Core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents

NASA Astrophysics Data System (ADS)

Li, Fenfen; Zhi, Debo; Luo, Yufeng; Zhang, Jiqian; Nan, Xiang; Zhang, Yunjiao; Zhou, Wei; Qiu, Bensheng; Wen, Longping; Liang, Gaolin

2016-06-01

T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes

Polyethylene glycol-covered ultra-small Gd2O3 nanoparticles for positive contrast at 1.5 T magnetic resonance clinical scanning

NASA Astrophysics Data System (ADS)

Fortin, Marc-André; Petoral, Rodrigo M., Jr.; Söderlind, Fredrik; Klasson, A.; Engström, Maria; Veres, Teodor; Käll, Per-Olof; Uvdal, Kajsa

2007-10-01

The size distribution and magnetic properties of ultra-small gadolinium oxide crystals (US-Gd2O3) were studied, and the impact of polyethylene glycol capping on the relaxivity constants (r1, r2) and signal intensity with this contrast agent was investigated. Size distribution and magnetic properties of US-Gd2O3 nanocrystals were measured with a TEM and PPMS magnetometer. For relaxation studies, diethylene glycol (DEG)-capped US-Gd2O3 nanocrystals were reacted with PEG-silane (MW 5000). Suspensions were adequately dialyzed in water to eliminate traces of Gd3+ and surfactants. The particle hydrodynamic radius was measured with dynamic light scattering (DLS) and the proton relaxation times were measured with a 1.5 T MRI scanner. Parallel studies were performed with DEG-Gd2O3 and PEG-silane-SPGO (Gd2O3,< 40 nm diameter). The small and narrow size distribution of US-Gd2O3 was confirmed with TEM (~3 nm) and DLS. PEG-silane-US-Gd2O3 relaxation parameters were twice as high as for Gd-DTPA and the r2/r1 ratio was 1.4. PEG-silane-SPGO gave low r1 relaxivities and high r2/r1 ratios, less compatible with positive contrast agent requirements. Higher r1 were obtained with PEG-silane in comparison to DEG-Gd2O3. Treatment of DEG-US-Gd2O3 with PEG-silane provides enhanced relaxivity while preventing aggregation of the oxide cores. This study confirms that PEG-covered Gd2O3 nanoparticles can be used for positively contrasted MR applications requiring stability, biocompatible coatings and nanocrystal functionalization.

Enhanced MRI relaxivity of aquated Gd3+ ions by carboxyphenylated water-dispersed graphene nanoribbons

NASA Astrophysics Data System (ADS)

Gizzatov, Ayrat; Keshishian, Vazrik; Guven, Adem; Dimiev, Ayrat M.; Qu, Feifei; Muthupillai, Raja; Decuzzi, Paolo; Bryant, Robert G.; Tour, James M.; Wilson, Lon J.

2014-02-01

The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd3+ ions can serve as a high-performance contrast agent (CA) for applications in T1- and T2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times for r1 and 21 times for r2.The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd3+ ions can serve as a high-performance contrast agent (CA) for applications in T1- and T2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times for r1 and 21 times for r2. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr06026h

Gadolinium-based magnetic resonance contrast agents at 7 Tesla: in vitro T1 relaxivities in human blood plasma.

PubMed

Noebauer-Huhmann, Iris M; Szomolanyi, Pavol; Juras, Vladimír; Kraff, Oliver; Ladd, Mark E; Trattnig, Siegfried

2010-09-01

PURPOSE/INTRODUCTION: The aim of this study was to determine the T1 relaxivities (r1) of 8 gadolinium (Gd)-based MR contrast agents in human blood plasma at 7 Tesla, compared with 3 Tesla. Eight commercially available Gd-based MR contrast agents were diluted in human blood plasma to concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. In vitro measurements were performed at 37 degrees C, on a 7 Tesla and on a 3 Tesla whole-body magnetic resonance imaging scanner. For the determination of T1 relaxation times, Inversion Recovery Sequences with inversion times from 0 to 3500 ms were used. The relaxivities were calculated. The r1 relaxivities of all agents, diluted in human blood plasma at body temperature, were lower at 7 Tesla than at 3 Tesla. The values at 3 Tesla were comparable to those published earlier. Notably, in some agents, a minor negative correlation of r1 with a concentration of up to 2 mmol/L could be observed. This was most pronounced in the agents with the highest protein-binding capacity. At 7 Tesla, the in vitro r1 relaxivities of Gd-based contrast agents in human blood plasma are lower than those at 3 Tesla. This work may serve as a basis for the application of Gd-based MR contrast agents at 7 Tesla. Further studies are required to optimize the contrast agent dose in vivo.

Zero field splitting fluctuations induced phase relaxation of Gd3+ in frozen solutions at cryogenic temperatures

NASA Astrophysics Data System (ADS)

Raitsimring, A.; Dalaloyan, A.; Collauto, A.; Feintuch, A.; Meade, T.; Goldfarb, D.

2014-11-01

Distance measurements using double electron-electron resonance (DEER) and Gd3+ chelates for spin labels (GdSL) have been shown to be an attractive alternative to nitroxide spin labels at W-band (95 GHz). The maximal distance that can be accessed by DEER measurements and the sensitivity of such measurements strongly depends on the phase relaxation of Gd3+ chelates in frozen, glassy solutions. In this work, we explore the phase relaxation of Gd3+-DOTA as a representative of GdSL in temperature and concentration ranges typically used for W-band DEER measurements. We observed that in addition to the usual mechanisms of phase relaxation known for nitroxide based spin labels, GdSL are subjected to an additional phase relaxation mechanism that features an increase in the relaxation rate from the center to the periphery of the EPR spectrum. Since the EPR spectrum of GdSL is the sum of subspectra of the individual EPR transitions, we attribute this field dependence to transition dependent phase relaxation. Using simulations of the EPR spectra and its decomposition into the individual transition subspectra, we isolated the phase relaxation of each transition and found that its rate increases with |ms|. We suggest that this mechanism is due to transient zero field splitting (tZFS), where its magnitude and correlation time are scaled down and distributed as compared with similar situations in liquids. This tZFS induced phase relaxation mechanism becomes dominant (or at least significant) when all other well-known phase relaxation mechanisms, such as spectral diffusion caused by nuclear spin diffusion, instantaneous and electron spin spectral diffusion, are significantly suppressed by matrix deuteration and low concentration, and when the temperature is sufficiently low to disable spin lattice interaction as a source of phase relaxation.

Evaluation of focal cartilage lesions of the knee using MRI T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC).

PubMed

Årøen, Asbjørn; Brøgger, Helga; Røtterud, Jan Harald; Sivertsen, Einar Andreas; Engebretsen, Lars; Risberg, May Arna

2016-02-11

Assessment of degenerative changes of the cartilage is important in knee cartilage repair surgery. Magnetic Resonance Imaging (MRI) T2 mapping and delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) are able to detect early degenerative changes. The hypothesis of the study was that cartilage surrounding a focal cartilage lesion in the knee does not possess degenerative changes. Twenty-eight consecutive patients included in a randomized controlled trial on cartilage repair were evaluated using MRI T2 mapping and dGEMRIC before cartilage treatment was initiated. Inclusion was based on disabling knee problems (Lysholm score of ≤ 75) due to an arthroscopically verified focal femoral condyle cartilage lesion. Furthermore, no major malalignments or knee ligament injuries were accepted. Mean patient age was 33 ± 9.6 years, and the mean duration of knee symptoms was 49 ± 60 months. The MRI T2 mapping and the dGEMRIC measurements were performed at three standardized regions of interest (ROIs) at the medial and lateral femoral condyle, avoiding the cartilage lesion The MRI T2 mapping of the cartilage did not demonstrate significant differences between condyles with or without cartilage lesions. The dGEMRIC results did not show significantly lower values of the affected condyle compared with the opposite condyle and the contra-lateral knee in any of the ROIs. The intraclass correlation coefficient (ICC) of the dGEMRIC readings was 0.882. The MRI T2 mapping and the dGEMRIC confirmed the arthroscopic findings that normal articular cartilage surrounded the cartilage lesion, reflecting normal variation in articular cartilage quality. NCT00885729 , registered April 17 2009.

Fluorescence-tagged amphiphilic brush copolymer encapsulated Gd2O3 core-shell nanostructures for enhanced T 1 contrast effect and fluorescent imaging

NASA Astrophysics Data System (ADS)

Wang, Fenghe; Peng, Erwin; Liu, Feng; Li, Pingjing; Fong Yau Li, Sam; Xue, Jun Min

2016-10-01

To obtain suitable T 1 contrast agents for magnetic resonance imaging (MRI) application, aqueous Gd2O3 nanoparticles (NPs) with high longitudinal relativity (r 1) are demanded. High quality Gd2O3 NPs are usually synthesized through a non-hydrolytic route which requires post-synthetic modification to render the NPs water soluble. The current challenge is to obtain aqueous Gd2O3 NPs with high colloidal stability and enhanced r 1 relaxivity. To overcome this challenge, fluorescence-tagged amphiphilic brush copolymer (AFCP) encapsulated Gd2O3 NPs were proposed as suitable T 1 contrast agents. Such a coating layer provided (i) superior aqueous stability, (ii) biocompatibility, as well as (iii) multi-modality (conjugation with fluorescence dye). The polymeric coating layer thickness was simply adjusted by varying the phase-transfer parameters. By reducing the coating thickness, i.e. the distance between the paramagnetic centre and surrounding water protons, the r 1 relaxivity could be enhanced. In contrast, a thicker polymeric layer coating prevents Gd3+ ions leakage, thus improving its biocompatibility. Therefore, it is important to strike a balance between the biocompatibility and the r 1 relaxivity behaviour. Lastly, by conjugating fluorescence moiety, an additional imaging modality was enabled, as demonstrated from the cell-labelling experiment.

Measuring hepatic functional reserve using T1 mapping of Gd-EOB-DTPA enhanced 3T MR imaging: A preliminary study comparing with 99mTc GSA scintigraphy and signal intensity based parameters.

PubMed

Nakagawa, Masataka; Namimoto, Tomohiro; Shimizu, Kie; Morita, Kosuke; Sakamoto, Fumi; Oda, Seitaro; Nakaura, Takeshi; Utsunomiya, Daisuke; Shiraishi, Shinya; Yamashita, Yasuyuki

2017-07-01

To determine the utility of liver T1-mapping on gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance (MR) imaging for the measurement of liver functional reserve compared with the signal intensity (SI) based parameters, technetium-99m-galactosyl serum albumin ( 99m Tc-GSA) scintigraphy and indocyanine green (ICG) clearance. This retrospective study included 111 patients (Child-Pugh-A 90; -B 21) performed with both Gd-EOB-DTPA enhanced liver MR imaging and 99m Tc-GSA (76 patients with ICG). Receiver operating characteristic (ROC) curve analysis was performed to compare diagnostic performances of T1-relaxation-time parameters [pre-(T1pre) and post-contrast (T1hb) Gd-EOB-DTPA], SI based parameters [relative enhancement (RE), liver-to-muscle-ratio (LMR), liver-to-spleen-ratio (LSR)] and 99m Tc-GSA scintigraphy blood clearance index (HH15)] for Child-Pugh classification. Pearson's correlation was used for comparisons among T1-relaxation-time parameters, SI-based parameters, HH15 and ICG. A significant difference was obtained for Child-Pugh classification with T1hb, ΔT1, all SI based parameters and HH15. T1hb had the highest AUC followed by RE, LMR, LSR, ΔT1, HH15 and T1pre. The correlation coefficients with HH15 were T1pre 0.22, T1hb 0.53, ΔT1 -0.38 of T1 relaxation parameters; RE -0.44, LMR -0.45, LSR -0.43 of SI-based parameters. T1hb was highest for correlation with HH15. The correlation coefficients with ICG were T1pre 0.29, T1hb 0.64, ΔT1 -0.42 of T1 relaxation parameters; RE -0.50, LMR -0.61, LSR -0.58 of SI-based parameters; 0.64 of HH15. Both T1hb and HH15 were highest for correlation with ICG. T1 relaxation time at post-contrast of Gd-EOB-DTPA (T1hb) was strongly correlated with ICG clearance and moderately correlated HH15 with 99m Tc-GSA. T1hb has the potential to provide robust parameter of liver functional reserve. Copyright © 2017 Elsevier B.V. All rights reserved.

Planar dGEMRIC Maps May Aid Imaging Assessment of Cartilage Damage in Femoroacetabular Impingement.

PubMed

Bulat, Evgeny; Bixby, Sarah D; Siversson, Carl; Kalish, Leslie A; Warfield, Simon K; Kim, Young-Jo

2016-02-01

Three-dimensional (3-D) delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) helps quantify biochemical changes in articular cartilage that correlate with early-stage osteoarthritis. However, dGEMRIC analysis is performed slice by slice, limiting the potential of 3-D data to give an overall impression of cartilage biochemistry. We previously developed a computational algorithm to produce unfolded, or "planar," dGEMRIC maps of acetabular cartilage, but have neither assessed their application nor determined whether MRI-based grading of cartilage damage or dGEMRIC measurements predict intraoperative findings in hips with symptomatic femoroacetabular impingement (FAI). (1) Does imaging-based assessment of acetabular cartilage damage correlate with intraoperative findings in hips with symptomatic FAI? (2) Does the planar dGEMRIC map improve this correlation? (3) Does the planar map improve the correlation between the dGEMRIC index and MRI-based grading of cartilage damage in hips with symptomatic FAI? (4) Does the planar map improve imaging-based evaluation time for hips with symptomatic FAI? We retrospectively studied 47 hips of 45 patients with symptomatic FAI who underwent hip surgery between 2009 and 2013 and had a 1.5-T 3-D dGEMRIC scan within 6 months preoperatively. Our cohort included 25 males and 20 females with a mean ± SD age at surgery of 29 ± 11 years. Planar dGEMRIC maps were generated from isotropic, sagittal oblique TrueFISP and T1 sequences. A pediatric musculoskeletal radiologist with experience in hip MRI evaluated studies using radially reformatted sequences. For six acetabular subregions (anterior-peripheral [AP]; anterior-central [AC]; superior-peripheral [SP]; superior-central [SC]; posterior-peripheral [PP]; posterior-central [PC]), modified Outerbridge cartilage damage grades were recorded and region-of-interest T1 averages (the dGEMRIC index) were measured. Beck's intraoperative cartilage damage grades were compared with the Outerbridge

Various ligand-coated ultrasmall gadolinium-oxide nanoparticles: Water proton relaxivity and in-vivo T1 MR image

NASA Astrophysics Data System (ADS)

Park, Ja Young; Kim, Sung June; Lee, Gang Ho; Jin, Seonguk; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok

2015-04-01

Surface coating of nanoparticles with ligands is essential in magnetic resonance imaging (MRI) because of solubility in water and biocompatibility. In this study, five organic molecules were used for surface coating of ultrasmall gadolinium-oxide (Gd2O3) nanoparticles (d avg = 2.0 nm). All of the samples showed large longitudinal (r1) and transverse (r2) water proton relaxivities with r2/r1 ratios that were close to one, corresponding to ideal conditions for T1 MRI contrast agents. Finally, in-vivo T1 MR images were acquired to prove the effectiveness of the surface-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent.

Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

PubMed

Gupta, Abhishek; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; de Campo, Liliana; Hwang, Dennis W; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

2015-09-28

Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-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 (17)O 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 (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo "model-free" approach. High payloads of Gd(III) 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phosphinic derivative of DTPA conjugated to a G5 PAMAM dendrimer: an 17O and 1H relaxation study of its Gd(III) complex.

PubMed

Lebdusková, Petra; Sour, Angélique; Helm, Lothar; Tóth, Eva; Kotek, Jan; Lukes, Ivan; Merbach, André E

2006-07-28

A DTPA-based chelate containing one phosphinate group was conjugated to a generation 5 polyamidoamine (PAMAM) dendrimer via a benzylthiourea linkage. The Gd(III) complex of this novel conjugate has potential as a contrast agent for magnetic resonance imaging (MRI). The chelates bind Gd3+via three nitrogen atoms, four carboxylates and one phosphinate oxygen, and one water molecule completes the inner coordination sphere. The monomer Gd(III) chelates bearing nitrobenzyl and aminobenzyl groups ([Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-) as well as the dendrimeric Gd(III) complex G5-(Gd(DTTAP))63) were studied by multiple-field, variable temperature 17O and 1H NMR. The rate of water exchange is faster than that of [Gd(DTPA)(H2O)]2- and very similar on the two monomeric complexes (8.9 and 8.3 x 10(6) s-1 for [Gd(DTTAP-bz-NO2)(H2O)]2- and [Gd(DTTAP-bz-NH2)(H2O)]2-, respectively), while it is decreased on the dendrimeric conjugate (5.0 x 10(6) s-1). The Gd(III) complex of the dendrimer conjugate has a relaxivity of 26.8 mM-1 s-1 at 37 degrees C and 0.47 T (corresponding to 1H Larmor frequency of 20 MHz). Given the contribution of the second sphere water molecules to the overall relaxivity, this value is slightly higher than those reported for similar size dendrimers. The experimental 17O and 1H NMR data were fitted to the Solomon-Bloembergen-Morgan equations extended with a contribution from second coordination sphere water molecules. The rotational dynamics of the dendrimeric conjugate was described in terms of global and local motions with the Lipari-Szabo approach.

Characterization of Fe3O4/SiO2/Gd2O(CO3)2 core/shell/shell nanoparticles as T1 and T2 dual mode MRI contrast agent.

PubMed

Yang, Meicheng; Gao, Lipeng; Liu, Kai; Luo, Chunhua; Wang, Yiting; Yu, Lei; Peng, Hui; Zhang, Wen

2015-01-01

Core/shell/shell structured Fe3O4/SiO2/Gd2O(CO3)2 nanoparticles were successfully synthesized. Their properties as a new type of T1-T2 dual model contrast agent for magnetic resonance imaging were investigated. Due to the introduce of a separating SiO2 layer, the magnetic coupling between Gd2O(CO3)2 and Fe3O4 could be modulated by the thickness of SiO2 layer and produce appropriate T1 and T2 signal. Additionally, the existence of Gd(3+) enhances the transverse relaxivity of Fe3O4 possibly because of the magnetic coupling between Gd(3+) and Fe3O4. The Fe3O4/SiO2/Gd2O(CO3)2 nanoparticles exhibit good biocompatibility, showing great potential for biomedical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging.

PubMed

Mi, Peng; Cabral, Horacio; Kokuryo, Daisuke; Rafi, Mohammad; Terada, Yasuko; Aoki, Ichio; Saga, Tsuneo; Takehiko, Ishii; Nishiyama, Nobuhiro; Kataoka, Kazunori

2013-01-01

Nanodevices for magnetic resonance imaging of cancer were self-assembled to core-shell micellar structures by metal complex formation of K(2)PtCl(6) with diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen (Gd-DTPA), a T(1)-contrast agent, and poly(ethylene glycol)-b-poly{N-[N'-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) copolymer in aqueous solution. Gd-DTPA-loaded polymeric micelles (Gd-DTPA/m) showed a hydrodynamic diameter of 45 nm and a core size of 22 nm. Confining Gd-DTPA inside the core of the micelles increased the relaxivity of Gd-DTPA more than 13 times (48 mM(-1) s(-1)). In physiological conditions Gd-DTPA/m sustainedly released Gd-DTPA, while the Pt(IV) complexes remain bound to the polymer. Gd-DTPA/m extended the circulation time in plasma and augmented the tumor accumulation of Gd-DTPA leading to successful contrast enhancement of solid tumors. μ-Synchrotron radiation-X-ray fluorescence results confirmed that Gd-DTPA was delivered to the tumor site by the micelles. Our study provides a facile strategy for incorporating contrast agents, dyes and bioactive molecules into nanodevices for developing safe and efficient drug carriers for clinical application. Copyright © 2012 Elsevier Ltd. All rights reserved.

Gd-complexes of macrocyclic DTPA conjugates of 1,1'-bis(amino)ferrocenes as high relaxivity MRI blood-pool contrast agents (BPCAs).

PubMed

Kim, Hee-Kyung; Park, Ji-Ae; Kim, Kyeong Min; Nasiruzzaman, Sk Md; Kang, Duk-Sik; Lee, Jongmin; Chang, Yongmin; Kim, Tae-Jeong

2010-11-28

We report the synthesis of macrocyclic DTPA conjugates of 1,1'-bis(amino)ferrocenes (1a-b) and their Gd-complexes [Gd(L)(H(2)O)] (2a-b, L = 1a-b) for use as new MRI blood-pool contrast agents. High R(1) relaxivity in HSA as well as high thermodynamic and kinetic stabilities is observed for 2a.

The in vivo relaxivity of MRI contrast agents

NASA Astrophysics Data System (ADS)

Shuter, Borys

1999-11-01

Post-contrast clinical 1H Magnetic Resonance Images have to date been interpreted with little regard for possible variations in the in-vivo properties of injected magnetic pharmaceuticals (contrast agents), particularly in their relaxivity or ability to alter tissue relaxation rates, T2-1 and T 2-1, per unit concentration. The relaxivities of contrast agents have only rarely been measured in-vivo, measurements usually being performed on excised tissues and at magnetic field strengths lower than used in clinical practice. Some researchers have simply assumed that relaxivities determined in homogeneous tissue phantoms were applicable in-vivo. In this thesis, the relaxivities of two contrast agents, Gd-DTPA and Gd-EOB-DTPA, were measured in simple tissue phantoms and in the kidney and liver of intact, but sacrificed, Wistar rats using a clinical MR scanner with a magnetic field of 1.5 Tesla. T1 and T2 were determined from sets of images acquired using a standard clinical spin-echo pulse sequence. The contrast agent concentration in tissue was assessed by radioassay of 153Gd-DTPA or 153Gd-EOB-DTPA, mixed with the normal compound prior to injection. Relaxivity was taken as the slope of a linear regression fit of relaxation rate against Gd concentration. The relaxivities of Gd-EOB-DTPA were similarly determined in normal and biliary- obstructed guinea pigs. Relaxivities in tissue differed significantly from values obtained in simple phantoms. Kidney T1 relaxivity was reduced for both compounds in normal animals. Three days or more of biliary obstruction produced further reductions in kidney T1 relaxivity of Gd-EOB-DTPA, providing strong evidence that disease affects contrast agent relaxivity. Kidney T2 relaxivity was much greater than T1 relaxivity and was also depressed by biliary obstruction. Liver T1 and T 2 relaxivites were increased above phantom values, but were not affected by the biliary obstruction. Water compartmentalisation, macromolecular binding, proton

Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

NASA Astrophysics Data System (ADS)

Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

2015-07-01

Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

Tumor-Microenvironment Relaxivity-Changeable Gd-Loaded Poly(L-lysine)/Carboxymethyl Chitosan Nanoparticles as Cancer-Recognizable Magnetic Resonance Imaging Contrast Agents.

PubMed

Jiang, Dandan; Zhang, Xiaopeng; Yu, Dexin; Xiao, Yanan; Wang, Tianqi; Su, Zhihui; Liu, Yongjun; Zhang, Na

2017-03-01

Magnetic resonance imaging (MRI) contrast agents with tumor-microenvironment changeable relaxivity are effective to increase the sensitivity and selectivity of MRI in tumor diagnosis. In this study, pH-sensitive Gd-loaded Poly(L-lysine)/ Carboxymethyl Chitosan Nanoparticles (Gd-PCNPs) were developed as relaxivity-changeable MRI contrast agents based on the "on–off" switchable strategy. The "on–off" switchable nano-contrast agents were capable of releasing Gd3+ in response to physical stimulation, with structure transformed. Gd-PCNPs could responsively disassemble in an acidic tumor-microenvironment and increase the exchange of protons between water molecules and Gd3+ ions, thus selectively enhance the relaxivity in tumor area. Gd-PCNPs were self-assembled via electrostatic interaction between poly(L-lysine)-diethylenetriamine pentaacetic acid-gadolinium and pH-sensitive carboxymethyl chitosan (CMCS). Gd-PCNPs exhibited spherical shape with uniform particle size distribution (166.00 ± 1 .71 nm) and negative zeta potential (–13.2 ± 4.7 mV). The relaxivity of Gd-PCNPs increased from 6.618 mM–1 · s–1 to 10.008 mM–1 · s–1 when the pH values decrease from 7.4 to 6.0, which was higher than Magnevist® (3.924 mM–1 · s–1 at both pH 7.4 and 6.0 (p <0 05). The changeable relaxivity of Gd/PCNPs would result in enhanced tumor/normal tissue signal contrast, which was verified by in vivo MRI test. In vivo MRI test showed that the signal of Gd-PCNPs was significantly enhanced with prolonged imaging time in tumor tissue compared to Magnevist® (p <0 05). Furthermore, Gd-PCNPs exhibited unobvious in vitro cytotoxicity under the experimental concentrations in B16 cells. No obvious damage was observed in the different tissues of mice. These results indicated that the relaxivity-changeable Gd-PCNPs exhibited demonstrated sensitivity and selectivity in tumor diagnosis with a great potential as a novel MRI contrast agent.

Relaxivity of Ferumoxytol at 1.5 T and 3.0 T.

PubMed

Knobloch, Gesine; Colgan, Timothy; Wiens, Curtis N; Wang, Xiaoke; Schubert, Tilman; Hernando, Diego; Sharma, Samir D; Reeder, Scott B

2018-05-01

The aim of this study was to determine the relaxation properties of ferumoxytol, an off-label alternative to gadolinium-based contrast agents, under physiological conditions at 1.5 T and 3.0 T. Ferumoxytol was diluted in gradually increasing concentrations (0.26-4.2 mM) in saline, human plasma, and human whole blood. Magnetic resonance relaxometry was performed at 37°C at 1.5 T and 3.0 T. Longitudinal and transverse relaxation rate constants (R1, R2, R2*) were measured as a function of ferumoxytol concentration, and relaxivities (r1, r2, r2*) were calculated. A linear dependence of R1, R2, and R2* on ferumoxytol concentration was found in saline and plasma with lower R1 values at 3.0 T and similar R2 and R2* values at 1.5 T and 3.0 T (1.5 T: r1saline = 19.9 ± 2.3 smM; r1plasma = 19.0 ± 1.7 smM; r2saline = 60.8 ± 3.8 smM; r2plasma = 64.9 ± 1.8 smM; r2*saline = 60.4 ± 4.7 smM; r2*plasma = 64.4 ± 2.5 smM; 3.0 T: r1saline = 10.0 ± 0.3 smM; r1plasma = 9.5 ± 0.2 smM; r2saline = 62.3 ± 3.7 smM; r2plasma = 65.2 ± 1.8 smM; r2*saline = 57.0 ± 4.7 smM; r2*plasma = 55.7 ± 4.4 smM). The dependence of relaxation rates on concentration in blood was nonlinear. Formulas from second-order polynomial fittings of the relaxation rates were calculated to characterize the relationship between R1blood and R2 blood with ferumoxytol. Ferumoxytol demonstrates strong longitudinal and transverse relaxivities. Awareness of the nonlinear relaxation behavior of ferumoxytol in blood is important for ferumoxytol-enhanced magnetic resonance imaging applications and for protocol optimization.

Rotation relaxation splitting for optimizing parallel RF excitation pulses with T1 - and T2 -relaxations in MRI

NASA Astrophysics Data System (ADS)

Majewski, Kurt

2018-03-01

Exact solutions of the Bloch equations with T1 - and T2 -relaxation terms for piecewise constant magnetic fields are numerically challenging. We therefore investigate an approximation for the achieved magnetization in which rotations and relaxations are split into separate operations. We develop an estimate for its accuracy and explicit first and second order derivatives with respect to the complex excitation radio frequency voltages. In practice, the deviation between an exact solution of the Bloch equations and this rotation relaxation splitting approximation seems negligible. Its computation times are similar to exact solutions without relaxation terms. We apply the developed theory to numerically optimize radio frequency excitation waveforms with T1 - and T2 -relaxations in several examples.

Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

Positive MRI contrast enhancement in THP-1 cells with Gd2O3 nanoparticles.

PubMed

Klasson, Anna; Ahrén, Maria; Hellqvist, Eva; Söderlind, Fredrik; Rosén, Anders; Käll, Per-Olov; Uvdal, Kajsa; Engström, Maria

2008-01-01

There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s(-1) mm(-1) for cell culture medium. The r2 was 17.4 and 12.9 s(-1) mm(-1), respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (p(r1) = 0.36), but r2 was significantly different for the two different series (p(r2) = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells. Copyright 2008 John Wiley & Sons, Ltd.

Engineered contrast agents in a single structure for T1-T2 dual magnetic resonance imaging.

PubMed

Cabrera-García, Alejandro; Checa-Chavarria, Elisa; Pacheco-Torres, Jesús; Bernabeu-Sanz, Ángela; Vidal-Moya, Alejandro; Rivero-Buceta, Eva; Sastre, Germán; Fernández, Eduardo; Botella, Pablo

2018-04-05

The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T1-T2 dual-mode relaxivity requires the accurate assembly of T1 and T2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)4[Fe(CN)6] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)4[Fe(CN)6]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T1- and T2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.

In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI

NASA Astrophysics Data System (ADS)

Juras, Vladimir; Bittsansky, Michal; Majdisova, Zuzana; Szomolanyi, Pavol; Sulzbacher, Irene; Gäbler, Stefan; Stampfl, Jürgen; Schüller, Georg; Trattnig, Siegfried

2009-03-01

The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3 T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T2 maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous ( I) and equilibrium ( Eq) modulus and relaxation time ( τ)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T1Gd vs Eq ( r = 0.8095), T1Gd vs I/ Eq ( r = -0.8441) and T1Gd vs τ ( r = 0.8469). The correlation of T2 and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T2 and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

Magnetocaloric effect and slow magnetic relaxation in CsGd(MoO4)2 induced by crystal-field anisotropy

NASA Astrophysics Data System (ADS)

Tkáč, V.; Tarasenko, R.; Orendáčová, A.; Orendáč, M.; Sechovský, V.; Feher, A.

2018-05-01

The experimental and theoretical study of magnetocaloric effect and magnetic relaxation of the powder sample of CsGd(MoO4)2 were performed. The large conventional magnetocaloric effect was found around 2 K with - ΔSmax ≈ 26.5 J/(kg K) for B = 7 T. AC susceptibility measurement revealed multiple-time scale magnetic relaxation effects on different time scales. Slowest relaxation effect was attributed to the direct process with a bottleneck effect and two faster relaxation processes are effectively temperature independent, probably as a result of averaging in the powder sample.

Ultra-wide range field-dependent measurements of the relaxivity of Gd1−xEuxVO4 nanoparticle contrast agents using a mechanical sample-shuttling relaxometer

PubMed Central

Chou, Ching-Yu; Abdesselem, Mouna; Bouzigues, Cedric; Chu, Minglee; Guiga, Angelo; Huang, Tai-Huang; Ferrage, Fabien; Gacoin, Thierry; Alexandrou, Antigoni; Sakellariou, Dimitris

2017-01-01

The current trend for Magnetic Resonance Imaging points towards higher magnetic fields. Even though sensitivity and resolution are increased in stronger fields, T1 contrast is often reduced, and this represents a challenge for contrast agent design. Field-dependent measurements of relaxivity are thus important to characterize contrast agents. At present, the field-dependent curves of relaxivity are usually carried out in the field range of 0 T to 2 T, using fast field cycling relaxometers. Here, we employ a high-speed sample shuttling device to switch the magnetic fields experienced by the nuclei between virtually zero field, and the center of any commercial spectrometer. We apply this approach on rare-earth (mixed Gadolinium-Europium) vanadate nanoparticles, and obtain the dispersion curves from very low magnetic field up to 11.7 T. In contrast to the relaxivity profiles of Gd chelates, commonly used for clinical applications, which display a plateau and then a decrease for increasing magnetic fields, these nanoparticles provide maximum contrast enhancement for magnetic fields around 1–1.5 T. These field-dependent curves are fitted using the so-called Magnetic Particle (MP) model and the extracted parameters discussed as a function of particle size and composition. We finally comment on the new possibilities offered by this approach. PMID:28317892

Obtaining T1-T2 distribution functions from 1-dimensional T1 and T2 measurements: The pseudo 2-D relaxation model

NASA Astrophysics Data System (ADS)

Williamson, Nathan H.; Röding, Magnus; Galvosas, Petrik; Miklavcic, Stanley J.; Nydén, Magnus

2016-08-01

We present the pseudo 2-D relaxation model (P2DRM), a method to estimate multidimensional probability distributions of material parameters from independent 1-D measurements. We illustrate its use on 1-D T1 and T2 relaxation measurements of saturated rock and evaluate it on both simulated and experimental T1-T2 correlation measurement data sets. Results were in excellent agreement with the actual, known 2-D distribution in the case of the simulated data set. In both the simulated and experimental case, the functional relationships between T1 and T2 were in good agreement with the T1-T2 correlation maps from the 2-D inverse Laplace transform of the full 2-D data sets. When a 1-D CPMG experiment is combined with a rapid T1 measurement, the P2DRM provides a double-shot method for obtaining a T1-T2 relationship, with significantly decreased experimental time in comparison to the full T1-T2 correlation measurement.

In Vivo MR Imaging of Glioma Recruitment of Adoptive T-Cells Labeled with NaGdF4 -TAT Nanoprobes.

PubMed

Zhang, Hua; Wu, Yue; Wang, Jing; Tang, Zhongmin; Ren, Yan; Ni, Dalong; Gao, Hongbo; Song, Ruixue; Jin, Teng; Li, Qiao; Bu, Wenbo; Yao, Zhenwei

2018-01-01

Adoptive T lymphocyte immunotherapy is one of the most promising methods to treat residual lesions after glioma surgery. However, the fate of the adoptively transferred T-cells in vivo is unclear, hampering the understanding of this emerging therapy. Thus, it is highly desirable to develop noninvasive and quantitative in vivo tracking of these T-cells to glioma for better identification of the migratory fate and to provide objective evaluation of outcomes of adoptive T-cell immunotherapy targeting glioma. In this work, ultrasmall T 1 MR-based nanoprobes, NaGdF 4 -TAT, as molecular probes with high longitudinal relaxivity (8.93 mm -1 s -1 ) are designed. By means of HIV-1 transactivator (TAT) peptides, nearly 95% of the adoptive T-cells are labeled with the NaGdF 4 -TAT nanoprobes without any measurable side effects on the labeled T-cells, which is remarkably superior to that of the control fluorescein isothiocyanate-NaGdF 4 concerning labeling efficacy. Labeled adoptive T-cell clusters can be sensitively tracked in an orthotopic GL261-glioma model 24 h after intravenous infusion of 10 7 labeled T-cells by T 1 -weighted MR imaging. Both in vitro and in vivo experiments show that the NaGdF 4 -TAT nanoprobes labeling of T-cells may be a promising method to track adoptive T-cells to improve our understanding of the pathophysiology in adoptive immunotherapy for gliomas. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of biochemical cartilage imaging techniques at 3 T MRI.

PubMed

Rehnitz, C; Kupfer, J; Streich, N A; Burkholder, I; Schmitt, B; Lauer, L; Kauczor, H-U; Weber, M-A

2014-10-01

To prospectively compare chemical-exchange saturation-transfer (CEST) with delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) and T2 mapping to assess the biochemical cartilage properties of the knee. Sixty-nine subjects were prospectively included (median age, 42 years; male/female = 32/37) in three cohorts: 10 healthy volunteers, 40 patients with clinically suspected cartilage lesions, and 19 patients about 1 year after microfracture therapy. T2 mapping, dGEMRIC, and CEST were performed at a 3 T MRI unit using a 15-channel knee coil. Parameter maps were evaluated using region-of-interest analysis of healthy cartilage, areas of chondromalacia and repair tissue. Differentiation of damaged from healthy cartilage was assessed using receiver-operating characteristic (ROC) analysis. Chondromalacia grade 2-3 had significantly higher CEST values (P = 0.001), lower dGEMRIC (T1-) values (P < 0.001) and higher T2 values (P < 0.001) when compared to the normal appearing cartilage. dGEMRIC and T2 mapping correlated moderately negative (Spearman coefficient r = -0.56, P = 0.0018) and T2 mapping and CEST moderately positive (r = 0.5, P = 0.007), while dGEMRIC and CEST did not significantly correlate (r = -0.311, P = 0.07). The repair tissue revealed lower dGEMRIC values (P < 0.001) and higher CEST values (P < 0.001) with a significant negative correlation (r = -0.589, P = 0.01), whereas T2 values were not different (P = 0.54). In healthy volunteers' cartilage, CEST and dGEMRIC showed moderate positive correlation (r = 0.56), however not reaching significance (P = 0.09). ROC-analysis demonstrated non-significant differences of T2 mapping vs CEST (P = 0.14), CEST vs dGEMRIC (P = 0.89), and T2 mapping vs dGEMRIC (P = 0.12). CEST is able to detect normal and damaged cartilage and is non-inferior in distinguishing both when compared to dGEMRIC and T2 mapping. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Gd-functionalised Au nanoparticles as targeted contrast agents in MRI: relaxivity enhancement by polyelectrolyte coating.

