do not provide the required contrast of a pathological tissue relative to a healthy one (as opposed to T2-weighted images) due to the strong longitudinal magnetization of the tomograph’s magnetic field. of T1-weighted images, together with the intravenous introduction of paramagnetic nanoparticles (manganese oxide, MnO) significantly increased the tumor/normal tissue contrast in the MRI images. The study of the dynamics of the tumor cell growth by means of T2-weighted images demonstrated that the tumor development starts no earlier than 3 weeks after the intracranial introduction of the U87 cell culture (and the tumor cells grow exponentially). Thus, the methods of T1- and T2-weighted and MnO-enforced MRI were developed and characterized on the model of orthotopic xenotransplantation of U87 human glioblastoma cells into immunodeficient SCID animals, which can be used as the in vivo experimental model for checking new antitumor drugs and schemes of the treatment of the human brain’s oncological diseases.

MRI monitoring and non-destructive quality measurement of polymeric patterns manufactured via stereolithography

The use of Magnetic Resonance Imaging (MRI) for monitoring, studying and performing output quality measurements of the acrylate-based polymeric patterns manufactured using stereolithography (SL) was introduced in this work. The effects of build parameters and humid environment on sample homogeneity, distribution of crosslink density, stability and defect formation were examined. The spatial resolution of the method was found to be sufficient to identify patterns according to the build parameters used and to detect specific hatch-predicted crosslink density variations. Qualitative information obtained using MRI visualisation was supplemented by quantitative measurements of Nuclear Magnetic Resonance (NMR) relaxation times and 1H NMR spectra. NMR spectroscopy confirmed the identity of the chemical composition among the patterns and showed that the crosslink density variation observed via spatially resolved T2-profiles stems from the difference of the build parameters. Different types of defects in the samples were observed and classified; some defects originated from local matrix continuity failures (partially cured resin trapping within the polymer or bubbles formation), while other defects were found in the form of bulk layering. MRI visualisation coupled with relaxometry and 1H spectroscopy of patterns during their interaction with humidity allowed tracking water distribution inside the sample and observing effects of swelling, fracturing and chemical decomposition. It was found that the initial inhomogeneous structure of the specimen has a crucial role in subsequent fracturing due to non-uniform expansion of the swollen parts. As a result, the approach presented in this work improves the output quality control and current testing techniques, provides insight how physical properties of the 3D parts are affected by different technical parameters, and eventually can help the use of SL technologies for a variety of applications.

MRI: first-line imaging modality for pregnant patients with suspected appendicitis.

The purpose of our study was to evaluate the sensitivity, specificity, and accuracy of ultrasound (US) as compared to magnetic resonance imaging (MRI) in pregnant patients with suspected appendicitis for visualization of the appendix, accuracy at diagnosing acute appendicitis, the ability of each modality to identify alternate diagnoses of pain and whether gestational age (GA) has an association with appendix identification rates. We retrospectively reviewed the records of 140 pregnant patients with suspected appendicitis to determine the efficacy of US and MRI to identify the appendix, diagnose or exclude acute appendicitis, identify alternative etiologies for clinical presentation, and the affect of GA on identification of the appendix. Imaging results were correlated with surgical pathology in patients who underwent surgery. The electronic medical record was used to assess clinical outcomes in patients who did not undergo surgery. The appendix was visualized in 7% (8/117) of US exams and in 80% (91/114) of MRI exams. Alternate etiologies of pathology were determined in 3% (3/117) of US exams and 12% (14/114) of MRI exams. The sensitivity and specificity of MRI for acute appendicitis were both 100% and 98%, respectively, as compared to 18% and 99%, respectively, with US. GA did not affect MRI or ultrasound visualization rates of the appendix. Given the low likelihood of visualization of the appendix at US, the excellent accuracy of MRI and the ability of MRI to identify alternate diagnoses, we suggest that at certain institutions MRI may be considered a first-line imaging modality for pregnant patients of any GA with suspected appendicitis.

