T1-weighted Contrast Research Articles

Abstract No. 471 Deep learning to distinguish benign from malignant renal lesions based on routine magetice resonance imaging

With increasing discovery of renal incidentalomas, it is important to make a pretreatment differentiation between benign renal masses and malignant tumors. We aimed to develop a deep learning model that distinguishes benign renal tumors from renal cell carcinoma (RCC) by applying a residual convolutional neural network (ResNet) on routine magnetic resonance imaging (MRI). Preoperative MR images (T2-weighted and T1-post contrast sequences) of 1162 renal lesions in a multicenter cohort with definitive pathology were divided into training, validation, and test sets (70:20:10 split). Two ResNet models were trained to predict renal tumor pathology, one on T2-weighted images and one on T1-post contrast images. A logistic regression model was trained based on clinical features of each patient. A final ensemble model based on a bagging classifier was trained on the outputs of the ResNet models and the clinical features model to predict renal tumor pathology. Final model performance was compared with the interpretation of four experts. Among the 1162 renal lesions, 655 were malignant and 507 were benign. The final ensemble model achieved a test accuracy of 0.68 (95% CI: 0.59-0.76), sensitivity of 0.89 (95% CI: 0.79-0.95), and specificity of 0.41 (95% CI: 0.28-0.55). Compared to all experts averaged, the ensemble deep learning model had higher test accuracy (0.68 vs. 0.6, P = 0.12), higher test sensitivity (0.89 vs. 0.8, P = 0.11) and higher test specificity (0.41 vs. 0.35, P = 0.45), although none of these was statistically significant. Deep learning can noninvasively distinguish benign renal tumors from RCC using conventional MRI in a multi-institutional dataset with high accuracy and sensitivity compared with experts.

Folic acid-modified Laponite®-stabilized Fe3O4 nanoparticles for targeted T2-weighted MR imaging of tumor

In this study, a targeted T2-weighted MR imaging agent based on laponite (LAP) was constructed for cancer cells overexpressing folate receptors. Firstly, LAP stabilized Fe3O4 NPs are synthesized by a controlled co-precipitation route, and then amphiphilic copolymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG-COOH) is assembled on the surface of LAP/Fe3O4 NPs to provide additional stability, followed by the conjugate of folic acid modified generation 2 polyamidoamine dendrimer (G2-FA) via EDC coupling chemistry. The formed LAP/Fe3O4-PLA-PEG-G2-FA NPs can display good colloidal stability and an enhanced r2 relaxivity of 327.6 mM−1 s−1. In vitro experiments demonstrate that the hybrid nanoparticles are cytocompatible in the studied concentration range, and could specific target cancer cells with FA receptors overexpression. Finally, the xenografted tumor model experiment verifies that LAP/Fe3O4-PLA-PEG-G2-FA NPs can significantly reduce the MR signal of tumor site by specific accumulation, and be metabolized from the mice within 24 h. Therefore, LAP/Fe3O4-PLA-PEG-G2-FA NPs with good biocompatibility, a high r2 relaxivity, and FA targetability show a huge potential as a targeted T2-weighted MR imaging contrast for the early diagnosis of tumors overexpressing FA receptors.

Evaluation of Improvement of Tissue Contrast and Reduction of Imaging Time by Shortening TR in Brain T<sub>2</sub> FLAIR Using MTC Pulse

