Gadobutrol Research Articles

MRI-based sensing of pH-responsive content release from mesoporous silica nanoparticles

A proof of principle study toward developing a novel methodology which could be applicable for a non-invasive monitoring of the release of cargo molecules from therapeutic and diagnostic nanoparticles, as well as for possible monitoring of tissue pH variations. This was achieved by quantifying changes in longitudinal relaxation time (T1) before and after the pH-responsive release of contrast agents, for magnetic resonance imaging (MRI), from the pores of mesoporous silica nanoparticles (MSNs). The pores were filled with the FDA-approved contrast agent Gadobutrol (GdB), and its retention inside the pores ensured by covalent attachment of β-cyclodextrin monoaldehyde to hydrazine-functionalized MSN, through acidification-cleavable hydrazone linkage. The release kinetics of GdB was measured by fluorescence spectroscopy which revealed that the release of the contrast agent was enhanced at pH 5.0 in comparison to the release at pH 6.0 and 7.4. Furthermore, the changes in T1, occurring in response to the enhanced release of GdB from the pores of MSN at weakly acidic conditions, were successfully demonstrated by MRI measurements. It is envisioned that this approach using contrast agent-loaded nanoparticles before the treatment with the drug-filled analogs, could be applied in the future for tracking the locations and efficacies of nanomedicines for therapeutic cargo delivery.Graphical Pores of of β-maleimidopropionic acid hydrazide (BMPH)-functionalized mercaptopropyl-functionalized mesoporous silica nanoparticles (MPMSNs) were loaded with the contrast agent Gadobutrol and capped with β-cyclodextrin monoaldehyde. In weakly acidic environment the release of contrast agents was induced, and the enhanced release of GdB at pH 5.0 vs. pH 7.4 was evidenced by magnetic resonance imaging measurements.

MR and fluorescence imaging of gadobutrol-induced optical clearing of red fluorescent protein signal in an in vivo cancer model.

Multimodality registration of optical and MR images in the same tissue volume in vivo may be enabled by MR contrast agents with an optical clearing (OC) effect. The goals of this study were to (a) investigate the effects of clinical MR contrast agent gadobutrol (GB) and its combinations as a potential OC agent assisting in fluorescence intensity (FI) imaging in vivo and (b) evaluate MRI as a tool for imaging of topical or systemic application of GB for the purpose of OC. Subcutaneous tumor xenografts expressing red fluorescent marker protein were used as disease models. MRI was performed at 1 T 1 H MRI using T1 -weighted 3D gradient-echo (T1w-3D GRE) sequences to measure time-dependent MR signal intensity changes by region of interest analysis after image segmentation. Topical application of 1.0 M or 0.7 M GB-containing OC mixture with water and dimethyl sulfoxide showed similar 30-40% increases of tumor FI during the initial 15 min. Afterwards, the OC effect of GB on FI and tumor/background FI ratio showed a decrease over time in the case of 1.0 M GB, unlike the 0.7 M GB mixture, which resulted in a steady increase of FI and tumor/background ratio for 15-60 min. The use of T1w-3D GRE MR pulse sequences showed that concentrated 1.0 M GB resulted in MR signal loss of the skin due to high magnetic susceptibility and that signal loss coincided with the OC effect. Intravenous injection of 0.3 mmol GB/kg resulted in a rapid but transient 40% increase of FI of the tumors. Overall, 1 T MRI enabled tracking of GB-containing OC compositions on the skin surface and tumor tissue, supporting the observation of a time-dependent FI increase in vivo.

PMU15 Comparison of Clinical and Economical Outcomes of Alternative Imaging Methods in Turkey

Magnetic resonance imaging (MRI) with Gadobutrol (GAD), MRI with Gadoteric Acid (GOT), and peripheral angiography (PA) methods are used in the diagnosis of vascular disease (VD). MRI with Gadoxetic-acid (GAX), MRI with extracellular contrast agent (ECCM), or contrast CT (CCT) are used for the diagnosis of liver metastasis (LM). The study aimed to compare the clinical and economic outcomes of alternative imaging methods in the diagnosis of VD and LM in Turkey. The clinical and economic data were examined through a literature review. An expert opinion survey conducted for the missing data. The data gathered from literature and expert opinions analyzed via the decision tree model. In case of no diagnosis with GAD for VD; it is modeled that MR contrast imaging applied with GOT; or vice versa. PA was performed in cases in which diagnoses couldn’t be made using both agents with MRI. The same model tree used for if the patient didn`t get diagnosed with GAX or ECCM or CCT for LM, then MRI contrast imaging was applied with another agent. Reimbursement guidelines of the Social Security Institution were used for cost calculations. The cost per patient with the diagnosis with VD was calculated via a decision tree as 245 TL for GAD and 251 TL for GOT. 7% less PA was needed in the GAD which avoids 29% less unnecessary treatment compared to GOT. The diagnosis rate was 99% with GAX, 82% with ECCM, and 60% with CCT for LM. The cost of diagnosis per patient with LM was 280 TL for CT, 229 TL for ECCM, and 280 TL for GAX. GAD offered more favorable cost, a higher rate of correct diagnosis, and fewer patients who needed PA. GAX as the gold standard in patients with LM according to clinical guidelines.

