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Purpose: Stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) has emerged as an alternative treatment option when curative treatment modalities cannot be applied. Although excellent local tumor control has been achieved with SBRT, the targeting accuracy in real-life practice remains poorly understood. We proposed an in vivo assessment of targeting accuracy using hepatic parenchymal changes observed on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images and applied this method to investigate the "real-life" targeting accuracy of image-guided SBRT.Methods and Materials: We selected 29 patients with available follow-up MR images acquired 2 to 4 months after completion of SBRT. All patients were administered 45 Gy in 3 fractions. The treated HCC and the region of hepatic parenchymal changes in the hepatobiliary phase of MR images were delineated. We evaluated the discrepancies between the center of the HCC and that of the parenchymal change area (intercenter discrepancy [ICD]). We also analyzed the difference in ICDs between those who underwent SBRT with intrahepatic marker guidance and those with diaphragm guidance.Results: The median ICD in the 3-dimensional direction was 6.81 mm (interquartile range [IQR], 4.27-9.61 mm). Those for the craniocaudal, left-right, and anteroposterior components were 2.70 mm (IQR, 1.83-4.06 mm), 1.63 mm (IQR, 0.76-3.49), and 4.12 mm (IQR, 1.20-6.96 mm), respectively. The median ICD for patients who underwent treatment with intrahepatic marker guidance and those with diaphragm guidance was 7.53 mm (IQR, 6.63-10.86 mm) and 5.60 mm (IQR, 4.28-8.18 mm), respectively. There was no significant difference in ICD between those who underwent treatment with intrahepatic marker guidance and those with diaphragm guidance (P = .296).Conclusions: The hepatic parenchymal changes observed on Gd-EOB-DTPA-enhanced MR images can be used to assess the targeting accuracy after SBRT for HCC. [ABSTRACT FROM AUTHOR]

A novel dimeric gadolinium(III) complex, bis(4-Gd-DTPA-aminophenyl)adamantane ( 5 ), was successfully synthesized using bis(4-aminophenyl)adamantane to link two Gd-DTPA units. All the intermediates and bis(4-Gd-DTPA-aminophenyl)adamantane ( 5 ) have been characterized by 1 H NMR, 13 C NMR, ES-API-MS, HR-ESI-MS, FT-IR and elemental analysis (EA). The longitudinal relaxivity of bis(4-Gd-DTPA-aminophenyl)adamantane is 8.43 mM −1  Gd −1  s −1 at 0.43 T (32 °C, pH 7.0), and 4.89 mM −1  Gd −1  s −1 at 3.0 T (32 °C, pH 7.4). The T 1 -weighted imaging in vitro showed that bis(4-Gd-DTPA-acetylaminophenyl)adamantane can enhance the contrast of images distinctly. But most of all, the kinetic inertness of bis(4-Gd-DTPA-aminophenyl)adamantane ( 5 ) was comparable to that of [Gd(DTPA)(H 2 O)] 2− (Magnetvist®). Moreover, cytotoxicity tests indicated that the bis(4-Gd-DTPA-acetylaminophenyl)adamantane exhibited low toxicity to healthy liver cells (L-02 cells). These results demonstrate that the Gd(III) complex 5 may be a promising MRI contrast agent candidate. [ABSTRACT FROM AUTHOR]

Background Insufficient enhancement of liver parenchyma negatively affects diagnostic accuracy of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI). Currently, there is no reliable method for predicting insufficient enhancement during the hepatobiliary phase (HBP) in Gd-EOB-DTPA-enhanced MRI. Purpose To develop a predictor for insufficient enhancement of liver parenchyma during HBP in Gd-EOB-DTPA-enhanced MRI. Material and Methods In order to formulate a HBP enhancement test (HBP-ET), clinical factors associated with relative enhancement ratio (RER) of liver parenchyma were retrospectively determined from the datasets of 156 patients (Development group) who underwent Gd-EOB-DTPA-enhanced MRI between November 2012 and May 2015. The independent clinical factors were identified by Pearson's correlation and multiple stepwise regression analysis; the performance of HBP-ET was compared to Child-Pugh score (CPS), Model for End-stage Liver Disease score (MELD), and total bilirubin (TBIL) using receiver operating characteristic (ROC) curve analysis. The datasets of 52 patients (Validation group), which were examined between June 2015 and Oct 2015, were applied to validate the HBP-ET. Results Six biochemical parameters independently influenced RER and were used to develop HBP-ET. The mean HBP-ET score of patients with insufficient enhancement was significantly higher than that of patients with sufficient enhancement ( P < 0.001) in both the Development and Validation groups. HBP-ET (area under the curve [AUC] = 0.895) had better performance in predicting insufficient enhancement than CPS (AUC = 0.707), MELD (AUC = 0.798), and TBIL (AUC = 0.729). Conclusion The HBP-ET is more accurate than routine indicators in predicting insufficient enhancement during HBP, which is valuable to aid clinical decisions. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate changes in liver function after right portal vein embolization (PVE) and extended right hemihepatectomy using gadolinium ethoxybenzyl-DTPA-enhanced (Gd-EOB-DTPA) MRI.Methods: In this prospective trial, 37 patients undergoing PVE were examined before and 14 and 28 days after PVE and 10 days after extended hemihepatectomy using Gd-EOB-DTPA-enhanced MRI. Lobar volume, kinetic growth rate (KGR), relative enhancement (RE) as well as hepatocellular uptake index (HUI) and fat signal fraction (FSF) were calculated for each lobe.Results: RE of the left liver lobe (LLL) was steadily increasing after PVE and decreased to 0.48 ± 0.19 10 days after surgery, which is significantly lower than 14 days and 28 days post PVE (P < 0.05). KGR was 14.06 ± 9.82%/week for the period from PVE to 14 days after PVE. HUI of the LLL increased steadily after PVE and was significantly higher at both 14 and 28 days after PVE compared to pre PVE (P < 0.05). HUI of the residual liver after surgery was lower than before.Conclusions: Gd-EOB-DTPA-enhanced MRI may be used to monitor the functional increase in the FLR after PVE and to depict the intraoperative liver injury leading to a decrease in liver remnant function.Key Points: • The most significant FLR volume increase happens within the first 14 days. • No MRI parameter was able to predict the success of FLR growth. • Our data suggest an early resection about 14 days after PVE. • Routine Gd-EOB-DTPA-enhanced MRI might be suitable to replace ICG-test. [ABSTRACT FROM AUTHOR]

Background: To compare the diagnostic accuracy of hepato-biliary (HB) phase with gadolinium-ethoxybenzyldiethylenetriamine- pentaacetic acid (Gd-EOB-DTPA) with dynamic contrast-enhanced MR imaging (DCEMRI) and contrast-enhanced CT (DCECT) for hepatocellular carcinoma (HCC) detection. Material/Methods: 73 patients underwent DCECT and Gd-EOB-DTPA-3T-MR. Lesions were classified using a fivepoint confidence scale. Reference standard was a combination of pathological evidence and tumor growth at follow-up CT/MR at 12 months. Receiver Operating Characteristic (ROC) curves were obtained. Results: A total of 125 lesions were confirmed in 73 patients. As many as 74 were HCCs and 51 were benign. Area under the curve (AUC) was 0.984 for DCEMRI+HB phase vs. 0.934 for DCEMRI (p<0.68) and 0.852 for DCECT (p<0.001). For lesions >20 mm (n.40), AUC was 0.984 for DCEMRI+HB phase, 0.999 for DCEMRI, and 0.913 for DCECT, (p=n.s.). For lesions <20 mm (n.85) AUC was 0.982 for DCEMRI+HB phase vs. 0.910 for DCEMRI (p<0.01) and 0.828 for DCECT (p<0.001). Conclusions: The addition of HB phase to DCEMRI provides an incremental accuracy of 4.5% compared to DCEMRI and DCECT for HCC detection. The accuracy of Gd-EOB-DTPA-3T-MR significantly improves for lesions <20 mm. No significant improvement is observed for lesions >20 mm and patients with Child-Pugh class B or C. [ABSTRACT FROM AUTHOR]