T2 fluid-attenuated inversion recovery (FLAIR) using inversion recovery pulse to suppress cerebrospinal fluid signal needs adequate T1 recovery time after data acquisition, otherwise, the T2-weighted contrast in brain tissue will get lower. Over 10000 ms of repetition time (TR) is recommended for the 1.5 T MR scanner, so it is difficult to shorten the imaging time. We verified whether T2 FLAIR combined with the magnetization transfer contrast (MTC) pulse shows better gray-to-white matter (GM/WM) and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR. Optimal parameters of the MTC pulse were determined with a self-produced phantom, which modeled on cerebral cortical gray and white matters. GM/WM contrasts of the phantom were measured in T2 FLAIR with the MTC pulse while decreasing TR gradually from 10000 ms to 6500 ms. Although GM/WM contrast of the phantom in T2 FLAIR with the MTC pulse gradually decreased as the TR got shortened, the T2 FLAIR with the MTC pulse of 6500 ms of TR still showed 27% higher contrast than the conventional T2 FLAIR (TR 10000 ms). GM/WM contrast in T2 FLAIR with the MTC pulse was improved also in healthy volunteers, but improvement in thalamo-medullary contrast was less than that of cerebral cortico-medullary and putamino-medullary contrasts. It seems to be because thalamus, which is a deep gray matter, shows a higher MTC effect than other gray matters. Thus, it is necessary to note that the tissue contrast might differ between T2 FLAIR with the MTC pulse and the conventional T2 FLAIR. Because general lesions with an elongated T2 value show lower MTC effect compared to the normal brain tissue, a clinical case with thalamic lesion showed that the lesion-to-normal tissue contrast improved in T2 FLAIR with the MTC pulse of 6500 ms of TR. Although it is necessary to note the difference in contrast between some tissues, T2 FLAIR with the MTC pulse improves GM/WM and lesion-to-normal tissue contrasts even when the TR is shortened compared to the conventional T2 FLAIR, and it enables to shorten the imaging time.

Gd(iii)-Pt(iv) theranostic contrast agents for tandem MR imaging and chemotherapy.

Pt(iv) prodrugs have emerged as versatile therapeutics for addressing issues regarding off-target toxicity and the chemoresistance of classic Pt(ii) drugs such as cisplatin and carboplatin. There is significant potential for Pt(iv) complexes to be used as theranostic agents, yet there are currently no reported examples of Gd(iii)–Pt(iv) agents for simultaneous MR imaging and chemotherapy. Here we report the synthesis, characterization, and in vitro efficacy of two Gd(iii)–Pt(iv) agents, GP1 and GP2. Both agents are water soluble and stable under extracellularly relevant conditions but are reduced under intracellular conditions. Both are cytotoxic in multiple cancer cell lines, cell permeable, and significantly enhance the T1-weighted MR contrast of multiple cell lines. Thus, GP1 and GP2 are promising agents for tandem MR imaging and chemotherapy and provide a versatile platform through which future Gd(iii)–Pt(iv) agents can be developed.

TME-activatable theranostic nanoplatform with ATP burning capability for tumor sensitization and synergistic therapy.

Adenosine triphosphate (ATP), as a key substance for regulating tumor progression in the tumor microenvironemnt (TME), is an emerging target for tumor theranostics. Herein, we report a minimalist but versatile nanoplatform with simultaneously TME-responsive drug release, TME-enhanced imaging, ATP-depletion sensitized chemotherapy and photothermal therapy for intelligent tumor theranostics.Methods: The Fe3+ and tannic acid (TA) coordination were self-deposited on doxorubicin (Dox) in a facile method to prepare Dox-encapsulated nanoparticles (DFTNPs).Results: When irradiated by a near infrared laser, the DFTNPs could elevate the temperature in the tumor region efficiently. Subsequently, the Dox could be released by the disassembly of Fe3+/TA in the TME to initiate chemotherapy. Particularly, the smart nanoagent not only enabled ATP-depletion and enhanced the therapeutic effect of chemotherapy, but also acted as photothermal transduction agent for photothermal therapy. Moreover, the nanoagent also acted as T1-weighted MR imaging,photoacoustic imaging and photothermal imaging contrast agent. The mice treated by DFTNPs plus laser showed a complete tumor eradication in 14d observation.Conclusion: This as-prepared versatile nanoplatform offers new insights toward the application of smart nanoagents for improved tumor theranostics.

An ultra-sensitive T 2-weighted MR contrast agent based on Gd3+ ion chelated Fe3O4 nanoparticles.

An ultra-sensitive T2-weighted MR imaging contrast agent was prepared based on Fe3O4 nanoparticles and Gd3+ ions (Fe3O4@Gd). Amino modified Fe3O4 nanoparticles were conjugated to diethylenetriamine pentaacetic acid, and finally coordinated with Gd3+ ions. The nanoparticles had a uniform morphology with a size of 100 nm and a Gd/Fe mass ratio of 1/110. The r2 (transverse relaxivity) of the Fe3O4 nanoparticles increased from 131.89 mM−1 s−1 to 202.06 mM−1 s−1 after coordination with Gd3+ ions. MR measurements showed that the aqueous dispersion of Fe3O4@Gd nanoparticles had an obvious concentration-dependent negative contrast enhancement. Hepatoma cells were selected to test the cytotoxicity and MR imaging effect. The application of Fe3O4@Gd nanoparticles as contrast agents was also exploited in vivo for T2-weighted MR imaging of rat livers. All the results showed the effectiveness of the nanoparticles in MR diagnosis.