SALINE ARTHROGRAPHY OF THE DISTAL INTERPHALANGEAL JOINT FOR LOW-FIELD MAGNETIC RESONANCE IMAGING OF THE EQUINE PODOTROCHLEAR BURSA: FEASIBILITY STUDY.

Abnormalities of the deep digital flexor tendon, navicular bone, and collateral sesamoidean ligament can be difficult to visualize using magnetic resonance imaging (MRI) if bursal fluid is absent. The use of saline podotrochlear bursography improves podotrochlear apparatus evaluation, however, the technique has disadvantages. The objective of this prospective feasibility study was to describe saline arthrography of the distal interphalangeal joint as an alternative technique for improving MRI visualization of the deep digital flexor tendon, navicular bone, collateral sesamoidean ligament, and podotrochlear bursa, and to compare this technique with saline podotrochlear bursography. Eight paired cadaver forelimbs were sampled. Saline podotrochlear bursography or saline arthrography techniques were randomly assigned to one limb, with the alternate technique performed on the contralateral limb. For precontrast and postcontrast studies using each technique, independent observers scored visualization of the dorsal aspect of the deep digital flexor tendon, palmar aspect of the navicular bone, collateral sesamoidean ligament, and podotrochlear bursa. Both contrast techniques improved visualization of structures over precontrast MR images and visualization scores for both techniques were similar. Findings from this study demonstrated that saline arthrography is feasible and comparable to saline podotrochlear bursography for producing podotrochlear bursa distension and separation of the structures of the podotrochlear apparatus on nonweight bearing limbs evaluated with low-field MRI. Clinical evaluation of saline arthrography on live animals is needed to determine if this technique is safe and effective as an alternative to saline podotrochlear bursography in horses with suspected pathology of the podotrochlear apparatus.

Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes.

Adipose tissue (AT) substitutes are being developed to answer the strong demand in reconstructive surgery. To facilitate the validation of their functional performance in vivo, and to avoid resorting to excessive number of animals, it is crucial at this stage to develop biomedical imaging methodologies, enabling the follow-up of reconstructed AT substitutes. Until now, biomedical imaging of AT substitutes has scarcely been reported in the literature. Therefore, the optimal parameters enabling good resolution, appropriate contrast, and graft delineation, as well as blood perfusion validation, must be studied and reported. In this study, human adipose substitutes produced from adipose-derived stem/stromal cells using the self-assembly approach of tissue engineering were implanted into athymic mice. The fate of the reconstructed AT substitutes implanted in vivo was successfully followed by magnetic resonance imaging (MRI), which is the imaging modality of choice for visualizing soft ATs. T1-weighted images allowed clear delineation of the grafts, followed by volume integration. The magnetic resonance (MR) signal of reconstructed AT was studied in vitro by proton nuclear magnetic resonance ((1)H-NMR). This confirmed the presence of a strong triglyceride peak of short longitudinal proton relaxation time (T1) values (200 ± 53 ms) in reconstructed AT substitutes (total T1=813 ± 76 ms), which establishes a clear signal difference between adjacent muscle, connective tissue, and native fat (total T1 ~300 ms). Graft volume retention was followed up to 6 weeks after implantation, revealing a gradual resorption rate averaging at 44% of initial substitute's volume. In addition, vascular perfusion measured by dynamic contrast-enhanced-MRI confirmed the graft's vascularization postimplantation (14 and 21 days after grafting). Histological analysis of the grafted tissues revealed the persistence of numerous adipocytes without evidence of cysts or tissue necrosis. This study describes the in vivo grafting of human adipose substitutes devoid of exogenous matrix components, and for the first time, the optimal parameters necessary to achieve efficient MRI visualization of grafted tissue-engineered adipose substitutes.

MRI-monitored intra-tumoral injection of iron-oxide labeled Clostridium novyi-NT anaerobes in pancreatic carcinoma mouse model.