In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid. [ABSTRACT FROM AUTHOR]

The pharmacokinetics (PK) of the contrast agent Gd-DTPA administered intravenously (i.v.) for contrast-enhanced MR imaging (DCE-MRI) is an important factor for quantitative data acquisition. We studied the effect of various initial bolus doses on the PK of Gd-DTPA and analyzed population PK of a lower dose for intra-subject variations in DCE-MRI. First, fifteen subjects (23–85 years, M/F) were randomly divided into four groups for DCE-MRI with different Gd-DTPA dose: group-I, 0.1 mmol/kg, n = 4; group-II, 0.05 mmol/kg, n = 4; group-III, 0.025 mmol/kg, n = 4; and group-IV, 0.0125 mmol/kg, n = 3. Sequential fast T1 mapping sequence, after a bolus i.v. Gd-DTPA administered, and a linear T1-[Gd-DTPA] relationship were used to estimate the PK of Gd-DTPA. Secondly, MR-acquired PKs of Gd-DTPA from 58 subjects (28–80 years, M/F) were collected retrospectively, from an ongoing study of the brain using DCE-MRI with Gd-DTPA at 0.025 mmol/kg, to statistically analyze population PK of Gd-DTPA. We found that the PK of Gd-DTPA (i.v. 0.025 mmol/kg) had a half-life of 37.3 ± 6.6 min, and was a better fit into a linear T1-[Gd-DTPA] relationship than higher doses (up to 0.1 mmol/kg). The area under the curve (AUC) for 0.025 mmol/kg was 3.37 ± 0.46, which was a quarter of AUC of 0.1 mmol/kg. In population analysis, a dose of 0.025 mmol/kg of Gd-DTPA provided less than 5% subject-dependent variation in the PK of Gd-DTPA. Administration of 0.025 mmol/kg Gd-DTPA enabled us to estimate [Gd-DTPA] from T1 by using a linear relationship that has a lower estimation error compared to a non-linear relationship. DCE-MRI with a quarter dose of Gd-DTPA is more sensitive to detect changes in [Gd-DTPA]. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dual-modal MRI/FI gents were made by incorporation of Gd-DTPA and RhB to Laminin/Fibronectin receptor-targeting sequences. • Dual-modal MRI/FI gents possessed low cell cytotoxicity, high relativity, good tumor-targeting and good fluorescent property. • Dual-modal MRI/FI gents showed good performance of combined MRI with FI and improve the accuracy of tumor detection. Dual-modal magnetic resonance/fluorescent imaging (MRI/FI) attracts more and more attentions in diagnosis of tumors. A corresponding dual-modal imaging agent with sufficient tumor sensitivity and specificity should be matched to improve imaging quality. Tripeptide (RGD) and pentapeptide (YIGSR) were selected as the tumor-targeting groups and attached to gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) and rhodamine B (RhB), and then make two novel polypeptide-based derivatives (RGD-Gd-DTPA-RhB and YIGSR-Gd-DTPA-RhB), respectively. These derivatives were further characterized and their properties, such as cell uptake, cell cytotoxicity, MRI and FI assay, were measured. YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB had high relaxivity, good tumor-targeting property, low cell cytotoxicity and good red FI in B16F10 melanoma cells. Moreover, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB possessed high uptake to B16F10 melanoma, and then achieve highly enhanced FI and MRI of tumors in mice for a prolonged time. Therefore, YIGSR-Gd-DTPA-RhB and RGD-Gd-DTPA-RhB can be applied as the potential agents for tumor targeted MRI/FI in vivo. [ABSTRACT FROM AUTHOR]

• The covalent functionalization of MXene with diethylenetriaminepentaacetic acid was proposed. • MXene-DTPA complexing with Gd3+ provided paramagnetic response to the diamagnetic MXene. • MXene-Gd showed T 1 -MR imaging activity. • MXene-Gd showed oxidative resistance in phosphate buffer saline and blood serum. • The chelation of Gd3+ ions by MXene-DTPA prevented leaking to bioliquids. MXenes are an excellent candidate for medical applications, including diagnostic approaches such as positron emission tomography, computed tomography, and magnetic resonance imaging (MRI). However, the utilization of MXenes for bioimaging is restricted by their commonly diamagnetic nature. MXenes can be functionalized using ferromagnetic or paramagnetic compounds and nanoparticles to develop efficient bioimaging tools. In contrast to previously published approaches based on electrostatic interactions, covalent approaches could enhance MXene stability and prevent self-aggregation with degradation. This work proposes covalent functionalization of Ti 3 C 2 T flakes with a chelating agent diethylenetriaminepentaacetic acid (DTPA) and further complexing with Gd3+ ions. The developed functionalization procedure provides a paramagnetic response to the intrinsically diamagnetic Ti 3 C 2 T flakes for T 1 -MR imaging. Moreover, we observed the apparent dependency of magnetic relaxation time on the flake concentration, which enabled us to estimate the spatially resolved flake distribution. The covalent decoration strategy for MXene led to surface protection against oxidation in phosphate buffer saline and blood serum, accompanied by increased cytocompatibility. Moreover, chelation of Gd3+ ions prevented leaking compared with electrostatic chemisorption. We demonstrated a high degree of photothermal conversion efficiency of MXene-Gd, anticipating future application in photothermal therapy. This work broadens the bioapplication of MXenes, not only by introducing an MRI contrast but also by developing covalent functionalization strategies for MXenes. [ABSTRACT FROM AUTHOR]

Objectives: To compare the role of DWI vs. gadoxetic-acid-disodium enhanced MRI in the detection of colorectal hepatic metastases.Methods: Fifty-four patients with 115 hepatic metastases were included in this retrospective study, approved by the Ethical Board. All patients underwent intraoperative-ultrasound and surgical resection within two weeks after MRI. Images were grouped in 4 sets, which were analyzed by two radiologists in different sessions: unenhanced T1-T2w (set A), set A plus DWI (set B), set A plus gadoxetic-acid-disodium (set C), set A plus DWI plus gadoxetic-acid-disodium (set D). For each set, metastases presence/size/site was reported. Interobserver agreement and statistical significance were assessed by Cohen's kappa and Mc-Nemar's test, respectively.Results: Readers' agreement was always very good (k>0.80). Mean sensitivity values were 84.3/92.1/95.6/97.3% for set A/B/C/D, respectively. Mean specificity, positive predicted, negative predicted, and accuracy values strongly and progressively increased in the various set too: from 62.5% (set A) to 85.0% as for specificity, from 92.8% to 97.3% as for positive predicted value, from 41.0% to 85.1% as for negative predicted value, and from 81.1% to 95.5% as for accuracy. For each reader from set A to D, the number of false negatives progressively decreases.Conclusions: For both readers, DWI improved all statistical parameters in the unenhanced examinations, as for nodules either smaller or greater than 1cm, while in the EOB-enhanced examinations DWI prevalently increased specificity/negative predictive value. [ABSTRACT FROM AUTHOR]