PubMed

Warsi, Muhammad Farooq; Adams, Ralph W; Duckett, Simon B; Chechik, Victor

2010-01-21

Monolayer-protected, Gd(3+)-functionalised gold nanoparticles with enhanced spin-lattice relaxivity (r(1)) were prepared; adsorption of polyelectrolytes on these materials further increased r(1) and ligand exchange with a biotin-derivatised disulfide led to a prototype avidin-targeted contrast agent.

No degeneration found in focal cartilage defects evaluated with dGEMRIC at 12-year follow-up.

PubMed

Engen, Cathrine Nørstad; Løken, Sverre; Årøen, Asbjørn; Ho, Charles; Engebretsen, Lars

2017-02-01

Background and purpose - The natural history of focal cartilage defects (FCDs) is still unresolved, as is the long-term cartilage quality after cartilage surgery. It has been suggested that delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a biomarker of early OA. We aimed to quantitatively evaluate the articular cartilage in knees with FCDs, 12 years after arthroscopic diagnosis. Patients and methods - We included 21 patients from a cohort of patients with knee pain who underwent arthroscopy in 1999. Patients with a full-thickness cartilage defect, stable knees, and at least 50% of both their menisci intact at baseline were eligible. 10 patients had cartilage repair performed at baseline (microfracture or autologous chondrocyte implantation), whereas 11 patients had either no additional surgery or simple debridement performed. Mean follow-up time was 12 (10-13) years. The morphology and biochemical features were evaluated with dGEMRIC and T2 mapping. Standing radiographs for Kellgren and Lawrence (K&L) classification of osteoarthritis (OA) were obtained. Knee function was assessed with VAS, Tegner, Lysholm, and KOOS. Results - The dGEMRIC showed varying results but, overall, no increased degeneration of the injured knees. Degenerative changes (K&L above 0) were, however, evident in 13 of the 21 knees. Interpretation - The natural history of untreated FCDs shows large dGEMRIC variations, as does the knee articular cartilage of surgically treated patients. In this study, radiographic OA changes did not correlate with cartilage quality, as assessed with dGEMRIC.

NMR relaxation in natural soils: Fast Field Cycling and T1-T2 Determination by IR-MEMS

NASA Astrophysics Data System (ADS)

Haber-Pohlmeier, S.; Pohlmeier, A.; Stapf, S.; van Dusschoten, D.

2009-04-01

Soils are natural porous media of highest importance for food production and sustainment of water resources. For these functions, prominent properties are their ability of water retainment and transport, which are mainly controlled by pore size distribution. The latter is related to NMR relaxation times of water molecules, of which the longitudinal relaxation time can be determined non-invasively by fast-field cycling relaxometry (FFC) and both are obtainable by inversion recovery - multi-echo- imaging (IR-MEMS) methods. The advantage of the FFC method is the determination of the field dependent dispersion of the spin-lattice relaxation rate, whereas MRI at high field is capable of yielding spatially resolved T1 and T2 times. Here we present results of T1- relaxation time distributions of water in three natural soils, obtained by the analysis of FFC data by means of the inverse Laplace transformation (CONTIN)1. Kaldenkirchen soil shows relatively broad bimodal distribution functions D(T1) which shift to higher relaxation rates with increasing relaxation field. These data are compared to spatially resolved T1- and T2 distributions, obtained by IR-MEMS. The distribution of T1 corresponds well to that obtained by FFC.

Ocular Pharmacokinetic Study Using T1 Mapping and Gd-Chelate-Labeled Polymers

PubMed Central

Shi, Xianfeng; Liu, Xin; Wu, Xueming; Lu, Zheng-Rong; Li, S. Kevin

2011-01-01

Purpose Recent advances in drug discovery have led to the development of a number of therapeutic macromolecules for treatment of posterior eye diseases. We aimed to investigate the clearance of macromolecular contrast probes (polymers conjugated with Gd-chelate) in the vitreous after intravitreal injections with the recently developed ms-DSEPI-T12 MRI and to examine the degradation of disulfide-containing biodegradable polymers in the vitreous humor in vivo. Methods Intravitreal injections of model contrast agents poly[N-(2-hydroxypropyl)methacrylamide]-GG-1,6-hexanediamine-(Gd-DO3A), biodegradable (Gd-DTPA)-cystine copolymers, and MultiHance were performed in rabbits; their distribution and elimination from the vitreous after injections were determined by MRI. Results Times for macromolecular contrast agents to decrease to half their initial concentrations in the vitreous ranged from 0.4–1.3 days post-injection. Non-biodegradable polymers demonstrated slower vitreal clearance than those of disulfide-biodegradable polymers. Biodegradable polymers had similar clearance as MultiHance. Conclusions Usefulness of T1 mapping and ms-DSEPI-T12 MRI to study ocular pharmacokinetics was demonstrated. Results suggest an enzymatic degradation mechanism for the disulfide linkage in polymers in the vitreous leading to breakup of polymers in vitreous humor over time. PMID:21691891

Gd2O3 nanoparticles stabilized by hydrothermally modified dextrose for positive contrast magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Babić-Stojić, Branka; Jokanović, Vukoman; Milivojević, Dušan; Požek, Miroslav; Jagličić, Zvonko; Makovec, Darko; Arsikin, Katarina; Paunović, Verica

2016-04-01

Gd2O3 nanoparticles of a few nm in size and their agglomerates dispersed in dextrose derived polymer template were synthesized by hydrothermal treatment. The produced nanosized material was investigated by TEM, FTIR spectroscopy, SQUID measurements and NMR relaxometry. Biological evaluation of this material was done by crystal violet and MTT assays to determine the cell viability. Longitudinal and transverse NMR relaxivities of water diluted Gd2O3 nanoparticle dispersions measured at the magnetic field of 1.5 T, estimated to be r1(Gd2O3)=9.6 s-1 mM-1 in the Gd concentration range 0.1-30 mM and r2(Gd2O3)=17.7 s-1 mM-1 in the lower concentration range 0.1-0.8 mM, are significantly higher than the corresponding relaxivities measured for the standard contrast agent r1(Gd-DTPA)=4.1 s-1 mM-1 and r2(Gd-DTPA)=5.1 s-1 mM-1. The ratio of the two relaxivities for Gd2O3 nanoparticles r2/r1=1.8 is suitable for T1-weighted imaging. Good MRI signal intensities of the water diluted Gd2O3 nanoparticle dispersions were recorded at lower Gd concentrations 0.2-0.8 mM. The Gd2O3 samples did not exert any significant cytotoxic effects at Gd concentrations of 0.2 mM and below. These properties of the produced Gd2O3 nanoparticles in hydrothermally modified dextrose make them promising for potential application in MRI for the design of a positive MRI contrast agent.

Quantitative Gd-DOTA uptake from cerebrospinal fluid into rat brain using 3D VFA-SPGR at 9.4T.

PubMed

Lee, Hedok; Mortensen, Kristian; Sanggaard, Simon; Koch, Palle; Brunner, Hans; Quistorff, Bjørn; Nedergaard, Maiken; Benveniste, Helene

2018-03-01

We propose a quantitative technique to assess solute uptake into the brain parenchyma based on dynamic contrast-enhanced MRI (DCE-MRI). With this approach, a small molecular weight paramagnetic contrast agent (Gd-DOTA) is infused in the cerebral spinal fluid (CSF) and whole brain gadolinium concentration maps are derived. We implemented a 3D variable flip angle spoiled gradient echo (VFA-SPGR) longitudinal relaxation time (T1) technique, the accuracy of which was cross-validated by way of inversion recovery rapid acquisition with relaxation enhancement (IR-RARE) using phantoms. Normal Wistar rats underwent Gd-DOTA infusion into CSF via the cisterna magna and continuous MRI for approximately 130 min using T1-weighted imaging. Dynamic Gd-DOTA concentration maps were calculated and parenchymal uptake was estimated. In the phantom study, T1 discrepancies between the VFA-SPGR and IR-RARE sequences were approximately 6% with a transmit coil inhomogeneity correction. In the in vivo study, contrast transport profiles indicated maximal parenchymal retention of approximately 19% relative to the total amount delivered into the cisterna magna. Imaging strategies for accurate 3D contrast concentration mapping at 9.4T were developed and whole brain dynamic concentration maps were derived to study solute transport via the glymphatic system. The newly developed approach will enable future quantitative studies of the glymphatic system in health and disease states. Magn Reson Med 79:1568-1578, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Relaxivity enhancement of aquated Tris(β-diketonate)gadolinium(III) chelates by confinement within ultrashort single-walled carbon nanotubes.

PubMed

Law, Justin J; Guven, Adem; Wilson, Lon J

2014-01-01

Ultrashort single-walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1 -weighted relaxivities (>100 mm(-1) s(-1) ). To further examine the effect of nanoconfinement on the relaxivity of gadolinium-based contrast agents for magnetic resonance imaging, a series of ultrashort single-walled carbon nanotube (US-tube) materials internally loaded with gadolinium chelates have been prepared and studied. US-tubes were loaded with Gd(acac)3  · 2H2 O, Gd(hfac)3  · 2H2 O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm(-1) s(-1) for Gd(acac)3  · 2H2 O@US-tubes, 105 mm(-1) s(-1) for Gd(hfac)3  · 2H2 O@US-tubes and 26 mm(-1) s(-1) for Gd(thd)3 @US-tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm(-1) s(-1) ) as well as accounting for the T1 reduction observed for the empty US-tubes, the boost in relaxivity for chelate-loaded US-tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules. Copyright © 2014 John Wiley & Sons, Ltd.

Delayed gadolinium-enhanced MRI of the fibrocartilage disc of the temporomandibular joint – a feasibility study

PubMed Central

Pittschieler, Elisabeth; Szomolanyi, Pavol; Schmid-Schwap, Martina; Weber, Michael; Egerbacher, Monika; Traxler, Hannes; Trattnig, Siegfried

2014-01-01

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. PMID:25131629

Delayed gadolinium-enhanced MRI of the fibrocartilage disc of the temporomandibular joint--a feasibility study.

PubMed

Pittschieler, Elisabeth; Szomolanyi, Pavol; Schmid-Schwap, Martina; Weber, Michael; Egerbacher, Monika; Traxler, Hannes; Trattnig, Siegfried

2014-12-01

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. 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. 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. 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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

High longitudinal relaxivity of ultra-small gadolinium oxide prepared by microsecond laser ablation in diethylene glycol

NASA Astrophysics Data System (ADS)

Luo, Ningqi; Tian, Xiumei; Xiao, Jun; Hu, Wenyong; Yang, Chuan; Li, Li; Chen, Dihu

2013-04-01

Ultra-small gadolinium oxide (Gd2O3) can be used as T1-weighted Magnetic Resonance Imaging (MRI) contrast agent own to its high longitudinal relaxivity (r1) and has attracted intensive attention in these years. In this paper, ultra-small Gd2O3 nanoparticles of 3.8 nm in diameter have been successfully synthesized by a microsecond laser ablating a gadolinium (Gd) target in diethylene glycol (DEG). The growth inhibition effect induced by the large viscosity of DEG makes it possible to synthesize ultra-small Gd2O3 by laser ablation in DEG. The r1 value and T1-weighted MR images are measured by a 3.0 T MRI spectroscope. The results show these nanoparticles with a high r1 value of 9.76 s-1 mM-1 to be good MRI contrast agents. We propose an explanation for the high r1 value of ultra-small Gd2O3 by considering the decreasing factor (surface to volume ratio of the nanoparticles, S/V) and the increasing factor (water hydration number of the Gd3+ on Gd2O3 surface, q), which offer a new look into the relaxivity studies of MRI contrast agents. Our research provides a new approach to preparing ultra-small Gd2O3 of high r1 value by laser ablation in DEG and develops the understanding of high relaxivity of ultra-small Gd2O3 MRI contrast agents.

Magnetic properties, water proton relaxivities, and in-vivo MR images of paramagnetic nanoparticles

NASA Astrophysics Data System (ADS)

Lee, Gang Ho; Chang, Yongmin

2015-07-01

In this mini review, magnetic resonance imaging (MRI) contrast agents based on lanthanideoxide (Ln2O3) nanoparticles are described. Ln2O3 (Ln = Gd, Dy, Ho, and Er) nanoparticles are paramagnetic, but show appreciable magnetic moments at room temperature and even at ultrasmall particle diameters. Among Ln2O3 nanoparticles, Gd2O3 nanoparticles show larger longitudinal water proton relaxivity (r1) values than Gd-chelates because of the large amount of Gd in the nanoparticle, and the other Ln2O3 nanoparticles (Ln = Dy, Ho, and Er) show appreciable transverse water proton relaxivity (r2) values. Therefore, Gd2O3 nanoparticles are potential T1 MRI contrast agents while the other Ln2O3 nanoparticles are potential T2 MRI contrast agents at high MR fields.

Gadolinium oxide nanoplates with high longitudinal relaxivity for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Cho, Minjung; Sethi, Richa; Ananta Narayanan, Jeyarama Subramanian; Lee, Seung Soo; Benoit, Denise N.; Taheri, Nasim; Decuzzi, Paolo; Colvin, Vicki L.

2014-10-01

Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents.Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values

Optimizing the relaxivity of GdIII complexes appended to InP/ZnS quantum dots by linker tuning.

PubMed

Stasiuk, Graeme J; Tamang, Sudarsan; Imbert, Daniel; Gateau, Christelle; Reiss, Peter; Fries, Pascal; Mazzanti, Marinella

2013-06-21

Three bimodal MRI/optical nanosized contrast agents with high per-nanoparticle relaxivity (up to 2523 mM(-1) s(-1) at 35 MHz and 932 mM(-1) s(-1) at 200 MHz) have been prepared connecting up to 115 tris-aqua Gd(III) complexes to fluorescent non-toxic InP/ZnS quantum dots. The structure of the linker has an important effect on the relaxivity of the final multimeric contrast agent.

Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.

PubMed

Fries, Peter; Runge, Val M; Bücker, Arno; Schürholz, Hellmut; Reith, Wolfgang; Robert, Philippe; Jackson, Carney; Lanz, Titus; Schneider, Günther

2009-04-01

The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA). Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90 degrees , acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm, FOV = 40 mm, acquisition matrix: 256 x 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study. P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0

Effects of pulmonary inhalation on hyperpolarized krypton-83 magnetic resonance T1 relaxation

NASA Astrophysics Data System (ADS)

Stupic, K. F.; Elkins, N. D.; Pavlovskaya, G. E.; Repine, J. E.; Meersmann, T.

2011-07-01

The 83Kr magnetic resonance (MR) relaxation time T1 of krypton gas in contact with model surfaces was previously found to be highly sensitive to surface composition, surface-to-volume ratio, and surface temperature. The work presented here explored aspects of pulmonary 83Kr T1 relaxation measurements in excised lungs from healthy rats using hyperpolarized (hp) 83Kr with approximately 4.4% spin polarization. MR spectroscopy without spatial resolution was applied to the ex vivo lungs that actively inhale hp 83Kr through a custom designed ventilation system. Various inhalation schemes were devised to study the influence of anatomical dead space upon the measured 83Kr T1 relaxation times. The longitudinal 83Kr relaxation times in the distal airways and the respiratory zones were independent of the lung inhalation volume, with T1 = 1.3 s and T1 = 1.0 s, depending only on the applied inhalation scheme. The obtained data were highly reproducible between different specimens. Further, the 83Kr T1 relaxation times in excised lungs were unaffected by the presence of up to 40% oxygen in the hp gas mixture. The results support the possible importance of 83Kr as a biomarker for evaluating lung function.

Local NMR relaxation rates T1-1 and T2-1 depending on the d -vector symmetry in the vortex state of chiral and helical p -wave superconductors

NASA Astrophysics Data System (ADS)

Tanaka, Kenta K.; Ichioka, Masanori; Onari, Seiichiro

2018-04-01

Local NMR relaxation rates in the vortex state of chiral and helical p -wave superconductors are investigated by the quasiclassical Eilenberger theory. We calculate the spatial and resonance frequency dependences of the local NMR spin-lattice relaxation rate T1-1 and spin-spin relaxation rate T2-1. Depending on the relation between the NMR relaxation direction and the d -vector symmetry, the local T1-1 and T2-1 in the vortex core region show different behaviors. When the NMR relaxation direction is parallel to the d -vector component, the local NMR relaxation rate is anomalously suppressed by the negative coherence effect due to the spin dependence of the odd-frequency s -wave spin-triplet Cooper pairs. The difference between the local T1-1 and T2-1 in the site-selective NMR measurement is expected to be a method to examine the d -vector symmetry of candidate materials for spin-triplet superconductors.

P16.31THERANOSTIC APPLICATION OF WATER-SOLUBLE GADOLINIUM FULLERENE (GD@FUL) IN EXPERIMENTAL GLIOMA MODEL

PubMed Central

Shevtsov, M.; Nikolaev, B.; Marchenko, Y.; Yakovleva, L.; Dobrodumov, A.; Török, G.; Pitkin, E.; Lebedev, V.

2014-01-01

Glioblastoma multiforme (GMB) is a highly invasive brain tumour with poor prognosis. Alternative treatments offering a better outcome are needed. Novel approach could be based on gadofullerenes that can be used as diagnostic MR imaging contrast agent and as a therapeutic drug. Water soluble gadofullerene Gd@Ful with composition Gd@C82(OH)x x ≥20 was synthesized for theranostic study. Nanosuspensions of Gd@Ful were used for magnetic relaxation measurements in vitro and for MR imaging of a rat with intracranially implanted C6 glioma. Gd@Ful was shown to reduce proton relaxation times in vitro, and provide dual contrast of T1- and T2-weighted images in a rat brain tumour model after paramagnetic intravenous delivery. Magnetic relaxation times and relaxivity of water protons under action of Gd@Ful were strongly shortened due to cluster formation and increase of motional correlation times of protons in the vicinity of the fulleren cage. The Gd@Ful administration promoted the improvement of glioma contrast enhancement at T2-weighted images due to accumulation of paramagnetic substance at the tumour site. The contrast efficiency of Gd@Ful corresponds to the characteristics of negative contrast agent. Retention of the Gd@Ful in the C6 glioma provides not only the tumor contrast enhancement but also has a high therapeutic relevance. We observed the increased survival rates in animals that were intravenously administered with Gd@Ful. Thus, in experimental group the survival was 75% higher then in the control group, constituting 34.2 ± 9.94 and 19.5 ± 3.02 days respectively (P < 0.001). The Gd@Ful solution is shown to be a contrast enhancer with high anti-tumour therapeutic potency.

Theranostic Gd(III)-lipid microbubbles for MRI-guided focused ultrasound surgery.

PubMed

Feshitan, Jameel A; Vlachos, Fotis; Sirsi, Shashank R; Konofagou, Elisa E; Borden, Mark A

2012-01-01

We have synthesized a biomaterial consisting of Gd(III) ions chelated to lipid-coated, size-selected microbubbles for utility in both magnetic resonance and ultrasound imaging. The macrocyclic ligand DOTA-NHS was bound to PE headgroups on the lipid shell of pre-synthesized microbubbles. Gd(III) was then chelated to DOTA on the microbubble shell. The reaction temperature was optimized to increase the rate of Gd(III) chelation while maintaining microbubble stability. ICP-OES analysis of the microbubbles determined a surface density of 7.5 × 10(5) ± 3.0 × 10(5) Gd(III)/μm(2) after chelation at 50 °C. The Gd(III)-bound microbubbles were found to be echogenic in vivo during high-frequency ultrasound imaging of the mouse kidney. The Gd(III)-bound microbubbles also were characterized by magnetic resonance imaging (MRI) at 9.4 T by a spin-echo technique and, surprisingly, both the longitudinal and transverse proton relaxation rates were found to be roughly equal to that of no-Gd(III) control microbubbles and saline. However, the relaxation rates increased significantly, and in a dose-dependent manner, after sonication was used to fragment the Gd(III)-bound microbubbles into non-gas-containing lipid bilayer remnants. The longitudinal (r(1)) and transverse (r(2)) molar relaxivities were 4.0 ± 0.4 and 120 ± 18 mM(-1)s(-1), respectively, based on Gd(III) content. The Gd(III)-bound microbubbles may find application in the measurement of cavitation events during MRI-guided focused ultrasound therapy and to track the biodistribution of shell remnants. Copyright © 2011 Elsevier Ltd. All rights reserved.

Optimizing Water Exchange Rates and Rotational Mobility for High-Relaxivity of a Novel Gd-DO3A Derivative Complex Conjugated to Inulin as Macromolecular Contrast Agents for MRI.

PubMed

Granato, Luigi; Vander Elst, Luce; Henoumont, Celine; Muller, Robert N; Laurent, Sophie

2018-02-01

Thanks to the understanding of the relationships between the residence lifetime τ M of the coordinated water molecules to macrocyclic Gd-complexes and the rotational mobility τ R of these structures, and according to the theory for paramagnetic relaxation, it is now possible to design macromolecular contrast agents with enhanced relaxivities by optimizing these two parameters through ligand structural modification. We succeeded in accelerating the water exchange rate by inducing steric compression around the water binding site, and by removing the amide function from the DOTA-AA ligand [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(p-aminoanilide)] (L) previously designed. This new ligand 10[2(1-oxo-1-p-propylthioureidophenylpropyl]-1,4,7,10-tetraazacyclodecane-1,4,7-tetraacetic acid (L 1 ) was then covalently conjugated to API [O-(aminopropyl)inulin] to get the complex API-(GdL 1 )x with intent to slow down the rotational correlation time (τ R ) of the macromolecular complex. The evaluation of the longitudinal relaxivity at different magnetic fields and the study of the 17 O-NMR at variable temperature of the low-molecular-weight compound (GdL 1 ) showed a slight decrease of the τ M value (τM310 = 331 ns vs. τM310 = 450 ns for the GdL complex). Consequently to the increase of the size of the API-(GdL 1 )x complex, the rotational correlation time becomes about 360 times longer compared to the monomeric GdL 1 complex (τ R  = 33,700 ps), which results in an enhanced proton relaxivity. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

NASA Astrophysics Data System (ADS)

Ni, Kaiyuan; Zhao, Zhenghuan; Zhang, Zongjun; Zhou, Zijian; Yang, Li; Wang, Lirong; Ai, Hua; Gao, Jinhao

2016-02-01

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy

Knee Cartilage Thickness, T1ρ and T2 Relaxation Time Are Related to Articular Cartilage Loading in Healthy Adults

PubMed Central

Van Rossom, Sam; Smith, Colin Robert; Zevenbergen, Lianne; Thelen, Darryl Gerard; Vanwanseele, Benedicte; Van Assche, Dieter; Jonkers, Ilse

2017-01-01

Cartilage is responsive to the loading imposed during cyclic routine activities. However, the local relation between cartilage in terms of thickness distribution and biochemical composition and the local contact pressure during walking has not been established. The objective of this study was to evaluate the relation between cartilage thickness, proteoglycan and collagen concentration in the knee joint and knee loading in terms of contact forces and pressure during walking. 3D gait analysis and MRI (3D-FSE, T1ρ relaxation time and T2 relaxation time sequence) of fifteen healthy subjects were acquired. Experimental gait data was processed using musculoskeletal modeling to calculate the contact forces, impulses and pressure distribution in the tibiofemoral joint. Correlates to local cartilage thickness and mean T1ρ and T2 relaxation times of the weight-bearing area of the femoral condyles were examined. Local thickness was significantly correlated with local pressure: medial thickness was correlated with medial condyle contact pressure and contact force, and lateral condyle thickness was correlated with lateral condyle contact pressure and contact force during stance. Furthermore, average T1ρ and T2 relaxation time correlated significantly with the peak contact forces and impulses. Increased T1ρ relaxation time correlated with increased shear loading, decreased T1ρ and T2 relaxation time correlated with increased compressive forces and pressures. Thicker cartilage was correlated with higher condylar loading during walking, suggesting that cartilage thickness is increased in those areas experiencing higher loading during a cyclic activity such as gait. Furthermore, the proteoglycan and collagen concentration and orientation derived from T1ρ and T2 relaxation measures were related to loading. PMID:28076431

A Comparative Study of T1 and T2 Relaxation in Shale

NASA Astrophysics Data System (ADS)

Keating, K.; Obasi, C. C.; Pashin, J. C.

2015-12-01

Nuclear magnetic resonance (NMR) relaxation measurement have been used extensively in petroleum and, more recently, in groundwater resource evaluation to estimate the porosity, pore-size distributions, permeability, fluid saturation, and fluid mobility. In shale, the transverse decay rate of NMR signal is sensitive to the microporosity, but is also affected by the paramagnetic contributions of clay and other iron-bearing minerals. Furthermore, contrasts in the magnetic susceptibility of the mineral matrix and pore fluids that result in an inhomogeneous magnetic field within the pore space results in an extra term in transverse relaxation. These issues can cause errors in NMR-based estimates of pore-size distribution and permeability. In this study we compare T1 and T2 relaxation time distributions in order to study the molecular mechanism of relaxation in brine-saturated mixtures of clay and other common minerals. We collected measurements on a range of mixtures of clay minerals common in shale (illite, glauconite, celadonite, chamosite, montmorillonite and kaolinite) and pyrite. To constrain the interpretation of the NMR data, we measured the magnetic susceptibility and surface area of all samples. We are confident that by accounting for the presence and variations of clay and pyrite in shale, we can substantially improve both the NMR estimate of pore-size distribution and permeability.

Gd-Complexes of New Arylpiperazinyl Conjugates of DTPA-Bis(amides): Synthesis, Characterization and Magnetic Relaxation Properties.

PubMed

Ba-Salem, Abdullah O; Ullah, Nisar; Shaikh, M Nasiruzzaman; Faiz, Mohamed; Ul-Haq, Zaheer

2015-04-29

Two new DTPA-bis(amide) based ligands conjugated with the arylpiperazinyl moiety were synthesized and subsequently transformed into their corresponding Gd(III) complexes 1 and 2 of the type [Gd(L)H2O]·nH2O. The relaxivity (R1) of these complexes was measured, which turned out to be comparable with that of Omniscan®, a commercially available MRI contrast agent. The cytotoxicity studies of these complexes indicated that they are non-toxic, which reveals their potential and physiological suitability as MRI contrast agents. All the synthesized ligands and complexes were characterized with the aid of analytical and spectroscopic methods, including elemental analysis, 1H-NMR, FT-IR, XPS and fast atom bombardment (FAB) mass spectrometry.

Comparison of T1 and T2 metabolite relaxation times in glioma and normal brain at 3 T

PubMed Central

Li, Yan; Srinivasan, Radhika; Ratiney, Helene; Lu, Ying; Chang, Susan M.; Nelson, Sarah J.

2011-01-01

Purpose To measure T1 and T2 relaxation times of metabolites in glioma patients at 3T and to investigate how these values influence the observed metabolite levels. Materials and Methods Twenty-three patients with gliomas and ten volunteers were studied with single voxel 2D J-resolved PRESS using a 3T MR scanner. Voxels were chosen in normal appearing white matter and in regions of tumor. The T1 and T2 of choline containing compounds (Cho), creatine (Cr) and N-acetyl aspartate (NAA) were estimated. Results Metabolite T1 relaxation values in gliomas were not significantly different from values in normal white matter. The T2 of Cho and Cr were statistically significantly longer for Grade 4 gliomas than for normal white matter but the T2 of NAA was similar. These differences were large enough to impact the corrections of metabolite levels for relaxation times with tumor grade in terms of metabolite ratios (P<0.001). Conclusion The differential increase in T2 for Cho and Cr relative to NAA means that the ratios of Cho/NAA and Cr/NAA are higher in tumor at longer echo times relative to values in normal appearing brain. Having this information may be useful in defining the acquisition parameters for optimizing contrast between tumor and normal tissue in MRSI data, where limited time is available and only one echo time can be used. PMID:18666155

Direct comparison of intra-articular versus intravenous delayed gadolinium-enhanced MRI of hip joint cartilage.

PubMed

Zilkens, Christoph; Miese, Falk; Kim, Young-Jo; Jäger, Marcus; Mamisch, Tallal C; Hosalkar, Harish; Antoch, Gerald; Krauspe, Rüdiger; Bittersohl, Bernd

2014-01-01

To investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) after intra-articular (ia) contrast agent administration at 3 Tesla (T), a paired study comparing intravenous (iv) dGEMRIC (standard) with ia-dGEMRIC was performed. Thirty-five symptomatic patients with suspected cartilage damage underwent ia- and iv-dGEMRIC. MRI was performed with a 3T system wherein the interval between both measurements was 2 weeks. For iv-dGEMRIC, FDA approved Gd-DOTA(-) was injected intravenously 45 min before the MRI scan. For ia-dGEMRIC, 10-20 mL of a 2 mM solution of Gd- DOTA(-) was injected under fluoroscopic guidance 30 min before the MRI scan. Both ia- and iv-dGEMRIC demonstrated the typical T1Gd pattern in hip joint cartilage with increasing values toward the superior regions in acetabular cartilage reflecting the higher glycosaminoglycan (GAG) content in the main weight-bearing area. Correlation analysis revealed a moderate correlation between both techniques (r = 0.439, P-value < 0.001), whereas the T1Gd values for iv-dGEMRIC were significantly higher than those for ia-dGEMRIC. This corresponds with the Bland-Altman plot analysis, which revealed a systemic bias (higher T1Gd values after iv gadolinium application) of ∼70 ms. Ia-dGEMRIC was able to reveal the characteristic T1Gd pattern in hip joint cartilage confirming the sensitivity of ia-dGEMRIC for GAG. In addition, there was a significant correlation between iv-dGEMRIC and ia-dGEMRIC. However, the T1Gd values after ia contrast media application were significantly lower than those after iv application that has to be considered for future studies. Copyright © 2013 Wiley Periodicals, Inc.

The viscosity and temperature dependence of 1H T1-NMRD of the Gd(H 2O) 83+ complex

NASA Astrophysics Data System (ADS)

Zhou, Xiangzhi; Westlund, Per-Olof

2005-11-01

Water proton T1-NMRD profiles of the Gd(H 2O) 83+ complex have been recorded at three temperatures and at four concentrations of glycerol. The analysis is performed using both the generalized Solomon-Bloembergen-Morgan (GSBM) theory [J. Magn. Reson. 167(2004), 147-160], and the stochastic Liouville approach (SLA). The GSBM approach uses a two processes dynamic model of the zero-field splitting (ZFS) correlation function whereas SLA uses a single process model. Both models reproduce the proton T1-NMRD profiles well. However, the model parameters extracted from the two analyses, yield different ESR X-band spectra which moreover do not reproduce the experimental ESR spectra. It is shown that the analyses of the proton T1-NMRD profiles recorded for a solution Gd(H 2O) 83+ ions are relatively insensitive to the slow modulation part of dynamic model of the ZFS interaction correlation function. The description of the electron spin system results in a very small static ZFS, while recent ESR lineshape analysis indicates that the contribution from the static ZFS is important. Analysis of proton T1-NMRD profiles of Gd(H 2O) 83+ complex do result in a description of the electron spin system but these microscopic parameters are uncertain unless they also are tested in a ESR-lineshape analysis.

T1 mapping combined with Gd-EOB-DTPA-enhanced magnetic resonance imaging in predicting the pathologic grading of hepatocellular carcinoma.

PubMed

Chen, C Y; Chen, J; Xia, C C; Huang, Z X; Song, B

2017-01-01

The aim of this study was to investigate the value of Gd-EOB-DTPA-enhanced MRI on hepatobiliary phase (HBP) imaging and T1 mapping sequence in the differentiation of hepatocellular carcinoma (HCC). A total of 45 patients with HCC who were to undergo a resection were enrolled in this study. Gd-EOB-DTPA-enhanced magnetic resonance examination was performed prior to resection. T1 mapping was performed before and 20 min after injection of Gd-EOB-DTPA. T1 values of the lesions were measured on pre-contrast (T1p) and during HBP (T1-HBP) on T1 maps. The signal intensity, the diameter and the margin of HCC lesions on HBP images were analyzed. The reduction in T1 value (T1d) and the reduction rate (ΔT1%) of T1 mapping between pre-contrast and HBP were calculated. The Edmondson-Steiner classification of each lesion was made after surgery. The SPSS software package was used for statistical analysis and the analysis of receiver operator characteristic (ROC) curve and area under the curve (AUC) were carried out by using MedCalc software package. Mean values of T1p and T1-HBP were 1935.4±730.8 ms and 1257.1±529.1 ms, respectively. T1p accuracy (AUC = 0.685, p = 0.037) in predicting pathological grading was similar to that of T1-HBP (AUC = 0.751, p = 0.005). A T1p of 1648.2 ms or greater had a sensitivity and specificity of 85.19% and 61.11%, respectively. A T1-HBP of 1006 ms or greater had a sensitivity and specificity of 81.84% and 61.11%, respectively. The number of HCCs with a non-smooth tumor margin was 20 (44.4%), and a non-smooth tumor margin correlated moderately with the Edmondson-Steiner grade (Spearman r = 0.491, p = 0.041). There was no significant correlation between T1d, ΔT1%, HCC signal intensity on HBP image and lesion diameter with pathologic grading. T1 mapping in pre-contrast and HBP of Gd-EOB-DTPA-enhanced MRI, a non-smooth tumor margin in the HBP of Gd-EOB-DTPA-enhanced MRI, are useful in predicting the pathologic grading of HCC.

Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer.

PubMed

Huang, Xin; Fan, Chengqi; Zhu, Huanhuan; Le, Wenjun; Cui, Shaobin; Chen, Xin; Li, Wei; Zhang, Fulei; Huang, Yong; Sh, Donglu; Cui, Zheng; Shao, Chengwei; Chen, Bingdi

2018-01-01

Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd-Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s -1 mM -1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s -1 mM -1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC.

Potential dual imaging nanoparticle: Gd2O3 nanoparticle

NASA Astrophysics Data System (ADS)

Ahmad, Md. Wasi; Xu, Wenlong; Kim, Sung June; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Park, Ji Ae; Kim, Tae Jeong; Lee, Gang Ho

2015-02-01

Gadolinium (Gd) is a unique and powerful element in chemistry and biomedicine which can be applied simultaneously to magnetic resonance imaging (MRI), X-ray computed tomography (CT), and neutron capture therapy for cancers. This multifunctionality can be maximized using gadolinium oxide (Gd2O3) nanoparticles (GNPs) because of the large amount of Gd per GNP, making both diagnosis and therapy (i.e., theragnosis) for cancers possible using only GNPs. In this study, the T1 MRI and CT dual imaging capability of GNPs is explored by synthesizing various iodine compound (IC) coated GNPs (IC-GNPs). All the IC-GNP samples showed stronger X-ray absorption and larger longitudinal water proton relaxivities (r1 = 26-38 s-1mM-1 and r2/r1 = 1.4-1.9) than the respective commercial contrast agents. In vivo T1 MR and CT images of mice were also acquired, supporting that the GNP is a potential dual imaging agent.