A biomimetic nanozyme/camptothecin hybrid system for synergistically enhanced radiotherapy.

Although radiotherapy (RT) has been an effective therapeutic regimen against most solid tumors, its effect is limited by the hypoxic tumor microenvironment and radio-tolerance of tumor cells to a large extent. Here we have designed a biomimetic nanozyme/camptothecin hybrid system for synergistically enhanced radiotherapy, which consists of an internal camptothecin (CPT)-loaded hollow MnO2 core and an external tumor cell membrane. The tumor cell membrane endows the system with excellent tumor targeting ability. The hollow MnO2 core can deliver the hydrophobic drug CPT and catalyze the production of oxygen from hydrogen peroxide in tumor tissues, which was finally degraded into Mn2+, a T1-weighted contrast agent. The anti-tumor mechanism of this system includes two aspects: (i) the generated oxygen can improve the hypoxic state of the tumor microenvironment and enhance the radiotherapy sensitivity and (ii) CPT can induce cell cycle arrest in the S-phase at a low dose, which further increases the radio-sensitivity of tumor cells and augmented radiation-induced tumor damage. The results of in vivo experiments showed that the biomimetic nanozyme drug delivery system improved the hypoxic microenvironment of the tumor tissue with a high tumor inhibition rate in a murine model. This platform achieved synergistic radiotherapy sensitization and provided a novel idea for the design of a radiotherapy sensitization system.

Fabrication of pH-responsive PAA-NaMnF3@DOX hybrid nanostructures for magnetic resonance imaging and drug delivery

The combination of diagnosis and treatment is considered as a promising strategy to improve the efficiency of cancer treatment. Here, the authors report an intelligent theranostic nanoplatform that combines diagnosis and chemotherapy based on the NaMnF3 nanoparticles (NPs). Poly (acrylic acid) (PAA) modified NaMnF3 NPs (PAA-NaMnF3 NPs) were synthesized by a facile and low cost reaction method. Doxorubicin hydrochloride (DOX)-loaded PAA-NaMnF3 (PAA-NaMnF3@DOX) hybrid nanostructures have been successfully developed via electrostatic interaction for dual-functional magnetic resonance imaging (MRI) and pH-responsive drug delivery. The obtained PAA-NaMnF3@DOX hybrid nanostructures could not only act as T1 and T2-weighted contrast agents for MRI as a result of the existence of Mn2+ ions but also exhibit a pH-responsive drug releasing behavior, which brings an obvious cytotoxicity to cancer cells via MTT assay. The endocytosis process of PAA-NaMnF3@DOX hybrid nanostructures was further evaluated using optical microscopy. These results demonstrate that the developed PAA-NaMnF3@DOX hybrid nanostructures as a multifunctional theranostic nanoplatform could serve as imaging contrast agents and drug delivery system for cancer imaging and therapy.

NIMG-64. IMPACT OF TUMOR LOCATION ON IMAGE-DERIVED VOLUME, PROLIFERATION RATE AND GROWTH VELOCITY IN GLIOBLASTOMA PATIENTS

Abstract INTRODUCTION Glioblastoma (GBM) is the most common malignant primary brain tumor in adults with a median overall survival (OS) of 15months. Despite advancements in treatments, prognosis is dismal and the prognostic significance of tumor location is not entirely understood. METHODOLOGY: In our study, we investigated sex-specific volumetric, tumor growth kinetics, and outcome differences among GBMs in various brain locations. Primary GBM patients with pretreatment magnetic resonance imaging (MRI) data (N=289, 173 males, 116 females) were selected from our brain tumor repository. Tumor abnormality was segmented on T1-weighted post-gadolinium contrast agent (T1Gd) MRIs. We utilized the Harvard-Oxford brain atlases to determine the location of GBMs. RESULTS Overall, our study found smaller tumors in the left hemisphere. This may be expected as left-hemispheric GBM symptoms could present earlier, leading to earlier diagnosis and treatment. However, when the cohort was split by sex, we found this observation significant for females only in the parietal lobe (p < 0.0001). Further, female GBMs demonstrated smaller necrotic volume in the left hemisphere (p = 0.030). Sex-specific differences in incidence were noted in the temporal and occipital lobes (2M:1F). Comparing tumor growth kinetics in different brain locations and hemispheres, females had significantly lower tumor proliferation rates in the left hemisphere (p = 0.009) and lower tumor proliferation rates in the left frontal lobe (p = 0.031). Controlling for treatment, patients with frontal lobe tumors had significantly longer OS compared to those with GBMs in the temporal lobe (p = 0.046, 312 days). Differences in growth velocities were noted between frontal and parietal lobe with frontal GBMs having lower velocities in comparison to parietal lobe GBMs. CONCLUSION Together, our results demonstrate that tumor growth and proliferation rates may vary based on location and sex. Additional research is needed to further explore the clinical significance of tumor location.