In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd 3 + , chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd 3 + in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd 3 + incubated with Ca 2 + was performed by using a dialysis membrane (MWCO 100–500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd 3 + , the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd 3 + were released from Gd-DTPA-Pullulan after 2 h incubation with Ca 2 + and Fe 2 + , respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t 1/2,α = 0.43 h, t 1/2,β = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the use of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI)-derived fat- and liver function-measurements for prediction of future liver remnant (FLR) growth after portal vein occlusion (PVO) in patients scheduled for major liver resection.Methods: Forty-five patients (age, 59 ± 13.9 y) who underwent Gd-EOB-DTPA-enhanced liver MRI within 24 ± 18 days prior to PVO were included in this study. Fat-Signal-Fraction (FSF), relative liver enhancement (RLE) and corrected liver-to-spleen ratio (corrLSR) of the FLR were calculated from in- and out-of-phase (n=42) as well as from unenhanced T1-weighted, and hepatocyte-phase images (n=35), respectively. Kinetic growth rate (KGR, volume increase/week) of the FLR after PVO was the primary endpoint. Receiver operating characteristics analysis was used to determine cutoff values for prediction of impaired FLR-growth.Results: FSF (%) showed significant inverse correlation with KGR (r=-0.41, p=0.008), whereas no significant correlation was found with RLE and corrLSR. FSF was significantly higher in patients with impaired FLR-growth than in those with normal growth (%FSF, 8.1 ± 9.3 vs. 3.0 ± 5.9, p=0.02). ROC-analysis revealed a cutoff-FSF of 4.9% for identification of patients with impaired FLR-growth with a specificity of 82% and sensitivity of 47% (AUC 0.71 [95%CI:0.54-0.87]). Patients with impaired FLR-growth according to the FSF-cutoff showed a tendency towards higher postoperative complication rates (posthepatectomy liver failure in 50% vs. 19%).Conclusions: Liver fat-content, but not liver function derived from Gd-EOB-DTPA-enhanced MRI is a predictor of FLR-growth after PVO. Thus, liver MRI could help in identifying patients at risk for insufficient FLR-growth, who may need re-evaluation of the therapeutic strategy. [ABSTRACT FROM AUTHOR]

Purpose: To determine the optimal hepatobiliary delay time after Gd-EOB-DTPA injection for lesion characterization in cirrhosis patients with different liver function.Materials and Methods: Ninety consecutive patients with liver cirrhosis who underwent Gd-EOB-DTPA-enhanced MRI for the evaluation of known or suspected focal liver lesions were enrolled in this retrospective study. The patients were divided into Child-Pugh A, B and C groups depending on their liver function through the Child-Pugh classification. Hepatobiliary phase images obtained at 5, 10, 15, and 20min were assessed in each group by the following items: parenchymal enhancement, contrast agent excretion into the bile ducts and ureter, and contrast- and signal-to-noise ratios for lesions.Results: In the Child-Pugh A group, parenchymal enhancement increased significantly from 5min to 15min (P<0.05), and stabilized at 20min (P=0.22). However, there was no significant difference in parenchymal enhancement among all of the hepatobiliary phases in the Child-Pugh B and C groups. The biliary contrast agent excretion was first observed before 20min in all of the patients in the Child-Pugh A group, at 20min in 4 patients (25%) in the Child-Pugh B group, and after 20min in 11 patients (78.6%) in the Child-Pugh C group. The numbers of patients whose urethral contrast agent excretion was first observed at 5min in the Child-Pugh A, B and C groups were 38 (63.3%), 12 (75.0%) and 11 (78.6%), respectively. The CNR of the lesions increased significantly (P<0.05), up to 15min after enhancement without a further increase at 20min in the Child-Pugh A group; however, no significant change was found from 5min to 20min in the Child-Pugh B and C groups. For the SNR of lesions, there was no significant difference at 5, 10, 15 and 20min in all of the groups.Conclusions: A delay time of 15min for the hepatobiliary phase was sufficient for patients with mild liver dysfunction who were classified as Child-Pugh A. Nevertheless, for the patients with moderate or severe liver dysfunction who were classified as Child-Pugh B or C, a delay time longer than 5min is meaningless for lesion characterization. [ABSTRACT FROM AUTHOR]

Introduction: The present study evaluated the threshold dose for hepatic parenchymal changes on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance (MR) images after stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC). Methods: Twenty patients with available data of follow-up MR images acquired 2-4 months after completion of SBRT were selected among the registered patients. SBRT was performed using multiple coplanar and non-coplanar beams with energies of 6 or 15 MV. All patients were treated with doses of 45 Gy administered in three fractions over 3 consecutive days. For image registration between planning computed tomography (CT) and MR images, landmark-based rigid body registration was performed using MIM software. Results: Seventeen patients were included in the analysis. The median discrepancies between planning CT and MR images in the left-right, anterior-posterior and superior-inferior directions were 1.38 mm, 1.24 mm and 1.72 mm, respectively. The median D50 value for the defect in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR images after SBRT was 19.8 Gy (range, 14.2-28.7 Gy), with R(2) values ranging from 0.76 to 0.99. Conclusions: The threshold dose for parenchymal changes in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MR images performed 2-4 months after 45 Gy of SBRT in three fractions was approximately 20 Gy. Our results provide the basis for further research on the functional loss of liver parenchyma after SBRT. [ABSTRACT FROM AUTHOR]

Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a GdIII-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature 17O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by 1H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo 'model-free' approach. High payloads of GdIII ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of two diethylenetriaminepentaacetic acid (DTPA) based heteropolymetallic metallostar lanthanide complexes with the general formulas (Gd L1)3Ln and (Gd L2)3Ln are described. The synthesis uses a synthetic approach recently developed in our group for the selective complexation of gadolinium(III) and luminescent lanthanide ions with a ditopic ligand to form highly paramagnetic and luminescent metallostar complexes. The luminescence data and relaxometric studies suggest the potential applicability of the complexes as bimodal contrast agents for magnetic resonance and optical imaging. Owing to the higher excited state of L1, better sensitization was observed for all (Gd L1)3Ln complexes than for (Gd L2)3Ln. A large increase of the quantum yield from 1.5 to 9.8 % was observed for the (Gd L1)3Eu complex compared with (Gd L2)3Eu, whereas the (Gd L1)3Tb complex exhibited a quantum yield (QY) of 30.9 % compared with 15.3 % for (Gd L2)3Tb. A slight increase of the QY from 0.8 to 1.2 % was observed for the Dy(III) complex when switching from ligand L2 to L1. The nuclear magnetic relaxation dispersion (NMRD) measurements of the (Gd L2)3Ln complexes (Ln = EuIII, DyIII, TbIII) showed respective longitudinal relaxivity ( r1) values of 24.27, 22.80 and 21.72 s-1 mmol-1 per metallostar complex at 310 K and 20 MHz. [ABSTRACT FROM AUTHOR]

This review reports recent advances on the use of dendrimer nanotechnology to build up various contrast agents for different single-mode or dual-mode molecular imaging applications. The versatile dendrimer scaffolds with 3-dimensional spherical shape, highly branched internal cavity, and tunable surface conjugation chemistry enable the facile modification of dendrimer surface with different imaging agents ( e.g. , fluorescent dyes, traditional small molecular contrast agents, or metal ion/chelator complexes) and targeting ligands, and convenient entrapment, stabilization, and self-assembly to form various organic or organic/inorganic hybrid nanoparticles that can be used as multifunctional contrast agents for both non-radionuclide- and radionuclide-based molecular imaging applications. In particular, strategies used to generate multifunctional nanoprobes for different modes of targeted molecular imaging of cancer are discussed in detail. [ABSTRACT FROM AUTHOR]