A small MRI contrast agent library of gadolinium(III)-encapsulated supramolecular nanoparticles for improved relaxivity and sensitivity**

PubMed Central

Chen, Kuan-Ju; Wolahan, Stephanie M.; Wang, Hao; Hsu, Chao-Hsiung; Chang, Hsing-Wei; Durazo, Armando; Hwang, Lian-Pin; Garcia, Mitch A.; Jiang, Ziyue Karen; Wu, Lily

2010-01-01

We introduce a new category of nanoparticle-based T1 MRI contrast agents (CAs) by encapsulating paramagnetic chelated gadolinium(III), i.e., Gd3+·DOTA, through supramolecular assembly of molecular building blocks that carry complementary molecular recognition motifs, including adamantane (Ad) and β-cyclodextrin (CD). A small library of Gd3+·DOTA-encapsulated supramolecular nanoparticles (Gd3+·DOTA⊂SNPs) was produced by systematically altering the molecular building block mixing ratios. A broad spectrum of relaxation rates was correlated to the resulting Gd3+·DOTA⊂SNP library. Consequently, an optimal synthetic formulation of Gd3+·DOTA⊂SNPs with an r1 of 17.3 s−1mM−1 (ca. 4-fold higher than clinical Gd3+ chelated complexes at high field strengths) was identified. T1-weighted imaging of Gd3+·DOTA⊂SNPs exhibits an enhanced sensitivity with a contrast-to-noise ratio (C/N ratio) ca. 3.6 times greater than that observed for free Gd3+·DTPA. A Gd3+·DOTA⊂SNPs solution was injected into foot pads of mice, and MRI was employed to monitor dynamic lymphatic drainage of the Gd3+·DOTA⊂SNPs-based CA. We observe an increase in signal intensity of the brachial lymph node in T1-weighted imaging after injecting Gd3+·DOTA⊂SNPs but not after injecting Gd3+·DTPA. The MRI results are supported by ICP-MS analysis ex vivo. These results show that Gd3+·DOTA⊂SNPs not only exhibits enhanced relaxivity and high sensitivity but also can serve as a potential tool for diagnosis of cancer metastasis. PMID:21167594

Graphene oxide-gadolinium (III) oxide nanoparticle composite: a novel MR contrast agent with high longitudinal and transverse relaxivity

NASA Astrophysics Data System (ADS)

Venkatesha, N.; Poojar, Pavan; Geethanath, Sairam; Srivastava, Chandan

2014-12-01

Production of bio-compatible contrast agent materials to enhance the sensitivity of the magnetic resonance imaging (MRI) technique is a highly active area in MRI related research. This work illustrates the potential of a new material: graphene oxide-gadolinium (III) oxide nanoparticle (GO-Gd2O3) composite in yielding both transverse (16.3 mM-1 s-1) and longitudinal relaxivity (40 mM-1 s-1) values which are significantly higher than the proton relaxivity values achieved using the gadolinium based contrast agents currently used in MRI. Such high proton relaxivity values can facilitate low dosage of GO-Gd2O3 composite for obtaining both T1 and T2 weighted high signal-to-noise ratio images in MRI.

Magnetic resonance properties of Gd(III)-bound lipid-coated microbubbles and their cavitation fragments.

PubMed

Feshitan, Jameel A; Boss, Michael A; Borden, Mark A

2012-10-30

Gas-filled microbubbles are potentially useful theranostic agents for magnetic resonance imaging-guided focused ultrasound surgery (MRIgFUS). Previously, MRI at 9.4 T was used to measure the contrast properties of lipid-coated microbubbles with gadolinium (Gd(III)) bound to lipid headgroups, which revealed that the longitudinal molar relaxivity (r(1)) increased after microbubble fragmentation. This behavior was attributed to an increase in water proton exchange with the Gd(III)-bound lipid fragments caused by an increase in the lipid headgroup area that accompanied the lipid shell monolayer-to-bilayer transition. In this article, we explore this mechanism by comparing the changes in r(1) and its transverse counterpart, r(2)*, after the fragmentation of microbubbles consisting of Gd(III) bound to two different locations on the lipid monolayer shell: the phosphatidylethanolamine (PE) lipid headgroup region or the distal region of the poly(ethylene glycol) (PEG) brush. Nuclear magnetic resonance (NMR) at 1.5 T was used to measure the contrast properties of the various microbubble constructs because this is the most common field strength used in clinical MRI. Results for the lipid-headgroup-labeled Gd(III) microbubbles revealed that r(1) increased after microbubble fragmentation, whereas r(2)* was unchanged. An analysis of PEG-labeled Gd(III) microbubbles revealed that both r(1) and r(2)* decreased after microbubble fragmentation. Further analysis revealed that the microbubble gas core enhanced the transverse MR signal (T(2)*) in a concentration-dependent manner but minimally affected the longitudinal (T(1)) signal. These results illustrate a new method for the use of NMR to measure the biomembrane packing structure and suggest that two mechanisms, proton-exchange enhancement by lipid membrane relaxation and magnetic field inhomogeneity imposed by the gas/liquid interface, may be used to detect and differentiate Gd(III)-labeled microbubbles and their cavitation

Nano-assemblies of cationic mPEG brush block copolymers with gadolinium polyoxotungstate [Gd(W5O18)2]9- form stable, high relaxivity MRI contrast agents.

PubMed

Ly, Joanne; Li, Yuhuan; Vu, Mai N; Moffat, Bradford A; Jack, Kevin S; Quinn, John F; Whittaker, Michael R; Davis, Thomas P

2018-04-19

Polyoxometalates (POMs) incorporating paramagnetic ions, such as gadolinium, show promise as contrast agents for application in magnetic resonance imaging (MRI). Specifically, [Gd(W5O18)2]9- (denoted as GdWO) has been reported to have a higher relaxivity than commercially available contrast agents, but it's clinical utility has been limited by the intrinsic instability of POMs at physiological pH (7.4). In the current report we present a stability study on neat GdWO and nano-assemblies of block copolymers with GdWO in the pH range 5.0-7.4 to assess their suitability as MRI contrast agents. Neat GdWO only maintained structural stability between pH 5.4 and 6.4, and demonstrated poor MRI contrast at pH 7.4. To address this pH instability, GdWO was self-assembled with cationic mPEG brush block copolymers containing 20 or 40 units derived from the cationic monomer, 2-dimethylaminoethyl methacrylate (DMAEMA). Nano-assemblies with different charge ratios were synthesised and characterised according to their size, stability, contrasting properties and toxicity. The longitudinal relaxivity (r1) of the nano-assemblies was found to be dependent on the charge ratio, but not on the length of the cationic polymer block. Further investigation of PDMAEMA20 nano-assemblies demonstrated that they were stable over the pH range 5.0-7.4, exhibiting a higher r1 than either neat GdWO (2.77 s-1 mM-1) or clinical MRI contrast agent Gd-DTPA (4.1 s-1 mM-1) at pH 7.4. Importantly, the nano-assembly with the lowest charge ratio (0.2), showed the highest r1 (12.1 s-1 mM-1) whilst, stabilising GdWO over the pH range studied, eliciting low toxicity with MDA-MB231 cells.

Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

2014-06-01

We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

Paramagnetic Ce3 + optical emitters in garnets: Optically detected magnetic resonance study and evidence of Gd-Ce cross-relaxation effects

NASA Astrophysics Data System (ADS)

Tolmachev, D. O.; Gurin, A. S.; Uspenskaya, Yu. A.; Asatryan, G. R.; Badalyan, A. G.; Romanov, N. G.; Petrosyan, A. G.; Baranov, P. G.; Wieczorek, H.; Ronda, C.

2017-06-01

Paramagnetic Ce3 +optical emitters have been studied by means of optically detected magnetic resonance (ODMR) via Ce3 + spin-dependent emission in cerium-doped garnet crystals which were both gadolinium free and contain gadolinium in a concentration from the lowest (0.1%) to 100%, i.e., to the superparamagnetic state. It has been shown that the intensity of photoluminescence excited by circularly polarized light into Ce3 + absorption bands can be used for selective monitoring the population of the Ce3 + ground-state spin sublevels. Direct evidence of the cross-relaxation effects in garnet crystals containing two electron spin systems, i.e., the simplest one of Ce3 + ions with the effective spin S =1/2 and the system of Gd3 + ions with the maximum spin S =7/2 , has been demonstrated. Magnetic resonance of Gd3 + has been found by monitoring Ce3 + emission in cerium-doped garnet crystals with gadolinium concentrations of 0.1 at. %, 4%-8%, and 100%, which implies the impact of the Gd3 + spin polarization on the optical properties of Ce3 +. Strong internal magnetic fields in superparamagnetic crystals were shown to modify the processes of recombination between UV-radiation-induced electron and hole centers that lead to the recombination-induced Ce3 + emission. Observation of spikes and subsequent decay in the cross-relaxation-induced ODMR signals under pulsed microwave excitation is suggested to be an informative method to investigate transient processes in the many-spin system of Ce3 +, Gd3 +, and electron and hole radiation-induced centers.

Modeling T1 and T2 relaxation in bovine white matter

NASA Astrophysics Data System (ADS)

Barta, R.; Kalantari, S.; Laule, C.; Vavasour, I. M.; MacKay, A. L.; Michal, C. A.

2015-10-01

The fundamental basis of T1 and T2 contrast in brain MRI is not well understood; recent literature contains conflicting views on the nature of relaxation in white matter (WM). We investigated the effects of inversion pulse bandwidth on measurements of T1 and T2 in WM. Hybrid inversion-recovery/Carr-Purcell-Meiboom-Gill experiments with broad or narrow bandwidth inversion pulses were applied to bovine WM in vitro. Data were analysed with the commonly used 1D-non-negative least squares (NNLS) algorithm, a 2D-NNLS algorithm, and a four-pool model which was based upon microscopically distinguishable WM compartments (myelin non-aqueous protons, myelin water, non-myelin non-aqueous protons and intra/extracellular water) and incorporated magnetization exchange between adjacent compartments. 1D-NNLS showed that different T2 components had different T1 behaviours and yielded dissimilar results for the two inversion conditions. 2D-NNLS revealed significantly more complicated T1/T2 distributions for narrow bandwidth than for broad bandwidth inversion pulses. The four-pool model fits allow physical interpretation of the parameters, fit better than the NNLS techniques, and fits results from both inversion conditions using the same parameters. The results demonstrate that exchange cannot be neglected when analysing experimental inversion recovery data from WM, in part because it can introduce exponential components having negative amplitude coefficients that cannot be correctly modeled with nonnegative fitting techniques. While assignment of an individual T1 to one particular pool is not possible, the results suggest that under carefully controlled experimental conditions the amplitude of an apparent short T1 component might be used to quantify myelin water.

Magnetic Resonance T1 Relaxation Time of Venous Thrombus Is Determined by Iron Processing and Predicts Susceptibility to Lysis

PubMed Central

Modarai, Bijan; Blume, Ulrike; Humphries, Julia; Patel, Ashish S.; Phinikaridou, Alkystis; Evans, Colin E.; Mattock, Katherine; Grover, Steven P.; Ahmad, Anwar; Lyons, Oliver T.; Attia, Rizwan Q.; Renné, Thomas; Premaratne, Sobath; Wiethoff, Andrea J.; Botnar, René M.; Schaeffter, Tobias; Waltham, Matthew; Smith, Alberto

2014-01-01

Background The magnetic resonance longitudinal relaxation time (T1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T1 signal in venous thrombi and whether changes in T1 relaxation time are informative of the susceptibility to lysis. Methods and Results Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T1 relaxation time correlated with thrombus composition. The mean T1 relaxation time of thrombus was shortest at 7days following thrombus induction and returned to that of blood as the thrombus resolved. T1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS−/−)–deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis–derived iron to paramagnetic Fe3+, which causes thrombus T1 relaxation time shortening. Studies using chemokine receptor-2–deficient mice (Ccr2−/−) revealed that the return of the T1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. Conclusions The source of the T1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T1 relaxation time appears to be a good predictor of the success of thrombolysis. PMID:23820077

Spatial Distribution and Relationship of T1ρ and T2 Relaxation Times in Knee Cartilage With Osteoarthritis

PubMed Central

Li, Xiaojuan; Pai, Alex; Blumenkrantz, Gabrielle; Carballido-Gamio, Julio; Link, Thomas; Ma, Benjamin; Ries, Michael; Majumdar, Sharmila

2009-01-01

T1ρ and T2 relaxation time constants have been proposed to probe biochemical changes in osteoarthritic cartilage. This study aimed to evaluate the spatial correlation and distribution of T1ρ and T2 values in osteoarthritic cartilage. Ten patients with osteoarthritis (OA) and 10 controls were studied at 3T. The spatial correlation of T1ρ and T2 values was investigated using Z-scores. The spatial variation of T1ρ and T2 values in patellar cartilage was studied in different cartilage layers. The distribution of these relaxation time constants was measured using texture analysis parameters based on gray-level co-occurrence matrices (GLCM). The mean Z-scores for T1ρ and T2 values were significantly higher in OA patients vs. controls (P < 0.05). Regional correlation coefficients of T1ρ and T2 Z-scores showed a large range in both controls and OA patients (0.2– 0.7). OA patients had significantly greater GLCM contrast and entropy of T1ρ values than controls (P < 0.05). In summary, T1ρ and T2 values are not only increased but are also more heterogeneous in osteoarthritic cartilage. T1ρ and T2 values show different spatial distributions and may provide complementary information regarding cartilage degeneration in OA. PMID:19319904

Real-time tracking of dissociation of hyperpolarized 89Y-DTPA: a model for degradation of open-chain Gd3+ MRI contrast agents

NASA Astrophysics Data System (ADS)

Ferguson, Sarah; Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika; Kovacs, Zoltan; Lumata, Lloyd

Gadolinium (Gd) complexes are widely used relaxation-based clinical contrast agents in magnetic resonance imaging (MRI). Gd-based MRI contrast agents with open-chain ligand such as Gd-DTPA, commercially known as magnevist, are less stable compared to Gd complexes with macrocyclic ligands such as GdDOTA (Dotarem). The dissociation of Gd-DPTA into Gd ion and DTPA ligand under certain biological conditions such as high zinc levels can potentially cause kidney damage. Since Gd is paramagnetic, direct NMR detection of the Gd-DTPA dissociation is quite challenging due to ultra-short relaxation times. In this work, we have investigated Y-DTPA as a model for Gd-DPTA dissociation under high zinc content solutions. Using dissolution dynamic nuclear polarization (DNP), the 89Y NMR signal is amplified by several thousand-fold. Due to the the relatively long T1 relaxation time of 89Y which translates to hyperpolarization lifetime of several minutes, the dissociation of Y-DTPA can be tracked in real-time by hyperpolarized 89Y NMR spectroscopy. Dissociation kinetic rates and implications on the degradation of open-chain Gd3+ MRI contrast agents will be discussed. This work was supported by the U.S. Department of Defense Award Number W81XWH-14-1-0048 and by the Robert A. Welch Foundation research Grant Number AT-1877.

Magnetic properties of Gd T2Zn20 (T =Fe , Co) investigated by x-ray diffraction and spectroscopy

NASA Astrophysics Data System (ADS)

Mardegan, J. R. L.; Francoual, S.; Fabbris, G.; Veiga, L. S. I.; Strempfer, J.; Haskel, D.; Ribeiro, R. A.; Avila, M. A.; Giles, C.

2016-01-01

We investigate the magnetic and electronic properties of the Gd T2Zn20 (T =Fe and Co) compounds using x-ray resonant magnetic scattering (XRMS), x-ray absorption near-edge structure (XANES), and x-ray magnetic circular dichroism (XMCD). The XRMS measurements reveal that GdCo2Zn20 has a commensurate antiferromagnetic spin structure with a magnetic propagation vector τ ⃗=(1/2 ,1/2 ,1/2 ) below the Néel temperature (TN˜ 5.7 K). Only the Gd ions carry a magnetic moment forming an antiferromagnetic structure with magnetic representation Γ6. For the ferromagnetic GdFe2Zn20 compound, an extensive investigation was performed at low temperature and under magnetic field using XANES and XMCD. A strong XMCD signal of about 12.5 % and 9.7 % is observed below the Curie temperature (TC˜85 K ) at the Gd L2 and L3 edges, respectively. In addition, a small magnetic signal of about 0.06 % of the jump is recorded at the Zn K edge, suggesting that the Zn 4 p states are spin polarized by the Gd 5 d extended orbitals.

Gd-doped BNNTs as T2-weighted MRI contrast agents

NASA Astrophysics Data System (ADS)

Ciofani, Gianni; Boni, Adriano; Calucci, Lucia; Forte, Claudia; Gozzi, Alessandro; Mazzolai, Barbara; Mattoli, Virgilio

2013-08-01

This work describes, for the first time, doping of boron nitride nanotubes (BNNTs) with gadolinium (Gd@BNNTs), a stable functionalization that permits non-invasive BNNT tracking via magnetic resonance imaging (MRI). We report the structure, Gd loading, and relaxometric properties in water suspension at 7 T of Gd@BNNTs, and show the behaviour of these nanostructures as promising T2-weighted contrast agents. Finally, we demonstrate their complete biocompatibility in vitro on human neuroblastoma cells, together with their ability to effectively label and affect contrast in MRI images at 7 T.

Europium-doped gadolinium sulfide nanoparticles as a dual-mode imaging agent for T1-weighted MR and photoluminescence imaging.

PubMed

Jung, Jongjin; Kim, Mi Ae; Cho, Jee-Hyun; Lee, Seung Jae; Yang, Ilseung; Cho, Janggeun; Kim, Seong Keun; Lee, Chulhyun; Park, Joung Kyu

2012-08-01

We present a facile synthesis of europium-doped gadolinium sulfide (GdS:Eu(3+)) opto-magnetic nanoparticles (NPs) via sonochemistry. Their photoluminescence and strong paramagnetic properties enable these NPs to be utilized as an in vitro cell imaging and in vivo T(1)-weighted MR imaging probe. The GdS:Eu(3+) NPs have a prominent longitudinal (r(1)) relaxivity value, which is a critical parameter for T(1)-weighted MR imaging. Here, we showed not only their strong positive contrast effect to blood vessels and organs of mice, but also blood half-life and biodistribution including clearance from organs, in order to assess the GdS:Eu(3+) NPs as a competent nanocrystal-based T(1) contrast agent. We further showed confocal images of breast cancer cells containing GdS:Eu(3+) NPs to evaluate as a photoluminescence probe. Dual-mode imaging capability obtained from the GdS:Eu(3+) NPs will allow target-oriented cellular imaging as well as the resulting disease-specific MR imaging. Copyright © 2012 Elsevier Ltd. All rights reserved.

Experimental validation of a T2 ρ transverse relaxation model using LASER and CPMG acquisitions

NASA Astrophysics Data System (ADS)

Nikolova, Simona; Bowen, Chris V.; Bartha, Robert

2006-07-01

The transverse relaxation rate (R2 = 1/T2) of many biological tissues are altered by endogenous magnetized particles (i.e., ferritin, deoxyhemoglobin), and may be sensitive to the pathological progression of neurodegenerative disorders associated with altered brain-iron stores. R2 measurements using Carr-Purcell-Meiboom-Gill (CPMG) acquisitions are sensitive to the refocusing pulse interval (2τcp), and have been modeled as a chemical exchange (CE) process, while R2 measurements using a localization by adiabatic selective refocusing (LASER) sequence have an additional relaxation rate contribution that has been modeled as a R2ρ process. However, no direct comparison of the R2 measured using these two sequences has been described for a controlled phantom model of magnetized particles. The three main objectives of this study were: (1) to compare the accuracy of R2 relaxation rate predictions from the CE model with experimental data acquired using a conventional CPMG sequence, (2) to compare R2 estimates obtained using LASER and CPMG acquisitions, and (3) to determine whether the CE model, modified to account for R2ρ relaxation, adequately describes the R2 measured by LASER for a full range of τcp values. In all cases, our analysis was confined to spherical magnetic particles that satisfied the weak field regime. Three phantoms were produced that contained spherical magnetic particles (10 μm diameter polyamide powders) suspended in Gd-DTPA (1.0, 1.5, and 2.0 mmol/L) doped gel. Mono-exponential R2 measurements were made at 4 T as a function of refocusing pulse interval. CPMG measurements of R2 agreed with CE model predictions while significant differences in R2 estimates were observed between LASER and CPMG measurements for short τcp acquisitions. The discrepancy between R2 estimates is shown to be attributable to contrast enhancement in LASER due to T2ρ relaxation.

Comparison of Different Magnetic Resonance Cholangiography Techniques in Living Liver Donors Including Gd-EOB-DTPA Enhanced T1-Weighted Sequences

PubMed Central

Kinner, Sonja; Steinweg, Verena; Maderwald, Stefan; Radtke, Arnold; Sotiropoulos, Georgios; Forsting, Michael; Schroeder, Tobias

2014-01-01

Objectives Preoperative evaluation of potential living liver donors (PLLDs) includes the assessment of the biliary anatomy to avoid postoperative complications. Aim of this study was to compare T2-weighted (T2w) and Gd-EOB-DTPA enhanced T1-weighted (T1w) magnetic resonance cholangiography (MRC) techniques in the evaluation of PLLDs. Materials and Methods 30 PLLDs underwent MRC on a 1.5 T Magnetom Avanto (Siemens, Erlangen, Germany) using (A) 2D T2w HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo) fat saturated (fs) in axial plane, (B) 2D T2w HASTE fs thick slices in coronal plane, (C) free breathing 3D T2w TSE (turbo spin echo) RESTORE (high-resolution navigator corrected) plus (D) maximum intensity projections (MIPs), (E) T2w SPACE (sampling perfection with application optimized contrasts using different flip angle evolutions) plus (F) MIPs and (G) T2w TSE BLADE as well as Gd-EOB-DTPA T1w images without (G) and with (H) inversion recovery. Contrast enhanced CT cholangiography served as reference imaging modality. Two independent reviewers evaluated the biliary tract anatomy on a 5-point scale subjectively and objectively. Data sets were compared using a Mann-Whitney-U-test. Kappa values were also calculated. Results Source images and maximum intensity projections of 3D T2w TSE sequences (RESTORE and SPACE) proved to be best for subjective and objective evaluation directly followed by 2D HASTE sequences. Interobserver variabilities were good to excellent (k = 0.622–0.804). Conclusions 3D T2w sequences are essential for preoperative biliary tract evaluation in potential living liver donors. Furthermore, our results underline the value of different MRCP sequence types for the evaluation of the biliary anatomy in PLLDs including Gd-EOB-DTPA enhanced T1w MRC. PMID:25426932

Preoperative Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) for Patients Undergoing Hip Arthroscopy: Indices Are Predictive of Magnitude of Improvement in Two-Year Patient-Reported Outcomes.

PubMed

Chandrasekaran, Sivashankar; Vemula, S Pavan; Lindner, Dror; Lodhia, Parth; Suarez-Ahedo, Carlos; Domb, Benjamin G

2015-08-19

Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) has been used in the detection of chondropathy. Our study aimed to determine whether dGEMRIC indices are predictive of two-year patient-reported outcomes and pain scores following hip arthroscopy. Between August 2008 and April 2012, sixty-five patients (seventy-four hips) underwent primary hip arthroscopy with preoperative dGEMRIC and a minimum of two years of follow-up. Exclusion criteria were previous hip surgery, slipped capital femoral epiphysis, inflammatory arthropathy, Legg-Calvé-Perthes disease, and arthritis of >1 Tönnis grade. Patients were classified in two groups on the basis of a dGEMRIC cutoff of 323 msec, which was one standard deviation (SD) below the study cohort mean dGEMRIC index of 426 msec. Patient-reported outcome tools used included the modified Harris hip score (mHHS), the Nonarthritic Hip Score (NAHS), the Hip Outcome Score Activities of Daily Living (HOS-ADL), and the Hip Outcome Score Sport-Specific Subscale (HOS-SSS) as well as a visual analog scale (VAS) for pain and a patient satisfaction score. There were sixty-four hips that met the inclusion criteria; fifty-two (81.3%) had a minimum of two years of follow-up. Twelve of the sixty-four hips had a dGEMRIC index of <323 msec (Group 1), and fifty-two hips had a dGEMRIC index of ≥323 msec (Group 2). There was no significant difference between the groups with respect to age, sex, and body mass index. There was no significant difference between the groups in mean preoperative patient-reported outcome scores and the VAS for pain. At the two-year follow-up, Group 1 had significant improvement in the mHHS, whereas Group 2 demonstrated significant improvement in all patient-reported outcome scores and the VAS. The improvement in all patient-reported outcome scores was significantly larger for Group 2 compared with Group 1. There was no significant difference in patient satisfaction between groups and no

Osmotic and aging effects in caviar oocytes throughout water and lipid changes assessed by 1H NMR T1 and T2 relaxation and MRI.

PubMed

Gussoni, Maristella; Greco, Fulvia; Vezzoli, Alessandra; Paleari, Maria Antonietta; Moretti, Vittorio Maria; Lanza, Barbara; Zetta, Lucia

2007-01-01

By combining NMR relaxation spectroscopy and magnetic resonance imaging techniques, unsalted (us) and salted (s) caviar (Acipenser transmontanus) oocytes were characterized over a storage period of up to 90 days. The aging and the salting effects on the two major cell constituents, water and lipids, were separately assessed. T1 and T2 decays were interpreted by assuming a two-site exchange model. At Day 0, two water compartments that were not in fast exchange were identified by the T1 relaxation measurements on the us oocytes. In the s samples, T1 decay was monoexponential. During the time of storage, an increment of the free water amount was found for the us oocytes, ascribed to an increased metabolism. T1 and T2 of the s oocytes shortened as a consequence of the osmotic stress produced by salting. Selective images showed the presence of water endowed with different regional mobility that severely changed during the storage. Lipid T1 relaxation decays collected on us and s samples were found to be biexponential, and the T1 values lengthened during storage. In us and s oocytes, the increased lipid mobility with the storage was ascribed to lipolysis. Selective images of us samples showed lipids that were confined to the cytoplasm for up to 60 days of storage.

Assessing the effect of football play on knee articular cartilage using delayed gadolinium-enhanced MRI of cartilage (dGEMRIC).

PubMed

Wei, Wenbo; Lambach, Becky; Jia, Guang; Flanigan, David; Chaudhari, Ajit M W; Wei, Lai; Rogers, Alan; Payne, Jason; Siston, Robert A; Knopp, Michael V

2017-06-01

The prevalence of cartilage lesions is much higher in football athletes than in the general population. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) has been shown to quantify regional variations of glycosaminoglycan (GAG) concentrations which is an indicator of early cartilage degeneration. The goal of this study is to determine whether dGEMRIC can be used to assess the influence in cartilage GAG concentration due to college level football play. Thirteen collegiate football players with one to four years of collegiate football play experience were recruited and both knee joints were scanned using a dedicated 8-channel phased array knee coil on a 3T MRI system. The contrast concentrations within cartilage were calculated based on the T 1 values from dGEMRIC scans. No substantial differences were found in the contrast concentrations between the pre- and post-season across all the cartilage compartments. One year collegiate football players presented an average contrast concentration at the pre-season of 0.116±0.011mM and post-season of 0.116±0.011mM. In players with multiple years of football play, contrast uptake was elevated to 0.141±0.012mM at the pre-season and 0.139±0.012mM at the post-season. The pre-season 0.023±0.016mM and post-season 0.025±0.016mM increase in contrast concentration within the group with multiple years of experience presented with a >20% increase in contrast uptake. This may indicate the gradual, cumulative damage of football play to the articular cartilage over years, even though the effect may not be noticeable after a season of play. Playing collegiate football for a longer period of time may lead to cartilage microstructural alterations, which may be linked to early knee cartilage degeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

Relief of frustration in the Heisenberg pyrochlore antiferromagnet Gd2Pt2O7

NASA Astrophysics Data System (ADS)

Hallas, A. M.; Sharma, A. Z.; Cai, Y.; Munsie, T. J.; Wilson, M. N.; Tachibana, M.; Wiebe, C. R.; Luke, G. M.

2016-10-01

The gadolinium pyrochlores Gd2B2O7 are among the best realizations of antiferromagnetically coupled Heisenberg spins on a pyrochlore lattice. We present a magnetic characterization of Gd2Pt2O7 , a unique member of this family. Magnetic susceptibility, heat capacity, and muon spin relaxation measurements show that Gd2Pt2O7 undergoes an antiferromagnetic ordering transition at TN=1.6 K. This transition is strongly first order, as indicated by the sharpness of the heat capacity anomaly, thermal hysteresis in the magnetic susceptibility, and a nondivergent relaxation rate in μ SR . The form of the heat capacity below TN suggests that the ground state is an anisotropic collinear antiferromagnet with an excitation spectrum that is gapped by 0.245(1) meV. The ordering temperature in Gd2Pt2O7,TN=1.6 K, is a substantial 160% increase from other gadolinium pyrochlores, which are all known to order at 1 K or lower. We attribute this enhancement in TN to the B -site cation, platinum. Despite being nonmagnetic, platinum has a filled 5 d t2 g orbital and an empty 5 d eg orbital that can facilitate superexchange. Thus, the magnetic frustration in Gd2Pt2O7 is partially "relieved," thereby promoting magnetic order.

Relationship between aging and T1 relaxation time in deep gray matter: A voxel-based analysis.

PubMed

Okubo, Gosuke; Okada, Tomohisa; Yamamoto, Akira; Fushimi, Yasutaka; Okada, Tsutomu; Murata, Katsutoshi; Togashi, Kaori

2017-09-01

To investigate age-related changes in T 1 relaxation time in deep gray matter structures in healthy volunteers using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE). In all, 70 healthy volunteers (aged 20-76, mean age 42.6 years) were scanned at 3T magnetic resonance imaging (MRI). A MP2RAGE sequence was employed to quantify T 1 relaxation times. After the spatial normalization of T 1 maps with the diffeomorphic anatomical registration using the exponentiated Lie algebra algorithm, voxel-based regression analysis was conducted. In addition, linear and quadratic regression analyses of regions of interest (ROIs) were also performed. With aging, voxel-based analysis (VBA) revealed significant T 1 value decreases in the ventral-inferior putamen, nucleus accumbens, and amygdala, whereas T 1 values significantly increased in the thalamus and white matter as well (P < 0.05 at cluster level, false discovery rate). ROI analysis revealed that T 1 values in the nucleus accumbens linearly decreased with aging (P = 0.0016), supporting the VBA result. T 1 values in the thalamus (P < 0.0001), substantia nigra (P = 0.0003), and globus pallidus (P < 0.0001) had a best fit to quadratic curves, with the minimum T 1 values observed between 30 and 50 years of age. Age-related changes in T 1 relaxation time vary by location in deep gray matter. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:724-731. © 2017 International Society for Magnetic Resonance in Medicine.

Synthesis and evaluation of novel polysaccharide-Gd-DTPA compounds as contrast agent for MRI

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Jing, Fengying; Pei, Fengkui; Liu, Maili

2003-09-01

Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca 2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5-1.7 times that of Gd-DTPA in D 2O at 25°C and 9.4 T. MR imaging of Sprague-Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65-85 min; kidney 144.9±14.5%, 199.9±25.4% at 10-30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI.

In vivo relaxation time measurements on a murine tumor model--prolongation of T1 after photodynamic therapy.

PubMed

Liu, Y H; Hawk, R M; Ramaprasad, S

1995-01-01

RIF tumors implanted on mice feet were investigated for changes in relaxation times (T1 and T2) after photodynamic therapy (PDT). Photodynamic therapy was performed using Photofrin II as the photosensitizer and laser light at 630 nm. A home-built proton solenoid coil in the balanced configuration was used to accommodate the tumors, and the relaxation times were measured before, immediately after, and up to several hours after therapy. Several control experiments were performed untreated tumors, tumors treated with Photofrin II alone, or tumors treated with laser light alone. Significant increases in T1s of water protons were observed after PDT treatment. In all experiments, 31P spectra were recorded before and after the therapy to study the tumor status and to confirm the onset of PDT. These studies show significant prolongation of T1s after the PDT treatment. The spin-spin relaxation measurements, on the other hand, did not show such prolongation in T2 values after PDT treatment.

Diagnostic value of T1 and T2 * relaxation times and off-resonance saturation effects in the evaluation of Achilles tendinopathy by MRI at 3T.

PubMed

Grosse, Ulrich; Syha, Roland; Hein, Tobias; Gatidis, Sergios; Grözinger, Gerd; Schabel, Christoph; Martirosian, Petros; Schick, Fritz; Springer, Fabian

2015-04-01

To evaluate and compare the diagnostic value of T1 , T2 * relaxation times and off-resonance saturation ratios (OSR) in healthy controls and patients with different clinical and morphological stages of Achilles tendinopathy. Forty-two healthy Achilles tendons and 34 tendons of 17 patients with symptomatic and asymptomatic tendinopathy were investigated clinically with conventional magnetic resonance imaging (MRI) sequences on a 3T whole-body MR scanner and a dynamic ultrasound examination. In addition, T1 and T2 * relaxation times were assessed using an ultrashort echo time (UTE) imaging sequence with flip angle and echo time variation. For the calculation of OSR values a Gaussian off-resonance saturation pulse (frequency offset: 750-5000 Hz) was used. The diagnostic value of the derived MR values was assessed and compared using receiver operating characteristic (ROC) curves. ROC curves demonstrate the highest overall test performance for OSR values at 2000 Hz off-resonance in differentiating slightly (OSR-2000 [AUC: 0.930] > T2 * [AUC: 0.884] > T1 [AUC: 0.737]) and more severe pathologically altered tendon areas (OSR-2000 [AUC: 0.964] > T2 * [AUC: 0.917] > T1 [AUC: 0.819]) from healthy ones. OSR values at a frequency offset of 2000 Hz demonstrated a better sensitivity and specificity for detecting mild and severe stages of tendinopathy compared to T2 * and particularly when compared to T1 relaxation times. © 2014 Wiley Periodicals, Inc.

Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging.

PubMed

Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Hübner, Frank; Waidmann, Oliver; Zeuzem, Stefan; Korf, Horst-Werner; Terfort, Andreas; Gelperina, Svetlana; Vogl, Thomas J; Kreuter, Jörg; Piiper, Albrecht

2015-02-10

Nanoparticle (NP)-based contrast agents that enable high resolution anatomic T1-weighted magnetic resonance imaging (MRI) offer the prospect of improving differential diagnosis of liver tumors such as hepatocellular carcinoma (HCC). In the present study, we investigated the possibility of employing novel non-toxic human serum albumin nanoparticles conjugated with Gd-DTPA and rhodamine 123 (Gd-Rho-HSA-NPs) for the detection of HCC by T1-weighted MRI. In addition, the influence of surface coating of the NPs with poloxamine 908, which alters the absorptive behavior of NPs and changes their distribution between the liver and tumor was examined. MRI of transgenic mice with endogenously formed HCCs following intravenous injection of Gd-Rho-HSA-NPs revealed a strong negative contrast of the tumors. Contrasting of the HCCs by NP-enhanced MRI required less Gd as compared to gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced MRI, which currently provides the most sensitive detection of HCC in patients. Immunohistochemical analyses revealed that the Gd-Rho-HSA-NPs were localized to macrophages, which were - similar to HCC in patients - fewer in number in HCC as compared to the liver tissue, which is in agreement with the negative contrasting of HCC in Gd-Rho-HSA-NP-enhanced MRI. Poloxamine-coated NPs showed lower accumulation in the tumor macrophages and caused a longer lasting enhancement of the MRI signal. These data indicate that Gd-Rho-HSA-NPs enable sensitive detection of HCC by T1-weighted MRI in mice with endogenous HCC through their uptake by macrophages. Poloxamine coating of the NPs delayed the tumor localization of the NPs. Copyright © 2014 Elsevier B.V. All rights reserved.

Tuning the relaxation rates of dual-mode T1/T2 nanoparticle contrast agents: a study into the ideal system

NASA Astrophysics Data System (ADS)

Keasberry, Natasha A.; Bañobre-López, Manuel; Wood, Christopher; Stasiuk, Graeme. J.; Gallo, Juan; Long, Nicholas. J.

2015-09-01

Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in each individual imaging mode acquisition. Recently, the combination of both T1 and T2 imaging capabilities into a single platform has emerged as a tool to reduce uncertainties in MR image analysis. To date, contradicting reports on the effect on the contrast of the coupling of a T1 and T2 agent have hampered the application of these specialised probes. Herein, we present a systematic experimental study on a range of gadolinium-labelled magnetite nanoparticles envisioned to bring some light into the mechanism of interaction between T1 and T2 components, and advance towards the design of efficient (dual) T1 and T2 MRI probes. Unexpected behaviours observed in some of the constructs will be discussed. In this study, we demonstrate that the relaxivity of such multimodal probes can be rationally tuned to obtain unmatched potentials in MR imaging, exemplified by preparation of the magnetite-based nanoparticle with the highest T2 relaxivity described to date.Magnetic resonance imaging (MRI) is an excellent imaging modality. However the low sensitivity of the technique poses a challenge to achieving an accurate image of function at the molecular level. To overcome this, contrast agents are used; typically gadolinium based agents for T1 weighted imaging, or iron oxide based agents for T2 imaging. Traditionally, only one imaging mode is used per diagnosis although several physiological situations are known to interfere with the signal induced by the contrast agents in

Magnetic properties of GdT 2Zn 20 (T = Fe, Co) investigated by x-ray diffraction and spectroscopy

DOE PAGES

J. R. L. Mardegan; Fabbris, G.; Francoual, S.; ...

2016-01-26

In this study, we investigate the magnetic and electronic properties of the GdT 2Zn 20 (T=Fe and Co) compounds using x-ray resonant magnetic scattering (XRMS), x-ray absorption near-edge structure (XANES), and x-ray magnetic circular dichroism (XMCD). The XRMS measurements reveal that GdCo 2Zn 20 has a commensurate antiferromagnetic spin structure with a magnetic propagation vector →/ τ = (12,12,12) below the Néel temperature (T N ~ 5.7 K). Only the Gd ions carry a magnetic moment forming an antiferromagnetic structure with magnetic representation Γ 6. For the ferromagnetic GdFe 2Zn 20 compound, an extensive investigation was performed at low temperaturemore » and under magnetic field using XANES and XMCD. A strong XMCD signal of about 12.5% and 9.7% is observed below the Curie temperature (T C ~ 85K) at the Gd L 2 and L 3 edges, respectively. In addition, a small magnetic signal of about 0.06% of the jump is recorded at the Zn K edge, suggesting that the Zn 4p states are spin polarized by the Gd 5d extended orbitals.« less

Selective modification of NMR relaxation time in human colorectal carcinoma by using gadolinium-diethylenetriaminepentaacetic acid conjugated with monoclonal antibody 19-9.