SCIDOT-16. T2-WEIGHTED IMAGING MAY BE INDICATIVE OF DRUG DISTRIBUTION IN GLIOBLASTOMA PATIENTS

Abstract OBJECTIVES Dogma suggests that for brain tumors, regions of enhancement on T1-weighted gadolinium contrast enhanced (T1Gd) magnetic resonance imaging (MRI) correlate with intravenously delivered drug distribution as enhancement indicates a compromised blood-brain barrier (BBB). However, poor response to intravenous therapies highlights the importance of the diffuse disease beyond enhancing regions. This study investigated whether imaging features can provide an accurate prediction of drug distribution. METHODS Eight brain tumor patients (7 gliomas and 1 metastatic adenocarcinoma) were included in this Phase 0 trial. Presurgery T1-weighted, T1Gd, T2-weighted gadolinium contrast enhanced (T2Gd), and T2-weighted Fluid Attenuated Inversion Recovery (T2FLAIR) MRIs were acquired. All images underwent bias correction using the N4 algorithm, standardization of intensities, and registration. Prior to incision, patients received both an antibiotic cefazolin (6% BBB penetrance) and levetiracetam (80% BBB penetrance), an anti-seizure drug. Subsequently, multiple blood samples and image-guided biopsies were taken and analyzed for drug concentration using liquid chromatography mass spectrometry. Biopsy drug levels are reported as Brain-Plasma Ratio (BPR), the ratio of biopsy concentration relative to plasma concentration. Mean image intensity was extracted from an 8x8 mm window surrounding each biopsy location. Regression analysis was performed to determine which combination of image types were linearly predictive of BPR for both drugs. Correlations were also analyzed according to the biopsy location radiographic appearance. RESULTS Regression analysis revealed that T2Gd intensity was linearly predictive of cefazolin BPR and FLAIR intensity was linearly predictive of levetiracetam BPR (p=0.009 and 0.041, respectively). Grouping samples according the the radiographic appearance revealed that levetiracetam BPR had a similar pattern of values to that of FLAIR intensities and cefazolin BPR had a similar pattern to T2, further supporting the regression analysis results. CONCLUSIONS Local concentrations of drug may be related to T2-weighted signals (T2Gd and T2FLAIR) rather than the gadolinium distribution on T1Gd images.

Construction of Pepstatin A-Conjugated ultrasmall SPIONs for targeted positive MR imaging of epilepsy-overexpressed P-glycoprotein

Surgical resection of the epileptogenic region is typically regarded to be practical and efficient for complete elimination of intractable seizures, which cannot be simply controlled by anti-epileptic drugs alone. To achieve a precision removal of the epileptogenic region and even a surgical cure, molecular imaging of epilepsy markers is highly essential for non-invasive accurate detection of the epileptogenic region. In this work, a peptide-targeted nanoprobe, based on ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), PA-USPIONs, was elaborately constructed to enable highly selective delivery and sensitive T1-weighted positive magnetic resonance (MR) imaging of the epileptogenic region. Especially, Pepstatin A (PA), a small peptide which can specifically target to P-glycoprotein (P-gp) overexpressed at the epileptogenic region in a kainic acid (KA)-induced mice model of seizures, was conjugated onto the surface of PEGylated USPIONs. It has been demonstrated that the as-constructed PA-USPIONs nanoprobes have favorable T1 contrast enhancement and high r1 relaxivity compared with the clinically used T1-MR contrast agent (Gd-DTPA) by systematic in vitro and vivo assessments. Importantly, the toxicity evaluation, especially to brains, was assessed by the histological as well as hematological examinations, demonstrating that the fabricated PA-USPIONs nanoprobes are featured with excellent biocompatibility, guaranteeing the further potential clinical application. This first report on the development of USPIONs as T1-weighted MR contrast agents for active targeting of the epileptogenic region holds the high potential for precise resection of the according lesion in order to achieve therapeutic, often curative purposes.