Objective To 1) test the feasibility of delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) at 3 T in the temporomandibular joint (TMJ) and 2) to determine the optimal delay for measurements of the TMJ disc after i.v. contrast agent (CA) administration. Design MRI of the right and left TMJ of six asymptomatic volunteers was performed at 3 T using a dedicated coil. 2D inversion recovery (2D-IR) sequences were performed at 4 time points covering 120 minutes and 3D gradient-echo (3D GRE) dual flip-angle sequences were performed at 14 time points covering 130 minutes after the administration of 0.2 mmol/kg of Gd-diethylenetriamine pentaacetic acid ion (Gd-DTPA) 2- , i.e., 0.4 mL of Magnevist™ per kg body weight. Pair-wise tests were used to assess differences between pre-and post-contrast T1 values. Results 2D-IR sequences showed a statistically significant drop ( p < 0.001) in T1 values after i.v. CA administration. The T1 drop of 50% was reached 60 minutes after bolus injection in the TMJ disc. The 3D GRE dual flip-angle sequences confirmed these results and show plateau of T1 after 60 minutes. Conclusions T1(Gd) maps calculated from dGEMRIC data allow in vivo assessment of the fibrocartilage disc of the TMJ. The recommended measurement time for dGEMRIC in the TMJ after i.v. CA administration is from 60 to 120 minutes. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate the added value of hepatospecific phase in Gd-EOB-DTPA enhanced magnetic resonance imaging (MRI) in patients with primary tumors in non-cirrhotic liver. Methods: Twenty-nine patients (median, 39 years; range, 18–81 years; 11 male) underwent preoperative Gd-EOB-DTPA enhanced MRI including hepatospecific phase after 10 and 20min of contrast injection at four institutions in Europe, North America and New Zealand. Images were evaluated by three different readers (R1–R3) who characterized liver tumors with and without consultation of the hepatospecific phase images. Confidence in diagnosis was scored on a visual analog scale from 1 to 10. Histopathology (adenoma, n =5; focal nodular hyperplasia, n =11 and hepatocellular carcinoma, n =13) in all patients served as the standard of reference. Differences were evaluated using the McNemar and Wilcoxon signed rank test. Results: Without hepatospecific phase images available, 22 (76%), 19 (66%) and 19 (66%) of 29 tumors were characterized correctly by the three readers respectively. Mean confidence in diagnosis was 6.1, 5.7 and 5.8. With the hepatospecific phase included, characterization of liver tumors did not change significantly with 21 (72%), 23 (79%) and 19 (66%) of 29 tumors diagnosed correctly (p >0.05). According confidence ratings increased to 6.3, 6.5 and 7.7, respectively. Increase in diagnostic confidence was significant for R2 and R3 (p <0.05) and independent of reader's experience. Conclusion: The additional hepatospecific phase in Gd-EOB-DTPA enhanced MRI did not significantly increase diagnostic accuracy in characterization of primary tumors in the non-cirrhotic liver. However, 2/3 readers showed a significant increase in diagnostic confidence after consultation of the hepatospecific phase. [Copyright &y& Elsevier]

Although paramagnetic contrast agents have a wide range of applications in medical studies involving magnetic resonance imaging (MRI), these agents are seldom used to enhance MRI images of plant root systems. To extend the application of MRI contrast agents to plant research and to develop related techniques to study root systems, we examined the applicability of the MRI contrast agent Gd-DTPA to the imaging of rice roots. Specifically, we examined the biological effects of various concentrations of Gd-DTPA on rice growth and MRI images. Analysis of electrical conductivity and plant height demonstrated that 5 mmol Gd-DTPA had little impact on rice in the short-term. The results of signal intensity and spin-lattice relaxation time (T1) analysis suggested that 5 mmol Gd-DTPA was the appropriate concentration for enhancing MRI signals. In addition, examination of the long-term effects of Gd-DTPA on plant height showed that levels of this compound up to 5 mmol had little impact on rice growth and (to some extent) increased the biomass of rice. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of two novel DTPA bisamide derivatives DTPA-BC12PheA and DTPA-BC14PheA functionalized with p-dodecylaniline and p-tetradecylaniline are described. The ligands were coordinated to Gd(III) and Eu(III), resulting in highly paramagnetic and luminescent complexes, respectively. Mixed micelles consisting of Gd/Eu-DTPA-BC12PheA and DTPA-BC14PheA with a homogeneous size distribution (33-40 nm) were prepared by the assembly of the amphiphilic complexes with phospholipid DPPC and a surfactant Tween 80®. Taking into account the sensitivity difference between magnetic resonance and optical imaging techniques, the ratios of Gd and Eu complexes (Gd/Eu) 1 : 1, 2 : 1, 3 : 1, 20 : 1 and 50 : 1 were combined in one single micelle and their optical and relaxometric properties were characterized in detail. Upon excitation at 290 nm, the micelles display characteristic red emission bands due to the 5D0→7FJ (J = 0-4) transitions of Eu(III). The number of water molecules in the first coordination sphere of Eu(III) (qEu = 0.1-0.2) was calculated from the lifetime measurements performed in H2O and D2O solutions. Micelles composed of exclusively europium complexes display quantum yields in the range of 1.0%, decreasing with the europium concentration when going from 1 : 1 to 50 : 1 Gd/Eu contents. The ligand-to-lanthanide sensitization efficiency for micelles consisting of Eu- DTPA-BC12PheA and Eu-DTPA-BC14PheA equals 3.8% and 4.1%, respectively. The relaxivity r1 per Gd(III) ion at 40 MHz and 310 K reaches a maximum value of 14.2 s-1 mM-1 for the Gd-DTPA-BC12PheA assemblies and 16.0 s-1 mM-1 for the micellar Gd-DTPA-BC14PheA assemblies compared to a value of 3.5 s-1 mM-1 for Gd-DTPA (Magnevist®). Theoretical fitting of the 1H NMRD profiles results in τR values of 4.2 to 6.6 ns. The optimal concentration ratio of Gd/Eu compounds in the micelles in order to provide the required bimodal performance has been determined to be 20 : 1. In the search for other bimodal systems, this discovery can be used as a guideline concerning the load of paramagnetic agents with respect to luminescent probes. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated the contrast-enhanced ultrasonography (US) imaging features of early hepatocellular carcinomas (HCCs) and compared these findings with those obtained using contrast-enhanced computed tomography (CT). Subjects and methods: Forty-three patients with 52 early HCCs with a mean maximal diameter of 15.6mm were enrolled in this retrospective study. After confirming the location of the target lesion using fusion imaging combining conventional US and hepatobiliary phase of contrast-enhanced magnetic resonance (MR) imaging with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid, we evaluated findings of contrast-enhanced US using a perflubutane-based contrast agent. The contrast-enhanced US detection rates for hyper-vascularity in early HCCs were compared with those obtained for contrast-enhanced CT. Results: Transient hypo-vascularity subsequent to iso-vascularity during arterial phase and iso-vascularity during portal and post-vascular phases were the predominant contrast-enhanced US findings seen for 25 (48.1%) of the 52 early HCCs. Nine (17.3%) showed iso-vascularity during all three phases, while 1 (1.9%) showed hypo-vascularity during all three phases. The remaining 17 (32.7%) showed partial or whole hyper-vascularity during arterial phase, iso-vascularity during portal phase, and iso- or hypo-vascularity during post-vascular phase. The detection rate for the hyper-vascularity of early HCCs using contrast-enhanced US (32.7%, 17/52) was significantly higher than that obtained using contrast-enhanced CT (21.2%, 11/52) (P <0.05 by McNemar test). Conclusion: Hypo-vascularity, iso-vascularity, and hyper-vascularity were observed during the arterial phase of contrast-enhanced US in 50.0%, 17.3%, and 32.7% of the early HCCs, respectively. Contrast-enhanced US was more sensitive than contrast-enhanced CT for the detection of hyper-vascularity in early HCCs. Of note, early HCCs might not exhibit the early arterial enhancement that is generally considered to be a typical finding for HCCs. [Copyright &y& Elsevier]