PubMed Central

Curtet, C; Tellier, C; Bohy, J; Conti, M L; Saccavini, J C; Thedrez, P; Douillard, J Y; Chatal, J F; Koprowski, H

1986-01-01

Monoclonal antibody 19-9 (mAb 19-9) against human colon adenocarcinoma was conjugated with gadolinium X diethylenetriaminepentaacetic acid (Gd X DTPA) and used as a contrast agent in nuclear magnetic resonance (NMR) in an effort to improve tumor target selectivity in nude mice. The data indicate that Gd X DTPA-mAb 19-9 in solution decreased the T1 relaxation of water protons at 90 MHz in direct proportion to the gadolinium concentration, and this effect was greater than in Gd X DTPA solutions. T1 relaxation time at 90 MHz, measured in tumors removed from nude mice 24 hr after injection of Gd X DTPA-mAb 19-9 (Gd, 20 mumol/kg; 16 DTPA molecules per mAb molecule), was significantly decreased (by 15%) as compared with the control group. Similar results were obtained in tumors from mice injected with Gd X DTPA-mAb 19-9 solutions in which Gd was used at 2, 6, or 10 mumol/kg (16 DTPA molecules per mAb molecule). These doses are lower than those commonly used for Gd X DTPA (10-100 mumol/kg) as contrast agent. Tumor localization by the Gd X DTPA-mAb 19-9 complex containing radioactive Gd (0.3 microCi/microgram of 153Gd) to confirm scintigraphy revealed significant concentrations of the complex (5% of the injected dose per gram of tissue) in the tumor. Scan images recorded in planar scintigraphy at day 5 showed good visualization of tumors. Images PMID:3459174

Synthesis of Gd2O3:Eu nanoplatelets for MRI and fluorescence imaging

NASA Astrophysics Data System (ADS)

Maalej, Nabil M.; Qurashi, Ahsanulhaq; Assadi, Achraf Amir; Maalej, Ramzi; Shaikh, Mohammed Nasiruzzaman; Ilyas, Muhammad; Gondal, Mohammad A.

2015-05-01

We synthesized Gd2O3 and Gd2O3 doped by europium (Eu) (2% to 10%) nanoplatelets using the polyol chemical method. The synthesized nanoplatelets were characterized by X-ray diffraction (XRD), FESEM, TEM, and EDX techniques. The optical properties of the synthesized nanoplatelets were investigated by photoluminescence spectroscopy. We also studied the magnetic resonance imaging (MRI) contrast enhancement of T1 relaxivity using 3 T MRI. The XRD for Gd2O3 revealed a cubic crystalline structure. The XRD of Gd2O3:Eu3+ nanoplatelets were highly consistent with Gd2O3 indicating the total incorporation of the Eu3+ ions in the Gd2O3 matrix. The Eu doping of Gd2O3 produced red luminescence around 612 nm corresponding to the radiative transitions from the Eu-excited state 5D0 to the 7F2. The photoluminescence was maximal at 5% Eu doping concentration. The stimulated CIE chromaticity coordinates were also calculated. Judd-Ofelt analysis was used to obtain the radiative properties of the sample from the emission spectra. The MRI contrast enhancement due to Gd2O3 was compared to DOTAREM commercial contrast agent at similar concentration of gadolinium oxide and provided similar contrast enhancement. The incorporation of Eu, however, decreased the MRI contrast due to replacement of gadolinium by Eu.

Synthesis of Gd2O3:Eu nanoplatelets for MRI and fluorescence imaging.

PubMed

Maalej, Nabil M; Qurashi, Ahsanulhaq; Assadi, Achraf Amir; Maalej, Ramzi; Shaikh, Mohammed Nasiruzzaman; Ilyas, Muhammad; Gondal, Mohammad A

2015-01-01

We synthesized Gd2O3 and Gd2O3 doped by europium (Eu) (2% to 10%) nanoplatelets using the polyol chemical method. The synthesized nanoplatelets were characterized by X-ray diffraction (XRD), FESEM, TEM, and EDX techniques. The optical properties of the synthesized nanoplatelets were investigated by photoluminescence spectroscopy. We also studied the magnetic resonance imaging (MRI) contrast enhancement of T1 relaxivity using 3 T MRI. The XRD for Gd2O3 revealed a cubic crystalline structure. The XRD of Gd2O3:Eu(3+) nanoplatelets were highly consistent with Gd2O3 indicating the total incorporation of the Eu(3+) ions in the Gd2O3 matrix. The Eu doping of Gd2O3 produced red luminescence around 612 nm corresponding to the radiative transitions from the Eu-excited state (5)D0 to the (7)F2. The photoluminescence was maximal at 5% Eu doping concentration. The stimulated CIE chromaticity coordinates were also calculated. Judd-Ofelt analysis was used to obtain the radiative properties of the sample from the emission spectra. The MRI contrast enhancement due to Gd2O3 was compared to DOTAREM commercial contrast agent at similar concentration of gadolinium oxide and provided similar contrast enhancement. The incorporation of Eu, however, decreased the MRI contrast due to replacement of gadolinium by Eu.

A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

PubMed

Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

2016-01-01

This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging. Copyright © 2015 John Wiley & Sons, Ltd.

Surface-NMR measurements of the longitudinal relaxation time T1 in a homogeneous sandy aquifer in Skive, Denmark

NASA Astrophysics Data System (ADS)

Walbrecker, J.; Behroozmand, A.

2011-12-01

Efficient groundwater management requires reliable means of characterizing shallow groundwater aquifers. One key parameter in this respect is hydraulic conductivity. Surface nuclear magnetic resonance (NMR) is a geophysical exploration technique that can potentially provide this type of information in a noninvasive, cost-effective way. The technique is based on measuring the precession of nuclear spins of protons in groundwater molecules. It involves large loop antennas deployed on Earth's surface to generate electromagnetic pulses tuned to specifically excite and detect groundwater proton spins. Naturally, the excited state of spins is transitory - once excited, spins relax back to their equilibrium state. This relaxation process is strongly influenced by the spin environment, which, in the case of groundwater, is defined by the aquifer. By employing empirical relations, changes in relaxation behavior can be used to identify changes in aquifer hydraulic conductivity, making the NMR relaxation signal a very important piece of information. Particularly, efforts are made to record the longitudinal relaxation parameter T1, because it is known from laboratory studies that it often reliably correlates with hydraulic conductivity, even in the presence of magnetic species. In surface NMR, T1 data are collected by recording the NMR signal amplitude following two sequential excitation pulses as a function of the delay time τ between the two pulses. In conventional acquisition, the two pulses have a mutual phase shift of π. Based on theoretical arguments it was recently shown that T1 times acquired according to this conventional surface-NMR scheme are systematically biased. It was proposed that the bias can be minimized by cycling the phase of the two pulses between π and zero in subsequent double-pulse experiments, and subtracting the resulting signal amplitudes (phase-cycled pseudosaturation recovery scheme, pcPSR). We present the first surface-NMR T1 data set recorded

Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA

NASA Astrophysics Data System (ADS)

Mroue, Kamal H.; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H.; Morris, Michael D.; Ramamoorthy, Ayyalusamy

2014-07-01

Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the 1H T1 values were calculated from data collected by 1H spin-inversion recovery method detected in natural-abundance 13C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the 1H T1 values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the 13C CPMAS spectra. These results obtained from 13C-detected CPMAS experiments were further confirmed using 1H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans.

Acceleration of natural-abundance solid-state MAS NMR measurements on bone by paramagnetic relaxation from gadolinium-DTPA.

PubMed

Mroue, Kamal H; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H; Morris, Michael D; Ramamoorthy, Ayyalusamy

2014-07-01

Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA=Diethylene triamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the (1)H T1 values were calculated from data collected by (1)H spin-inversion recovery method detected in natural-abundance (13)C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the (1)H T1 values can be successfully reduced by a factor of 3.5 using as low as 10mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the (13)C CPMAS spectra. These results obtained from (13)C-detected CPMAS experiments were further confirmed using (1)H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans. Copyright © 2014 Elsevier Inc. All rights reserved.

3D T2-weighted and Gd-EOB-DTPA-enhanced 3D T1-weighted MR cholangiography for evaluation of biliary anatomy in living liver donors.

PubMed

Cai, Larry; Yeh, Benjamin M; Westphalen, Antonio C; Roberts, John; Wang, Zhen J

2017-03-01

To investigate whether the addition of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced 3D T1-weighted MR cholangiography (T1w-MRC) to 3D T2-weighted MRC (T2w-MRC) improves the confidence and diagnostic accuracy of biliary anatomy in living liver donors. Two abdominal radiologists retrospectively and independently reviewed pre-operative MR studies in 58 consecutive living liver donors. The second-order bile duct visualization on T1w- and T2w-MRC images was rated on a 4-point scale. The readers also independently recorded the biliary anatomy and their diagnostic confidence using (1) combined T1w- and T2w-MRC, and (2) T2w-MRC. In the 23 right lobe donors, the biliary anatomy at imaging and the imaging-predicted number of duct orifices at surgery were compared to intra-operative findings. T1w-MRC had a higher proportion of excellent visualization than T2w-MRC, 66% vs. 45% for reader 1 and 60% vs. 31% for reader 2. The median confidence score for biliary anatomy diagnosis was significantly higher with combined T1w- and T2w-MRC than T2w-MRC alone for both readers (Reader 1: 3 vs. 2, p < 0.001; Reader 2: 3 vs. 1, p < 0.001). Compared to intra-operative findings, the accuracy of imaging-predicted number of duct orifices using combined T1w-and T2w-MRC was significantly higher than that using T2w-MRC alone (p = 0.034 for reader 1, p = 0.0082 for reader 2). The addition of Gd-EOB-DTPA-enhanced 3D T1w-MRC to 3D T2w-MRC improves second-order bile duct visualization and increases the confidence in biliary anatomy diagnosis and the accuracy in the imaging-predicted number of duct orifices acquired during right lobe harvesting.

High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model

PubMed Central

Richman, Sarah A.; Nunez-Cruz, Selene; Moghimi, Babak; Li, Lucy Z.; Gershenson, Zachary T.; Mourelatos, Zissimos; Barrett, David M.; Grupp, Stephan A.; Milone, Michael C.

2018-01-01

The GD2 ganglioside, which is abundant on the surface of neuroblastoma cells, is targeted by an FDA-approved therapeutic monoclonal antibody and is an attractive tumor-associated antigen for cellular immunotherapy. Chimeric antigen receptor (CAR)–modified T cells can have potent antitumor activity in B-cell malignancies, and trials to harness this cytolytic activity toward GD2 in neuroblastoma are under way. In an effort to enhance the antitumor activity of CAR T cells that target GD2, we generated variant CAR constructs predicted to improve the stability and the affinity of the GD2-binding, 14G2a-based, single-chain variable fragment (scFv) of the CAR and compared their properties in vivo. We included the E101K mutation of GD2 scFv (GD2-E101K) that has enhanced antitumor activity against a GD2+ human neuroblastoma xenograft in vivo. However, this enhanced antitumor efficacy in vivo was concomitantly associated with lethal central nervous system (CNS) toxicity comprised of extensive CAR T-cell infiltration and proliferation within the brain and neuronal destruction. The encephalitis was localized to the cerebellum and basal regions of the brain that display low amounts of GD2. Our results highlight the challenges associated with target antigens that exhibit shared expression on critical normal tissues. Despite the success of GD2-specific antibody therapies in the treatment of neuroblastoma, the fatal neurotoxicity of GD2-specific CAR T-cell therapy observed in our studies suggests that GD2 may be a difficult target antigen for CAR T-cell therapy without additional strategies that can control CAR T-cell function within the CNS. PMID:29180536

Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model.

PubMed

Trivedi, Evan R; Ma, Zhidong; Waters, Emily A; Macrenaris, Keith W; Subramanian, Rohit; Barrett, Anthony G M; Meade, Thomas J; Hoffman, Brian M

2014-01-01

Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu-Pz-Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or 'click' chemistry between an azide functionalized Pz and alkyne functionalized DOTA-Gd(III) analog for use as an MRI contrast agent. This agent, Cu-Pz-Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1  = 11.5 mM(-1) s(-1)) that is approximately four times higher than that of a clinically used monomeric Gd(III) contrast agent, DOTA-Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu-Pz-Gd(III) in vitro, where significant contrast enhancement (9.336 ± 0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg(-1) Cu-Pz-Gd(III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu-Pz-Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu-Pz-Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue. Copyright © 2014 John Wiley & Sons, Ltd.

Octahedral tilt independent magnetism in confined GdTiO3 films

NASA Astrophysics Data System (ADS)

Need, R. F.; Isaac, B. J.; Kirby, B. J.; Borchers, J. A.; Stemmer, S.; Wilson, Stephen D.

2018-03-01

Low temperature polarized neutron reflectometry measurements are presented, exploring the evolution of ferrimagnetism in thin GdTiO3 films embedded within a SrTiO3 matrix. In GdTiO3 films thinner than ˜4 nm, the TiO6 octahedral tilts endemic to GdTiO3 coherently relax toward the undistorted, cubic phase of SrTiO3. Our measurements indicate that the ferrimagnetic state within the GdTiO3 layers survives as these TiO6 octahedral tilts are suppressed. Furthermore, our data suggest that layers of suppressed magnetization (i.e., magnetic dead layers) develop within the GdTiO3 layer at each GdTiO3/SrTiO3 interface and explain the apparent magnetization suppression observed in thin GdTiO3 films when using volume-averaged techniques. Our data show that the low temperature magnetic moment inherent to the core GdTiO3 layers is only weakly impacted as the octahedral tilt angles are suppressed by more than 50% and the t2 g bandwidth is dramatically renormalized.

Topographical Variation of Human Femoral Articular Cartilage Thickness, T1rho and T2 Relaxation Times Is Related to Local Loading during Walking.

PubMed

Van Rossom, Sam; Wesseling, Mariska; Van Assche, Dieter; Jonkers, Ilse

2018-01-01

Objective Early detection of degenerative changes in the cartilage matrix composition is essential for evaluating early interventions that slow down osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be effective for detecting early changes in proteoglycan and collagen content. To use these magnetic resonance imaging (MRI) methods, it is important to document the topographical variation in cartilage thickness, T1rho and T2 relaxation times in a healthy population. As OA is partially mechanically driven, the relation between these MRI-based parameters and localized mechanical loading during walking was investigated. Design MR images were acquired in 14 healthy adults and cartilage thickness and T1rho and T2 relaxation times were determined. Experimental gait data was collected and processed using musculoskeletal modeling to identify weight-bearing zones and estimate the contact force impulse during gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over the femoral cartilage was analyzed and compared between the weight-bearing and non-weight-bearing zone of the medial and lateral condyle as well as the trochlea. Results Medial condyle cartilage thickness was correlated to the contact force impulse ( r = 0.78). Lower T1rho, indicating increased proteoglycan content, was found in the medial weight-bearing zone. T2 was higher in all weight-bearing zones compared with the non-weight-bearing zones, indicating lower relative collagen content. Conclusions The current results suggest that medial condyle cartilage is adapted as a long-term protective response to localized loading during a frequently performed task and that the weight-bearing zone of the medial condyle has superior weight bearing capacities compared with the non-weight-bearing zones.

Short-term stability of T1 and T2 relaxation measures in multiple sclerosis normal appearing white matter.

PubMed

Liang, Alice L W; Vavasour, Irene M; Mädler, Burkhard; Traboulsee, Anthony L; Lang, Donna J; Li, David K B; MacKay, Alex L; Laule, Cornelia

2012-06-01

The presence of diffuse and widespread abnormalities within the 'normal appearing' white matter (NAWM) of multiple sclerosis (MS) brain has been established. T(1) histogram analysis has revealed increased T(1) (related to water content) in segmented NAWM, while quantitative assessment of T(2) relaxation measures has demonstrated decreased myelin water fraction (MWF, related to myelin content) and increased geometric mean T(2) (GMT(2)) of the intra/extracellular water pool. Previous studies with follow-up periods of 1-5 years have demonstrated longitudinal changes in T(1) histogram metrics over time; however, longitudinal changes in MWF and GMT(2) of segmented NAWM have not been examined. We examined the short-term evolution of MWF, GMT(2) and T(1) in MS NAWM based on monthly scanning over 6 months in 18 relapsing remitting (RR) MS subjects. Histogram metrics demonstrated short-term stability of T(1), MWF and remitting (RR) MS subjects. We observed no change in MWF, GMT(2) or T(1) histogram metrics in NAWM in RRMS over the course of 6 months. Longer follow-up periods may be required to establish demonstrable changes in NAWM based on of MWF, GMT(2) and T(1) metrics.

Magnetism and 155Gd Mössbauer spectroscopy of GdAuMg

NASA Astrophysics Data System (ADS)

Łątka, Kazimierz; Kmieć, Roman; Pacyna, Andrzej W.; Fickenscher, Thomas; Hoffmann, Rolf-Dieter; Pöttgen, Rainer

2004-03-01

GdAuMg was synthesized by reaction of the elements in a sealed tantalum ampule in a high-frequency furnace. The structure was investigated by X-ray diffraction on both powders and single crystals: ZrNiAl type, P 6¯2m , a=756.3(1), c=412.71(7) pm, wR2=0.0285 for 308 F2 values, 14 variables. Geometrical motifs of the GdAuMg structure are gold centered tricapped trigonal prisms [Au1Mg 3Gd 6] and [Au2Mg 6Gd 3]. Together the gold and magnesium atoms form a three-dimensional [AuMg] network in which the gadolinium atoms fill distorted hexagonal channels. Bulk magnetic properties have been investigated by means of AC and DC magnetic susceptibility measurements and 155Gd Mössbauer spectroscopy was used to monitor the local electronic and magnetic structure. Two magnetic phase transitions were found. One transition, at T1= TN=81.1(1) K, is from a paramagnetic to an antiferromagnetic state of collinear character and the other at T2=19.0(1) from the antiferromagnetic to a kind of canted magnetic ordering characterized by a very narrow hysteresis loop.

Luminescent GdVO4:Eu3+ functionalized mesoporous silica nanoparticles for magnetic resonance imaging and drug delivery.

PubMed

Huang, Shanshan; Cheng, Ziyong; Ma, Ping'an; Kang, Xiaojiao; Dai, Yunlu; Lin, Jun

2013-05-14

Luminescent GdVO4:Eu(3+) nanophosphor functionalized mesoporous silica nanoparticles (MSN) were prepared (denoted as GdVO4:Eu(3+)@MSN). The in vitro cytotoxicity tests show that the sample has good biocompatibility, which indicates that the nanocomposite could be a promising candidate for drug delivery. Flow cytometry and confocal laser scanning microscopy (CLSM) confirm that the sample can be effectively taken up by SKOV3 ovarian cancer cells and A549 lung adenocarcinoma cells. It was also shown that the GdVO4:Eu(3+)@MSN brightened the T1-weighted images and enhanced the r1 relaxivity of water protons, which suggested that they could act as T1 contrast agents for magnetic resonance (MR) imaging. It was found that the carriers present a pH-dependent drug release behavior for doxorubicin (DOX). The composites show a red emission under UV irradiation due to the GdVO4:Eu(3+) nanophosphors. Furthermore, the PL intensity of the composite shows correlation with the cumulative release of DOX. These results suggest that the composite can potentially act as a multifunctional drug carrier system with luminescent tagging, MR imaging and pH-controlled release property for DOX.

High resolution NMR study of T{sub 1} magnetic relaxation dispersion. IV. Proton relaxation in amino acids and Met-enkephalin pentapeptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pravdivtsev, Andrey N.; Yurkovskaya, Alexandra V.; Ivanov, Konstantin L., E-mail: ivanov@tomo.nsc.ru

2014-10-21

Nuclear Magnetic Relaxation Dispersion (NMRD) of protons was studied in the pentapeptide Met-enkephalin and the amino acids, which constitute it. Experiments were run by using high-resolution Nuclear Magnetic Resonance (NMR) in combination with fast field-cycling, thus enabling measuring NMRD curves for all individual protons. As in earlier works, Papers I–III, pronounced effects of intramolecular scalar spin-spin interactions, J-couplings, on spin relaxation were found. Notably, at low fields J-couplings tend to equalize the apparent relaxation rates within networks of coupled protons. In Met-enkephalin, in contrast to the free amino acids, there is a sharp increase in the proton T{sub 1}-relaxation timesmore » at high fields due to the changes in the regime of molecular motion. The experimental data are in good agreement with theory. From modelling the relaxation experiments we were able to determine motional correlation times of different residues in Met-enkephalin with atomic resolution. This allows us to draw conclusions about preferential conformation of the pentapeptide in solution, which is also in agreement with data from two-dimensional NMR experiments (rotating frame Overhauser effect spectroscopy). Altogether, our study demonstrates that high-resolution NMR studies of magnetic field-dependent relaxation allow one to probe molecular mobility in biomolecules with atomic resolution.« less

Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM

PubMed Central

Miyake, Yuka; Ishikawa, Syungo; Kimura, Yu; Son, Aoi; Imai, Hirohiko; Matsuda, Tetsuya; Yamada, Hisatsugu; Toshimitsu, Akio; Kondo, Teruyuki

2015-01-01

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r1) values about four times higher than that of clinically used Gd-DTPA (Magnevist®, Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (Ka) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The Ka values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo. PMID:26694418

Avidin-dendrimer-(1B4M-Gd)(254): a tumor-targeting therapeutic agent for gadolinium neutron capture therapy of intraperitoneal disseminated tumor which can be monitored by MRI.

PubMed

Kobayashi, H; Kawamoto, S; Saga, T; Sato, N; Ishimori, T; Konishi, J; Ono, K; Togashi, K; Brechbiel, M W

2001-01-01

Peritoneal carcinomatosis is a late stage in cancer progress, for which no effective therapeutic modality exists. Targeting therapeutic agents to disseminated lesions may be a promising modality for treating peritoneal carcinomatosis. Gadolinium ((157,155)Gd) is known to generate Auger and internal conversion electrons efficiently by irradiation with a neutron beam. Auger electrons from neutron-activated Gd(III) are strongly cytotoxic, but only when Gd(III) atoms have been internalized into the cells. In the present investigation, we have developed a quickly internalizing tumor-targeting system to deliver large quantities of Gd(III) atoms into tumor cells to generate the Auger emission with an external neutron beam. Simultaneously, one would be able to image its biodistribution by MRI with a shortened T1 relaxation time. Avidin-G6-(1B4M-Gd)(254) (Av-G6Gd) was synthesized from generation-6 polyamidoamine dendrimer, biotin, avidin, and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). The Av-G6Gd was radiolabeled with Gd(III) doped with (153)Gd. All of the 1B4M's on the conjugate were fully saturated with Gd(III) atoms. An in vitro internalization study showed that Av-G6Gd accumulated and was internalized into SHIN3 cells (a human ovarian cancer) 50- and 3.5-fold greater than Gd-DTPA (Magnevist) and G6-(1B4M-Gd)(256) (G6Gd). In addition, accumulation of Gd(III) in the cells was detected by the increased signal on T1-weighted MRI. A biodistribution study was performed in nude mice bearing intraperitoneally disseminated SHIN3 tumors. Av-G6Gd showed specific accumulation in the SHIN3 tumor (103% ID/g) 366- and 3.4-fold greater than Gd-DTPA (0.28% ID/g, p < 0.001) and G6Gd (30% ID/g, p < 0.001) 1 day after i.p. injection. Seventy-eight percent of the tumor-related radioactivity of Av-G6Gd in the SHIN3 tumor was located inside the cells. The SHIN3 tumor-to-normal tissue ratio was greater than 17:1 in all organs and increased up to 638:1 at 1

Silica-coated Gd(DOTA)-loaded protein nanoparticles enable magnetic resonance imaging of macrophages

PubMed Central

Bruckman, Michael A.; Randolph, Lauren N.; Gulati, Neetu M.; Stewart, Phoebe L.; Steinmetz, Nicole F.

2015-01-01

The molecular imaging of in vivo targets allows non-invasive disease diagnosis. Nanoparticles offer a promising platform for molecular imaging because they can deliver large payloads of imaging reagents to the site of disease. Magnetic resonance imaging (MRI) is often preferred for clinical diagnosis because it uses non-ionizing radiation and offers both high spatial resolution and excellent penetration. We have explored the use of plant viruses as the basis of for MRI contrast reagents, specifically Tobacco mosaic virus (TMV), which can assemble to form either stiff rods or spheres. We loaded TMV particles with paramagnetic Gd ions, increasing the ionic relaxivity compared to free Gd ions. The loaded TMV particles were then coated with silica maintaining high relaxivities. Interestingly, we found that when Gd(DOTA) was loaded into the interior channel of TMV and the exterior was coated with silica, the T1 relaxivities increased by three-fold from 10.9 mM−1 s−1 to 29.7 mM−1s−1 at 60 MHz compared to uncoated Gd-loaded TMV. To test the performance of the contrast agents in a biological setting, we focused on interactions with macrophages because the active or passive targeting of immune cells is a popular strategy to investigate the cellular components involved in disease progression associated with inflammation. In vitro assays and phantom MRI experiments indicate efficient targeting and imaging of macrophages, enhanced contrast-to-noise ratio was observed by shape-engineering (SNP > TMV) and silica-coating (Si-TMV/SNP > TMV/SNP). Because plant viruses are in the food chain, antibodies may be prevalent in the population. Therefore we investigated whether the silica-coating could prevent antibody recognition; indeed our data indicate that mineralization can be used as a stealth coating option to reduce clearance. Therefore, we conclude that the silica-coated protein-based contrast agent may provide an interesting candidate material for further investigation

Atomistic study on the site preference and lattice vibration of Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} (T=Al and Ge)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Hai-Xia; Wang, Xiao-Xu; Department of Materials Engineering, National Ping Tung University of Technology and Science, Ping-Tung 91201, Taiwan

The effects of the Y substitution for Gd on the structural stability and the site preference of intermetallics Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} (T=Al and Ge) are studied by using a series of interatomic pair potentials. The calculated results show Y can stabilize Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} with the tetragonal structure, and Y substitute for Gd with a strong preference for the 2b sites. The calculated lattice parameters are in good agreement with the experimental data. Furthermore, the total and partial phonon densities of states are evaluated for the Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} compounds withmore » the tetragonal structure. A qualitative analysis is carried out with the relevant potentials for the vibrational modes, which makes it possible to predict some properties related to lattice vibration. - Graphical abstract: The lattice cell of Gd{sub 3}Co{sub 29}T{sub 4}B{sub 10} consists of 92 atoms, or two Gd{sub 3}Co{sub 29}T{sub 4}B{sub 10} formula units, with fourteen distinct kinds of site. Rare-earth atoms occupy 2b and 4d sites, Co atoms occupy the Co1(2c), Co2(8i1), Co3(8i2), Co4(8i3), Co5(8j1), Co6(8j2) and Co7(16k), T atoms occupy the T(8i) sites, and B atoms occupy the B1(2c1), B2(2c2), B3(8i) and B4(8j) sites. - Highlights: • The application of the pair potentials obtained from lattice-inversion method. • The lattice vibrations for Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} (T=Ge and Al) are first evaluated. • The Y atoms should prefer the 2b site of Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} compounds. • The total and partial phonon densities of states are evaluated for the Gd{sub 3−x}Y{sub x}Co{sub 29}T{sub 4}B{sub 10} compounds with the tetragonal structure. • A qualitative analysis is carried out with the relevant potentials for the vibrational modes.« less

Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

2004-10-01

Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

Quantum process tomography with informational incomplete data of two J-coupled heterogeneous spins relaxation in a time window much greater than T1

NASA Astrophysics Data System (ADS)

Maciel, Thiago O.; Vianna, Reinaldo O.; Sarthour, Roberto S.; Oliveira, Ivan S.

2015-11-01

We reconstruct the time dependent quantum map corresponding to the relaxation process of a two-spin system in liquid-state NMR at room temperature. By means of quantum tomography techniques that handle informational incomplete data, we show how to properly post-process and normalize the measurements data for the simulation of quantum information processing, overcoming the unknown number of molecules prepared in a non-equilibrium magnetization state (Nj) by an initial sequence of radiofrequency pulses. From the reconstructed quantum map, we infer both longitudinal (T1) and transversal (T2) relaxation times, and introduce the J-coupling relaxation times ({T}1J,{T}2J), which are relevant for quantum information processing simulations. We show that the map associated to the relaxation process cannot be assumed approximated unital and trace-preserving for times greater than {T}2J.

Particle- $$\\gamma$$ γ coincidence spectroscopy of the N = 90 nucleus 154Gd by ( $$p,t\\gamma$$ p , t γ )

DOE PAGES

Allmond, J. M.; Beausang, C. W.; Ross, T. J.; ...

2017-03-01

A segmented Si-telescope and HPGe array, STARS-LIBERACE, was used to study the 156Gd(p,t )154Gd direct reaction by particle- coincidence spectroscopy. New cross sections with a 25- MeV proton beam are reported and compared to previous (p,t) and (t,p) studies. Furthermore, additional evidence for coexisting K = 0+1 , 2+1 and 0+2 , 2+2 configurations at N = 90 is presented. Direct and indirect population patterns of the low-lying states are also explored. Review of the new and existing evidence fa- vors an interpretation based on a configuration-dependent pairing interaction. The weakening of monopole pairing strength and an increase in quadrupolemore » pairing strength could bring 2p-2h 0+ states below 2 . This may account for a large number of the low-lying 0+ states observed in two-nucleon transfer reactions. A hypothesis for the the origin of the 0+2 and 0+3 states is provided.« less

Medial meniscal posterior root/horn radial tears correlate with cartilage degeneration detected by T1ρ relaxation mapping.

PubMed

Takahashi, Kenji; Hashimoto, Sanshiro; Nakamura, Hiroshi; Mori, Atsushi; Sato, Akiko; Majima, Tokifumi; Takai, Shinro

2015-06-01

This study aimed to identify factors on routine pulse sequence MRI associated with cartilage degeneration observed on T1ρ relaxation mapping. This study included 137 subjects with knee pain. T1ρ values were measured in the regions of interest on the surface layer of the cartilage on mid-coronal images of the femorotibial joint. Assessment of cartilage, subchondral bone, meniscus and ligaments was performed using routine pulse sequence MRI. Radiographic evaluation for osteoarthritis was also performed. Multiple regression analysis revealed posterior root/horn tears to be independent factors increasing the T1ρ values of the cartilage in the medial compartment of the femorotibial joint. Even when adjusted for radiographically defined early-stage osteoarthritis, medial posterior meniscal radial tears significantly increased the T1ρ values. This study showed that posterior root/horn radial tears in the medial meniscus are particularly important MRI findings associated with cartilage degeneration observed on T1ρ relaxation mapping. Morphological factors of the medial meniscus on MRI provide findings useful for screening early-stage osteoarthritis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells.

PubMed

Fisher, Jonathan P H; Flutter, Barry; Wesemann, Florian; Frosch, Jennifer; Rossig, Claudia; Gustafsson, Kenth; Anderson, John

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma. To explore the hypothesis that zoledronic acid, IL-2 and anti-GD2 antibodies will synergize in a therapeutic combination, we evaluated in vitro cytotoxicity and tumor growth inhibition in the GD2 expressing cancers neuroblastoma and Ewing's sarcoma. Vδ2 T cells exert ADCC against GD2-expressing Ewing's sarcoma and neuroblastoma cell lines, an effect which correlates with the brightness of GD2 expression. In an immunodeficient mouse model of small established GD2-expressing Ewing's sarcoma or neuroblastoma tumors, the combination of adoptively transferred Vδ2+ T cells, expanded in vitro with zoledronic acid and IL-2, with anti-GD2 antibody ch14.18/CHO, and with systemic zoledronic acid, significantly suppressed tumor growth compared to antibody or γδT cell-free controls. Combination treatment using ch14.18/CHO, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as neuroblastoma or Ewing's sarcoma both rational and feasible.

Effective combination treatment of GD2-expressing neuroblastoma and Ewing's sarcoma using anti-GD2 ch14.18/CHO antibody with Vγ9Vδ2+ γδT cells

PubMed Central

Fisher, Jonathan P H; Flutter, Barry; Wesemann, Florian; Frosch, Jennifer; Rossig, Claudia; Gustafsson, Kenth; Anderson, John

2016-01-01

Gamma delta T lymphocytes (γδT cells) have pleiotropic properties including innate cytotoxicity, which make them attractive effectors for cancer immunotherapy. Combination treatment with zoledronic acid and IL-2 can activate and expand the most common subset of blood γδT, which express the Vγ9Vδ2 T cell receptor (TCR) (Vδ2 T cells). Vγ9Vδ2 T cells are equipped for antibody-dependent cell-mediated cytotoxicity (ADCC) through expression of the low-affinity FcγR CD16. GD2 is a highly ranked tumor associated antigen for immunotherapy due to bright expression on the cell surface, absent expression on normal tissues and availability of therapeutic antibodies with known efficacy in neuroblastoma. To explore the hypothesis that zoledronic acid, IL-2 and anti-GD2 antibodies will synergize in a therapeutic combination, we evaluated in vitro cytotoxicity and tumor growth inhibition in the GD2 expressing cancers neuroblastoma and Ewing's sarcoma. Vδ2 T cells exert ADCC against GD2-expressing Ewing's sarcoma and neuroblastoma cell lines, an effect which correlates with the brightness of GD2 expression. In an immunodeficient mouse model of small established GD2-expressing Ewing's sarcoma or neuroblastoma tumors, the combination of adoptively transferred Vδ2+ T cells, expanded in vitro with zoledronic acid and IL-2, with anti-GD2 antibody ch14.18/CHO, and with systemic zoledronic acid, significantly suppressed tumor growth compared to antibody or γδT cell-free controls. Combination treatment using ch14.18/CHO, zoledronic acid and IL-2 is more effective than their use in isolation. The already-established safety profiles of these agents make testing of the combination in GD2 positive cancers such as neuroblastoma or Ewing's sarcoma both rational and feasible. PMID:26942051

Tumor-penetrating Peptide Conjugated and Doxorubicin Loaded T1-T2 Dual Mode MRI Contrast Agents Nanoparticles for Tumor Theranostics

PubMed Central

Gao, Lipeng; Yu, Jing; Liu, Yang; Zhou, Jinge; Sun, Lei; Wang, Jing; Zhu, Jianzhong; Peng, Hui; Lu, Weiyue; Yu, Lei; Yan, Zhiqiang; Wang, Yiting

2018-01-01

The conventional chemotherapeutics could not be traced in vivo and provide timely feedback on the clinical effectiveness of drugs. Methods: In this study, a tumor-penetrating peptide RGERPPR (RGE) modified, Gd-DTPA conjugated, and doxorubicin (DOX) loaded Fe3O4@SiO2@mSiO2 nanoparticle drug delivery system (Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs) was prepared for tumor theranostics. Results: The Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs showed a z-average hydrodynamic diameter of about 90 nm, and a pH-sensitive DOX release profile. The 3 T MRI results confirmed the relaxivity of the NPs (r1 = 6.13 mM-1S-1, r2 = 36.89 mM-1S-1). The in vitro cellular uptake and cytotoxicity assays on U87MG cells confirmed that the conjugation of RGERPPR played a significant role in increasing the cellular uptake and cytotoxicity of the NPs. The near-infrared fluorescence in vivo imaging results showed that the NPs could be significantly accumulated in the U87MG tumor tissue, which should result from the mediation of the tumor-penetrating peptide RGERPPR. The MRI results showed that the NPs offered a T1-T2 dual mode contrast imaging effect which would lead to a more precise diagnosis. Compared with unmodified NPs, the RGE-modified NPs showed significantly enhanced MR imaging signal in tumor tissue and antitumor effect, which should also be attributed to the tumor penetrating ability of RGERPPR peptide. Furthermore, the Hematoxylin and Eosin (H&E) staining and TUNEL assay proved that the NPs produced obvious cell apoptosis in tumor tissue. Conclusions: These results indicated that Fe3O4@SiO2@mSiO2/DOX-(Gd-DTPA)-PEG-RGE NPs are an effective targeted delivery system for tumor theranostics, and should have a potential value in the personalized treatment of tumor. PMID:29290795

Cluster analysis of quantitative MRI T2 and T1ρ relaxation times of cartilage identifies differences between healthy and ACL-injured individuals at 3T.