PCV26 COMPARISON OF CLINICAL AND ECONOMIC OUTCOMES OF MAGNETIC RESONANCE IMAGING WITH GADOBUTROL, GADOTERIC ACID AND PERIPHERAL ANGIOGRAPHY IN DIAGNOSIS OF VASCULAR DISEASES

Vascular disease(VD) is an important disease with a high mortality rate when diagnosed late. Magnetic resonance imaging(MR) with Gadobutrol(GAD), MR with Gadoteric Acid(GOT) and peripheral angiography(PA) methods are used in the diagnosis of VD in Turkey. The aim of the study was to compare the clinical and economic outcomes of alternative imaging methods in the diagnosis of vascular disease.

The effect of contrast agents on left ventricular parameters calculated by a threshold-based software module: does it truly matter?

The acquisition of short-axis (SA) cine magnetic resonance (MR) images after the administration of contrast agent (CA) is a common, time-saving technique, but a decreased difference in the blood-myocardium contrast on these steady-state free precession (SSFP) cine scans could change the calculated parameters when using threshold-based papillary and trabecular muscle (PTM) quantification. We studied the effect of CA on the parameters calculated from pre- and post-CA SA cine images in noncompaction cardiomyopathy (NC-CMP) and healthy (H) participants using a threshold-based module. A total of 39 individuals (20 patients and 19 healthy) were included prospectively in this study. After the pre-CA SA images were acquired, i.v. gadobutrol (GA) or gadobenate dimeglumine (GD) (GA vs. GD: NC-CMP = 12 vs. 8; C = 12 vs. 7) was administered, and SA scans were repeated after two minutes. A threshold-based PTM software was used for postprocessing. Pre-CA and post-CA SA images were analyzed, and the parameters were compared in both the NC-CMP and H groups. The left ventricular volumes were significantly larger, while the left ventricular myocardial (LVmass) and trabecular mass (LVtrab) values were significantly smaller on the post-CA scans (NC-CMP: pre-CA vs. post-CA, EDV: 74.0 ± 13.6 vs. 81.1 ± 16.3 ml/m2, ESV: 25.3 ± 7.3 vs. 30.1 ± 11.2 ml/m2, LVmass-ED: 82.5 ± 17.5 vs. 75.7 ± 15.9 g/m2, LVtrab-ED: 25.0 ± 6.6 vs. 18.9 ± 4.7 g/m2; Healthy: preCA vs. post-CA, EDV: 69.7 ± 11.9 vs. 72.2 ± 10.7 ml/m2, ESV: 22.6 ± 5.7 vs. 23.9 ± 6.3 ml/m2, LVmass-ED: 71.3 ± 13.6 vs. 68.7 ± 13.9 g/m2, LVtrab-ED: 19.4 ± 2.6 vs. 16.2 ± 3.0 g/m2; p < 0.05). The decreased blood-myocardium contrast difference on post-CA SSFP SA cine images leads to altered cardiac parameters when using threshold-based software for evaluation.