Hydrophobic macromolecular contrastagents (MMCAs) are highly desirableto provide safe and efficient magnetic resonance (MR) visibility toimplantable medical devices. In this study, we report on the synthesisand evaluation of novel biodegradable poly(ε-caprolactone)-basedMMCAs. Poly(α-propargyl-ε-caprolactone-co-ε-caprolactone)s containing 2, 5, and 10 mol % of propargylgroups have been prepared by ring-opening copolymerization of ε-caprolactoneand the corresponding propargylated lactone. In parallel, a diazidoderivative of the clinically used diethylenetriaminepentaacetic acid(DTPA)/Gd3+complex has been synthesized. Finally, MRI-visiblepoly(ε-caprolactone)s (PCLs) were obtained by the efficientclick ligation of these compounds via a CuI-catalyzed [3+ 2] cycloaddition. ICP-MS analyses confirmed the efficient couplingof the complex on the PCL backbone with the MRI-visible PCLs containing1.0, 2.6, and 3.6 wt % of Gd3+. The influence of the Gd3+grafting density on the T1relaxationtimes and on the MRI visibility of the novel biodegradable MMCAs wasevaluated. Finally, their stability and cytocompatibility were assessedwith regard to their potential as innovative MRI-visible biomaterialsfor biomedical applications. [ABSTRACT FROM AUTHOR]

Abstract: This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n =6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r 1), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r 1 of Gd-DTPA-CS 11 was up to 11.65mM−1·s−1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS 11 showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA. [Copyright &y& Elsevier]

Abstract: A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd–DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting contrast agent (CA) was administered by gavage to C3H mice. Passage of the CA through the gastrointestinal (GI) tract was followed by T 1-weighted magnetic resonance imaging (MRI) over a period of 47h, by which time the CA had exited the GI tract. No evidence for leakage of the CA from the GI tract was observed. Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated. [Copyright &y& Elsevier]

Abstract: Objectives: To analyze intranodular signal intensity pattern of hypovascular high-risk borderline lesions of HCC that illustrate multi-step hepatocarcinogenesis within the nodule on Gd–EOB–DTPA-enhanced MRI. Methods: A total of 73 nodules showing hypervascular foci in hypovascular high-risk borderline lesions identified by angiography-assisted CT were included in this study. The intranodular signal intensities of both the hypervascular foci and the hypovascular high-risk borderline lesions were evaluated on hepatobiliary-phase EOB-enhanced MRI obtained 20min after intravenous injection of contrast media. Results: Among 59 hypervascular foci within hypointense hypovascular high-risk borderline lesions, 6 showed more hypointensity, 32 isointensity, and 21 hyperintensity compared to the surrounding hypointense, hypovascular portion of the nodules. Among 14 hypervascular foci within isointense hypovascular high-risk borderline lesions, 5 showed isointensity, and 9 hypointensity compared to the surrounding isointense hypovascular high-risk borderline lesions. No hypervascular foci showed hyperintensity compared to the surrounding isointense hypovascular high-risk borderline lesions. Conclusions: In most of the hypovascular high-risk borderline lesions containing hypervascular foci within the nodule, the signal intensity was decreased in hypervascular foci as compared with hypovascular high-risk borderline lesions and the surrounding background liver parenchyma. This supports the concept of signal intensity decrease during the dedifferentiation process in multistep hepatocarcinogenesis. However, around 30% of the nodules did not follow this rule, and hypervascular foci showed hyperintensity relative to the hypovascular high-risk borderline lesions. [Copyright &y& Elsevier]

Abstract: The magnetic-luminescent multifunctional nanoparticles based on Gd-DTPA and NaYF4:Yb, Er were successfully synthesized by the conjugation of activated DTPA and silica-coated/surface-aminolated NaYF4:Yb, Er nanoparticles through EDC/NHS coupling chemistry. The as-prepared products were characterized by powder X-ray diffraction, transmission electron microscopy, dynamic light scattering, energy dispersive X-ray analysis, and fourier transform infrared spectrometry. The room-temperature upconversion luminescent spectra and T 1-weighted maps of the obtained nanoparticles were carried out by 980nm NIR light excitation and a 3T MR imaging scanner, respectively. The results indicated that the as-synthesized multifunctional nanoparticles with small size, highly solubility in water, and both high MR relaxivities and upconversion luminescence may have potential usage for MR imaging in future. [Copyright &y& Elsevier]

Abstract: The design and synthesis of a combined MRI-optical probe for bio-imaging are reported. The materials studied join the properties of lanthanide (Ln3+) complexes and nanoparticles (NPs), offering an excellent solution for bimodal imaging. The hybrid SiO2@APS/DTPA:Gd:Ln (Ln = Eu3+ or Tb3+) (APS: 3-aminopropyltriethoxysilane, DTPA: diethylenetriamine pentaacetic acid) system increases the payload of the active magnetic centre (Gd3+) and introduces a Ln3+ long-life excited state (Eu3+: 0.35 ± 0.02 ms, Tb3+: 1.87 ± 0.02 ms), with resistance to photobleaching and sharp emission bands. The Eu3+ ions reside in a single low-symmetry site. Although the photoluminescence emission is not influenced by the simultaneous presence of Gd3+ and Eu3+, a moderate r1 increase and a larger enhancement of r2 are observed, particularly at high fields, due to susceptibility effects on r2. The presence of Tb3+ instead of Eu3+ further raises r1 but decreases r2. These values are constant over a wide (5–13) pH range, indicating the paramagnetic NPs stability and absence of leaching. The uptake of NPs by living cells is fast and results in an intensity increase in the T 1-weighted MRI images. The optical properties of the NPs in cellular pellets are also studied, confirming their potential as bimodal imaging agents. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a d-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. Methods: This novel contrast agent was specifically studied because of its ability to “target” metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2mmolGd/kg over a 120min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. Results: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15min after injection of Gd-DTPA-DG (p <0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. Conclusion: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI. [Copyright &y& Elsevier]