PubMed

Monu, U D; Jordan, C D; Samuelson, B L; Hargreaves, B A; Gold, G E; McWalter, E J

2017-04-01

To identify focal lesions of elevated MRI T 2 and T 1ρ relaxation times in articular cartilage of an ACL-injured group using a novel cluster analysis technique. Eighteen ACL-injured patients underwent 3T MRI T 2 and T 1ρ relaxometry at baseline, 6 months and 1 year and six healthy volunteers at baseline, 1 day and 1 year. Clusters of contiguous pixels above or below T 2 and T 1ρ intensity and area thresholds were identified on a projection map of the 3D femoral cartilage surface. The total area of femoral cartilage plate covered by clusters (%CA) was split into areas above (%CA+) and below (%CA-) the thresholds and the differences in %CA(+ or -) over time in the ACL-injured group were determined using the Wilcoxon signed rank test. %CA+ was greater in the ACL-injured patients than the healthy volunteers at 6 months and 1 year with average %CA+ of 5.2 ± 4.0% (p = 0.0054) and 6.6 ± 3.7% (p = 0.0041) for T 2 and 6.2 ± 7.1% (p = 0.063) and 8.2 ± 6.9% (p = 0.042) for T 1ρ , respectively. %CA- at 6 months and 1 year was 3.0 ± 1.8% (p > 0.1) and 5.9 ± 5.0% (p > 0.1) for T 2 and 4.4 ± 4.9% (p > 0.1) and 4.5 ± 4.6% (p > 0.1) for T 1ρ , respectively. With the proposed cluster analysis technique, we have quantified cartilage lesion coverage and demonstrated that the ACL-injured group had greater areas of elevated T 2 and T 1ρ relaxation times as compared to healthy volunteers. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Quantitative assessment of hepatic fibrosis in chronic hepatitis B and C: T1 mapping on Gd-EOB-DTPA-enhanced liver magnetic resonance imaging.

PubMed

Pan, Shen; Wang, Xiao-Qi; Guo, Qi-Yong

2018-05-14

To assess the accuracy of Look-Locker on gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for staging liver fibrosis in chronic hepatitis B/C (CHB/C). We prospectively included 109 patients with CHB or CHC who underwent a 3.0-Tesla MRI examination, including T1-weighted and Look-Locker sequences for T1 mapping. Hepatocyte fractions (HeF) and relaxation time reduction rate (RE) were measured for staging liver fibrosis. A receiver operating characteristic analysis using the area under the receiver operating characteristic curve (AUC) was used to compare the diagnostic performance in predicting liver fibrosis between HeF and RE. A total of 73 patients had both pathological results and MRI information. The number of patients in each fibrosis stage was evaluated semiquantitatively according to the METAVIR scoring system: F0, n = 23 (31.5%); F1, n = 19 (26.0%); F2, n = 13 (17.8%); F3, n = 6 (8.2%), and F4, n = 12 (16.4%). HeF by EOB enhancement imaging was significantly correlated with fibrosis stage ( r = -0.808, P < 0.05). AUC values for diagnosis of any (≥ F1), significant (≥ F2) or advanced (≥ F3) fibrosis, and cirrhosis (F4) using HeF were 0.837 (0.733-0.913), 0.890 (0.795-0.951), 0.957 (0.881-0.990), and 0.957 (0.882-0.991), respectively. HeF measurement was more accurate than use of RE in establishing liver fibrosis staging, suggesting that calculation of HeF is a superior noninvasive liver fibrosis staging method. A T1 mapping-based HeF method is an efficient diagnostic tool for the staging of liver fibrosis.

Target binding improves relaxivity in aptamer-gadolinium conjugates.

PubMed

Bernard, Elyse D; Beking, Michael A; Rajamanickam, Karunanithi; Tsai, Eve C; Derosa, Maria C

2012-12-01

MRI contrast agents (CA) have been heavily used over the past several decades to enhance the diagnostic value of the obtained images. From a design perspective, two avenues to improve the efficacy of contrast agents are readily evident: optimization of magnetic properties of the CA, and optimization of the pharmacokinetics and distribution of the CA in the patient. Contrast agents consisting of DNA aptamer-gadolinium(III) conjugates provide a single system in which these factors can be addressed simultaneously. In this proof-of-concept study, the 15mer thrombin aptamer was conjugated to diethylenetriaminepentaacetic (DTPA) dianhydride to form a monoamide derivative of the linear open-chain chelate present in the commonly used contrast agent Magnevist(®). The stability of the conjugated DNA aptamer-DTPA-Gd(III) chelate in a transmetallation study using Zn(II) was found to be similar to that reported for DTPA-Gd(III). Relaxivity enhancements of 35 ± 4 and 20 ± 1 % were observed in the presence of thrombin compared to a control protein at fields of 9.4 and 1.5 T, respectively. The inclusion of spacers between the aptamer and the DTPA to eliminate possible steric effects was also investigated but not found to improve the relaxation enhancement achieved in comparison to the unaltered aptamer conjugate.

17O Relaxation Times in the Rat Brain at 16.4T

PubMed Central

Wiesner, Hannes M.; Balla, Dávid Z.; Shajan, G.; Scheffler, Klaus; Uğurbil, Kâmil; Chen, Wei; Uludağ, Kâmil; Pohmann, Rolf

2015-01-01

Purpose Measurement of the cerebral metabolic rate of oxygen (CMRO2) via direct imaging of the 17O signal can be a valuable tool in neuroscientific research. However, knowledge of the longitudinal and transverse relaxation times of different brain tissue types is required, which is difficult to obtain because of the low sensitivity of natural abundance H217O measurements. Methods Using the improved sensitivity at a field strength of 16.4 T, relaxation time measurements in the rat brain were performed in vivo and postmortem with relatively high spatial resolutions, using a chemical shift imaging sequence. Results In vivo relaxation times of rat brain were found to be T1 = 6.84 ± 0.67 ms and T2* = 1.77 ± 0.04 ms. Postmortem H217O relaxometry at enriched concentrations after inhalation of 17O2 showed similar T2* values for gray (1.87 ± 0.04 ms) and white matter, significantly longer than muscle (1.27 ± 0.05 ms) and shorter than CSF (2.30 ± 0.16 ms). Conclusion Relaxation times of brain H217O were measured for the first time in vivo in different types of tissues with high spatial resolution. Since the relaxation times of H217O are expected to be independent of field strength, our results should help in optimizing the acquisition parameters for experiments also at other MRI field strengths. PMID:26098931

In-vitro Gd-DTPA Relaxometry Studies in Oxygenated Venous Human Blood and Aqueous Solution at 3 and 7T

PubMed Central

Kalavagunta, Chaitanya; Michaeli, Shalom; Metzger, Gregory J.

2014-01-01

In-vitro T1 and T2* relaxivities (r1 and r2*) of Gd-DTPA (GaD) in oxygenated human venous blood (OVB) and aqueous solution (AS) at 3T and 7T were calculated. GaD concentrations ([GaD]) in OVB and AS were prepared in the range 0–5 mM. All measurements were acquired at 37±2 °C. At both 3T and 7T, a linear relationship was observed between [GaD] and R1 in both AS and OVB. At 7T, r1 in AS decreased by 7.5% (p = 0.045) while there was a negligible change in OVB. With respect to R2*, a linear relationship with [GaD] was only observed in AS, while a more complex relationship was observed in OVB; quadratic below and linear above 2 mM at both field strengths. There was a significant increase of over four-fold in r2* with GaD in OVB at 7T (for [GaD] above 2mM, p ≪0.01) as compared to 3T. Furthermore, in comparison to r1, r2* in AS was less than two-fold higher at both field strengths while in OVB it was ~twenty-fold and ~ninety-fold higher at 3T and 7T, respectively. This observation emphasizes the importance of r2* knowledge at high magnetic fields, ≥3T. The comparison between r1 and r2* presented in this work is crucial in the design and optimization of high field MRI studies making use of paramagnetic contrast agents. This is especially true in multiple compartment systems such as blood where r2* dramatically increases while r1 remains relatively constant with increasing magnetic field strength. PMID:24523062

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

NASA Astrophysics Data System (ADS)

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-01

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs ml-1 using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T1-weighted turbo-spin-echo sequence MR imaging. Heavy T2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2- and T2*-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s-1mM-1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

PubMed

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-07

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual

T(2) relaxation time of hyaline cartilage in presence of different gadolinium-based contrast agents.

PubMed

Wiener, Edzard; Settles, Marcus; Diederichs, Gerd

2010-01-01

The transverse relaxation time, T(2), of native cartilage is used to quantify cartilage degradation. T(2) is frequently measured after contrast administration, assuming that the impact of gadolinium-based contrast agents on cartilage T(2) is negligible. To verify this assumption the depth-dependent variation of T(2) in the presence of gadopentetate dimeglumine, gadobenate dimeglumine and gadoteridol was investigated. Furthermore, the r(2)/r(1) relaxivity ratios were quantified in different cartilage layers to demonstrate differences between T(2) and T(1) relaxation effects. Transverse high-spatial-resolution T(1)- and T(2)-maps were simultaneously acquired on a 1.5 T MR scanner before and after contrast administration in nine bovine patellae using a turbo-mixed sequence. The r(2)/r(1) ratios were calculated for each contrast agent in cartilage. Profiles of T(1), T(2) and r(2)/r(1) across cartilage thickness were generated in the absence and presence of contrast agent. The mean values in different cartilage layers were compared for global variance using the Kruskal-Wallis test and pairwise using the Mann-Whitney U-test. T(2) of unenhanced cartilage was 98 +/- 5 ms at 1 mm and 65 +/- 4 ms at 3 mm depth. Eleven hours after contrast administration significant differences (p < 0.001) were measurable for all three contrast agents. T(2) values were 58 +/- 2 and 62 +/- 3 ms for gadopentetate dimeglumine, 46 +/- 2 and 57 +/- 2 ms for gadobenate dimeglumine, and 38 +/- 2 and 42 +/- 2 ms for gadoteridol at 1 and 3 mm depths, respectively. The r(2)/r(1) relaxivity ratios across cartilage thickness were close to 1.0 (range 0.9-1.3). At 1.5 T, T(2) decreased significantly in the presence of contrast agents, more pronounced in superficial than in deep cartilage. The change in T(2) relaxation rate was similar to the change in T(1). Cartilage T(2) measurements after contrast administration will lead to systematic errors in the quantification of cartilage degradation. 2010 John

Gd-DTPA L-cystine bisamide copolymers as novel biodegradable macromolecular contrast agents for MR blood pool imaging.

PubMed

Kaneshiro, Todd L; Ke, Tianyi; Jeong, Eun-Kee; Parker, Dennis L; Lu, Zheng-Rong

2006-06-01

The purpose of this study was to synthesize biodegradable Gd-DTPA L-cystine bisamide copolymers (GCAC) as safe and effective, macromolecular contrast agents for magnetic resonance imaging (MRI) and to evaluate their biodegradability and efficacy in MR blood pool imaging in an animal model. Three new biodegradable GCAC with different substituents at the cystine bisamide [R = H (GCAC), CH2CH2CH3 (Gd-DTPA L-cystine bispropyl amide copolymers, GCPC), and CH(CH3)2 (Gd-DTPA cystine bisisopropyl copolymers, GCIC)] were prepared by the condensation copolymerization of diethylenetriamine pentaacetic acid (DTPA) dianhydride with cystine bisamide or bisalkyl amides, followed by complexation with gadolinium triacetate. The degradability of the agents was studied in vitro by incubation in 15 microM cysteine and in vivo with Sprague-Dawley rats. The kinetics of in vivo contrast enhancement was investigated in Sprague-Dawley rats on a Siemens Trio 3 T scanner. The apparent molecular weight of the polydisulfide Gd(III) chelates ranged from 22 to 25 kDa. The longitudinal (T1) relaxivities of GCAC, GCPC, and GCIC were 4.37, 5.28, and 5.56 mM(-1) s(-1) at 3 T, respectively. The polymeric ligands and polymeric Gd(III) chelates readily degraded into smaller molecules in incubation with 15 microM cysteine via disulfide-thiol exchange reactions. The in vitro degradation rates of both the polymeric ligands and macromolecular Gd(III) chelates decreased as the steric effect around the disulfide bonds increased. The agents readily degraded in vivo, and the catabolic degradation products were detected in rat urine samples collected after intravenous injection. The agents showed strong contrast enhancement in the blood pool, major organs, and tissues at a dose of 0.1 mmol Gd/kg. The difference of their in vitro degradability did not significantly alter the kinetics of in vivo contrast enhancement of the agents. These novel GCAC are promising contrast agents for cardiovascular and tumor MRI

NMR T1 relaxation time measurements and calculations with translational and rotational components for liquid electrolytes containing LiBF4 and propylene carbonate.

PubMed

Richardson, P M; Voice, A M; Ward, I M

2013-12-07

Longitudinal relaxation (T1) measurements of (19)F, (7)Li, and (1)H in propylene carbonate/LiBF4 liquid electrolytes are reported. Comparison of T1 values with those for the transverse relaxation time (T2) confirm that the measurements are in the high temperature (low correlation time) limit of the T1 minimum. Using data from pulsed field gradient measurements of self-diffusion coefficients and measurements of solution viscosity measured elsewhere, it is concluded that although in general there are contributions to T1 from both translational and rotational motions. For the lithium ions, this is mainly translational, and for the fluorine ions mainly rotational.

Hyperpolarized 13C NMR lifetimes in the liquid-state: relating structures and T1 relaxation times

NASA Astrophysics Data System (ADS)

Parish, Christopher; Niedbalski, Peter; Hashami, Zohreh; Fidelino, Leila; Kovacs, Zoltan; Lumata, Lloyd

Among the various attempts to solve the insensitivity problem in nuclear magnetic resonance (NMR), the physics-based technique dissolution dynamic nuclear polarization (DNP) is probably the most successful method of hyperpolarization or amplifying NMR signals. Using this technique, liquid-state NMR signal enhancements of several thousand-fold are expected for low-gamma nuclei such as carbon-13. The lifetimes of these hyperpolarized 13C NMR signals are directly related to their 13C spin-lattice relaxation times T1. Depending upon the 13C isotopic location, the lifetimes of hyperpolarized 13C compounds can range from a few seconds to minutes. In this study, we have investigated the hyperpolarized 13C NMR lifetimes of several 13C compounds with various chemical structures from glucose, acetate, citric acid, naphthalene to tetramethylallene and their deuterated analogs at 9.4 T and 25 deg C. Our results show that the 13C T1s of these compounds can range from a few seconds to more than 60 s at this field. Correlations between the chemical structures and T1 relaxation times will be discussed and corresponding implications of these results on 13C DNP experiments will be revealed. US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

NMR spin-lattice relaxation time T1 of thin films obtained by magnetic resonance force microscopy

NASA Astrophysics Data System (ADS)

Saun, Seung-Bo; Won, Soonho; Kwon, Sungmin; Lee, Soonchil

2015-05-01

We obtained the NMR spectrum and the spin-lattice relaxation time (T1) for thin film samples by magnetic resonance force microscopy (MRFM). The samples were CaF2 thin films which were 50 nm and 150 nm thick. T1 was measured at 18 K using a cyclic adiabatic inversion method at a fixed frequency. A comparison of the bulk and two thin films showed that T1 becomes shorter as the film thickness decreases. To make the comparison as accurate as possible, all three samples were loaded onto different beams of a multi-cantilever array and measured in the same experimental environment.

GD2-specific CAR T Cells Undergo Potent Activation and Deletion Following Antigen Encounter but can be Protected From Activation-induced Cell Death by PD-1 Blockade

PubMed Central

Gargett, Tessa; Yu, Wenbo; Dotti, Gianpietro; Yvon, Eric S; Christo, Susan N; Hayball, John D; Lewis, Ian D; Brenner, Malcolm K; Brown, Michael P

2016-01-01

Chimeric antigen receptor (CAR) T cells have shown great promise in the treatment of hematologic malignancies but more variable results in the treatment of solid tumors and the persistence and expansion of CAR T cells within patients has been identified as a key correlate of antitumor efficacy. Lack of immunological “space”, functional exhaustion, and deletion have all been proposed as mechanisms that hamper CAR T-cell persistence. Here we describe the events following activation of third-generation CAR T cells specific for GD2. CAR T cells had highly potent immediate effector functions without evidence of functional exhaustion in vitro, although reduced cytokine production reversible by PD-1 blockade was observed after longer-term culture. Significant activation-induced cell death (AICD) of CAR T cells was observed after repeated antigen stimulation, and PD-1 blockade enhanced both CAR T-cell survival and promoted killing of PD-L1+ tumor cell lines. Finally, we assessed CAR T-cell persistence in patients enrolled in the CARPETS phase 1 clinical trial of GD2-specific CAR T cells in the treatment of metastatic melanoma. Together, these data suggest that deletion also occurs in vivo and that PD-1-targeted combination therapy approaches may be useful to augment CAR T-cell efficacy and persistence in patients. PMID:27019998

Gd³⁺ Tethered Gold Nanorods for Combined Magnetic Resonance Imaging and Photo-Thermal Therapy.

PubMed

Pitchaimani, Arunkumar; Duong, Tuyen; Nguyen, Thanh; Maurmann, Leila; Key, Jaehong; Bossmann, Stefan H; Aryal, Santosh

2017-04-01

Near infrared (NIR) mediated photothermal therapy and magnetic resonance imaging (MRI) are promising treatment and imaging modalities in the field of cancer theranostics. Gold nanorods are the first choice of materials for NIR-mediated photothermal therapy due to their strong localized surface plasmon resonance (LSPR) at NIR region. Similarly, gadolinium based MRI contrast agents have an ability to increase the ionic and molecular relaxivity, thereby enhancing the solvent proton relaxation rate resulting in contrast enhancement. Herein, the effort has been made to engineer a dual front theranostic agent with combined photothermal and magnetic resonance imaging capacity using gadolinium tethered gold nanorods (Gd3+-AuNR). NIR-responsive gold nanorods were surface fabricated by means of Au-thiol interaction using a thiolated macrocyclic chelator that chelates Gd3+ ions, and further stabilized by thiolated polyethylene glycol (PEG-SH). The magnetic properties of the Gd3+-AuNR displayed an enhanced r 1 relaxivity of 12.1 mM–1s–1, with higher biological stability, and contrast enhancement in both solution state and in cell pellets. In-vitro (cell-free) and ex-vivo (on pig skin) analysis of the Gd3+-AuNR shows enhanced photothermal properties as equivalent to that of the raw AuNR. Furthermore, Gd3+-AuNR showed competent cellular entry and intracellular distribution as revealed by hyperspectral microscopy. In addition, Gd3+-AuNR also exhibits significant thermal ablation of B16–F10 cells in the presence of NIR. Thus, Gd3+-AuNR features a significant theranostic potential with combined photothermal and imaging modality, suggesting a great potential in anticancer therapy.

Fabrication of Gd/Eu-codoped SmPO4 nanorods for dual-modal magnetic resonance and bio-optical imaging.

PubMed

Wu, Zhi; Huang, Zhongbing; Yin, Guangfu; Wang, Lei; Gao, Fabao

2016-03-15

Ln-based complexes can be used as T1-enhanced contrast agents of magnetic resonance (MR) imaging in clinical field. Herein, we present a facile and feasible biomineralization process to fabricate Gd/Eu-codoped SmPO4 nanorods (NRs) with silk fibroin (SF) peptides (codoped SF-NRs) as T1-enhanced contrast agents, which possess paramagnetic property, photoluminescence (PL), better cyto-/tissue-compatibility and longer half-life in blood due to SF coating on their surface. Their bio-distributions in TB-N mice via tail-vein injection indicated that, although SF-NRs could be safely cleared away through renal and fecal excretion, SF-NRs easily permeated and aggregated in tumors. The results of in vitro MR imaging demonstrate that the longitudinal relaxivity r1 value of codoped SF-NRs (0.31 Sm-Gd mM(-1) s(-1)) is not only significantly higher than those of Gd-doped and Eu-doped SmPO4 SF-NRs, but also higher than those of codoped pure NRs. The tests of in vivo T1 weighted MR imaging via intro-tumor injection and tail-vein injection confirm that, compared to the pure NRs, the codoped SF-NRs exhibited higher positive signal-enhancement ability. Furthermore, the better luminescence imaging of living cells under the fluorescence microscope (94% stronger than that of the NRs without SF). A formation mechanism of codoped SF-NRs is proposed, to explain the synergistic effect of Gd/Eu codoping and SF coating on their enhanced bio-compatibility, half-life in blood, T1-weighted MR imaging and PL imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Gaussian signal relaxation around spin echoes: Implications for precise reversible transverse relaxation quantification of pulmonary tissue at 1.5 and 3 Tesla.

PubMed

Zapp, Jascha; Domsch, Sebastian; Weingärtner, Sebastian; Schad, Lothar R

2017-05-01

To characterize the reversible transverse relaxation in pulmonary tissue and to study the benefit of a quadratic exponential (Gaussian) model over the commonly used linear exponential model for increased quantification precision. A point-resolved spectroscopy sequence was used for comprehensive sampling of the relaxation around spin echoes. Measurements were performed in an ex vivo tissue sample and in healthy volunteers at 1.5 Tesla (T) and 3 T. The goodness of fit using χred2 and the precision of the fitted relaxation time by means of its confidence interval were compared between the two relaxation models. The Gaussian model provides enhanced descriptions of pulmonary relaxation with lower χred2 by average factors of 4 ex vivo and 3 in volunteers. The Gaussian model indicates higher sensitivity to tissue structure alteration with increased precision of reversible transverse relaxation time measurements also by average factors of 4 ex vivo and 3 in volunteers. The mean relaxation times of the Gaussian model in volunteers are T2,G' = (1.97 ± 0.27) msec at 1.5 T and T2,G' = (0.83 ± 0.21) msec at 3 T. Pulmonary signal relaxation was found to be accurately modeled as Gaussian, providing a potential biomarker T2,G' with high sensitivity. Magn Reson Med 77:1938-1945, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Magnetic resonance fingerprinting using echo-planar imaging: Joint quantification of T1 and T2∗ relaxation times.

PubMed

Rieger, Benedikt; Zimmer, Fabian; Zapp, Jascha; Weingärtner, Sebastian; Schad, Lothar R

2017-11-01

To develop an implementation of the magnetic resonance fingerprinting (MRF) paradigm for quantitative imaging using echo-planar imaging (EPI) for simultaneous assessment of T 1 and T2∗. The proposed MRF method (MRF-EPI) is based on the acquisition of 160 gradient-spoiled EPI images with rapid, parallel-imaging accelerated, Cartesian readout and a measurement time of 10 s per slice. Contrast variation is induced using an initial inversion pulse, and varying the flip angles, echo times, and repetition times throughout the sequence. Joint quantification of T 1 and T2∗ is performed using dictionary matching with integrated B1+ correction. The quantification accuracy of the method was validated in phantom scans and in vivo in 6 healthy subjects. Joint T 1 and T2∗ parameter maps acquired with MRF-EPI in phantoms are in good agreement with reference measurements, showing deviations under 5% and 4% for T 1 and T2∗, respectively. In vivo baseline images were visually free of artifacts. In vivo relaxation times are in good agreement with gold-standard techniques (deviation T 1 : 4 ± 2%, T2∗: 4 ± 5%). The visual quality was comparable to the in vivo gold standard, despite substantially shortened scan times. The proposed MRF-EPI method provides fast and accurate T 1 and T2∗ quantification. This approach offers a rapid supplement to the non-Cartesian MRF portfolio, with potentially increased usability and robustness. Magn Reson Med 78:1724-1733, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Formation of Gd coordination polymer with 1D chains mediated by Bronsted acidic ionic liquids

NASA Astrophysics Data System (ADS)

Luo, Qianqian; Han, Ying; Lin, Hechun; Zhang, Yuanyuan; Duan, Chungang; Peng, Hui

2017-03-01

One dimensional coordination polymer Gd[(SO4)(NO3)(C2H6SO)2] (1) is prepared through the mediation of Bronsted acid ionic liquid, which crystallized in the monoclinic space of C2/c. In this polymer, adjacent Gd atoms are linked by two SO42- ions to generate a 1-D chain, and all oxygen atoms in SO42- groups are connected to three nearest Gd atoms in μ3:η1:η1:η2 fashion. Gd, S and N from SO42- and NO3- are precisely coplanar. The planar is coordinated by a pair of DMSO molecules, which is parallel and linked by hydrogen bonding to form a three-dimensional supramolecular network. Magnetic susceptibility measurement of 1 reveals weak antiferromagnetic interactions between the Gd (III) ions. It exhibits relatively large magneto-caloric effect with -ΔSm=28.8 J Kg-1 K-1 for ΔH=7 T.

A general approach to the electronic spin relaxation of Gd(III) complexes in solutions. Monte Carlo simulations beyond the Redfield limit

NASA Astrophysics Data System (ADS)

Rast, S.; Fries, P. H.; Belorizky, E.; Borel, A.; Helm, L.; Merbach, A. E.

2001-10-01

The time correlation functions of the electronic spin components of a metal ion without orbital degeneracy in solution are computed. The approach is based on the numerical solution of the time-dependent Schrödinger equation for a stochastic perturbing Hamiltonian which is simulated by a Monte Carlo algorithm using discrete time steps. The perturbing Hamiltonian is quite general, including the superposition of both the static mean crystal field contribution in the molecular frame and the usual transient ligand field term. The Hamiltonian of the static crystal field can involve the terms of all orders, which are invariant under the local group of the average geometry of the complex. In the laboratory frame, the random rotation of the complex is the only source of modulation of this Hamiltonian, whereas an additional Ornstein-Uhlenbeck process is needed to describe the time fluctuations of the Hamiltonian of the transient crystal field. A numerical procedure for computing the electronic paramagnetic resonance (EPR) spectra is proposed and discussed. For the [Gd(H2O)8]3+ octa-aqua ion and the [Gd(DOTA)(H2O)]- complex [DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclo dodecane] in water, the predictions of the Redfield relaxation theory are compared with those of the Monte Carlo approach. The Redfield approximation is shown to be accurate for all temperatures and for electronic resonance frequencies at and above X-band, justifying the previous interpretations of EPR spectra. At lower frequencies the transverse and longitudinal relaxation functions derived from the Redfield approximation display significantly faster decays than the corresponding simulated functions. The practical interest of this simulation approach is underlined.

Effects of B1 inhomogeneity correction for three-dimensional variable flip angle T1 measurements in hip dGEMRIC at 3 T and 1.5 T.

PubMed

Siversson, Carl; Chan, Jenny; Tiderius, Carl-Johan; Mamisch, Tallal Charles; Jellus, Vladimir; Svensson, Jonas; Kim, Young-Jo

2012-06-01

Delayed gadolinium-enhanced MRI of cartilage is a technique for studying the development of osteoarthritis using quantitative T(1) measurements. Three-dimensional variable flip angle is a promising method for performing such measurements rapidly, by using two successive spoiled gradient echo sequences with different excitation pulse flip angles. However, the three-dimensional variable flip angle method is very sensitive to inhomogeneities in the transmitted B(1) field in vivo. In this study, a method for correcting for such inhomogeneities, using an additional B(1) mapping spin-echo sequence, was evaluated. Phantom studies concluded that three-dimensional variable flip angle with B(1) correction calculates accurate T(1) values also in areas with high B(1) deviation. Retrospective analysis of in vivo hip delayed gadolinium-enhanced MRI of cartilage data from 40 subjects showed the difference between three-dimensional variable flip angle with and without B(1) correction to be generally two to three times higher at 3 T than at 1.5 T. In conclusion, the B(1) variations should always be taken into account, both at 1.5 T and at 3 T. Copyright © 2011 Wiley-Liss, Inc.

Effects of the magnetic resonance imaging contrast agent Gd-DTPA on plant growth and root imaging in rice.

PubMed

Liu, Zan; Qian, Junchao; Liu, Binmei; Wang, Qi; Ni, Xiaoyu; Dong, Yaling; Zhong, Kai; Wu, Yuejin

2014-01-01

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.

Prestructural cartilage assessment using MRI.

PubMed

Link, Thomas M; Neumann, Jan; Li, Xiaojuan

2017-04-01

Cartilage loss is irreversible, and to date, no effective pharmacotherapies are available to protect or regenerate cartilage. Quantitative prestructural/compositional MR imaging techniques have been developed to characterize the cartilage matrix quality at a stage where abnormal findings are early and potentially reversible, allowing intervention to halt disease progression. The goal of this article is to critically review currently available technologies, present the basic concept behind these techniques, but also to investigate their suitability as imaging biomarkers including their validity, reproducibility, risk prediction and monitoring of therapy. Moreover, we highlighted important clinical applications. This review article focuses on the currently most relevant and clinically applicable technologies, such as T2 mapping, T2*, T1ρ, delayed gadolinium enhanced MRI of cartilage (dGEMRIC), sodium imaging and glycosaminoglycan chemical exchange saturation transfer (gagCEST). To date, most information is available for T2 and T1ρ mapping. dGEMRIC has also been used in multiple clinical studies, although it requires Gd contrast administration. Sodium imaging and gagCEST are promising technologies but are dependent on high field strength and sophisticated software and hardware. 5 J. Magn. Reson. Imaging 2017;45:949-965. © 2016 International Society for Magnetic Resonance in Medicine.

Building 1D lanthanide chains and non-symmetrical [Ln2] "triple-decker" clusters using salen-type ligands: magnetic cooling and relaxation phenomena.

PubMed

Canaj, Angelos B; Siczek, Milosz; Otręba, Marta; Lis, Tadeusz; Lorusso, Giulia; Evangelisti, Marco; Milios, Constantinos J

2016-11-22

A solvothermal reaction between Ln(NO 3 ) 3 ·6H 2 O (Ln: Gd, Tb and Dy), 2-hydroxy-1-naphthaldehyde, 2-OH-naphth, and ethylenediamine, en, in MeOH in the presence of a base, NEt 3 , led to the formation of the 1D coordination polymers [Ln(L)(MeO)(MeOH) 0.5 ] n ·MeOH (Ln = Gd (1·MeOH), Tb(2), Dy (3·MeOH); H 2 L = 1,1'-((1E,1'E)-(ethane-1,2-diylbis(azanylylidene))bis(methanylylidene))bis(naphthalen-2-ol), the Schiff-base ligand derived from the condensation of 2-OH-naphth and en), while a similar reaction in an excess of NaN 3 yielded 1D coordination polymers [Ln(L)(N 3 ) 0.75 (MeO) 0.25 (MeOH)] n (Ln = Gd (4), Tb (5), Dy (6)). Finally, upon replacing ethylenediamine with o-phenylenediamine, o-phen, we managed to isolate the discrete dimers [Dy 2 (L') 3 (MeOH)]·2MeOH (7·2MeOH) and [Gd 2 (L') 3 (MeOH)]·2MeOH (8·2MeOH) (H 2 L' = 1,1'-((1E,1'E)-(1,2-phenylenebis(azanylylidene))bis(methanylylidene))bis (naphthalen-2-ol), the Schiff-base ligand from the condensation of 2-OH-naphth and o-phen). Polymers 1-3 describe one-dimensional chains, containing alternating seven- and eight-coordinate Ln III metal centers, polymers 4-6 contain eight-coordinate lanthanide ions, while in both 7 and 8 the two Ln III centers are eight- and seven-coordinate, adopting square antiprismatic and "piano-stool" geometry, respectively. The magnetocaloric properties of the three Gd III analogues were determined from magnetic measurements, yielding the magnetic entropy change -ΔS m = 21.8, 23.0 and 16.0 J kg -1 K -1 at T = 3.0 K on demagnetization of 7 T to 0, for 1, 4 and 8, respectively. The study of the magnetic properties also revealed that all three Dy III analogues (3, 6 and 7) display out-of-phase signals, therefore suggesting slow magnetic relaxation, while such behaviour was not established in the Tb III analogues.

Facile preparation of multifunctional uniform magnetic microspheres for T1-T2 dual modal magnetic resonance and optical imaging.

PubMed

Zhang, Li; Liang, Shuang; Liu, Ruiqing; Yuan, Tianmeng; Zhang, Shulai; Xu, Zushun; Xu, Haibo

2016-08-01

Molecular imaging is of significant importance for early detection and diagnosis of cancer. Herein, a novel core-shell magnetic microsphere for dual modal magnetic resonance imaging (MRI) and optical imaging was produced by one-pot emulsifier-free emulsion polymerization, which could provide high resolution rate of histologic structure information and realize high sensitive detection at the same time. The synthesized magnetic microspheres composed of cores containing oleic acid (OA) and sodium undecylenate (NaUA) modified Fe3O4 nanoparticles and styrene (St), Glycidyl methacrylate (GMA), and polymerizable lanthanide complexes (Gd(AA)3Phen and Eu(AA)3Phen) polymerized on the surface for outer shells. Fluorescence spectra show characteristic emission peaks from Eu(3+) at 590nm and 615nm and vivid red fluorescence luminescence can be observed by 2-photon confocal scanning laser microscopy (CLSM). In vitro cytotoxicity tests based on the MTT assay demonstrate good cytocompatibility, the composites have longitudinal relaxivity value (r1) of 8.39mM(-1)s(-1) and also have transverse relaxivity value (r2) of 71.18mM(-1)s(-1) at clinical 3.0 T MR scanner. In vitro and in vivo MRI studies exhibit high signal enhancement on both T1- and T2-weighted MR images. These fascinating multifunctional properties suggest that the polymer microspheres have large clinical potential as multi-modal MRI/optical probes. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

Coupling Gd-DTPA with a bispecific, recombinant protein anti-EGFR-iRGD complex improves tumor targeting in MRI

PubMed Central

XIN, XIAOYAN; SHA, HUIZI; SHEN, JINGTAO; ZHANG, BING; ZHU, BIN; LIU, BAORUI

2016-01-01

Recombinant anti-epidermal growth factor receptor-internalizing arginine-glycine-aspartic acid (anti-EGFR single-domain antibody fused with iRGD peptide) protein efficiently targets the EGFR extracellular domain and integrin αvβ/β5, and shows a high penetration into cells. Thus, this protein may improve penetration of conjugated drugs into the deep zone of gastric cancer multicellular 3D spheroids. In the present study, a novel tumor-targeting contrast agent for magnetic resonance imaging (MRI) was developed, by coupling gadolinium-diethylene triamine pentaacetate (Gd-DTPA) with the bispecific recombinant anti-EGFR-iRGD protein. The anti-EGFR-iRGD protein was extracted from Escherichia coli and Gd was loaded onto the recombinant protein by chelation using DTPA anhydride. Single-targeting agent anti-EGFR-DTPA-Gd, which served as the control, was also prepared. The results of the present study showed that anti-EGFR-iRGD-DTPA-Gd exhibited no significant cyto toxicity to human gastric carcinoma cells (BGC-823) under the experimental conditions used. Compared with a conventional contrast agent (Magnevist), anti-EGFR-iRGD-DTPA-Gd showed higher T1 relaxivity (10.157/mM/sec at 3T) and better tumor-targeting ability. In addition, the signal intensity and the area under curve for the enhanced signal time in tumor, in vivo, were stronger than Gd-DTPA alone or the anti-EGFR-Gd control. Thus, Gd-labelled anti-EGFR-iRGD has potential as a tumor-targeting contrast agent for improved MRI. PMID:27035336

Intramolecular Hydrogen Bonding Restricts Gd-Aqua-Ligand Dynamics [The Day the Water Stood Still: Intramolecular Hydrogen Bonding to Restrict Gd-Aqua Ligand Dynamics

DOE PAGES

Boros, Eszter; Srinivas, Raja; Kim, Hee -Kyung; ...

2017-04-11

Aqua ligands can undergo rapid internal rotation about the M-O bond. For magnetic resonance contrast agents, this rotation results in diminished relaxivity. Herein, we show that an intramolecular hydrogen bond to the aqua ligand can reduce this internal rotation and increase relaxivity. Molecular modeling was used to design a series of four Gd complexes capable of forming an intramolecular H-bond to the coordinated water ligand, and these complexes had anomalously high relaxivities compared to similar complexes lacking a H-bond acceptor. Molecular dynamics simulations supported the formation of a stable intramolecular H-bond, while alternative hypotheses that could explain the higher relaxivitymore » were systematically ruled out. Finally, intramolecular H-bonding represents a useful strategy to limit internal water rotational motion and increase relaxivity of Gd complexes.« less

Musculoskeletal MRI at 3.0 T and 7.0 T: a comparison of relaxation times and image contrast.