A Deep Convolutional Neural Network for Annotation of Magnetic Resonance Imaging Sequence Type.

The explosion of medical imaging data along with the advent of big data analytics has launched an exciting era for clinical research. One factor affecting the ability to aggregate large medical image collections for research is the lack of infrastructure for automated data annotation. Among all imaging modalities, annotation of magnetic resonance (MR) images is particularly challenging due to the non-standard labeling of MR image types. In this work, we aimed to train a deep neural network to annotate MR image sequence type for scans of brain tumor patients. We focused on the four most common MR sequence types within neuroimaging: T1-weighted (T1W), T1-weighted post-gadolinium contrast (T1Gd), T2-weighted (T2W), and T2-weighted fluid-attenuated inversion recovery (FLAIR). Our repository contains images acquired using a variety of pulse sequences, sequence parameters, field strengths, and scanner manufacturers. Image selection was agnostic to patient demographics, diagnosis, and the presence of tumor in the imaging field of view. We used a total of 14,400 two-dimensional images, each visualizing a different part of the brain. Data was split into train, validation, and test sets (9600, 2400, and 2400 images, respectively) and sets consisted of equal-sized groups of image types. Overall, the model reached an accuracy of 99% on the test set. Our results showed excellent performance of deep learning techniques in predicting sequence types for brain tumor MR images. We conclude deep learning models can serve as tools to support clinical research and facilitate efficient database management.

Evaluation of giant arachnoid granulations with high-resolution 3D-volumetric MR sequences at 3T

PurposeTo evaluate the contribution to the diagnosis of the giant arachnoid granulations (AGs) of three-dimensional (3D) high-resolution magnetic resonance (MR) imaging sequences such as T2-weighted sampling perfection with application optimized contrasts using different flip-angle evolution (SPACE) and post-contrast T1-weighted magnetization prepared rapid gradient echo (MPRAGE). Materials and MethodsPatients with 45 giant AGs were included in this retrospective study. All the patients were performed 3D T2-weighted SPACE and contrast enhanced MR venography sequences, as well as conventional cerebral MR imaging sequences. Post-contrast T1 weighted MPRAGE sequence were performed on 38/45 patients. All cerebral MR examinations were reviewed by the 2 neuroradiologists. Each GA was evaluated carefully to assess location and mean diameter. ResultsThe most common location for giant AGs was at both transverse sinuses. Fluid signal feature within the giant AGs was not isointense to CSF on SE T1 and FLAIR MR imaging in 32 of 45 giant AGs. There were cerebral herniation into AG in 10 (22.2 %) of 45 giant AGs. 33 (73.3 %) of 45 giant AGs had central vein finding into AG in contrast enhanced MR venography. Signal void phenomenon into AG in 3D T2-weighted SPACE MR sequence was identified in 28 (62.2 %) of 45 giant AGs. ConclusionsFluid within giant AGs had no completely CSF-like signal intensity on conventional and 3D high-resolution MR imaging sequences. Majority of CSF-incongruent fluid within giant AGs on conventional sequences is mostly due to intra-AG CSF flow.

Mn-Porphyrin-Based Metal-Organic Framework with High Longitudinal Relaxivity for Magnetic Resonance Imaging Guidance and Oxygen Self-Supplementing Photodynamic Therapy.

A nanoplatform for magnetic resonance imaging guidance and oxygen self-supplementing photodynamic therapy (PDT) was constructed on the basis of a porous metal-organic framework (PCN-222(Mn)), which was built by simple Mn-porphyrin ligands and biocompatible Zr4+ ions. Because of the good dispersibility of Mn3+ in the open framework and the high water affinity of the channel, PCN-222(Mn) exhibits a high longitudinal relaxivity of ∼35.3 mM-1 s-1 (1.0 T). In addition, it shows good catalytic activity for the conversion of endogenous hydrogen peroxide into oxygen, thereby improving tumor hypoxia during photodynamic therapy. The intravenous injection of PCN-222(Mn) into tumor-bearing mice mode provided good T1-weighted contrast of the tumor site and effectively inhibited tumor growth upon a single-laser irradiation. The findings provide insights for the development of multifunctional theranostic nanoplatforms based on simple components.