We report the synthesis of macrocyclic DTPA conjugates of 2,2′-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H2O)]·xH2O (2a,b; L= 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R1relaxivity reaches 10.9 mM–1s–1, which is approximately 3 times as high as that of structurally related Gd-DOTA (R1= 3.7 mM–1s–1). The R1relaxivity in HSA goes up to 37.2 mM–1s–1, which is almost twice as high as that of MS-325, a leading BPCA, demonstrating a strong blood pool effect. The in vivo MR images of mice obtained with 2bare coherent, showing strong signal enhancement in heart, abdominal aorta, and small vessels. Even the brain tumor is vividly enhanced for an extended period of time. The structural uniqueness of 2is that it is neutral in charge and thus makes no resort to electrostatic interaction, supposedly one of the essential factors for the blood-pool effect. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: A substantial, common shortcoming of the currently used semiautomated techniques for the quantification of myocardial infarct with delayed enhancement magnetic resonance imaging is the assumption that the whole myocardial slab that corresponds to the hyperenhanced tomographic area is 100% nonviable. This assumption is, however, incorrect. To resolve this conflict, we have recently proposed the signal intensity percent-infarct mapping method and validated it in an ex vivo, canine experiment. The purpose of the current study has been the validation of the signal intensity percent-infarct mapping method in vivo, using a porcine model of reperfused myocardial infarct. Methods: In swines (n=6), reperfused myocardial infarct was generated occluding for 90 min by an angioplasty balloon either the left anterior descending or the left circumflex coronary artery. To obtain DE images, Gd(DTPA) enhanced inversion-recovery fast gradient-echo acquisitions were carried out on day 28 after myocardial infarction. Scanning started 15 min after intravenous injection of 0.2 mmol/kg Gd(DTPA). At the end of the MRI session, the animal was sacrificed and 2,3,5-triphenyltetrazolium chloride staining was used to validate the existence and to determine the accurate size of the myocardial infarct. Tissue samples were taken and stained with hematoxylin–eosin and Masson''s trichrome for histological assessment of the infarct and the periinfarct zone. The signal intensity percent-infarct mapping data were compared with corresponding data from the delayed enhancement images analyzed with SIremote+2S.D. thresholding, and with corresponding triphenyltetrazolium-chloride staining data using Friedman''s repeated measure analysis of variance on ranks. Results: The infarct volume determined by the triphenyltetrazolium chloride, SIremote+2S.D. and signal intensity percent-infarct mapping methods was 3.04 ml [2.74, 3.45], 13.62 ml [9.06, 18.45] and 4.27 ml [3.45, 6.33], respectively. Median infarct volume determined by SIremote+2S.D. significantly differed from that determined by triphenyltetrazolium chloride (P<.05). The Bland–Altman overall bias was 12.49% of the volume of the left ventricle. Median infarct volume determined by signal intensity percent-infarct mapping, however, did not differ significantly (NS) from that obtained by triphenyltetrazolium chloride. Signal intensity percent-infarct mapping yielded only a 1.99% Bland–Altman overall bias of the left ventricular volume. Conclusions: This in vivo study in the porcine reperfused myocardial infarct model demonstrates that signal intensity percent-infarct mapping is a highly accurate method for the determination of the extent of myocardial infarct. MRI images for signal intensity percent-infarct mapping are obtained with the pulse sequence of conventional delayed enhancement imaging and are acquired within clinically acceptable scanning time. This makes signal intensity percent-infarct mapping a practical method for clinical implementation. [Copyright &y& Elsevier]

Abstract: Budd-Chiari syndrome (BCS) is a rare disorder caused by the obstruction of hepatic venous outflow, leading to sinusoidal congestion, ischemic injury to liver cells and portal hypertension. Long-term survival largely depends on whether hepatocellular carcinoma occurs. A recently available liver-specific contrast medium, gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA), reportedly has high diagnostic capability for detection of malignant liver tumors. However, there has been no report of the sue of Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) for BCS. We present a case of chronic BCS who underwent both gadopentetate dimeglumine (Gd-DTPA) and Gd-EOB-DTPA-enhanced MRI. Hepatic congestion and edema were seen as slightly hypointense areas on Gd-EOB-DTPA-enhanced hepatobiliary-phase images, although these areas were observed as slightly hyperintense on previously obtained Gd-DTPA-enhanced delayed-phase image. Reduced uptake of Gd-EOB-DTPA by hepatocytes in the region of congestion or edema may account for this difference, which should be recognized in image interpretations. [Copyright &y& Elsevier]

Abstract: Novel conjugates of narrow molecular weight distribution of chitosan oligosaccharides (CSn; n=6, 8, 11) with manganese–diethylenetriaminepentaacetic acid (Mn–DTPA) as potential magnetic resonance imaging (MRI) contrast agents were synthesized. The structures were characterized by means of Fourier transform infrared spectra, 13C nuclear magnetic resonance, size exclusion chromatography and inductively coupled plasma atomic emission spectrometry. The characterization results showed that Mn–DTPA was successfully linked to aminated CSn by an amide function. The magnetic properties were characterized by in vitro and T 1-weighted FLASH image experiments. Relaxivities studies indicated that Mn–DTPA–CSn (n=8, 11) provided higher relaxivity, either in aqueous or bovine serum albumin solution (0.725 mM), than commercial contrast agent Gd–DTPA. The stability results showed that Mn–DTPA–CSn in aqueous were stable enough to prevent MnII ions from releasing. The preliminary in vitro and T 1-weighted FLASH image studies suggested that Mn–DTPA–CSn had the advantage of becoming promising MRI contrast agents. [Copyright &y& Elsevier]

Abstract: Porphyrin-containing polyaspartamide ligands (APTSPP–PHEA–DTPA) were synthesized by the incorporation of diethylenetriaminepentaacetic acid (DTPA) and 5-(4′-aminophenyl)-10,15,20-tris(4′-sulfonatophenyl) porphyrin, trisodium salt (APTSPP) into poly-α,β-[N-(2-hydroxyethyl)-l-aspartamide] (PHEA). These ligands were further reacted with gadolinium chloride to produce macromolecule-gadolinium complexes (APTSPP–PHEA–DTPA–Gd). Experimental data of 1H NMR, IR, UV and elemental analysis evidenced the formation of the polyaspartamide ligands and gadolinium complexes. In vitro and in vivo property tests indicated that APTSPP–PHEA–DTPA–Gd possessed noticeably higher relaxation effectiveness, less toxicity to HeLa cells, and significantly higher enhanced signal intensities (SI) of the VX2 carcinoma in rabbits with lower injection dose requirement than that of Gd–DTPA. Moreover, APTSPP–PHEA–DTPA–Gd was found to greatly enhance the contrast of MR images of the VX2 carcinoma, providing prolonged intravascular duration, and distinguished the VX2 carcinoma and normal tissues in rabbits according to MR image signal enhancements. These porphyrin-containing polyaspartamide gadolinium complexes can be used as the candidates of contrast agents for targeted MRI to tumors. [Copyright &y& Elsevier]

Abstract: With the purpose to develop macromolecular magnetic resonance imaging contrast agents, we herein report three different synthetic approaches to the covalent attachment of bifunctional chelating agents to human serum albumin followed by coordination to contrast enhancing gadolinium(III). Applied methods cover active ester-mediated conjugation, linkage through glutaryl spacer, as well as the connection by the employment of glutaraldehyde. The content of gadolinium(III) was evaluated by inductively-coupled-plasma mass-spectrometry (ICP-MS) measurements and indicated reproducible amounts of conjugated contrast enhancing material. Small angle X-ray scattering (SAXS) experiments provided the size and altered shape of the gadolinium loaded proteins in comparison to unmodified albumin. Finally, the magnetic resonance properties of the protein conjugates were evaluated. The results indicated suitability of the gadolinium(III) loaded protein conjugates for use as macromolecular contrast agents in magnetic resonance imaging (MRI). [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The investigation of pulmonary perfusion by three-dimensional (3D) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was proposed recently. Subtraction images are generated for clinical evaluation, but temporal information is lost and perfusion defects might therefore be masked in this process. The aim of this study is to demonstrate a simple analysis strategy and classification for 3D-DCE-MRI perfusion datasets in the lung without omitting the temporal information. Materials and methods: Pulmonary perfusion measurements were performed in patients with different lung diseases using a 1.5T MR-scanner with a time-resolved 3D-GRE pulse sequence. 25 3D-volumes were acquired after iv-injection of 0.1mmol/kg KG Gadolinium-DTPA. Three parameters were determined for each pixel: (1) peak enhancement S n,max normalized to the arterial input function to detect regions of reduced perfusion; (2) time between arterial peak enhancement in the large pulmonary artery and tissue peak enhancement τ to visualize regions with delayed bolus onset; and (3) ratio R = S n,max/τ was calculated to visualize impaired perfusion, irrespectively of whether related to reduced or delayed perfusion. Results: A manual selection of peak perfusion images is not required. Five different types of perfusion can be found: (1) normal perfusion; (2) delayed non-reduced perfusion; (3) reduced non-delayed perfusion; (4) reduced and delayed perfusion; and (5) no perfusion. Types II and IV could not be seen in subtraction images since the temporal information is necessary for this purpose. Conclusions: The analysis strategy in this study allows for a simple and observer-independent visualization and classification of impaired perfusion in dynamic contrast-enhanced pulmonary perfusion MRI by using the temporal information of the datasets. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study is to label rabbit neural stem cells (NSCs) by using standard contrast agents (Gd-DTPA) in combination with PKH26 and in vitro track them with MR imaging. Materials and methods: NSCs from prenatal brains of rabbits were cultured and propagated. Intracellular uptake of Gd-DTPA was achieved by using a non-liposomal lipid transfection reagent (Effectene) as the transfection agent. After labeling with Gd-DTPA, cells were incubated with cellular membrane fluorescent dye PKH26. The labeling effectiveness and the longevity of Gd-DTPA maintenance were measured on a 1.5T MR scanner. The influence of labeling on the cellular biological behaviors was assessed by cellular viability, proliferation and differentiation assessment. Results: The labeling efficiency of Gd-DTPA was up to 90%. The signal intensity on T1-weighted imaging and T1 values of labeled cells were significantly higher than those of unlabeled cells (P <0.05). The minimal number of detectable cells for T1-weighted imaging was 5×103. Cellular uptake of Gd-DTPA was maintained until 15 days after initially labeling. There was no significant difference in the cellular viability and proliferation between the labeled and unlabeled NSCs (P >0.05). Normal glial and neuronal differentiation remained in labeled NSCs like unlabeled NSCs. Conclusion: Highly efficient labeling NSCs with Gd-DTPA could be achieved by using Effectene. This method of labeling NSCs allows for tracking cells with MR imaging, and without alterations of cellular biological behaviors. [Copyright &y& Elsevier]