PubMed

Jordan, Caroline D; Saranathan, Manojkumar; Bangerter, Neal K; Hargreaves, Brian A; Gold, Garry E

2013-05-01

The purpose of this study was to measure and compare the relaxation times of musculoskeletal tissues at 3.0 T and 7.0 T, and to use these measurements to select appropriate parameters for musculoskeletal protocols at 7.0 T. We measured the T₁ and T₂ relaxation times of cartilage, muscle, synovial fluid, bone marrow and subcutaneous fat at both 3.0 T and 7.0 T in the knees of five healthy volunteers. The T₁ relaxation times were measured using a spin-echo inversion recovery sequence with six inversion times. The T₂ relaxation times were measured using a spin-echo sequence with seven echo times. The accuracy of both the T₁ and T₂ measurement techniques was verified in phantoms at both magnetic field strengths. We used the measured relaxation times to help design 7.0 T musculoskeletal protocols that preserve the favorable contrast characteristics of our 3.0 T protocols, while achieving significantly higher resolution at higher SNR efficiency. The T₁ relaxation times in all tissues at 7.0 T were consistently higher than those measured at 3.0 T, while the T₂ relaxation times at 7.0 T were consistently lower than those measured at 3.0 T. The measured relaxation times were used to help develop high resolution 7.0 T protocols that had similar fluid-to-cartilage contrast to that of the standard clinical 3.0 T protocols for the following sequences: proton-density-weighted fast spin-echo (FSE), T₂-weighted FSE, and 3D-FSE-Cube. The T₁ and T₂ changes were within the expected ranges. Parameters for musculoskeletal protocols at 7.0 T can be optimized based on these values, yielding improved resolution in musculoskeletal imaging with similar contrast to that of standard 3.0 T clinical protocols. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

MRI image plane nonuniformity in evaluation of ferrous sulphate dosimeter gel (FeGel) by means of T1-relaxation time.

PubMed

Magnusson, P; Bäck, S A; Olsson, L E

1999-11-01

MR image nonuniformity can vary significantly with the spin-echo pulse sequence repetition time. When MR images with different nonuniformity shapes are used in a T1-calculation the resulting T1-image becomes nonuniform. As shown in this work the uniformity TR-dependence of the spin-echo pulse sequence is a critical property for T1 measurements in general and for ferrous sulfate dosimeter gel (FeGel) applications in particular. The purpose was to study the characteristics of the MR image plane nonuniformity in FeGel evaluation. This included studies of the possibility of decreasing nonuniformities by selecting uniformity optimized repetition times, studies of the transmitted and received RF-fields and studies of the effectiveness of the correction methods background subtraction and quotient correction. A pronounced MR image nonuniformity variation with repetition and T1 relaxation time was observed, and was found to originate from nonuniform RF-transmission in combination with the inherent differences in T1 relaxation for different repetition times. The T1 calculation itself, the uniformity optimized repetition times, nor none of the correction methods studied could sufficiently correct the nonuniformities observed in the T1 images. The nonuniformities were found to vary considerably less with inversion time for the inversion-recovery pulse sequence, than with repetition time for the spin-echo pulse sequence, resulting in considerably lower T1 image nonuniformity levels.

NMR relaxometric properties and cytotoxicity of Gd2O3 nanoparticle suspensions in an organic liquid

NASA Astrophysics Data System (ADS)

Babić-Stojić, Branka; Jokanović, Vukoman; Milivojević, Dušan; Požek, Miroslav; Jagličić, Zvonko; Makovec, Darko; Arsikin, Katarina; Paunović, Verica

2014-10-01

Gd2O3 nanoparticles and their agglomerates from approximately 10 to 80 nm in size suspended in an organic liquid were synthesized via polyol route. The reaction between diethylene glycol and added acetic acid, which occurred simultaneously with the synthesis of Gd2O3 nanoparticles, was catalyzed by sodium bisulfate to transform as much as possible diethylene glycol in corresponding ester at the end of complete reaction. The produced nanosized material of gadolinium oxide was investigated by TEM, DLS, FTIR spectroscopy, and NMR relaxometry. Biological evaluation of this material was done by MTT and crystal violet assays to determine the cell viability. Longitudinal and transverse relaxivities of water-diluted Gd2O3 nanoparticle suspensions estimated to be r 1 = 13.6 and r 2 = 14.7 s-1 mM-1 are about three times higher compared to the relaxivities obtained for standard contrast agent Gd-DTPA (Magnevist). Good MRI signal intensities of the water-diluted Gd2O3 nanoparticle suspensions were recorded in the Gd concentration range 0.2-0.3 mM for which the suspensions were not toxic exhibiting simultaneously higher signal intensities than those for Magnevist in the Gd concentration range 0.4-1 mM for which this standard contrast agent was not toxic. These properties make the produced Gd2O3 nanoparticle material promising for potential application as MRI contrast agent.

Quantitative Study of Longitudinal Relaxation (T 1) Contrast Mechanisms in Brain MRI

NASA Astrophysics Data System (ADS)

Jiang, Xu

Longitudinal relaxation (T1) contrast in MRI is important for studying brain morphology and is widely used in clinical applications. Although MRI only detects signals from water hydrogen ( 1H) protons (WPs), T1 contrast is known to be influenced by other species of 1H protons, including those in macromolecules (MPs), such as lipids and proteins, through magnetization transfer (MT) between WPs and MPs. This complicates the use and quantification of T1 contrast for studying the underlying tissue composition and the physiology of the brain. MT contributes to T1 contrast to an extent that is generally dependent on MT kinetics, as well as the concentration and NMR spectral properties of MPs. However, the MP spectral properties and MT kinetics are both difficult to measure directly, as the signal from MPs is generally invisible to MRI. Therefore, to investigate MT kinetics and further quantify T1 contrast, we first developed a reliable way to indirectly measure the MP fraction and their exchange rate with WPs, with minimal dependence on the spectral properties of MPs. For this purpose, we used brief, highpower radiofrequency (RF) NMR excitation pulses to almost completely saturate the magnetization of MPs. Based on this, both MT kinetics and the contribution of MPs to T1 contrast through MT were studied. The thus obtained knowledge allowed us to subsequently infer the spectral properties of MPs by applying low-power, frequencyselective off-resonance RF pulses and measuring the offset-frequency dependent effect of MPs on the WP MRI signal. A two-pool exchange model was used in both cases to account for direct effects of the RF pulse on WP magnetization. Consistent with earlier works using MRI at low-field and post-mortem analysis of brain tissue, our novel measurement approach found that MPs constitute an up to 27% fraction of the total 1H protons in human brain white matter, and their spectrum follows a super-Lorentzian line with a T2 of 9.6+/-0.6 mus and a resonance

Development of PEGylated KMnF3 nanoparticles as a T1-weighted contrast agent: chemical synthesis, in vivo brain MR imaging, and accounting for high relaxivity

NASA Astrophysics Data System (ADS)

Liu, Zhi-Jun; Song, Xiao-Xia; Tang, Qun

2013-05-01

Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM-1 s-1) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF3 nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility.Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM-1 s-1) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or

Ligand protons in a frozen solution of copper histidine relax via a T1e-driven three-spin mechanism

NASA Astrophysics Data System (ADS)

Stoll, S.; Epel, B.; Vega, S.; Goldfarb, D.

2007-10-01

Davies electron-nuclear double resonance spectra can exhibit strong asymmetries for long mixing times, short repetition times, and large thermal polarizations. These asymmetries can be used to determine nuclear relaxation rates in paramagnetic systems. Measurements of frozen solutions of copper(L-histidine)2 reveal a strong field dependence of the relaxation rates of the protons in the histidine ligand, increasing from low (g‖) to high (g⊥) field. It is shown that this can be attributed to a concentration-dependent T1e-driven relaxation process involving strongly mixed states of three spins: the histidine proton, the Cu(II) electron spin of the same complex, and another distant electron spin with a resonance frequency differing from the spectrometer frequency approximately by the proton Larmor frequency. The protons relax more efficiently in the g⊥ region, since the number of distant electrons able to participate in this relaxation mechanism is higher than in the g‖ region. Analytical expressions for the associated nuclear polarization decay rate Teen-1 are developed and Monte Carlo simulations are carried out, reproducing both the field and the concentration dependences of the nuclear relaxation.

Gd(III)-DOTA-modified sonosensitive liposomes for ultrasound-triggered release and MR imaging

NASA Astrophysics Data System (ADS)

Jung, Suk Hyun; Na, Kyunga; Lee, Seul A.; Cho, Sun Hang; Seong, Hasoo; Shin, Byung Cheol

2012-08-01

Ultrasound-sensitive (sonosensitive) liposomes for tumor targeting have been studied in order to increase the antitumor efficacy of drugs and decrease the associated severe side effects. Liposomal contrast agents having Gd(III) are known as a nano-contrast agent system for the efficient and selective delivery of contrast agents into pathological sites. The objective of this study was to prepare Gd(III)-DOTA-modified sonosensitive liposomes (GdSL), which could deliver a model drug, doxorubicin (DOX), to a specific site and, at the same time, be capable of magnetic resonance (MR) imaging. The GdSL was prepared using synthesized Gd(III)-DOTA-1,2-distearoyl- sn-glycero-3-phosphoethanolamine lipid. Sonosensitivity of GdSL to 20-kHz ultrasound induced 33% to 40% of DOX release. The relaxivities ( r 1) of GdSL were 6.6 to 7.8 mM-1 s-1, which were higher than that of MR-bester®. Intracellular uptake properties of GdSL were evaluated according to the intensity of ultrasound. Intracellular uptake of DOX for ultrasound-triggered GdSL was higher than that for non-ultrasound-triggered GdSL. The results of our study suggest that the paramagnetic and sonosensitive liposomes, GdSL, may provide a versatile platform for molecular imaging and targeted drug delivery.

Pharmacokinetics of Chiral Dendrimer-Triamine-Coordinated Gd-MRI Contrast Agents Evaluated by in Vivo MRI and Estimated by in Vitro QCM.

PubMed

Miyake, Yuka; Ishikawa, Syungo; Kimura, Yu; Son, Aoi; Imai, Hirohiko; Matsuda, Tetsuya; Yamada, Hisatsugu; Toshimitsu, Akio; Kondo, Teruyuki

2015-12-18

Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r₁) values about four times higher than that of clinically used Gd-DTPA (Magnevist(®), Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (K(a)) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The K(a) values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.

Transverse water relaxation in whole blood and erythrocytes at 3T, 7T, 9.4T, 11.7T and 16.4T; determination of intracellular hemoglobin and extracellular albumin relaxivities.

PubMed

Grgac, Ksenija; Li, Wenbo; Huang, Alan; Qin, Qin; van Zijl, Peter C M

2017-05-01

Blood is a physiological substance with multiple water compartments, which contain water-binding proteins such as hemoglobin in erythrocytes and albumin in plasma. Knowing the water transverse (R 2 ) relaxation rates from these different blood compartments is a prerequisite for quantifying the blood oxygenation level-dependent (BOLD) effect. Here, we report the Carr-Purcell-Meiboom-Gill (CPMG) based transverse (R 2CPMG ) relaxation rates of water in bovine blood samples circulated in a perfusion system at physiological temperature in order to mimic blood perfusion in humans. R 2CPMG values of blood plasma, lysed packed erythrocytes, lysed plasma/erythrocyte mixtures, and whole blood at 3 T, 7 T, 9.4 T, 11.7 T and 16.4 T were measured as a function of hematocrit or hemoglobin concentration, oxygenation, and CPMG inter-echo spacing (τ cp ). R 2CPMG in lysed cells showed a small τ cp dependence, attributed to the water exchange rate between free and hemoglobin-bound water to be much faster than τ cp . This was contrary to the tangential dependence in whole blood, where a much slower exchange between cells and blood plasma applies. Whole blood data were fitted as a function of τ cp using a general tangential correlation time model applicable for exchange as well as diffusion contributions to R 2CPMG , and the intercept R 20blood at infinitely short τ cp was determined. The R 20blood values at different hematocrit and the R 2CPMG values of lysed erythrocyte/plasma mixtures at different hemoglobin concentration were used to determine the relaxivity of hemoglobin inside the erythrocyte (r 2Hb ) and albumin (r 2Alb ) in plasma. The r 2Hb values obtained from lysed erythrocytes and whole blood were comparable at full oxygenation. However, while r 2Hb determined from lysed cells showed a linear dependence on oxygenation, this dependence became quadratic in whole blood. This possibly suggests an additional relaxation effect inside intact cells, perhaps due to hemoglobin

Relaxation of the environment of Gd3+ and Eu2+ impurity ions in the Y3Al5O12 garnet

NASA Astrophysics Data System (ADS)

Vazhenin, V. A.; Artyomov, M. Yu.; Potapov, A. P.; Chernyshev, V. A.; Fokin, A. V.; Serdtsev, A. V.

2017-05-01

The second-rank spin Hamiltonian parameters of Gd3+ and Eu2+ orthorhombic centers in crystals of the yttrium aluminum garnet Y3Al5O12 have been analyzed within the framework of the superposition model for the zero-field splitting of the ground state. It has been shown that the description of the experimental data in this model is possible only under the assumption of relaxation of the ligand environment of the paramagnetic impurity.

Paramagnetic Gd IIIFe III heterobimetallic complexes of DTPA-bis-salicylamide

NASA Astrophysics Data System (ADS)

Aime, S.; Botta, M.; Fasano, M.; Terreno, E.

1993-08-01

The reaction between DTPA (diethylenetriaminepenta-acetic acid)-anhydride and p-aminosalicylic acid (PAS) affords a novel ligand, [DTPA(PAS) 2], able to form stable heterobimetallic complexes with Gd 3+ and Fe 3+ ions. The lanthanide ion occupies an internal coordination cage formed by three nitrogen atoms, two carboxylate and two carboxoamido groups of the ligand, whereas the outer salicylic moieties form stable chelate rings with Fe III ions. The stoichiometry of the resulting heterobimetallic complexes, established by measurements of water proton relaxation enhancement, is [(H 2O)-Gd-DTPA(PAS) 2] 2-Fe(H 2O) 2 or [(H 2O)-Gd-DTPA(PAS) 2] 3-Fe depending on the pH of the aqueous solution. The individual contributions to the observed relaxation enhancement from Gd 3+ and Fe 3+ paramagnetic ions have been clearly distinguished and analysed.

Quantitative evaluation of liver cirrhosis using T1 relaxation time with 3 tesla MRI before and after oxygen inhalation.

PubMed

Kim, Kyung Ah; Park, Mi-Suk; Kim, In-Seong; Kiefer, Berthold; Chung, Woo-Suk; Kim, Myeong-Jin; Kim, Ki Whang

2012-08-01

To quantify liver T1 relaxation times before and after oxygen inhalation in patients with and without liver cirrhosis using a 3 Tesla (T) MRI. Institutional Review Board approval and written informed consent were obtained. Ninety-two noncirrhotic patients and 87 patients with hepatitis B viral liver cirrhosis (72 Child-Pugh class A and 15 Child-Pugh class B or C) underwent MRI with a 3.0T system before and after the supply of 100% oxygen at a rate of 15 L/min by means of a nonrebreather ventilation mask for 3 min. T1 maps were acquired using three-dimensional spoiled gradient echo sequences with two different flip angles (2° and 14°) and a fixed TR/TE (2.54 ms/0.95 ms). Liver T1 values were obtained using a T1 processing tool (MapIT software). The mean baseline T1 values of three groups (control, Child-Pugh class A, and Child-Pugh class B/C) were compared using an analysis of variance test. Liver T1 value before and after oxygenation was compared using a paired t-test for each group. The baseline liver T1 value was significantly higher in the control group (941 ± 136 ms) than in Child-Pugh A (858 ± 143 ms) and Child-Pugh B/C (783 ± 164 ms) group (P < 0.001 and P < 0.0001). The reduction in the liver T1 value after oxygen inhalation was significant in the control group (P = 0.012) but not significant in Child-Pugh class A (P = 0.079) and Child-Pugh class B/C (P = 0.752). The baseline liver T1 relaxation time was significantly different between the patients with and without liver cirrhosis. The shortening effect of oxygen on the liver T1 value was significant in the control group but not in the cirrhotic patients. Copyright © 2012 Wiley Periodicals, Inc.

Optical and relaxometric properties of monometallic (Eu(III), Tb(III), Gd(III)) and heterobimetallic (Re(I)/Gd(III)) systems based on a functionalized bipyridine-containing acyclic ligand.

PubMed

Leygue, Nadine; Boulay, Alexandre; Galaup, Chantal; Benoist, Eric; Laurent, Sophie; Vander Elst, Luce; Mestre-Voegtlé, Béatrice; Picard, Claude

2016-05-17

A series of lanthanide complexes of [LnL(H2O)](2-) composition where Ln = Eu(III), Tb(III) or Gd(III) has been studied for determining their photophysical and relaxometric properties in aqueous solution. The bifunctional ligand L (H5BPMNTA) is an acyclic chelator based on a central functionalized 2,2'-bipyridine core and two iminodiacetate coordinating arms. The mono-aqua Eu(III) and Tb(III) complexes display attractive spectroscopic properties with an excitation wavelength at 316 nm, similar excited state lifetimes and overall quantum yields (in the ranges 0.5-0.6 ms and 10-13%, respectively) in Tris buffer (pH 7.4). The proton longitudinal relaxivity, r1, of the Gd(III) complex is 4.4 mM(-1) s(-1) at 20 MHz and 310 K, which is comparable to that of the clinically used Gd-DTPA (Magnevist®). Interestingly, the water exchange rate between the coordination site and the bulk solvent is very fast (Kex = 2.6 × 10(8) s(-1) at 310 K). The ability of the complex to bind non-covalently to human serum albumin (HSA) was also examined by relaxometric measurements. We also report the synthesis and properties of a bimetallic complex based on Gd-BPMNTA and Re(I)(bpy)(CO)3 components. In this system, the Re core exhibits interesting photophysical properties (λem = 588 nm, Φ = 1.4%) and the Gd-BPMNTA core displays improved relaxivity (r1 = 6.6 mM(-1) s(-1) at 20 MHz and 310 K), due to an increase of the rotational correlation time. Besides these appealing optical and relaxometric properties, the presence of a reactive function on the structure proposes this potential dual imaging probe for conjugation to biomolecules or nanomaterials.

Biochemical validity of imaging techniques (X-ray, MRI, and dGEMRIC) in degenerative disc disease of the human cervical spine-an in vivo study.

PubMed

Bostelmann, Richard; Bostelmann, Tamara; Nasaca, Adrian; Steiger, Hans Jakob; Zaucke, Frank; Schleich, Christoph

2017-02-01

On a molecular level, maturation or degeneration of human intervertebral disc is among others expressed by the content of glycosaminoglycans (GAGs). According to the degenerative status, the disc content can differ in nucleus pulposus (NP) and annulus fibrosus (AF), respectively. Research in this area was conducted mostly on postmortem samples. Although several radiological classification systems exist, none includes biochemical features. Therefore, we focused our in vivo study on a widely spread and less expensive imaging technique for the cervical spine and the correlation of radiological patterns to biochemical equivalents in the intervertebral discs. The aim of this pilot study was to (1) measure the GAG content in human cervical discs, (2) to investigate whether a topographic biochemical GAG pattern can be found, and (3) whether there is a correlation between imaging data (X-ray and magnetic resonance imaging [MRI] including delayed gadolinium-enhanced MRI of cartilage [dGEMRIC] as a special imaging technique of cartilage) and the biochemical data. We conducted a prospective experimental pilot study. Only non-responders to conservative therapy were included. All subjects were physically and neurologically examined, and they completed their questionnaires. Visual analogue scale neck and arm, Neck Disability Index score, radiological parameters (X-rays, MRI, dGEMRIC), and the content of GAG in the cervical disc were assessed. After surgical removal of 12 discs, 96 fractions of AF and NP were biochemically analyzed for the GAG content using dimethylmethylene blue assay. A quantitative pattern of GAGs in the human cervical disc was identified. There were (1) significantly (p<.001) higher values of GAGs (µg GAG/mg tissue) in the NP (169.9 SD 37.3) compared with the AF (132.4 SD 42.2), and (2) significantly (p<.005) higher values of GAGs in the posterior (right/left: 149.9/160.2) compared with the anterior (right/left: 112.0/120.2) part of the AF. Third, we found

T1ρ Dispersion in Articular Cartilage

PubMed Central

Besier, Thor F.; Pauly, John M.; Smith, R. Lane; Delp, Scott L.; Beaupre, Gary S.; Gold, Garry E.

2015-01-01

Objective This study assessed T1ρ relaxation dispersion, measured by magnetic resonance imaging (MRI), as a tool to noninvasively evaluate cartilage material and biochemical properties. The specific objective was to answer two questions: (1) does cartilage initial elastic modulus (E0) correlate with T1ρ dispersion effects and (2) does collagen or proteoglycan content correlate with T1ρ dispersion effects? Design Cadaveric patellae with and without visible cartilage damage on conventional MR were included. T2 and T1ρ relaxation times at 500 and 1000 Hz spin-lock field amplitudes were measured. We estimated T1ρ dispersion effects by measuring T1ρ relaxation time at 500 and 1000 Hz and T2 relaxation time and using a new tool, the ratio T1ρ/T2. Cartilage initial elastic modulus, E0, was measured from initial response of mechanical indentation creep tests. Collagen and proteoglycan contents were measured at the indentation test sites; proteoglycan content was measured by their covalently linked sulfated glycosaminoglycans (sGAG). Pearson correlation coefficients were determined, taking into account the clustering of multiple samples within a single patella specimen. Results Cartilage initial elastic modulus, E0, increased with decreasing values of T1ρ/T2 measurements at both 500 Hz (P = 0.034) and 1000 Hz (P = 0.022). 1/T1ρ relaxation time (500 Hz) increased with increasing sGAG content (P = 0.041). Conclusions T1ρ/T2 ratio, a new tool, and cartilage initial elastic modulus are both measures of water–protein interactions, are dependent on the cartilage structure, and were correlated in this study. PMID:26069714

Magnetostructural phase transitions and magnetocaloric effect in (Gd 5-xSc x)Si 1.8Ge 2.2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rudolph, Kirk; Pathak, Arjun K.; Mudryk, Yaroslav

Future advancements in magnetocaloric refrigeration/heat pumping technologies depend on the discovery of new materials that demonstrate large, tunable magnetocaloric effects (MCEs) in the vicinity of coupled magnetic and structural phase transitions that occur reversibly with minimum hysteresis. Here, with this in mind, we investigate phase transitions, microstructure, magnetic, thermal, magnetocaloric, and transport properties of (Gd 5-xSc x)Si 1.8Ge 2.2 compounds. Replacement of magnetic Gd with non-magnetic Sc in Gd 5-xSc xSi 1.8Ge 2.2 increases the ferromagnetic to paramagnetic first order phase transition temperature, T C, with only a minor reduction in MCE when x ≤ 0.2. We also demonstrate thatmore » hydrostatic pressure further increases T C and reduces the hysteresis of the first order phase transition in Gd 4.8Sc 0.2Si 1.8Ge 2.2 from 7 to 4 K. Temperature-dependent x-ray powder diffraction study of Gd 4.8Sc 0.2Si 1.8Ge 2.2 confirms the monoclinic ↔ orthorhombic structural transformation at T C, in agreement with magnetic, calorimetric, and electrical transport measurements. In addition to the substantial magnetocaloric effect, a large magnetoresistance of ~20% is also observed in Gd 4.8Sc 0.2Si 1.8Ge 2.2 for ΔH = 50 kOe in the vicinity of the magnetostructural transition. Finally, in a drastic reversal of the initial doping behavior further additions of Sc (x > 0.2) suppress formation of the monoclinic phase, change the nature of the transition from first-to second-order, and reduce both the transition temperature and magnetocaloric effect.« less

Magnetostructural phase transitions and magnetocaloric effect in (Gd 5-xSc x)Si 1.8Ge 2.2

DOE PAGES

Rudolph, Kirk; Pathak, Arjun K.; Mudryk, Yaroslav; ...

2017-12-21

Future advancements in magnetocaloric refrigeration/heat pumping technologies depend on the discovery of new materials that demonstrate large, tunable magnetocaloric effects (MCEs) in the vicinity of coupled magnetic and structural phase transitions that occur reversibly with minimum hysteresis. Here, with this in mind, we investigate phase transitions, microstructure, magnetic, thermal, magnetocaloric, and transport properties of (Gd 5-xSc x)Si 1.8Ge 2.2 compounds. Replacement of magnetic Gd with non-magnetic Sc in Gd 5-xSc xSi 1.8Ge 2.2 increases the ferromagnetic to paramagnetic first order phase transition temperature, T C, with only a minor reduction in MCE when x ≤ 0.2. We also demonstrate thatmore » hydrostatic pressure further increases T C and reduces the hysteresis of the first order phase transition in Gd 4.8Sc 0.2Si 1.8Ge 2.2 from 7 to 4 K. Temperature-dependent x-ray powder diffraction study of Gd 4.8Sc 0.2Si 1.8Ge 2.2 confirms the monoclinic ↔ orthorhombic structural transformation at T C, in agreement with magnetic, calorimetric, and electrical transport measurements. In addition to the substantial magnetocaloric effect, a large magnetoresistance of ~20% is also observed in Gd 4.8Sc 0.2Si 1.8Ge 2.2 for ΔH = 50 kOe in the vicinity of the magnetostructural transition. Finally, in a drastic reversal of the initial doping behavior further additions of Sc (x > 0.2) suppress formation of the monoclinic phase, change the nature of the transition from first-to second-order, and reduce both the transition temperature and magnetocaloric effect.« less

Artificial local magnetic field inhomogeneity enhances T2 relaxivity

PubMed Central

Zhou, Zijian; Tian, Rui; Wang, Zhenyu; Yang, Zhen; Liu, Yijing; Liu, Gang; Wang, Ruifang; Song, Jibin; Nie, Liming; Chen, Xiaoyuan

2017-01-01

Clustering of magnetic nanoparticles (MNPs) is perhaps the most effective, yet intriguing strategy to enhance T2 relaxivity in magnetic resonance imaging (MRI). However, the underlying mechanism is still not fully understood and the attempts to generalize the classic outersphere theory from single particles to clusters have been found to be inadequate. Here we show that clustering of MNPs enhances local field inhomogeneity due to reduced field symmetry, which can be further elevated by artificially involving iron oxide NPs with heterogeneous geometries in terms of size and shape. The r2 values of iron oxide clusters and Landau–Lifshitz–Gilbert simulations confirmed our hypothesis, indicating that solving magnetic field inhomogeneity may become a powerful way to build correlation between magnetization and T2 relaxivity of MNPs, especially magnetic clusters. This study provides a simple yet distinct mechanism to interpret T2 relaxivity of MNPs, which is crucial to the design of high-performance MRI contrast agents. PMID:28516947

Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

PubMed

Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

2016-01-01

Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

Synthesis and physicochemical characterization of carbon backbone modified [Gd(TTDA)(H2O)]2- derivatives.

PubMed

Chang, Ya-Hui; Chen, Chiao-Yun; Singh, Gyan; Chen, Hsing-Yin; Liu, Gin-Chung; Goan, Yih-Gang; Aime, Silvio; Wang, Yun-Ming

2011-02-21

The present study was designed to exploit optimum lipophilicity and high water-exchange rate (k(ex)) on low molecular weight Gd(III) complexes to generate high bound relaxivity (r(1)(b)), upon binding to the lipophilic site of human serum albumin (HSA). Two new carbon backbone modified TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triazadodecanedioic acid) derivatives, CB-TTDA and Bz-CB-TTDA, were synthesized. The complexes [Gd(CB-TTDA)(H(2)O)](2-) and [Gd(Bz-CB-TTDA)(H(2)O)](2-) both display high stability constant (log K(GdL) = 20.28 and 20.09, respectively). Furthermore, CB-TTDA (log K(Gd/Zn) = 4.22) and Bz-CB-TTDA (log K(Gd/Zn) = 4.12) exhibit superior selectivity of Gd(III) against Zn(II) than those of TTDA (log K(Gd/Zn) = 2.93), EPTPA-bz-NO(2) (log K(Gd/Zn) = 3.19), and DTPA (log K(Gd/Zn) = 3.76). However, the stability constant values of [Gd(CB-TTDA)(H(2)O)](2-) and [Gd(Bz-CB-TTDA)(H(2)O)](2-) are lower than that of MS-325. The parameters that affect proton relaxivity have been determined in a combined variable temperature (17)O NMR and NMRD study. The water exchange rates are comparable for the two complexes, 232 × 10(6) s(-1) for [Gd(CB-TTDA)(H(2)O)](2-) and 271 × 10(6) s(-1) for [Gd(Bz-CB-TTDA)(H(2)O)](2-). They are higher than those of [Gd(TTDA)(H(2)O)](2-) (146 × 10(6) s(-1)), [Gd(DTPA)(H(2)O)](2-) (4.1 × 10(6) s(-1)), and MS-325 (6.1 × 10(6) s(-1)). Elevated stability and water exchange rate indicate that the presence of cyclobutyl on the carbon backbone imparts rigidity and steric constraint to [Gd(CB-TTDA)(H(2)O)](2-)and [Gd(Bz-CB-TTDA)(H(2)O)](2-). In addition, the major objective for selecting the cyclobutyl is to tune the lipophilicity of [Gd(Bz-CB-TTDA)(H(2)O)](2-). The binding affinity of [Gd(Bz-CB-TTDA)(H(2)O)](2-) to HSA was evaluated by ultrafiltration study across a membrane with a 30 kDa MW cutoff, and the first three stepwise binding constants were determined by fitting the data to a stoichiometric model. The binding association constants (K

Development of PEGylated KMnF3 nanoparticles as a T1-weighted contrast agent: chemical synthesis, in vivo brain MR imaging, and accounting for high relaxivity.

PubMed

Liu, Zhi-jun; Song, Xiao-xia; Tang, Qun

2013-06-07

Magnetic nanoparticles consisting of manganese-based T1-weighted contrast agents have rapidly achieved clinical application, however low proton relaxivity impedes further development. In this report, by analyzing nanoparticles' surface oxidation states we propose the possible reason for the low r1 relaxivity of common MnO nanoparticles and develop PEGylated fluoroperovskite KMnF3 nanoparticles as new T1-weighted contrast agents, which exhibit the highest longitudinal relaxivity (r1 = 23.15 mM(-1) s(-1)) among all the reported manganese-based T1-weighted contrast agents. We, for the first time, illustrate a typical example showing that the surface oxidation states of metal ions exposed on the nanoparticles' surfaces are able to influence not only the optical, magnetic, electronic or catalytic properties but also water proton longitudinal relaxivity when applied as an MRI contrast agent. Cytotoxicity tests demonstrate that the PEGylated KMnF3 nanoparticles are free from toxicity. Further in vivo MRI experiments distinctively depict fine anatomical features in brain imaging at a low dose of 5 mg of Mn per kg and possible removal from the kidneys due to their small size and biocompatibility.

The impact of fibre orientation on T1-relaxation and apparent tissue water content in white matter.

PubMed

Schyboll, Felix; Jaekel, Uwe; Weber, Bernd; Neeb, Heiko

2018-02-20

Recent MRI studies have shown that the orientation of nerve fibres relative to the main magnetic field affects the R 2 *(= 1/T 2 *) relaxation rate in white matter (WM) structures. The underlying physical causes have been discussed in several studies but are still not completely understood. However, understanding these effects in detail is of great importance since this might serve as a basis for the development of new diagnostic tools and/or improve quantitative susceptibility mapping techniques. Therefore, in addition to the known angular dependence of R 2 *, the current study investigates the relationship between fibre orientation and the longitudinal relaxation rate, R 1 (= 1/T 1 ), as well as the apparent water content. For a group of 16 healthy subjects, a series of gradient echo, echo-planar and diffusion weighted images were acquired at 3T from which the decay rates, the apparent water content and the diffusion direction were reconstructed. The diffusion weighted data were used to determine the angle between the principle fibre direction and the main magnetic field to examine the angular dependence of R 1 and apparent water content. The obtained results demonstrate that both parameters depend on the fibre orientation and exhibit a positive correlation with the angle between fibre direction and main magnetic field. These observations could be helpful to improve and/or constrain existing biophysical models of brain microstructure by imposing additional constraints resulting from the observed angular dependence R 1 and apparent water content in white matter.

Photo-cured PMMA/PEI core/shell nanoparticles surface-modified with Gd-DTPA for T1 MR imaging.

PubMed

Ratanajanchai, Montri; Lee, Don Haeng; Sunintaboon, Panya; Yang, Su-Geun

2014-02-01

Herein, we introduced amine-functionalized core-shell nanoparticles (Polymethyl methacrylate/Polyethyleneimine; PMMA/PEI) with surface primary amines (3.15×10(5) groups/particle) and uniform size distribution (150-200nm) that were prepared by one-step photo-induced emulsion polymerization. Further PEI-surface was modified with diethylenetriamine pentaacetic acid (DTPA) and introduced with Gd(III). The modified particles possessing DTPA can entrap a high content of Gd(III) ions of over 5.5×10(4)Gd/particle with stable chelation (no release of free Gd) at least 7h. The Gd-DTPA-conjugated core-shell nanoparticles (PMMA/PEI-DTPA-Gd NPs) enhanced the MRI intensity more than Primovist (a commercial hepatic contrast agent). Moreover, the PMMA/PEI-DTPA-Gd NPs showed non-cytotoxicity up to 250μM in normal liver cells. Thus, in vitro data suggested the PMMA/PEI-DTPA-Gd NPs is promising delivery system as a superior MRI contrast agent, especially for hepatic lesion targeted MR imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

Gd(III) complexes for electron-electron dipolar spectroscopy: Effects of deuteration, pH and zero field splitting.

PubMed

Garbuio, Luca; Zimmermann, Kaspar; Häussinger, Daniel; Yulikov, Maxim

2015-10-01

Spectral parameters of Gd(III) complexes are intimately linked to the performance of the Gd(III)-nitroxide or Gd(III)-Gd(III) double electron-electron resonance (DEER or PELDOR) techniques, as well as to that of relaxation induced dipolar modulation enhancement (RIDME) spectroscopy with Gd(III) ions. These techniques are of interest for applications in structural biology, since they can selectively detect site-to-site distances in biomolecules or biomolecular complexes in the nanometer range. Here we report relaxation properties, echo detected EPR spectra, as well as the magnitude of the echo reduction effect in Gd(III)-nitroxide DEER for a series of Gadolinium(III) complexes with chelating agents derived from tetraazacyclododecane. We observed that solvent deuteration does not only lengthen the relaxation times of Gd(III) centers but also weakens the DEER echo reduction effect. Both of these phenomena lead to an improved signal-to-noise ratios or, alternatively, longer accessible distance range in pulse EPR measurements. The presented data enrich the knowledge on paramagnetic Gd(III) chelate complexes in frozen solutions, and can help optimize the experimental conditions for most types of the pulse measurements of the electron-electron dipolar interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

Polymorphisms of endothelin 1 (G5665T and T-1370G) and endothelin receptor type A (C+70G and G-231A) in Graves' disease.

PubMed

Aydın, A Fatih; Develi-İş, Seval; Doğru-Abbasoğlu, Semra; Vural, Pervin; Ozderya, Ayşenur; Karadağ, Berrin; Uysal, Müjdat

2014-01-01

Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves' disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD. We analyzed genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients with GD and 181 healthy controls by real-time PCR combined with melting curve analysis. No significant associations between GD and variant alleles of the studied polymorphisms were observed. However, the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype were higher than those in T allele carriers (GT+TT) (p=0.001 and p=0.026, respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous patients were found to be higher than in mutant gene carrying patients (GT+GG) (p=0.006). The presence of EDNRA+70G allele was associated with 3.37-fold increased risk for development of ophthalmopathy in GD patients (p=0.009). Although there were no associations between EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T-1370G polymorphisms were related to alterations of autoantibody production and EDNRA C+70G polymorphism is related with increased risk for ophthalmopathy in GD patients. Copyright © 2013 Elsevier B.V. All rights reserved.