Peptide-Decorated Ultrasmall Superparamagnetic Nanoparticles as Active Targeting MRI Contrast Agents for Ovarian Tumors

Magnetic resonance imaging (MRI) is widely applied in medical research and diagnosis, and a MRI contrast medium plays a crucial role in improving the sensitivity of detection. Ultrasmall superparamagnetic iron oxides (USPIOs) exhibit the potential as a T2 enhancement contrast medium for MRI due to their excellent magnetic response performance; however, to endow them with specific tumor targetability, long-term circulation performance has always been a hot topic in this field. In this study, a well-designed procedure of chemical coprecipitation, surface modification, and peptide grafting was applied to prepare the active tumor-targeting USPIOs@F127-WSG, in which Pluronic F127 (F127) and the peptide WSGPGVWGASVK (peptide-WSG) were selected as the template agent and the ovarian tumor-targeting ligand, respectively. The results showed that single USPIOs@F127-WSG particles were Fe3O4 nanoparticles regulated by the confinement effect of F127 micelles with a uniform globular morphology and size (∼9 nm), and peptide-WSG was grafted for their tumor targetability. USPIOs@F127-WSG particles presented superparamagnetic behavior with high T2 relaxivity (r2 = 278.15 mM-1 s-1) and in vitro targetability for SKOV-3 cells due to the special binding between peptide-WSG and specific receptors of SKOV-3. The test results in vivo verified the targetability of USPIOs@F127-WSG by their specific aggregation in the tumor regions, leading to the T2-weighted MRI contrast enhancement. These outstanding properties indicate that USPIOs@F127-WSG have great potential to be applied as the active tumor-targeting contrast agent for MRI.

Experimental sepsis-associated encephalopathy is accompanied by altered cerebral blood perfusion and water diffusion and related to changes in cyclooxygenase-2 expression and glial cell morphology but not to blood-brain barrier breakdown

Sepsis-associated encephalopathy (SAE) refers to brain dysfunction, including delirium, occurs during severe infection and is associated with development of post-traumatic stress disorder. SAE has been proposed to be related to reduced cerebral blood flow (CBF), blood–brain barrier breakdown (BBB), white matter edema and disruption and glia cell activation, but their exact relationships remain to be determined. In the present work, we set out to study CBF using Arterial Spin Labeling (ASL) and grey and white matter structure with T2- and diffusion magnetic resonance imaging (dMRI) in rats with cecal ligation and puncture (CLP)-induced encephalopathy. Using immunohistochemistry, the distribution of the vasoactive prostaglandin-synthesizing enzyme cyclooxygenase-2 (COX-2), perivascular immunoglobulins G (IgG), aquaporin-4 (AQP4) and the morphology of glial cell were subsequently assessed in brains of the same animals. CLP induced deficits in the righting reflex and resulted in higher T2-weighted contrast intensities in the cortex, striatum and at the base of the brain, decreased blood perfusion distribution to the cortex and increased water diffusion parallel to the fibers of the corpus callosum compared to sham surgery. In addition, CLP reduced staining for microglia- and astrocytic-specific proteins in the corpus callosum, decreased neuronal COX-2 and AQP4 expression in the cortex while inducing perivascular COX-2 expression, but did not induce widespread perivascular IgG diffusion. In conclusion, our findings indicate that experimental SAE can occur in the absence of BBB breakdown and is accompanied by increased water diffusion anisotropy and altered glia cell morphology in brain white matter.

Synthesis and Evaluation of a Gd (III) Complex as T1-Weighted MRI Contrast Agent

Synthesis and Evaluation of a Gd (III) Complex as T1-Weighted MRI Contrast Agent

Microwave-Assisted Synthesis of SPION-Reduced Graphene Oxide Hybrids for Magnetic Resonance Imaging (MRI).