Abstract: We have prepared chitosan (CH)–gadolinium (Gd) diethylenetriaminepentaacetic acid (DTPA) conjugates that have potential as contrast agents for magnetic resonance imaging. Conjugates were synthesized starting with low molecular weight chitosan (25kDa and 96% degree of deacetylation (noted DDA)) by covalent linkage of DTPA to chitosan amine groups confirmed by Fourier transform infrared spectroscopy (FTIR). Different DTPA/amine ratios were used to obtain different degrees of DTPA conjugation (10–20%), determined by nuclear magnetic resonance (1H NMR) spectroscopy, a colorimetric assay, and isothermal titration calorimetry (ITC). After preparation of chitosan–DTPA complexes with Gd, polyelectrolyte complexes were assembled with plasmid DNA pEGFPLuc (6367bp) and investigated using scanning electron microscopy and scanning transmission electron microscopy. Particles were spherical with diameters in the range of 30–150nm. The presence of gadolinium in the nanoparticles was confirmed by energy dispersive X-ray spectroscopy. Gd was located preferentially in a 2–5nm wide area surrounding the nanoparticles. [Copyright &y& Elsevier]

Abstract: The synthesis and characterization of gold nanoparticles coated with Gd-chelate (Au@GdL), where L is a conjugate of DTPA and cysteine, is described. These particles are obtained by the replacement of citrate from the gold nanoparticle surfaces with gadolinium chelate (GdL). The average size of Au@GdL is 14nm with a loading of GdL reaching up to 2.9×103 per particles, and they demonstrate very high R1 relaxivity (∼105 mM−1 s−1) as well as X-ray attenuation. The R1 relaxivity per [Gd] is 17.9mM−1 s−1. The present system also exhibits macrophage-specific property, as demonstrated by histological and TEM images as well as CT and MR, rendering itself as a new class of T1 multimodal CT/MR contrast agent. [Copyright &y& Elsevier]

Abstract: 5-(4-Aminophenyl)-10,15,20-tris(4-sulfonatophenyl) manganese(III) porphyrin conjugated with dextran was synthesized. Its potential of being used as a tumor-targeting magnetic resonance imaging contrast agent was evaluated in vitro and in vivo. The results demonstrated that the compound has a longitudinal relaxivity (R 1) higher than Gd-DTPA, low cytotoxicity and binding specificity to tumor cell membrane. [Copyright &y& Elsevier]

Abstract: Objective: To investigate value of magnetic resonance cholangiopancreatography (MRCP) using oral diluted gadolinium (Gd)-diethylenetriamine penta-acetic acid (DTPA) as negative contrast materials in diagnosis of juxtapapillary duodenal diverticulum with atypical imaging features. Methods: Nineteen patients with juxtapapillary duodenal diverticula of which imaging findings were atypical underwent MRCP using oral diluted Gd-DTPA as negative contrast materials after conventional MRCP without any oral contrast materials. Results: Twenty diverticula were revealed in the 19 patients. At conventional MRCP, the diverticula appeared as rounded lesion with high signal intensity. After oral administration of diluted Gd-DTPA, they disappeared at MRCP. These entities were diagnosed as duodenal diverticula for they communicate with duodenal lumen. Conclusion: MRCP using oral Gd-DTPA as negative contrast materials can be helpful in obtaining definitive diagnosis of those juxtapapillary duodenal diverticula without typical imaging features. [Copyright &y& Elsevier]

To study transmetalation effects of the gadolinium-based contrast agent Magnevist (Gd--DTPA), the first analytical method for the simultaneous determination of Gd--DTPA and its transmetalation products in complex clinical samples was developed. The high separation efficiency of capillary electrophoresis (CE) was employed to separate Gd--DTPA, Fe--DTPA, Cu--DTPA, Zn--DTPA, and the free DTPA (diethylenetriaminepentaacetic acid) ligand. The coupling of CE with electrospray ionization lime-of-flight mass spectrometry (ESI-TOF-MS) provided the required sensitivity and excellent selectivity for the analysis of complex samples, such as blood plasma and whole blood. Separation and detection parameters were optimized, and crucial steps for CE/MS method development are pointed out. Limit of detection (LOD) is 5 × 10-7 mol/L, limit of quantification (LOQ) is 1.7 × 10-6 mol/L, and the linear range comprises 2 decades, starting at the limit of quantification. To determine recovery rates, precision, and accuracy of the method, blank plasma samples were spiked with Gd--TPA in three different concentrations. Blood plasma samples from 10 patients with normal renal function, having received Magnevist, were analyzed for Gd--DTPA and possible transmetalation products by CE/ESI-TOF-MS. The method was validated by determination of the total Gd concentration using inductively coupled plasma optical emission spectroscopy (ICP-OES). Transmetalation assays of Magnevist with and without supplementary iron were carried out in incubated whole blood samples. [ABSTRACT FROM AUTHOR]

Introduction: Diffusion-weighted imaging (DWI) is usually performed before injection of intra- venous paramagnetic contrast medium. Occasionally, it may be necessary to perform or to repeat DWI after such administration. Our purpose was to evaluate the effect of intravenous gadodiamide (Gd [DTPA-BMA]) on DWI. Methods: DWI was performed on 88 brain lesions immediately before, immediately after, and 5- 10 mm following the end of 0.1 mmol/kg Gd [DTPA-BMA] administration. Signal-to-noise ratios (SNR5) and contrast-to-noise ratios (CNRs) of the lesions, and the SNRs of normal brain tissue were calculated on b=0 s/mm² and b=1,000 s/mm² DW images. Apparent diffusion coefficient (ADC) values of the lesions were measured on ADC maps. A paired (-test was used to determine the significance of differences between the values before and after administration of contrast medium. Results: The lesions consisted of 23 intraaxial and 11 extraaxial masses, 19 ischemic strokes, 15 intracranial hemorrhages and 20 demyelinating lesions. Images before and after contrast administration were not significantly different regarding SNRs and CNRs on DWI. This statement was also true for strongly enhanced lesions. However, ADC values significantly decreased after contrast medium injection on early post-contrast DWI in normal brain tissue (1%, P<0.049) and (3%, P<0.008) in lesions. By contrast, on late images, ADC values were normalized. Conclusion: Contrast medium injection had significant and time-dependent effects on ADC values. Therefore, only pre-contrast and late DW images should be used in quantitative ADC studies. [ABSTRACT FROM AUTHOR]