Longitudinal T1 relaxation rate (R1) captures changes in short-term Mn exposure in welders

PubMed Central

Lewis, Mechelle M.; Flynn, Michael R.; Lee, Eun-Young; Van Buren, Scott; Van Buren, Eric; Du, Guangwei; Fry, Rebecca C.; Herring, Amy H.; Kong, Lan; Mailman, Richard B.; Huang, Xuemei

2016-01-01

Objectives We demonstrated recently that the T1 relaxation rate (R1) captured short-term Mn exposure in welders with chronic, relatively low exposure levels in a cross-sectional study. In the current study, we used a longitudinal design to examine whether R1 values reflect the short-term dynamics of Mn exposure. Methods Twenty-nine welders were evaluated at baseline and 12 months. Occupational questionnaires estimated short-term welding exposure using welding hours in the 90 days prior to each study visit (HrsW90). In addition, blood Mn levels, the pallidal index (PI; globus pallidus T1-weighted intensity (T1WI)/frontal white matter T1WI), and R1 values in brain regions of interest (ROIs) were determined as Mn biomarkers at each visit. Associations between changes in estimated welding exposure and changes in purported Mn biomarkers were assessed by Spearman’s correlations with adjustment for age and baseline R1, HrsW90, and blood Mn values. Results Changes in welding hours (HrsW90: the short-term welding exposure estimate), was associated significantly with changes in R1 values in the putamen (r=0.541, p=0.005), caudate (R=0.453, p=0.023), globus pallidus (R=0.430, p=0.032), amygdala (R=0.461, p=0.020), and hippocampus (R=0.447, p=0.025), but not with changes in blood Mn levels or the PI. Discussion Changes in R1 values correlated with changes in the short-term welding exposure estimate, but not with more traditional measures of Mn exposure (blood Mn levels or PI). These results suggest that R1 may serve as a useful marker to capture the short-term dynamics in Mn brain accumulation related to welding exposure. PMID:27567731

Framework for Automated GD&T Inspection Using 3D Scanner

NASA Astrophysics Data System (ADS)

Pathak, Vimal Kumar; Singh, Amit Kumar; Sivadasan, M.; Singh, N. K.

2018-04-01

Geometric Dimensioning and Tolerancing (GD&T) is a typical dialect that helps designers, production faculty and quality monitors to convey design specifications in an effective and efficient manner. GD&T has been practiced since the start of machine component assembly but without overly naming it. However, in recent times industries have started increasingly emphasizing on it. One prominent area where most of the industries struggle with is quality inspection. Complete inspection process is mostly human intensive. Also, the use of conventional gauges and templates for inspection purpose highly depends on skill of workers and quality inspectors. In industries, the concept of 3D scanning is not new but is used only for creating 3D drawings or modelling of physical parts. However, the potential of 3D scanning as a powerful inspection tool is hardly explored. This study is centred on designing a procedure for automated inspection using 3D scanner. Linear, geometric and dimensional inspection of the most popular test bar-stepped bar, as a simple example was also carried out as per the new framework. The new generation engineering industries would definitely welcome this automated inspection procedure being quick and reliable with reduced human intervention.

Controlling the metal-to-insulator relaxation of the metastable hidden quantum state in 1T-TaS2.

PubMed

Vaskivskyi, Igor; Gospodaric, Jan; Brazovskii, Serguei; Svetin, Damjan; Sutar, Petra; Goreshnik, Evgeny; Mihailovic, Ian A; Mertelj, Tomaz; Mihailovic, Dragan

2015-07-01

Controllable switching between metastable macroscopic quantum states under nonequilibrium conditions induced either by light or with an external electric field is rapidly becoming of great fundamental interest. We investigate the relaxation properties of a "hidden" (H) charge density wave (CDW) state in thin single crystals of the layered dichalcogenide 1T-TaS2, which can be reached by either a single 35-fs optical laser pulse or an ~30-ps electrical pulse. From measurements of the temperature dependence of the resistivity under different excitation conditions, we find that the metallic H state relaxes to the insulating Mott ground state through a sequence of intermediate metastable states via discrete jumps over a "Devil's staircase." In between the discrete steps, an underlying glassy relaxation process is observed, which arises because of reciprocal-space commensurability frustration between the CDW and the underlying lattice. We show that the metastable state relaxation rate may be externally stabilized by substrate strain, thus opening the way to the design of nonvolatile ultrafast high-temperature memory devices based on switching between CDW states with large intrinsic differences in electrical resistance.

Simultaneous acquisition of perfusion and permeability from corrected relaxation rates with dynamic susceptibility contrast dual gradient echo.

PubMed

Kim, Eun-Ju; Kim, Dae-Hong; Lee, Sang Hoon; Huh, Yong-Min; Song, Ho-Taek; Suh, Jin-Suck

2004-04-01

This study compared two methods, corrected (separation of T(1) and T(2)* effects) and uncorrected, in order to determine the suitability of the perfusion and permeability measures through Delta R(2)* and Delta R(1) analyses. A dynamic susceptibility contrast dual gradient echo (DSC-DGE) was used to image the fixed phantoms and flow phantoms (Sephadex perfusion phantoms and dialyzer phantom for the permeability measurements). The results confirmed that the corrected relaxation rate was linearly proportional to gadolinium-diethyltriamine pentaacetic acid (Gd-DTPA) concentration, whereas the uncorrected relaxation rate did not in the fixed phantom and simulation experiments. For the perfusion measurements, it was found that the correction process was necessary not only for the Delta R(1) time curve but also for the Delta R(2)* time curve analyses. Perfusion could not be measured without correcting the Delta R(2)* time curve. The water volume, which was expressed as the perfusion amount, was found to be closer to the theoretical value when using the corrected Delta R(1) curve in the calculations. However, this may occur in the low concentration of Gd-DTPA in tissue used in this study. For the permeability measurements based on the two-compartment model, the permeability factor (k(ev); e = extravascular, v = vascular) from the outside to the inside of the hollow fibers was greater in the corrected Delta R(1) method than in the uncorrected Delta R(1) method. The differences between the corrected and the uncorrected Delta R(1) values were confirmed by the simulation experiments. In conclusion, this study proposes that the correction for the relaxation rates, Delta R(2)* and Delta R(1), is indispensable in making accurate perfusion and permeability measurements, and that DSC-DGE is a useful method for obtaining information on perfusion and permeability, simultaneously.

Development of a Gd(III)-based receptor-induced magnetization enhancement (RIME) contrast agent for β-glucuronidase activity profiling.

PubMed

Chen, Shih-Hsien; Kuo, Yu-Ting; Singh, Gyan; Cheng, Tian-Lu; Su, Yu-Zheng; Wang, Tzu-Pin; Chiu, Yen-Yu; Lai, Jui-Jen; Chang, Chih-Ching; Jaw, Twei-Shiun; Tzou, Shey-Cherng; Liu, Gin-Chung; Wang, Yun-Ming

2012-11-19

β-Glucuronidase is a key lysosomal enzyme and is often overexpressed in necrotic tumor masses. We report here the synthesis of a pro receptor-induced magnetization enhancement (pro-RIME) magnetic resonance imaging (MRI) contrast agent ([Gd(DOTA-FPβGu)]) for molecular imaging of β-glucuronidase activity in tumor tissues. The contrast agent consists of two parts, a gadolinium complex and a β-glucuronidase substrate (β-d-glucopyranuronic acid). The binding association constant (KA) of [Gd(DOTA-FPβGu)] is 7.42 × 10(2), which is significantly lower than that of a commercially available MS-325 (KA = 3.0 × 10(4)) RIME contrast agent. The low KA value of [Gd(DOTA-FPβGu)] is due to the pendant β-d-glucopyranuronic acid moiety. Therefore, [Gd(DOTA-FPβGu)] can be used for detection of β-glucuronidase through RIME modulation. The detail mechanism of enzymatic activation of [Gd(DOTA-FPβGu)] was elucidated by LC-MS. The kinetics of β-glucuronidase catalyzed hydrolysis of [Eu(DOTA-FPβGu)] at pH 7.4 best fit the Miechalis-Menten kinetic mode with Km = 1.38 mM, kcat = 3.76 × 10(3), and kcat/Km = 2.72 × 10(3) M(-1) s(-1). The low Km value indicates high affinity of β-glucuronidase for [Gd(DOTA-FPβGu)] at physiological pH. Relaxometric studies revealed that T1 relaxivity of [Gd(DOTA-FPβGu)] changes in response to the concentration of β-glucuronidase. Consistent with the relaxometric studies, [Gd(DOTA-FPβGu)] showed significant change in MR image signal in the presence of β-glucuronidase and HSA. In vitro and in vivo MR images demonstrated appreciable differences in signal enhancement in the cell lines and tumor xenografts in accordance to their expression levels of β-glucuronidase.

Phase relations in the system Cu-Gd-O and Gibbs energy of formation of CuGd[sub 2]O[sub 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, K.T.; Mathews, T.; Hajra, J.P.

1993-07-01

The phase relations in the system Cu-Gd-O have been determined at 1,273 K by X-ray diffraction, optical microscopy, and electron microprobe analysis of samples equilibrated in quartz ampules and in pure oxygen. Only one ternary compound, CuGd[sub 2]O[sub 4], was found to be stable. The Gibbs free energy of formation of this compound has been measured using the solid-state cell Pt, Cu[sub 2]O + CuGd[sub 2]O[sub 4] + Gd[sub 2]O[sub 3]//(Y[sub 2]O[sub 3])ZrO[sub 2]//CuO + Cu[sub 2]O, Pt in the temperature range of 900 to 1,350 K. For the formation of CuGd[sub 2]O[sub 4] from its binary component oxides, CuOmore » (s) + Gd[sub 2]O[sub 3] (s) [r arrow] CuGd[sub 2]O[sub 4] (s) [Delta]G[degree] = 8230 - 11.2T([plus minus]50)J/mol. Since the formation is endothermic, CuGd[sub 2]O[sub 4] becomes thermodynamically unstable with respect to CuO and Gd[sub 2]O[sub 3] below 735 K. When the oxygen partial pressure over CuGd[sub 2]O[sub 4] is lowered, it decomposes according to the reaction 4CuGd[sub 2]O[sub 4] (s) [r arrow] 4Gd[sub 2]O[sub 3] (s) + 2Cu[sub 2]O (s) + O[sub 2] (g) for which the equilibrium oxygen potential is given by [Delta][mu][sub o][sub 2] = [minus]227,970 + 143.2T([plus minus]500)J/mol. An oxygen potential diagram for the system Cu-Gd-O at 1,273 is presented.« less

Nuclear magnetic resonance study of Gd-based nanoparticles to tag boron compounds in boron neutron capture therapy

NASA Astrophysics Data System (ADS)

Corti, M.; Bonora, M.; Borsa, F.; Bortolussi, S.; Protti, N.; Santoro, D.; Stella, S.; Altieri, S.; Zonta, C.; Clerici, A. M.; Cansolino, L.; Ferrari, C.; Dionigi, P.; Porta, A.; Zanoni, G.; Vidari, G.

2011-04-01

We report the investigation of new organic complexes containing a magnetic moment (Gd-based molecular nanomagnets), which can serve the double purpose of acting as boron neutron capture therapy (BNCT) agents, and at the same time act as contrast agents to detect the molecule in the tissue by a proton magnetic resonance imaging (MRI). We also explore the possibility of monitoring the concentration of the BNCT agent directly via proton and boron NMR relaxation. The absorption of 10B-enriched molecules inside tumoral liver tissues has been shown by NMR measurements and confirmed by α spectroscopy. A new molecular Gd-tagged nanomagnet and BNCT agent (GdBPA) has been synthesized and characterized measuring its relaxivity R1 between 10 kHz and 66 MHz, and its use as a contrast agent in MRI has been demonstrated. The NMR-based evidence of the absorption of GdBPA into living tumoral cells is also shown.

Magnetic structure and magnetocalorics of GdPO 4

DOE PAGES

Palacios, E.; Rodriguez-Velamazsn, J. A.; Evangelisti, Marco; ...

2014-12-12

The magnetic ordering structure of GdPO 4 is determined at T = 60 mK by diffraction of hot neutrons with wavelength = 0.4696 Å. It corresponds to a non-collinear antiferromagnetic arrangement of the Gd moments with propagation vector k = (1/2, 0, 1/2). This arrangement is found to minimize the dipole-dipole interaction and the crystal field anisotropy energy, the magnetic superexchange being much smaller. The intensity of the magnetic reflections decreases with increasing temperature and vanishes at T ≈ 0.8 K, in agreement with the magnetic ordering temperature T N = 0.77 K, as reported in previous works based onmore » heat capacity and magnetic susceptibility measurements. The magnetocaloric parameters have been determined from heat capacity data at constant applied fields up to 7 T, as well as from isothermal magnetization data. Lastly, the magnetocaloric effect, for a field change ΔB = 0 – 7T, reaches –ΔS T = 375.8mJ / cm 3K –1 at T = 2.1 K, largely exceeding the maximum values reported to date for Gd-based magnetic refrigerants.« less

Analysis of pharmacokinetics of Gd-DTPA for dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Taheri, Saeid; Shah, N Jon; Rosenberg, Gary A

2016-09-01

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 (23-85years, M/F) were randomly divided into four groups for DCE-MRI with different Gd-DTPA dose: group-I, 0.1mmol/kg, n=4; group-II, 0.05mmol/kg, n=4; group-III, 0.025mmol/kg, n=4; and group-IV, 0.0125mmol/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 (28-80years, M/F) were collected retrospectively, from an ongoing study of the brain using DCE-MRI with Gd-DTPA at 0.025mmol/kg, to statistically analyze population PK of Gd-DTPA. We found that the PK of Gd-DTPA (i.v. 0.025mmol/kg) had a half-life of 37.3±6.6min, and was a better fit into a linear T1-[Gd-DTPA] relationship than higher doses (up to 0.1mmol/kg). The area under the curve (AUC) for 0.025mmol/kg was 3.37±0.46, which was a quarter of AUC of 0.1mmol/kg. In population analysis, a dose of 0.025mmol/kg of Gd-DTPA provided less than 5% subject-dependent variation in the PK of Gd-DTPA. Administration of 0.025mmol/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]. Copyright © 2016 Elsevier Inc. All rights reserved.

High-field 1H T1 and T2 NMR relaxation time measurements of H2O in homeopathic preparations of quartz, sulfur, and copper sulfate

NASA Astrophysics Data System (ADS)

Baumgartner, Stephan; Wolf, Martin; Skrabal, Peter; Bangerter, Felix; Heusser, Peter; Thurneysen, André; Wolf, Ursula

2009-09-01

Quantitative meta-analyses of randomized clinical trials investigating the specific therapeutic efficacy of homeopathic remedies yielded statistically significant differences compared to placebo. Since the remedies used contained mostly only very low concentrations of pharmacologically active compounds, these effects cannot be accounted for within the framework of current pharmacology. Theories to explain clinical effects of homeopathic remedies are partially based upon changes in diluent structure. To investigate the latter, we measured for the first time high-field (600/500 MHz) 1H T1 and T2 nuclear magnetic resonance relaxation times of H2O in homeopathic preparations with concurrent contamination control by inductively coupled plasma mass spectrometry (ICP-MS). Homeopathic preparations of quartz (10 c-30 c, n = 21, corresponding to iterative dilutions of 100-10-100-30), sulfur (13 x-30 x, n = 18, 10-13-10-30), and copper sulfate (11 c-30 c, n = 20, 100-11-100-30) were compared to n = 10 independent controls each (analogously agitated dilution medium) in randomized and blinded experiments. In none of the samples, the concentration of any element analyzed by ICP-MS exceeded 10 ppb. In the first measurement series (600 MHz), there was a significant increase in T1 for all samples as a function of time, and there were no significant differences between homeopathic potencies and controls. In the second measurement series (500 MHz) 1 year after preparation, we observed statistically significant increased T1 relaxation times for homeopathic sulfur preparations compared to controls. Fifteen out of 18 correlations between sample triplicates were higher for controls than for homeopathic preparations. No conclusive explanation for these phenomena can be given at present. Possible hypotheses involve differential leaching from the measurement vessel walls or a change in water molecule dynamics, i.e., in rotational correlation time and/or diffusion. Homeopathic preparations

The MRI-measured arterial input function resulting from a bolus injection of Gd-DTPA in a rat model of stroke slightly underestimates that of Gd-[14C]DTPA and marginally overestimates the blood-to-brain influx rate constant determined by Patlak plots

PubMed Central

Nagaraja, Tavarekere N.; Karki, Kishor; Ewing, James R.; Divine, George W.; Fenstermacher, Joseph D.; Patlak, Clifford S.; Knight, Robert A.

2009-01-01

The hypothesis that the arterial input function (AIF) of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) injected by intravenous (iv) bolus and measured by the change in the T1-relaxation rate (ΔR1; R1=1/T1) of superior sagittal sinus blood (AIF-I) approximates the AIF of 14C-labeled Gd-DTPA measured in arterial blood (AIF*) was tested in a rat stroke model (n=13). Contrary to the hypothesis, the initial part of the ΔR1-time curve was underestimated, and the area under the normalized curve for AIF-I was about 15% lower than that for AIF*, the reference AIF. Hypothetical AIF’s for Gd-DTPA (AIF-II) were derived from the AIF* values and averaged to obtain AIF-III. Influx rate constants (Ki) and proton distribution volumes at zero time (Vp+Vo) were estimated with Patlak plots of AIF-I, -II and -III and tissue ΔR1 data. For the regions of interest, the Ki’s estimated with AIF-I were slightly but not significantly higher than those obtained with AIF-II and AIF-III. In contrast, Vp+Vo was significantly higher when calculated with AIF-I. Similar estimates of Ki and Vp+Vo were obtained with AIF-II and AIF-III. In summary, AIF-I underestimated the reference AIF (AIF*); this shortcoming had little effect on the Ki calculated by Patlak plot but produced a significant overestimation of Vp+Vo. PMID:20512853

Longitudinal evaluation of T1ρ and T2 spatial distribution in osteoarthritic and healthy medial knee cartilage.

PubMed

Schooler, J; Kumar, D; Nardo, L; McCulloch, C; Li, X; Link, T M; Majumdar, S

2014-01-01

To investigate longitudinal changes in laminar and spatial distribution of knee articular cartilage magnetic resonance imaging (MRI) T1ρ and T2 relaxation times, in individuals with and without medial compartment cartilage defects. All subjects (at baseline n = 88, >18 years old) underwent 3-Tesla knee MRI at baseline and annually thereafter for 3 years. The MR studies were evaluated for presence of cartilage defects (modified Whole-Organ Magnetic Resonance Imaging Scoring - mWORMS), and quantitative T1ρ and T2 relaxation time maps. Subjects were segregated into those with (mWORMS ≥2) and without (mWORMS ≤1) cartilage lesions at the medial tibia (MT) or medial femur (MF) at each time point. Laminar (bone and articular layer) and spatial (gray level co-occurrence matrix - GLCM) distribution of the T1ρ and T2 relaxation time maps were calculated. Linear regression models (cross-sectional) and Generalized Estimating Equations (GEEs) (longitudinal) were used. Global T1ρ, global T2 and articular layer T2 relaxation times at the MF, and global and articular layer T2 relaxation times at the MT, were higher in subjects with cartilage lesions compared to those without lesions. At the MT global T1ρ relaxation times were higher at each time point in subjects with lesions. MT T1ρ and T2 became progressively more heterogeneous than control compartments over the course of the study. Spatial distribution of T1ρ and T2 relaxation time maps in medial knee OA using GLCM technique may be a sensitive indicator of cartilage deterioration, in addition to whole-compartment relaxation time data. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Controlling the metal-to-insulator relaxation of the metastable hidden quantum state in 1T-TaS2

PubMed Central

Vaskivskyi, Igor; Gospodaric, Jan; Brazovskii, Serguei; Svetin, Damjan; Sutar, Petra; Goreshnik, Evgeny; Mihailovic, Ian A.; Mertelj, Tomaz; Mihailovic, Dragan

2015-01-01

Controllable switching between metastable macroscopic quantum states under nonequilibrium conditions induced either by light or with an external electric field is rapidly becoming of great fundamental interest. We investigate the relaxation properties of a “hidden” (H) charge density wave (CDW) state in thin single crystals of the layered dichalcogenide 1T-TaS2, which can be reached by either a single 35-fs optical laser pulse or an ~30-ps electrical pulse. From measurements of the temperature dependence of the resistivity under different excitation conditions, we find that the metallic H state relaxes to the insulating Mott ground state through a sequence of intermediate metastable states via discrete jumps over a “Devil’s staircase.” In between the discrete steps, an underlying glassy relaxation process is observed, which arises because of reciprocal-space commensurability frustration between the CDW and the underlying lattice. We show that the metastable state relaxation rate may be externally stabilized by substrate strain, thus opening the way to the design of nonvolatile ultrafast high-temperature memory devices based on switching between CDW states with large intrinsic differences in electrical resistance. PMID:26601218

Simultaneous acquisition for T2 -T2 Exchange and T1 -T2 correlation NMR experiments

NASA Astrophysics Data System (ADS)

Montrazi, Elton T.; Lucas-Oliveira, Everton; Araujo-Ferreira, Arthur G.; Barsi-Andreeta, Mariane; Bonagamba, Tito J.

2018-04-01

The NMR measurements of longitudinal and transverse relaxation times and its multidimensional correlations provide useful information about molecular dynamics. However, these experiments are very time-consuming, and many researchers proposed faster experiments to reduce this issue. This paper presents a new way to simultaneously perform T2 -T2 Exchange and T1 -T2 correlation experiments by taking the advantage of the storage time and the two steps phase cycling used for running the relaxation exchange experiment. The data corresponding to each step is either summed or subtracted to produce the T2 -T2 and T1 -T2 data, enhancing the information obtained while maintaining the experiment duration. Comparing the results from this technique with traditional NMR experiments it was possible to validate the method.

The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging

PubMed Central

Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

2016-01-01

Objective: To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0 T in young healthy adults. Methods: 30 healthy male adults (18–31 years) who perform sports at an amateur level underwent an initial MRI at 3.0 T with T2 weighted [16 echo times (TEs): 9.7–154.6 ms] and T2* weighted (24 TEs: 4.6–53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product–moment correlation coefficients and confidence intervals were computed. Results: Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. Conclusion: A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. Advances in knowledge: This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults. PMID:27336705

The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging.

PubMed

Behzadi, Cyrus; Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

2016-08-01

To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0 T in young healthy adults. 30 healthy male adults (18-31 years) who perform sports at an amateur level underwent an initial MRI at 3.0 T with T2 weighted [16 echo times (TEs): 9.7-154.6 ms] and T2* weighted (24 TEs: 4.6-53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product-moment correlation coefficients and confidence intervals were computed. Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults.

In vivo comparison of delayed gadolinium-enhanced MRI of cartilage and delayed quantitative CT arthrography in imaging of articular cartilage.

PubMed

Hirvasniemi, J; Kulmala, K A M; Lammentausta, E; Ojala, R; Lehenkari, P; Kamel, A; Jurvelin, J S; Töyräs, J; Nieminen, M T; Saarakkala, S

2013-03-01

To compare delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) and delayed quantitative computed tomography (CT) arthrography (dQCTA) to each other, and their association to arthroscopy. Additionally, the relationship between dGEMRIC with intravenous (dGEMRIC(IV)) and intra-articular contrast agent administration (dGEMRIC(IA)) was determined. Eleven patients with knee pain were scanned at 3 T MRI and 64-slice CT before arthroscopy. dQCTA was performed at 5 and 45 min after intra-articular injection of ioxaglate. Both dGEMRIC(IV) and dGEMRIC(IA) were performed at 90 min after gadopentetate injection. dGEMRIC indices and change in relaxation rates (ΔR(1)) were separately calculated for dGEMRIC(IV) and dGEMRIC(IA). dGEMRIC and dQCTA parameters were calculated for predetermined sites at the knee joint that were International Cartilage Repair Society (ICRS) graded in arthroscopy. dQCTA normalized with the contrast agent concentration in synovial fluid (SF) and dGEMRIC(IV) correlated significantly, whereas dGEMRIC(IA) correlated with the normalized dQCTA only when dGEMRIC(IA) was also normalized with the contrast agent concentration in SF. Correlation was strongest between normalized dQCTA at 45 min and ΔR(1,IV) (r(s) = 0.72 [95% CI 0.56-0.83], n = 49, P < 0.01) and ΔR(1,IA) normalized with ΔR(1) in SF (r(s) = 0.70 [0.53-0.82], n = 52, P < 0.01). Neither dGEMRIC nor dQCTA correlated with arthroscopic grading. dGEMRIC(IV) and non-normalized dGEMRIC(IA) were not related while ΔR(1,IV) correlated with normalized ΔR(1,IA) (r(s) = 0.52 [0.28-0.70], n = 50, P < 0.01). This study suggests that dQCTA is in best agreement with dGEMRIC(IV) at 45 min after CT contrast agent injection. dQCTA and dGEMRIC were not related to arthroscopy, probably because the remaining cartilage is analysed in dGEMRIC and dQCTA, whereas in arthroscopy the absence of cartilage defines the grading. The findings indicate the importance to take

Development of Bifunctional Gadolinium-Labeled Superparamagnetic Nanoparticles (Gd-MnMEIO) for In Vivo MR Imaging of the Liver in an Animal Model.

PubMed

Kuo, Yu-Ting; Chen, Chiao-Yun; Liu, Gin-Chung; Wang, Yun-Ming

2016-01-01

Liver tumors are common and imaging methods, particularly magnetic resonance imaging (MRI), play an important role in their non-invasive diagnosis. Previous studies have shown that detection of liver tumors can be improved by injection of two different MR contrast agents. Here, we developed a new contrast agent, Gd-manganese-doped magnetism-engineered iron oxide (Gd-MnMEIO), with enhancement effects on both T1- and T2-weighted MR images of the liver. A 3.0T clinical MR scanner equipped with transmit/receiver coil for mouse was used to obtain both T1-weighted spoiled gradient-echo and T2-weighted fast spin-echo axial images of the liver before and after intravenous contrast agent injection into Balb/c mice with and without tumors. After pre-contrast scanning, six mice per group were intravenously injected with 0.1 mmol/kg Gd-MnMEIO, or the control agents, i.e., Gd-DTPA or SPIO. The scanning time points for T1-weighted images were 0.5, 5, 10, 15, 20, 25, and 30 min after contrast administration. The post-enhanced T2-weighted images were then acquired immediately after T1-weighted acquisition. We found that T1-weighted images were positively enhanced by both Gd-DTPA and Gd-MnMEIO and negatively enhanced by SPIO. The enhancement by both Gd-DTPA and Gd-MnMEIO peaked at 0.5 min and gradually declined thereafter. Gd-MnMEIO (like Gd-DTPA) enhanced T1-weighted images and (like SPIO) T2-weighted images. Marked vascular enhancement was clearly visible on dynamic T1-weighted images with Gd-MnMEIO. In addition, the T2 signal was significantly decreased at 30 min after administration of Gd-MnMEIO. Whereas the effects of Gd-MnMEIO and SPIO on T2-weighted images were similar (p = 0.5824), those of Gd-MnMEIO and Gd-DTPA differed, with Gd-MnMEIO having a significant T2 contrast effect (p = 0.0086). Our study confirms the feasibility of synthesizing an MR contrast agent with both T1 and T2 shortening effects and using such an agent in vivo. This agent enables tumor detection and

Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

PubMed Central

Herrmann, Kelsey; Johansen, Mette L.; Craig, Sonya E.; Vincent, Jason; Howell, Michael; Gao, Ying; Lu, Lan; Erokwu, Bernadette; Agnes, Richard S.; Lu, Zheng-Rong; Pokorski, Jonathan K.; Basilion, James; Gulani, Vikas; Griswold, Mark; Flask, Chris; Brady-Kalnay, Susann M.

2015-01-01

Magnetic resonance imaging (MRI) of glioblastoma multiforme (GBM) with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA)3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA)3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA)3 agent, a scrambled-Tris-(Gd-DOTA)3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA)3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA)3 agent over time compared to the non-specific contrast agent currently in clinical use. PMID:26435847

The Application of Stress-Relaxation Test to Life Assessment of T911/T22 Weld Metal

NASA Astrophysics Data System (ADS)

Cao, Tieshan; Zhao, Jie; Cheng, Congqian; Li, Huifang

2016-03-01

A dissimilar weld metal was obtained through submerged arc welding of a T911 steel to a T22 steel, and its creep property was explored by stress-relaxation test assisted by some conventional creep tests. The creep rate information of the stress-relaxation test was compared to the minimum and the average creep rates of the conventional creep test. Log-log graph showed that the creep rate of the stress-relaxation test was in a linear relationship with the minimum creep rate of the conventional creep test. Thus, the creep rate of stress-relaxation test could be used in the Monkman-Grant relation to calculate the rupture life. The creep rate of the stress-relaxation test was similar to the average creep rate, and thereby the rupture life could be evaluated by a method of "time to rupture strain." The results also showed that rupture life which was assessed by the Monkman-Grant relation was more accurate than that obtained through the method of "time to rupture strain."

Gadolinia nanofibers as a multimodal bioimaging and potential radiation therapy agent

NASA Astrophysics Data System (ADS)

Grishin, A. M.; Jalalian, A.; Tsindlekht, M. I.

2015-05-01

Continuous bead-free C-type cubic gadolinium oxide (Gd2O3) nanofibers 20-30 μm long and 40-100 nm in diameter were sintered by sol-gel calcination assisted electrospinning technique. Dipole-dipole interaction of neighboring Gd3+ ions in nanofibers with large length-to-diameter aspect ratio results in some kind of superparamagnetic behavior: fibers are magnetized twice stronger than Gd2O3 powder. Being compared with commercial Gd-DTPA/Magnevist®, Gd2O3 diethyleneglycol-coated (Gd2O3-DEG) fibers show high 1/T1 and 1/T2 proton relaxivities. Intense room temperature photoluminescence, high NMR relaxivity and high neutron scattering cross-section of 157Gd nucleus promise to integrate Gd2O3 fibers for multimodal bioimaging and neutron capture therapy.

Pharmacokinetic and in vivo evaluation of a self-assembled gadolinium(III)-iron(II) contrast agent with high relaxivity.

PubMed

Parac-Vogt, Tatjana N; Vander Elst, Luce; Kimpe, Kristof; Laurent, Sophie; Burtéa, Carmen; Chen, Feng; Van Deun, Rik; Ni, Yicheng; Muller, Robert N; Binnemans, Koen

2006-01-01

A high-molecular weight tetrametallic supramolecular complex [(Ln-DTPA-phen)3Fe]- (Ln = Gd, Eu, La) has been obtained upon self-assembly around one iron(II) ion of three 1,10-phenantroline-based molecules substituted in 5'-position with the polyaminocarboxylate diethylenetriamine-N,N,N',N',N'-pentaacetate, DTPA-phen(4-). The ICP-MS measurements indicated that the lanthanide:iron ratio is 3:1. Photoluminescence spectra of [Eu-DTPA-phen](-) and of [(Eu-DTPA-phen)3Fe]- are nearly identical, implying that the first coordination sphere of the lanthanide(III) ion has not been changed upon coordination of phenantroline unit to iron(II) ion. NMRD measurements revealed that at 20 MHz and 310 K the relaxivity of the [(Gd-DTPA-phen)3Fe]- is equal to 9.5 +/- 0.3 s(-1) mM(-1) of Gd (28.5 s(-1) per millimole per liter of complex) which is significantly higher than that for Gd-DTPA (3.9 s(-1) mM(-1)). The pharmacokinetic parameters of [(Gd-DTPA-phen)3Fe]- in rats indicate that the elimination of [(Gd-DTPA-phen)3Fe]- is significantly slower than that of Gd-DTPA and is correlated with a reduced volume of distribution. The low volume of distribution and the longer elimination time (T(e1/2)) suggest that the agent is confined to the blood compartment, so it could have an important potential as a blood pool contrast agent. The biodistribution profile of [(Gd-DTPA-phen)3Fe]- 2 h after injection indicates significantly higher concentrations of [(Gd-DTPA-phen)3Fe]- as compared with Gd-DTPA in kidney, liver, lungs, heart and spleen. The images obtained on rats by MR angiography show the enhancement of the abdominal blood vessels. The signal intensity reaches a maximum of 55% at 7 min post-contrast and remains around 25% after 90 min. MRI-histomorphological correlation studies of [Gd-DTPA-phen]- and [(Gd-DTPA-phen)3Fe]- showed that both agents displayed potent contrast enhancement in organs including the liver. The necrosis avidity tests indicated that, in contrast to the [Gd

T1- Thresholds in Black Holes Increase Clinical-Radiological Correlation in Multiple Sclerosis Patients.

PubMed

Thaler, Christian; Faizy, Tobias; Sedlacik, Jan; Holst, Brigitte; Stellmann, Jan-Patrick; Young, Kim Lea; Heesen, Christoph; Fiehler, Jens; Siemonsen, Susanne

2015-01-01

Magnetic Resonance Imaging (MRI) is an established tool in diagnosing and evaluating disease activity in Multiple Sclerosis (MS). While clinical-radiological correlations are limited in general, hypointense T1 lesions (also known as Black Holes (BH)) have shown some promising results. The definition of BHs is very heterogeneous and depends on subjective visual evaluation. We aimed to improve clinical-radiological correlations by defining BHs using T1 relaxation time (T1-RT) thresholds to achieve best possible correlation between BH lesion volume and clinical disability. 40 patients with mainly relapsing-remitting MS underwent MRI including 3-dimensional fluid attenuated inversion recovery (FLAIR), magnetization-prepared rapid gradient echo (MPRAGE) before and after Gadolinium (GD) injection and double inversion-contrast magnetization-prepared rapid gradient echo (MP2RAGE) sequences. BHs (BHvis) were marked by two raters on native T1-weighted (T1w)-MPRAGE, contrast-enhancing lesions (CE lesions) on T1w-MPRAGE after GD and FLAIR lesions (total-FLAIR lesions) were detected separately. BHvis and total-FLAIR lesion maps were registered to MP2RAGE images, and the mean T1-RT were calculated for all lesion ROIs. Mean T1 values of the cortex (CTX) were calculated for each patient. Subsequently, Spearman rank correlations between clinical scores (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite) and lesion volume were determined for different T1-RT thresholds. Significant differences in T1-RT were obtained between all different lesion types with highest T1 values in visually marked BHs (BHvis: 1453.3±213.4 ms, total-FLAIR lesions: 1394.33±187.38 ms, CTX: 1305.6±35.8 ms; p<0.05). Significant correlations between BHvis/total-FLAIR lesion volume and clinical disability were obtained for a wide range of T1-RT thresholds. The highest correlation for BHvis and total-FLAIR lesion masks were found at T1-RT>1500 ms (Expanded Disability Status Scale vs

Local structures of the tetragonal Gd3 -VM and Gd3 -Li centers in perovskite fluorides

NASA Astrophysics Data System (ADS)

Zheng, W. C.

The zero-field splittings b20 of the tetragonal Gd3+-VM and Gd3+-Li+ centers for Gd3+ ions in fluoroperovskite crystals have been studied on the basis of the superposition model in which the value of t2

Synthesis and magneto-structural studies on a new family of carbonato bridged 3d-4f complexes featuring a [CoLn(CO3)] (Ln = La, Gd, Tb, Dy and Ho) core: slow magnetic relaxation displayed by the cobalt(ii)-dysprosium(iii) analogue.

PubMed

Majee, Mithun Chandra; Towsif Abtab, Sk Md; Mondal, Dhrubajyoti; Maity, Manoranjan; Weselski, Marek; Witwicki, Maciej; Bieńko, Alina; Antkowiak, Michał; Kamieniarz, Grzegorz; Chaudhury, Muktimoy

2018-03-06

A new family of [3 + 3] hexanuclear 3d-4f complexes [(μ 3 -CO 3 ){Co II Ln III L(μ 3 -OH)(OH 2 )} 3 ]-(ClO 4 )·mC 2 H 5 OH·nH 2 O (1-5) [Ln = La (1), Gd (2), Tb (3), Dy (4), and Ho (5)] have been prepared in moderate to high yields (62-78%) following a self-assembly reaction between the ligand 6,6',6''-(nitrilotris(methylene))tris-(2-methoxy-4-methylphenol) (H 3 L), Co(OAc) 2 ·4H 2 O and the lanthanide ion precursors in the mandatory presence of tetrabutylammonium hydroxide. During the reaction, atmospheric carbon dioxide is fixed in the product molecule as a bridging carbonato ligand which connects all the three lanthanide centers of this molecular assembly through a rare η 2 :η 2 :η 2 -μ 3 mode of bridging as revealed from X-ray crystallography. The metal centers in all these compounds, except the Gd III analogue (2), are coupled in antiferromagnetic manner while the nature of coupling in the CoGd complex is ferromagnetic. DFT calculations revealed that this ferromagnetic interaction occurs most likely by the Co II -Gd III superexchange, mediated via the bridging oxygen atoms. Only the Co II -Dy III compound (4) displayed a slow relaxation of the magnetization at a very low temperature as established by AC susceptibility measurements. The data provides an estimation of the activation energy U/k B = 9.2 K and the relaxation time constant τ 0 = 1.0 × 10 -7 s.