Magnetic resonance imaging (MRI) is a useful tool for disease diagnosis and treatment monitoring. Superparamagnetic iron oxide nanoparticles (SPION) show good performance as transverse relaxation (T2) contrast agents, thus facilitating the interpretation of the acquired images. Attachment of SPION onto nanocarriers prevents their agglomeration, improving the circulation time and efficiency. Graphene derivatives, such as graphene oxide (GO) and reduced graphene oxide (RGO), are appealing nanocarriers since they have both high surface area and functional moieties that make them ideal substrates for the attachment of nanoparticles. We have employed a fast, simple and environmentally friendly microwave-assisted approach for the synthesis of SPION-RGO hybrids. Different iron precursor/GO ratios were used leading to SPION, with a median diameter of 7.1 nm, homogeneously distributed along the RGO surface. Good relaxivity (r2*) values were obtained in MRI studies and no significant toxicity was detected within in vitro tests following GL261 glioma and J774 macrophage-like cells for 24 h with SPION-RGO, demonstrating the applicability of the hybrids as T2-weighted MRI contrast agents.

MR Neurography: Normative Values in Correlation to Demographic Determinants in Children and Adolescents.

To determine normative morphological and functional magnetic resonance (MR) neurography values in children and adolescents in correlation to demographic determinants. In this study 29 healthy underage subjects (mean age 13.9 years, range10-17 years) were examined using astandardized MR neurography protocol of the lumbosacral plexus and the right lower extremity at 3 T. Volumes of the dorsal root ganglia L3-S2, cross-sectional area of the sciatic and tibial nerves, as well as T2-weighted contrast nerve-muscle ratio and quantitative diffusion tensor imaging(DTI) values of the sciatic nerve were obtained and correlated with the demographic parameters sex, age, height and weight. While all obtained morphological and functional MR neurography values did not differ between male and female sex, dorsal root ganglia volume, sciatic and tibial nerve cross-sectional area correlated positively with age, height, and weight. The T2-weighted signal of the sciatic nerve was independent of demographic determinants. Negative correlation was found for fractional anisotropy (FA) with age, height, and weight, whereas radial diffusivity (RD) showed apositive correlation only with age. Mean diffusivity(MD) and axial diffusivity (AD) revealed no correlation with demographic determinants. The results of this study suggest that selection of sex-matched controls for further studies assessing peripheral nerve pathologies in underage patients may not be necessary; however, control subjects should be adapted to age, height, and weight of the patient population, especially if assessing dorsal root ganglia volume, nerve cross-sectional area andDTI.

Understanding the High Longitudinal Relaxivity of Gd(DTPA)-Intercalated (Zn,Al)-Layered Double Hydroxide Nanoparticles.

In this study, biocompatible gadolinium diethylenetriaminepentaacetate (Gd(DTPA))-intercalated (Zn,Al)-layered double hydroxide (LDH) nanoparticles were synthesized, characterized for Gd(DTPA) loading percentage and nanostructure, and the spin-lattice relaxation times (T1) measured to determine their suitability as a potential T1-weighted contrast agent for magnetic resonance imaging (MRI). Compared to the most commonly used contrast agent in clinical MRI (i.e., molecular Gd(DTPA)), significant increases in longitudinal relaxivity (r1) were measured for all Gd(DTPA)-intercalated nanoparticles. For a specific Zn2Al(OH)6(Cl,0.5CO3)0.56Gd(DTPA)0.086·xH2O composition, r1 was found to be 28.38 s-1 mM-1, which is over 6 times the r1 of molecular Gd(DTPA). This dramatic increase in r1 is attributed to (a) the much longer rotational correlation time (τR) of nanoparticles and (b) the inherent water of LDH that forms the second-/outer-sphere in the vicinity of intercalated Gd(DTPA)2-. The latter, with an extensive hydrogen bonding network and insignificant translational motion, results in a longer mean residence lifetime (τM), which makes the contribution of second-/outer-sphere significant. Therefore, when the Gd(DTPA)2- loading percentage increases from 8.6 to 55%, the diminution of the ratio of inherent water to Gd(DTPA)2- concomitantly diminishes the contributions by second-/outer-sphere water to r1. Additionally, the modest increase in r1 with decreasing particle size (∼315-540 nm) is perhaps due to the shortening of τM. Finally, the spin-spin relaxation times (T2) of 17O, determined at various temperatures, show a negligible exchange of water molecules at room temperature. Therefore, the very high r1 of nanoparticles indicate that protons of the bulk water are still accessible to the Gd3+ centers, possibly dominated by prototropic exchange through the hydrogen bonding network.