We report the synthesis of macrocyclic DTPA conjugates of 1,1′-bis(amino)ferrocenes (1a–b) and their Gd-complexes [Gd(L)(H2O)] (2a–b, L = 1a–b) for use as new MRI blood-pool contrast agents. High R1relaxivity in HSA as well as high thermodynamic and kinetic stabilities is observed for 2a. [ABSTRACT FROM AUTHOR]

Abstract: A new type of dendritic molecules, Gd–DTPA derivatives, which work as a functionalized ligand coordinating gadolinium(III) ion at the center of their frameworks with different terminal moieties on the molecular surfaces, was readily synthesized with high yield. The structures were established by 1H, 13C NMR, and mass spectral studies. In vitro studies showed them to have enhanced r 1 value in albumin medium and good potentiality as MRI contrast agent. [Copyright &y& Elsevier]

Aim: To investigate whether time-resolved imaging with interleaved stochastic trajectories (TWIST)-volumetric interpolated breath-hold examination (VIBE) hepatic arterial phase imaging technique improves image quality in patients experiencing transient severe motion (TSM) during abdominal magnetic resonance imaging (MRI) with gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA).Materials and Methods: This retrospective study compares TSM in MRI images from 28 patients with focal liver lesions imaged with gadopentetic acid (Gd-DTPA) and 28 patients with focal liver lesions imaged with Gd-EOB-DTPA. Images were taken during the precontrast phase, five hepatic arterial phases acquired with a single breath-hold, portal venous phase, and late dynamic phase.Results: There was a significant difference in the mean motion scores for the arterial phase in Gd-EOB-DTPA cohort before, and after, enhancement (p<0.001); however, there was no significant difference in the Gd-DTPA cohort for the same (p<0.05). The mean motion scores in the five hepatic arterial phases in the Gd-EOB-DTPA cohort after enhancement were significantly higher than that in the Gd-DTPA cohort (p<0.001). TSM occurred significantly more frequently in the Gd-EOB-DTPA cohort (64.2%) than in the Gd-DTPA cohort (3.5%, p<0.001). The highest motion score in Gd-EOB-DTPA cohort occurred during the fourth arterial phase, which was significantly higher than the other four arterial phases after enhancement (p<0.001). Moderate and severe TSM (motion score ≥3) occurred mainly in the mid and mid-late arterial phase. All patients with arterial phase images affected by TSM (motion scores ≥3) had at least one arterial phase image with TSM score <3, which was of adequate image quality for diagnostic purposes.Conclusion: The TWIST-VIBE hepatic arterial phase imaging technique can be used to acquire arterial images at abdominal MRI with Gd-EOB-DTPA, and these images have adequate quality for diagnosis in patients who are affected by TSM. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced liver MRI is widely used for detection and differentiation of focal liver lesions. Diffusion weighted imaging (DWI) including apparent diffusion coefficient (ADC) measurements is increasingly utilised as a fast and, with limitations, quantitative method for liver lesion detection and characterisation. Herein we investigate whether the administration of Gd-EOB-DTPA affects DWI. Materials and methods: 31 consecutive patients referred to standardised liver MRI (1.5T, Gd-EOB-DTPA, 0.025mmol/kg) were retrospectively reviewed. All underwent a breathhold DWI sequence before and after contrast agent administration (EPI-DWI, TR/TE (effective): 2100/62ms, b-values: 0 and 800s/mm2). Patients with previously treated liver lesions were excluded. Signal intensity of lesion, parenchyma and noise on DWI images as well as the ADC value were measured after identification by two observers in consensus using manually placed regions of interest. The reference standard was imaging follow-up determined separately by two radiologists. Data analysis included signal-to-noise (SNR) ratio and contrast-to-noise ratio (CNR) calculations, comparisons were drawn by employing multiple Bonferroni corrected Wilcoxon signed-rank tests. Results: 50 malignant and 39 benign lesions were identified. Neither SNR, CNR nor ADC values showed significant differences between pre- and postcontrast DWI. Both pre- and postcontrast ADC values differed significantly between benign and malignant lesions (P <0.001). Conclusion: We did not identify a significant influence of Gd-EOB-DTPA on DWI of liver lesions. This allows for individual tailoring of imaging protocols according to clinical needs. [Copyright &y& Elsevier]

Abstract: Objective: To compare three different injection methods for optimizing hepatic arterial phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) enhanced MR imaging. Methods: Arterial phase images were obtained after the injection of contrast agent at a rate of 3mL/s with diluted Gd-EOB-DTPA (dilution method) in 27 patients, 3mL/s with undiluted Gd-EOB-DTPA (3mL method) in 26 patients and 1mL/s with undiluted Gd-EOB-DTPA (1mL method) in 28 patients. In the quantitative evaluation, signal-to-phantom ratios (SPR) of the liver parenchyma, pancreas, renal cortex, portal vein and aorta were evaluated. In the qualitative evaluation, the seven items for image quality of hepatic arterial phase were assessed, and the total score of all items in each subject was calculated. Results: The score of enhancement of abdominal aorta and total score of seven items in 1mL method were significantly higher than those in 3mL method. The SPR of the liver parenchyma in 3mL method was significantly higher than that in 1mL method, suggesting substantial hepatic inflow from portal venous return. Conclusion: For the optimal arterial phase imaging, injection rate of 1mL/s with undiluted Gd-EOB-DTPA is convenient and preferable, compared with other two methods, based on our qualitative analysis. [Copyright &y& Elsevier]

Background. Several late sequelae of the administration of gadolinium (Gd)-containing MRI contrast agents have been described in patients with advanced renal failure. In an observational series, we found a remarkable frequency of peracute reactions after administration of Gd-DTPA used for cardiovascular evaluation before renal transplantation. Methods. In a 26-month observational period, 13 of 136 haemodialyzed or CAPD patients exhibited onset of fever, chills and nausea within hours after administration of Gd-DTPA peracute. A minority showed persistent cessation of residual diuresis. We performed blood cultures in most patients and evaluated white blood cell (WBC) counts, eosinophils, CRP, heart rate and blood pressure. Results. Within an average of 12 h (range 12–36 h) after Gd administration, the 13 patients (9 males, 4 females; median age 61 years, range 47–79) developed consistent symptomatology with fever (median 39.0°C, range 37.5–39.5), chills, malaise, hypotension, vomiting, dyspnoea—initially raising suspicion of septicaemia. Subsequent blood cultures on bacterial contamination of the injected product remained negative throughout; bacterial or endotoxin contamination of the reagent was excluded. Steroids were tried in the first two patients without a noticeable effect. In all subsequent patients, symptoms were attenuated during the first 5 h dialysis (F60HPS with 280 ml/min blood flow) and disappeared within 72 h. CRP levels remained markedly elevated up to 14 days. Lymphopenia was seen in all patients, and polymorphic neutrophils (PMN) remained normal. Two polyuric patients developed persistent anuria. After a median of 16 months, none of these patients developed nephrogenic systemic fibrosis. Conclusion. This series with unusually severe acute phase reactions was caused by one specific preparation. Such peracute reactions may be relevant for the so-far largely unresolved pathogenesis of the skin reaction to some Gd products in end-stage renal disease (ESRD) patients. It remains unresolved whether the reaction observed with Gd-DTPA do in principle also occur with other Gd reagents. [ABSTRACT FROM AUTHOR]