Synthesized Gd2O3 nanoparticles as contrast agent

Introduction: Gd (III) ion has been known to be the best metal ion in the periodic table that can be used as a T1 MRI contrast agent. Gadolinium have 7 unpaired electrons and these electrons can make magnetic area. No other metal ions possess unpaired electron more than this. CAs based on the element Gd are classified as “positive”, by opposition to “negative” CAs. Nowadays, Gd (III) chelates is prevailing in clinical use because it can be generally used for all organ. Around 35% of all MRI exams occur with contrast agents, and Gd (III) complexes are by far the most widely used contrast agents in clinical practice. The presence of superparamagnetic iron oxide particles in a tissue significantly changes the local magnetic field. Therefore, the optimal conditions to achieve 1H Larmor resonance are very sensitively affected. Suspensions of USPIO and SPIO typically express R2/R1 larger than 2. Physical properties of this magnetic element nanostructure have not studied so much yet. In this paper we have synthesized nanoparticles of Gadolinium Oxide in Polyol method and we try to compare it with commercial MRI contrast agent. On the other hand, there are reports about the effects of hyperthermia through the applying of strong magnetic fields on iron oxide superparamagnetism nanostructures. Later this property was used to treat cancer. Materials and Methods: We use Gd(NO3)3.6H2O, DEG, PVP 1.300.000 and NaOH that prepared by Sigma Merck to synthesized nanoparticles. We have verified this structure using Transmission electron microscopy (TEM), Dynamic light scattering (DLS) and X-ray crystallography (XRD) tests. Also we use Hyperthermia to calculate the temperature rise in magnetic field. Then we study magnetic properties of these nanoparticles with VSM and MRI images and compare it with two conventional contrast agents: Dotarem and Gadovist. Results: The DLS and TEM results show a diameter of 5 nm for the particles, with homogenous distributions among the solution. The XRD pattern show that we have crystal of Gd2O3. However, VSM results show that the anisotropy of this nanoparticles is 5.4 ×10-3 (J/m3) and a superparamagnetic loop, this value means we could have better relaxation time compared to Dotarem and Gadovist in magnetic area. By calculate the values we could find the relaxation time of our nanoparticles are 100 time smaller than commercial contrast agents. Hyperthermia shows 14ᵒ temperature rise in 0.15 T magnetic area that it could be used in cancer treatment. Conclusion: At the end of paper, we put the same concentration of Dotarem, Gadovist and nanoparticles in MRI image. By the results that calculate in VSM we guess that the contrast of nanoparticles must be better than commercial contrast agents. The results show that the highest contrast among these three structures refers to nanostructures. These results were obtained based on Hydrogens relaxation. This can be the base of using this nanoparticles as a MRI contrast agent in future.

Comparison of MRI contrast agents gadopentetate dimeglumine, gadodiamide and gadovist: their relaxation rates and effects on imaging

Objective To evaluate the relaxation rates and imaging effects of three MRI contrast agents gadopentetate dimeglumine(0.5 mol/L), gadodiamine and gadovist(1.0 mol/L)in the nervous system. Methods Relaxation rate differences between the three contrast agents were assessed using the GE Signa HDx 3.0 T MR scanner and phantom solutions of different albumin concentrations.Twenty leukemia patients whose initial scans had been conducted with the injection of a standard dose(0.5 mol/L)of gadopentetate dimeglumine as the contrast agent were recalled to have a follow-up scan for signs of brain infections with the same imaging protocols, except that a high concentration(1.0 mol/L)gadovist was used this time as the contrast agent.CNR and SNR in the ROI were measured for quantitative analysis. Results Changes in dosage of the three contrast agents produced no difference in intensity of the image signal for each phantom solution of a specific albumin concentration(5.0 g/L: P=0.35, 6.5g/L: P=0.27, 8.0 g/L: P=0.23). Two sets of scans of the leukemia patients showed that high concentration(1.0 mol/L)gadovist generated higher SNR and CNR in the ROI of the white matter, gray matter and vasculature than standard concentration(0.5 mol/L)gadopentetate dimeglumine(P< 0.05). Conclusions A half dose of high concentration(1.0 mol/L)gadovist generates better imaging enhancement than standard concentration(0.5 mol/L)gadopentetate dimegluminethe.Gadopentetate dimeglumine, gadodiamide and gadovist have no significant difference in relaxation rate. Key words: Magnetic resonance imaging; Contrast; Gadovist; Gadopentetate dimeglumine; Brain

MODERATED EPOSTERS1385Longitudinal strain assessment in dilated cardiomyopathy patients using a novel accelerated DENSE sequence1407Simultaneous T1 and T2 cardiac quantification with CABIRIA: initial clinical experience1423Head-to-head comparison of acceleration algorithms in 4-dimensional flow CMR1502Left ventricular function and size evaluated by hybrid cardiac positron emission tomography-magnetic resonance: Intraindividual comparison of left ventricular ejection fraction and ventricular volumes derived by two modalities1510Left Atrium assessed

MODERATED EPOSTERS1385Longitudinal strain assessment in dilated cardiomyopathy patients using a novel accelerated DENSE sequence1407Simultaneous T1 and T2 cardiac quantification with CABIRIA: initial clinical experience1423Head-to-head comparison of acceleration algorithms in 4-dimensional flow CMR1502Left ventricular function and size evaluated by hybrid cardiac positron emission tomography-magnetic resonance: Intraindividual comparison of left ventricular ejection fraction and ventricular volumes derived by two modalities1510Left Atrium assessed

Whole-body CE-MRA with Gadovist.

Whole-body CE-MRA with Gadovist.