ObjectivesTo validate the feasibility of labeling Clostridium novyi-NT (C.novyi-NT) anaerobes with iron-oxide nanoparticles for magnetic resonance imaging (MRI) and demonstrate the potential to use MRI to visualize intra-tumoral delivery of these iron-oxide labeled C.novyi-NT during percutaneous injection procedures.Materials and MethodsAll studies were approved by IACUC. C.novyi-NT were labeled with hybrid iron-oxide Texas red nanoparticles. Growth of labeled and control samples were evaluated with optical density. Labeling was confirmed with confocal fluorescence and transmission electron microscopy (TEM). MRI were performed using a 7 Tesla scanner with T2*-weighted (T2*W) sequence. Contrast-to-noise ratio (CNR) measurements were performed for phantoms and signal-to-noise ratio (SNR) measurements performed in C57BL/6 mice (n = 12) with Panc02 xenografts before and after percutaneous injection of iron-oxide labeled C.novyi-NT. MRI was repeated 3 and 7 days post-injection. Hematoxylin-eosin (HE), Prussian blue and Gram staining of tumor specimens were performed for confirmation of intra-tumoral delivery.ResultsIron-oxide labeling had no influence upon C.novyi-NT growth. The signal intensity (SI) within T2*W images was significantly decreased for iron-oxide labeled C.novyi-NT phantoms compared to unlabeled controls. Under confocal fluorescence microscopy, the iron-oxide labeled C.novyi-NT exhibited a uniform red fluorescence consistent with observed regions of DAPI staining and overall labeling efficiency was 100% (all DAPI stained C.novyi-NT exhibited red fluorescence). Within TEM images, a large number iron granules were observed within the iron-oxide labeled C.novyi-NT; these were not observed within unlabeled controls. Intra-procedural MRI measurements permitted in vivo visualization of the intra-tumoral distribution of iron-oxide labeled C.novyi-NT following percutaneous injection (depicted as punctate regions of SI reductions within T2*-weighted images); tumor SNR decreased significantly following intra-tumoral injection of C.novyi-NT (p<0.05); these SNR reductions were maintained at 3 and 7 day follow-up intervals. Prussian blue and Gram staining confirmed presence of the iron-oxide labeled anaerobes.Conclusions C.novyi-NT can be labeled with iron-oxide nanoparticles for MRI visualization of intra-tumoral deposition following percutaneous injection during bacteriolytic therapy.

Suppression of the PI3K pathway in vivo reduces cystitis-induced bladder hypertrophy and restores bladder capacity examined by magnetic resonance imaging.

This study utilized magnetic resonance imaging (MRI) to monitor the real-time status of the urinary bladder in normal and diseased states following cyclophosphamide (CYP)-induced cystitis, and also examined the role of the phosphoinositide 3-kinase (PI3K) pathway in the regulation of urinary bladder hypertrophy in vivo. Our results showed that under MRI visualization the urinary bladder wall was significantly thickened at 8 h and 48 h post CYP injection. The intravesical volume of the urinary bladder was also markedly reduced. Treatment of the cystitis animals with a specific PI3K inhibitor LY294002 reduced cystitis-induced bladder wall thickening and enlarged the intravesical volumes. To confirm the MRI results, we performed H&E stain postmortem and examined the levels of type I collagen by real-time PCR and western blot. Inhibition of the PI3K in vivo reduced the levels of type I collagen mRNA and protein in the urinary bladder ultimately attenuating cystitis-induced bladder hypertrophy. The bladder mass calculated according to MRI data was consistent to the bladder weight measured ex vivo under each drug treatment. MRI results also showed that the urinary bladder from animals with cystitis demonstrated high magnetic signal intensity indicating considerable inflammation of the urinary bladder when compared to normal animals. This was confirmed by examination of the pro-inflammatory factors showing that interleukin (IL)-1α, IL-6 and tumor necrosis factor (TNF)α levels in the urinary bladder were increased with cystitis. Our results suggest that MRI can be a useful technique in tracing bladder anatomy and examining bladder hypertrophy in vivo during disease development and the PI3K pathway has a critical role in regulating bladder hypertrophy during cystitis.