Gd complexes of macrocyclic diethylenetriaminepentaacetic acid (DTPA) biphenyl-2,2'-bisamides as strong blood-pool magnetic resonance imaging contrast agents.

PubMed

Jung, Ki-Hye; Kim, Hee-Kyung; Lee, Gang Ho; Kang, Duk-Sik; Park, Ji-Ae; Kim, Kyeong Min; Chang, Yongmin; Kim, Tae-Jeong

2011-08-11

We report the synthesis of macrocyclic DTPA conjugates of 2,2'-diaminobiphenyl and their Gd complexes of the type [Gd(L)(H(2)O)]·xH(2)O (2a,b; L = 1a,b) for use as new MRI blood-pool contrast agents (MRI BPCAs). Pharmacokinetic inertness of 2 compares well with those of analogous Gd-DTPA MRI CAs currently in use. The present system also shows very high stability in human serum. The R(1) relaxivity reaches 10.9 mM(-1) s(-1), which is approximately 3 times as high as that of structurally related Gd-DOTA (R(1) = 3.7 mM(-1) s(-1)). The R(1) relaxivity in HSA goes up to 37.2 mM(-1) s(-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 2b are 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 2 is 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.

Structural, magnetic and Mossbauer studies of TI doped Gd2Fe17-xTix and Gd2Fe16Ga1-xTix (0≤x≤1)

NASA Astrophysics Data System (ADS)

Pokharel, G.; Syed Ali, K. S.; Mishra, S. R.

2015-05-01

Magnetic compounds of the type Gd2Fe17-xTix and Gd2Fe16Ga1-xTix (x=0.0-1.0) were prepared by arc melting and their structural and magnetic properties were studied by X-ray diffraction (XRD), magnetometery and Mossbauer spectroscopy. The Rietveld analysis of X-ray data shows that these α-Fe free solid-solutions crystallize with Th2Ni17-type structure as main phase along with GdFe2 and TiFe2 as additional phases at higher, x≥0.5 contents. The unit cell volume expands with Ga and Ti content. The Rietveld analysis indicate that both Ti and Ga atoms prefer 12j and 12k sites in both compounds. The effect of Ti and co-substituted Ga-Ti on the bond length are quite different. The saturation magnetization Ms, at 300 K for Gd2Fe17-xTix and Gd2Fe16Ga1-xTix was found to decrease linearly with increasing Ti content. The Ms in both compounds at x=1 reduced by 9% as compared to their parent compounds at x=0. The Curie temperature, Tc, for Gd2Fe17-xTix increased from 513 K (x=0) to 544 K (x=1) while Tc for Gd2Fe16Ga1-xTix reduced from 560 (x=0) to 544 K (x=1) with increase in Ti content. Thus the observed variation in Tc follows Gd2Fe17<Gd2Fe16Ti<Gd2Fe16Ga. The observed changes in Tc with Ti substitution may result from the variation in the unit cell volume of compounds which has direct effect on the strength of Fe-Fe exchange-interaction. The Mossbauer results indicate decrease in hyperfine fields and increase in the isomer shifts with the increase in Ti content. Overall co-substituted Ga-Ti, Gd2Fe16Ga1-xTix show high Tc with marginal decline in saturation magnetization. Thus α-Fe free Gd2Fe16Ga1-xTix compounds can be potential candidate for high temperature permanent magnet industrial applications.

TU-EF-BRA-02: Longitudinal Proton Spin Relaxation and T1-Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemen, L.

NMR, and Proton Density MRI of the 1D Patient - Anthony Wolbarst Net Voxel Magnetization, m(x,t). T1-MRI; The MRI Device - Lisa Lemen ‘Classical’ NMR; FID Imaging in 1D via k-Space - Nathan Yanasak Spin-Echo; S-E/Spin Warp in a 2D Slice - Ronald Price Magnetic resonance imaging not only reveals the structural, anatomic details of the body, as does CT, but also it can provide information on the physiological status and pathologies of its tissues, like nuclear medicine. It can display high-quality slice and 3D images of organs and vessels viewed from any perspective, with resolution better than 1 mm.more » MRI is perhaps most extraordinary and notable for the plethora of ways in which it can create unique forms of image contrast, reflective of fundamentally different biophysical phenomena. As with ultrasound, there is no risk from ionizing radiation to the patient or staff, since no X-rays or radioactive nuclei are involved. Instead, MRI harnesses magnetic fields and radio waves to probe the stable nuclei of the ordinary hydrogen atoms (isolated protons) occurring in water and lipid molecules within and around cells. MRI consists, in essence, of creating spatial maps of the electromagnetic environments around these hydrogen nuclei. Spatial variations in the proton milieus can be related to clinical differences in the biochemical and physiological properties and conditions of the associated tissues. Imaging of proton density (PD), and of the tissue proton spin relaxation times known as T1 and T2, all can reveal important clinical information, but they do so with approaches so dissimilar from one another that each is chosen for only certain clinical situations. T1 and T2 in a voxel are determined by different aspects of the rotations and other motions of the water and lipid molecules involved, as constrained by the local biophysical surroundings within and between its cells – and they, in turn, depend on the type of tissue and its state of health. Three other

A general model to calculate the spin-lattice (T1) relaxation time of blood, accounting for haematocrit, oxygen saturation and magnetic field strength.

PubMed

Hales, Patrick W; Kirkham, Fenella J; Clark, Christopher A

2016-02-01

Many MRI techniques require prior knowledge of the T1-relaxation time of blood (T1bl). An assumed/fixed value is often used; however, T1bl is sensitive to magnetic field (B0), haematocrit (Hct), and oxygen saturation (Y). We aimed to combine data from previous in vitro measurements into a mathematical model, to estimate T1bl as a function of B0, Hct, and Y. The model was shown to predict T1bl from in vivo studies with a good accuracy (± 87 ms). This model allows for improved estimation of T1bl between 1.5-7.0 T while accounting for variations in Hct and Y, leading to improved accuracy of MRI-derived perfusion measurements. © The Author(s) 2015.

Nanoparticles, [Gd@C82(OH)22]n, induces dendritic cell maturation and activates Th1 immune responses

PubMed Central

Yang, De; Zhao, Yuliang; Guo, Hua; Li, Yana; Tewary, Poonam; Xing, Gengmei; Hou, Wei; Oppenheim, Joost J.; Zhang, Ning

2010-01-01

Dendritic cells play a pivotal role in host immune defense, such as elimination of foreign pathogen and inhibition of tumorigenesis. In this paper, we report that [Gd@C82(OH)22]n could induce phenotypic maturation of dendritic cells by stimulating DC production of cytokines including IL-12p70, upregulating DC costimulatory (CD80, CD83, and CD86) and MHC (HLA-A,B,C and HLA-DR) molecules, and switching DCs from a CCL5-responsive to a CCL19-responsive phenotype. We found that [Gd@C82(OH)22]n can induce dendritic cells to become functionally mature as illustrated by their capacity to activate allogeneic T cells. Mice immunized with ovalbumin in the presence of [Gd@C82(OH)22]n exhibit enhanced ovalbumin-specific Th1-polarized immune response as evidenced by the predominantly increased production of IFNγ, IL-1β, and IL-2. The [Gd@C82(OH)22]n nanoparticle is a potent activator of dendritic cells and Th1 immune responses. These new findings also provide a rational understanding of the potent anticancer activities of [Gd@C82(OH)22]n nanoparticles reported previously. PMID:20121217

T1-Weighted MR imaging of liver tumor by gadolinium-encapsulated glycol chitosan nanoparticles without non-specific toxicity in normal tissues

NASA Astrophysics Data System (ADS)

Na, Jin Hee; Lee, Sangmin; Koo, Heebeom; Han, Hyounkoo; Lee, Kyung Eun; Han, Seung Jin; Choi, Seung Hong; Kim, Hyuncheol; Lee, Seulki; Kwon, Ick Chan; Choi, Kuiwon; Kim, Kwangmeyung

2016-05-01

Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the amine groups on the surface of Gd(iii)-CNPs could be protonated and could induce fast cellular uptake at acidic pH in tumor tissue. To assay the tumor-targeting ability of Cy5.5-labeled Gd(iii)-CNPs, near-infrared fluorescence (NIRF) imaging and MR imaging were used in a liver tumor model as well as a subcutaneous tumor model. Cy5.5-labeled Gd(iii)-CNPs generated highly intense fluorescence and T1 MR signals in tumor tissues after intravenous injection, while DOTAREM®, the commercialized control MR contrast agent, showed very low tumor-targeting efficiency on MR images. Furthermore, damaged tissues were found in the livers and kidneys of mice injected with DOTAREM®, but there were no obvious adverse effects with Gd(iii)-CNPs. Taken together, these results demonstrate the superiority of Gd(iii)-CNPs as a tumor-targeting T1 MR agent.Herein, we have synthesized Gd(iii)-encapsulated glycol chitosan nanoparticles (Gd(iii)-CNPs) for tumor-targeted T1-weighted magnetic resonance (MR) imaging. The T1 contrast agent, Gd(iii), was successfully encapsulated into 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-modified CNPs to form stable Gd(iii)-encapsulated CNPs (Gd(iii)-CNPs) with an average particle size of approximately 280 nm. The stable nanoparticle structure of Gd(iii)-CNPs is beneficial for liver tumor accumulation by the enhanced permeation and retention (EPR) effect. Moreover, the

Water diffusion-exchange effect on the paramagnetic relaxation enhancement in off-resonance rotating frame

NASA Astrophysics Data System (ADS)

Zhang, Huiming; Xie, Yang; Ji, Tongyu

2007-06-01

The off-resonance rotating frame technique based on the spin relaxation properties of off-resonance T1 ρ can significantly increase the sensitivity of detecting paramagnetic labeling at high magnetic fields by MRI. However, the in vivo detectable dimension for labeled cell clusters/tissues in T1 ρ-weighted images is limited by the water diffusion-exchange between mesoscopic scale compartments. An experimental investigation of the effect of water diffusion-exchange between compartments on the paramagnetic relaxation enhancement of paramagnetic agent compartment is presented for in vitro/ in vivo models. In these models, the size of paramagnetic agent compartment is comparable to the mean diffusion displacement of water molecules during the long RF pulses that are used to generate the off-resonance rotating frame. The three main objectives of this study were: (1) to qualitatively correlate the effect of water diffusion-exchange with the RF parameters of the long pulse and the rates of water diffusion, (2) to explore the effect of water diffusion-exchange on the paramagnetic relaxation enhancement in vitro, and (3) to demonstrate the paramagnetic relaxation enhancement in vivo. The in vitro models include the water permeable dialysis tubes or water permeable hollow fibers embedded in cross-linked proteins gels. The MWCO of the dialysis tubes was chosen from 0.1 to 15 kDa to control the water diffusion rate. Thin hollow fibers were chosen to provide sub-millimeter scale compartments for the paramagnetic agents. The in vivo model utilized the rat cerebral vasculatures as a paramagnetic agent compartment, and intravascular agents (Gd-DTPA) 30-BSA were administrated into the compartment via bolus injections. Both in vitro and in vivo results demonstrate that the paramagnetic relaxation enhancement is predominant in the T1 ρ-weighted image in the presence of water diffusion-exchange. The T1 ρ contrast has substantially higher sensitivity than the conventional T1

19F spin-lattice relaxation of perfluoropolyethers: Dependence on temperature and magnetic field strength (7.0-14.1 T)

NASA Astrophysics Data System (ADS)

Kadayakkara, Deepak K.; Damodaran, Krishnan; Hitchens, T. Kevin; Bulte, Jeff W. M.; Ahrens, Eric T.

2014-05-01

Fluorine (19F) MRI of perfluorocarbon-labeled cells has become a powerful technique to track the migration and accumulation of cells in living organisms. It is common to label cells for 19F MRI with nanoemulsions of perfluoropolyethers that contain a large number of chemically equivalent fluorine atoms. Understanding the mechanisms of 19F nuclear relaxation, and in particular the spin-lattice relaxation of these molecules, is critical to improving experimental sensitivity. To date, the temperature and magnetic field strength dependence of spin-lattice relaxation rate constant (R1) for perfluoropolyethers has not been described in detail. In this study, we evaluated the R1 of linear perfluoropolyether (PFPE) and cyclic perfluoro-15-crown-5 ether (PCE) at three magnetic field strengths (7.0, 9.4, and 14.1 T) and at temperatures ranging from 256-323 K. Our results show that R1 of perfluoropolyethers is dominated by dipole-dipole interactions and chemical shift anisotropy. R1 increased with magnetic field strength for both PCE and PFPE. In the temperature range studied, PCE was in the fast motion regime (ωτc < 1) at all field strengths, but for PFPE, R1 passed through a maximum, from which the rotational correlation time was estimated. The importance of these measurements for the rational design of new 19F MRI agents and methods is discussed.

19F Spin-lattice Relaxation of Perfluoropolyethers: Dependence on Temperature and Magnetic Field Strength (7.0-14.1T)

PubMed Central

Kadayakkara, Deepak K.; Damodaran, Krishnan; Hitchens, T. Kevin; Bulte, Jeff W.M.; Ahrens, Eric T.

2014-01-01

Fluorine (19F) MRI of perfluorocarbon labeled cells has become a powerful technique to track the migration and accumulation of cells in living organisms. It is common to label cells for 19F MRI with nanoemulsions of perfluoropolyethers that contain a large number of chemically equivalent fluorine atoms. Understanding the mechanisms of 19F nuclear relaxation, and in particular the spin-lattice relaxation of these molecules, is critical to improving experimental sensitivity. To date, the temperature and magnetic field strength dependence of spin-lattice relaxation rate constant (R1) for perfluoropolyethers has not been described in detail. In this study, we evaluated R1 of linear perfluoropolyether (PFPE) and cyclic perfluoro-15-crown-5 ether (PCE) at three magnetic field strengths (7.0, 9.4, and 14.1 T) and at temperatures ranging from 256-323K. Our results show that R1 of perfluoropolyethers is dominated by dipole-dipole interactions and chemical shift anisotropy. R1 increased with magnetic field strength for both PCE and PFPE. In the temperature range studied, PCE was in the fast motion regime (ωτc < 1) at all field strengths, but for PFPE, R1 passed through a maximum, from which the rotational correlation time was estimated. The importance of these measurements for the rational design of new 19F MRI agents and methods is discussed. PMID:24594752

Rapid Parametric Mapping of the Longitudinal Relaxation Time T1 Using Two-Dimensional Variable Flip Angle Magnetic Resonance Imaging at 1.5 Tesla, 3 Tesla, and 7 Tesla

PubMed Central

Dieringer, Matthias A.; Deimling, Michael; Santoro, Davide; Wuerfel, Jens; Madai, Vince I.; Sobesky, Jan; von Knobelsdorff-Brenkenhoff, Florian; Schulz-Menger, Jeanette; Niendorf, Thoralf

2014-01-01

Introduction Visual but subjective reading of longitudinal relaxation time (T1) weighted magnetic resonance images is commonly used for the detection of brain pathologies. For this non-quantitative measure, diagnostic quality depends on hardware configuration, imaging parameters, radio frequency transmission field (B1+) uniformity, as well as observer experience. Parametric quantification of the tissue T1 relaxation parameter offsets the propensity for these effects, but is typically time consuming. For this reason, this study examines the feasibility of rapid 2D T1 quantification using a variable flip angles (VFA) approach at magnetic field strengths of 1.5 Tesla, 3 Tesla, and 7 Tesla. These efforts include validation in phantom experiments and application for brain T1 mapping. Methods T1 quantification included simulations of the Bloch equations to correct for slice profile imperfections, and a correction for B1+. Fast gradient echo acquisitions were conducted using three adjusted flip angles for the proposed T1 quantification approach that was benchmarked against slice profile uncorrected 2D VFA and an inversion-recovery spin-echo based reference method. Brain T1 mapping was performed in six healthy subjects, one multiple sclerosis patient, and one stroke patient. Results Phantom experiments showed a mean T1 estimation error of (-63±1.5)% for slice profile uncorrected 2D VFA and (0.2±1.4)% for the proposed approach compared to the reference method. Scan time for single slice T1 mapping including B1+ mapping could be reduced to 5 seconds using an in-plane resolution of (2×2) mm2, which equals a scan time reduction of more than 99% compared to the reference method. Conclusion Our results demonstrate that rapid 2D T1 quantification using a variable flip angle approach is feasible at 1.5T/3T/7T. It represents a valuable alternative for rapid T1 mapping due to the gain in speed versus conventional approaches. This progress may serve to enhance the capabilities of

Rapid parametric mapping of the longitudinal relaxation time T1 using two-dimensional variable flip angle magnetic resonance imaging at 1.5 Tesla, 3 Tesla, and 7 Tesla.

PubMed

Dieringer, Matthias A; Deimling, Michael; Santoro, Davide; Wuerfel, Jens; Madai, Vince I; Sobesky, Jan; von Knobelsdorff-Brenkenhoff, Florian; Schulz-Menger, Jeanette; Niendorf, Thoralf

2014-01-01

Visual but subjective reading of longitudinal relaxation time (T1) weighted magnetic resonance images is commonly used for the detection of brain pathologies. For this non-quantitative measure, diagnostic quality depends on hardware configuration, imaging parameters, radio frequency transmission field (B1+) uniformity, as well as observer experience. Parametric quantification of the tissue T1 relaxation parameter offsets the propensity for these effects, but is typically time consuming. For this reason, this study examines the feasibility of rapid 2D T1 quantification using a variable flip angles (VFA) approach at magnetic field strengths of 1.5 Tesla, 3 Tesla, and 7 Tesla. These efforts include validation in phantom experiments and application for brain T1 mapping. T1 quantification included simulations of the Bloch equations to correct for slice profile imperfections, and a correction for B1+. Fast gradient echo acquisitions were conducted using three adjusted flip angles for the proposed T1 quantification approach that was benchmarked against slice profile uncorrected 2D VFA and an inversion-recovery spin-echo based reference method. Brain T1 mapping was performed in six healthy subjects, one multiple sclerosis patient, and one stroke patient. Phantom experiments showed a mean T1 estimation error of (-63±1.5)% for slice profile uncorrected 2D VFA and (0.2±1.4)% for the proposed approach compared to the reference method. Scan time for single slice T1 mapping including B1+ mapping could be reduced to 5 seconds using an in-plane resolution of (2×2) mm2, which equals a scan time reduction of more than 99% compared to the reference method. Our results demonstrate that rapid 2D T1 quantification using a variable flip angle approach is feasible at 1.5T/3T/7T. It represents a valuable alternative for rapid T1 mapping due to the gain in speed versus conventional approaches. This progress may serve to enhance the capabilities of parametric MR based lesion detection and

Understanding the Mechanism of Magnetic Relaxation in Pentanuclear {MnIVMnIII2LnIII2} Single-Molecule Magnets.

PubMed

Vignesh, Kuduva R; Langley, Stuart K; Moubaraki, Boujemaa; Murray, Keith S; Rajaraman, Gopalan

2018-02-05

A new family of heterometallic pentanuclear complexes of formulas [Mn IV Mn III 2 Ln III 2 O 2 (benz) 4 (mdea) 3 (NO 3 ) 2 (MeOH)] (Ln = Dy (1-Dy), Tb (2-Tb), Gd (3-Gd), Eu (4-Eu), Sm (5-Sm), Nd (6-Nd), Pr (7-Pr); benz(H) = benzoic acid; mdeaH 2 = N-methyldiethanolamine) and [Mn IV Mn III 2 Ln III 2 O 2 (o-tol) 4 (mdea) 3 (NO 3 ) 2 (MeOH)] (Ln = Gd (8-Gd), Eu (9-Eu); o-tol(H) = o-toluic acid) have been isolated and structurally, magnetically, and theoretically characterized. dc magnetic susceptibility measurements reveal dominant antiferromagnetic magnetic interactions for each complex, except for 2-Tb and 3-Gd, which reveal an upturn in the χ M T product at low temperatures. The magnetic interactions between the spin centers in the Gd derivatives, 3-Gd and 8-Gd, which display markedly different χ M T vs T profiles, were found to be due to the interactions of the Gd III -Gd III ions which change from ferromagnetic (3-Gd) to antiferromagnetic (8-Gd) due to structural differences. ac magnetic susceptibility measurements reveal a nonzero out-of-phase component for 1-Dy and 7-Pr, but no maxima were observed above 2 K (H dc = 0 Oe), which suggests single-molecule magnet (SMM) behavior. Out-of-phase signals were observed for complexes 2-Tb, 4-Eu, 8-Gd, and 9-Eu, in the presence of a static dc field (H dc = 2000, 3000 Oe). The anisotropic nature of the lanthanide ions in the benzoate series (1-Dy, 2-Tb, 5-Sm, 6-Nd, and 7-Pr) were thoroughly investigated using ab initio methods. CASSCF calculations predict that the origin of SMM behavior in 1-Dy and 7-Pr and the applied field SMM behavior in 2-Tb does not solely originate from the single-ion anisotropy of the lanthanide ions. To fully understand the relaxation mechanism, we have employed the Lines model to fit the susceptibility data using the POLY_ANISO program, which suggests that the zero-field SMM behavior observed in complexes 1-Dy and 7-Pr is due to weak Mn III/IV -Ln III and Ln III -Ln III couplings and an

Synthesis and functionalization of NaGdF4:Yb,Er@NaGdF4 core-shell nanoparticles for possible application as multimodal contrast agents.

PubMed

Baziulyte-Paulaviciene, Dovile; Karabanovas, Vitalijus; Stasys, Marius; Jarockyte, Greta; Poderys, Vilius; Sakirzanovas, Simas; Rotomskis, Ricardas

2017-01-01

Upconverting nanoparticles (UCNPs) are promising, new imaging probes capable of serving as multimodal contrast agents. In this study, monodisperse and ultrasmall core and core-shell UCNPs were synthesized via a thermal decomposition method. Furthermore, it was shown that the epitaxial growth of a NaGdF 4 optical inert layer covering the NaGdF 4 :Yb,Er core effectively minimizes surface quenching due to the spatial isolation of the core from the surroundings. The mean diameter of the synthesized core and core-shell nanoparticles was ≈8 and ≈16 nm, respectively. Hydrophobic UCNPs were converted into hydrophilic ones using a nonionic surfactant Tween 80. The successful coating of the UCNPs by Tween 80 has been confirmed by Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM), powder X-ray diffraction (XRD), photoluminescence (PL) spectra and magnetic resonance (MR) T1 relaxation measurements were used to characterize the size, crystal structure, optical and magnetic properties of the core and core-shell nanoparticles. Moreover, Tween 80-coated core-shell nanoparticles presented enhanced optical and MR signal intensity, good colloidal stability, low cytotoxicity and nonspecific internalization into two different breast cancer cell lines, which indicates that these nanoparticles could be applied as an efficient, dual-modal contrast probe for in vivo bioimaging.

Electron spin resonance of Gd3+ in the intermetallic Gd1-xYxNi3Ga9 (0 ≤ x ≤ 0.90) compounds

NASA Astrophysics Data System (ADS)

Mendonça, E. C.; Silva, L. S.; Mercena, S. G.; Meneses, C. T.; Jesus, C. B. R.; Duque, J. G. S.; Souza, J. C.; Pagliuso, P. G.; Lora-Serrano, R.; Teixeira-Neto, A. A.

2017-10-01

In this work, experiments of X-ray diffraction, magnetic susceptibility, heat capacitance, and Electron Spin Resonance (ESR) carried out in the Gd1-xYxNi3Ga9 (0 ≤ x ≤ 0.90) compounds grown through a Ga self flux method are reported. The X-ray diffraction data indicate that these compounds crystallize in a trigonal crystal structure with a space group R32. This crystal structure is unaffected by Y-substitution, which produces a monotonic decrease of the lattice parameters. For the x = 0 compound, an antiferromagnetic phase transition is observed at TN = 19.2 K, which is continuously suppressed as a function of the Y-doping and extrapolates to zero at x ≈ 0.85. The ESR data, taken in the temperature range 15 ≤ T ≤ 300 K, show a single Dysonian Gd3+ line with nearly temperature independent g-values. The linewidth follows a Korringa-like behavior as a function of temperature for all samples. The Korringa rates (b = ΔH /ΔT ) are Y-concentration-dependent indicating a "bottleneck" regime. For the most diluted sample (x = 0.90), when it is believed that the "bottleneck" effect is minimized, we have calculated the q-dependent effective exchange interactions between Gd3+ local moments and the c-e of 〈Jf-ce 2(q ) 〉 1 /2 = 18(2) meV and Jf -c e(q =0 ) = 90(10) meV.

Measurement of the Spin Relaxation Lifetime (T 1) in a One-Electron Strained-Si Accumulation-Mode Quantum Dot

NASA Astrophysics Data System (ADS)

Croke, Edward; Borselli, Matthew; Kiselev, Andrey; Deelman, Peter; Milosavljevic, Ivan; Alvarado-Rodriguez, Ivan; Ross, Richard; Schmitz, Adele; Gyure, Mark; Hunter, Andrew

2011-03-01

We report measurements of the spin-relaxation lifetime (T1) as a function of magnetic field in a strained-Si, accumulation-mode quantum dot. An integrated quantum-point contact (QPC) charge sensor was used to detect changes in dot occupancy as a function of bias applied to a single gate electrode. The addition spectra we obtained are consistent with theoretical predictions starting at N=0. The conductance of the charge sensor was measured by applying an AC voltage across the QPC and a 3 k Ω resistor. Lifetime measurements were conducted using a three-pulse technique consisting of a load, read, and flush sequence. T1 was measured by observing the decay of the spin bump amplitude as a function of the load pulse length. We measured decay times ranging from approximately 75 msec at 2T to 12 msec at 3T, consistent with previous reports and theoretical predictions. Sponsored by United States Department of Defense. Approved for Public Release, Distribution Unlimited.

Gd-Si Oxide Nanoparticles as Contrast Agents in Magnetic Resonance Imaging

PubMed Central

Cabrera-García, Alejandro; Vidal-Moya, Alejandro; Bernabeu, Ángela; Pacheco-Torres, Jesús; Checa-Chavarria, Elisa; Fernández, Eduardo; Botella, Pablo

2016-01-01

We describe the synthesis, characterization and application as contrast agents in magnetic resonance imaging of a novel type of magnetic nanoparticle based on Gd-Si oxide, which presents high Gd3+ atom density. For this purpose, we have used a Prussian Blue analogue as the sacrificial template by reacting with soluble silicate, obtaining particles with nanorod morphology and of small size (75 nm). These nanoparticles present good biocompatibility and higher longitudinal and transversal relaxivity values than commercial Gd3+ solutions, which significantly improves the sensitivity of in vivo magnetic resonance images. PMID:28335240

Thermal behaviour of GdCo1-xMnxO3 cobaltates

NASA Astrophysics Data System (ADS)

Thakur, Rasna; Thakur, Rajesh K.; Gaur, N. K.

2018-05-01

With the objective of exploring the unknown thermodynamic behavior of GdCo1-xMnxO3 family, we present here an investigation of the temperature-dependent (10K≤T≤1000K) thermodynamic properties of GdCo1-xMnxO3 (x=0.1 to 0.8). The specific heat of GdCoO3 with Mn doping in the perovskite structure at B-site has been studied by means of a Modified Rigid Ion Model (MRIM). The cohesive energy, specific heat (C), volume thermal expansion (α) and Gruneisen parameter (γ) of GdCo1-xMnxO3 compounds are also discussed.

Particle- γ coincidence spectroscopy of the N = 90 nucleus 154Gd by (p,tγ)

NASA Astrophysics Data System (ADS)

Allmond, J. M.; Beausang, C. W.; Ross, T. J.; Humby, P.; Basunia, M. S.; Bernstein, L. A.; Bleuel, D. L.; Brooks, W.; Brown, N.; Burke, J. T.; Darakchieva, B. K.; Dudziak, K. R.; Evans, K. E.; Fallon, P.; Jeppesen, H. B.; LeBlanc, J. D.; Lesher, S. R.; McMahan, M. A.; Meyer, D. A.; Phair, L.; Rasmussen, J. O.; Scielzo, N. D.; Stroberg, S. R.; Wiedeking, M.

2017-03-01

A segmented Si-telescope and HPGe array, STARS-LIBERACE, was used to study the 156Gd(p,tγ)154Gd direct reaction by particle- γ coincidence spectroscopy. New cross sections with a 25MeV proton beam are reported and compared to previous (p,t) and (t,p) studies. Furthermore, additional evidence for coexisting K^{π}=01+,21+ and 02+, 22+ configurations at N = 90 is presented. Direct and indirect population patterns of the low-lying states are also explored. Review of the new and existing evidence favors an interpretation based on a configuration-dependent pairing interaction. The weakening of monopole pairing strength and an increase in quadrupole pairing strength could bring 2p-2h 0+ states below 2Δ. This may account for a large number of the low-lying 0+ states observed in two-nucleon transfer reactions. A hypothesis for the origin of the 02+ and 03+ states is provided.

Non-invasive evaluation of blood oxygen saturation and hematocrit from T1 and T2 relaxation times: In-vitro validation in fetal blood.

PubMed

Portnoy, Sharon; Seed, Mike; Sled, John G; Macgowan, Christopher K

2017-12-01

We propose an analytical method for calculating blood hematocrit (Hct) and oxygen saturation (sO 2 ) from measurements of its T 1 and T 2 relaxation times. Through algebraic substitution, established two-compartment relationships describing R1=T1-1 and R2=T2-1 as a function of hematocrit and oxygen saturation were rearranged to solve for Hct and sO 2 in terms of R 1 and R 2 . Resulting solutions for Hct and sO 2 are the roots of cubic polynomials. Feasibility of the method was established by comparison of Hct and sO 2 estimates obtained from relaxometry measurements (at 1.5 Tesla) in cord blood specimens to ground-truth values obtained by blood gas analysis. Monte Carlo simulations were also conducted to assess the effect of T 1 , T 2 measurement uncertainty on precision of Hct and sO 2 estimates. Good agreement was observed between estimated and ground-truth blood properties (bias = 0.01; 95% limits of agreement = ±0.13 for Hct and sO 2 ). Considering the combined effects of biological variability and random measurement noise, we estimate a typical uncertainty of ±0.1 for Hct, sO 2 estimates. Results demonstrate accurate quantification of Hct and sO 2 from T 1 and T 2 . This method is applicable to noninvasive fetal vessel oximetry-an application where existing oximetry devices are unusable or require risky blood-sampling procedures. Magn Reson Med 78:2352-2359, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Multicomponent T2 relaxation studies of the avian egg.

PubMed

Mitsouras, Dimitris; Mulkern, Robert V; Maier, Stephan E

2016-05-01

To investigate the tissue-like multiexponential T2 signal decays in avian eggs. Transverse relaxation studies of raw, soft-boiled and hard-boiled eggs were performed at 3 Tesla using a three-dimensional Carr-Purcell-Meiboom-Gill imaging sequence. Signal decays over a TE range of 11 to 354 ms were fitted assuming single- and multicomponent signal decays with up to three separately decaying components. Fat saturation was used to facilitate spectral assignment of observed decay components. Egg white, yolk and the centrally located latebra all demonstrate nonmonoexponential T2 decays. Specifically, egg white exhibits two-component decays with intermediate and long T2 times. Meanwhile, yolk and latebra are generally best characterized with triexponential decays, with short, intermediate and very long T2 decay times. Fat saturation revealed that the intermediate component of yolk could be attributed to lipids. Cooking of the egg profoundly altered the decay curves. Avian egg T2 decay curves cover a wide range of decay times. Observed T2 components in yolk and latebra as short as 10 ms, may prove valuable for testing clinical sequences designed to measure short T2 components, such as myelin-associated water in the brain. Thus we propose that the egg can be a versatile and widely available MR transverse relaxation phantom. © 2015 Wiley Periodicals, Inc.

A New Bis(aquated) High Relaxivity Mn(II) Complex as an Alternative to Gd(III)-Based MRI Contrast Agent.

PubMed

Phukan, Bedika; Mukherjee, Chandan; Goswami, Upashi; Sarmah, Amrit; Mukherjee, Subhajit; Sahoo, Suban K; Moi, Sankar Ch

2018-03-05

Disclosed here are a piperazine, a pyridine, and two carboxylate groups containing pentadentate ligand H 2 pmpa and its corresponding water-soluble Mn(II) complex (1). DFT-based structural optimization implied that the complex had pentagonal bipyramidal geometry where the axial positions were occupied by two water molecules, and the equatorial plane was constituted by the ligand ON 3 O donor set. Thus, a bis(aquated) disc-like Mn(II) complex has been synthesized. The complex showed higher stability compared with Mn(II)-EDTA complex [log K MnL = 14.29(3)] and showed a very high r 1 relaxivity value of 5.88 mM -1 s -1 at 1.41 T, 25 °C, and pH = 7.4. The relaxivity value remained almost unaffected by the pH of the medium in the range of 6-10. Although the presence of 200 equiv of fluoride and bicarbonate anions did not affect the relaxivity value appreciably, an increase in the value was noticed in the presence of phosphate anion due to slow tumbling of the complex. Cell viability measurements, as well as phantom MR images using clinical MRI imager, consolidated the possible candidature of complex 1 as a positive contrast agent.

Gadolinium embedded iron oxide nanoclusters as T1-T2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

NASA Astrophysics Data System (ADS)

Wang, Xiaoyong; Zhou, Zijian; Wang, Zhiyong; Xue, Yunxin; Zeng, Yun; Gao, Jinhao; Zhu, Lei; Zhang, Xianzhong; Liu, Gang; Chen, Xiaoyuan

2013-08-01

This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability.This report illustrates a new strategy of designing a T1-T2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T1-T2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T1-T2 dual-modal MRI monitoring capability. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr02797j

Gadolinia nanofibers as a multimodal bioimaging and potential radiation therapy agent

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grishin, A. M., E-mail: grishin@kth.se, E-mail: grishin@inmatech.com; INMATECH Intelligent Materials Technology, SE-127 45 Skärholmen; Petrozavodsk State University, 185910 Petrozavodsk, Karelian Republic

2015-05-15

Continuous bead-free C-type cubic gadolinium oxide (Gd{sub 2}O{sub 3}) nanofibers 20-30 μm long and 40-100 nm in diameter were sintered by sol-gel calcination assisted electrospinning technique. Dipole-dipole interaction of neighboring Gd{sup 3+} ions in nanofibers with large length-to-diameter aspect ratio results in some kind of superparamagnetic behavior: fibers are magnetized twice stronger than Gd{sub 2}O{sub 3} powder. Being compared with commercial Gd-DTPA/Magnevist{sup ®}, Gd{sub 2}O{sub 3} diethyleneglycol-coated (Gd{sub 2}O{sub 3}-DEG) fibers show high 1/T{sub 1} and 1/T{sub 2} proton relaxivities. Intense room temperature photoluminescence, high NMR relaxivity and high neutron scattering cross-section of {sup 157}Gd nucleus promise to integrate Gd{submore » 2}O{sub 3} fibers for multimodal bioimaging and neutron capture therapy.« less

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer

PubMed Central

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S.; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J.; Liu, Xuewu; Decuzzi, Paolo

2015-01-01

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1,000 × 400 nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities – small pore (SP: ~ 5 nm) and huge pore (HP: ~ 40 nm) – and of bulk, non-porous silica beads (1,000 nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ~ 17 (mM·s)−1, which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. PMID:24931336

Temperature evolution of polar states in GdMn2O5 and Gd0.8Ce0.2Mn2O5

NASA Astrophysics Data System (ADS)

Sanina, V. A.; Golovenchits, E. I.; Khannanov, B. Kh.; Scheglov, M. P.; Zalesskii, V. G.

2014-11-01

The polar order along the c axis is revealed in GdMn2O5 and Gd0.8Ce0.2Mn2O5 at T ≤ T C1 ≈ 160 K for the first time. This polar order is induced by the charge disproportion in the 2D superstructures emerged due to phase separation. The dynamic state with restricted polar domains of different sizes is found at T > T C1 which is typical of the diffuse ferroelectric phase transition. At the lowest temperatures ( T < 40 K) two polar orders of different origins with perpendicular orientations (along the b and c axes) coexist. The 1D superlattices studied by us earlier in the set of RMn2O5 multiferroics are the charged domain walls which separate of these polar order domains.

Temperature Sensing Above 1000 C Using Cr-Doped GdAlO3 Spin-Allowed Broadband Luminescence

NASA Technical Reports Server (NTRS)

Eldridge, Jeffrey I.; Chambers, Matthew D.

2012-01-01

Cr-doped GdAlO3 (Cr:GdAlO3) is shown to produce remarkably high-intensity spin-allowed broadband luminescence with sufficiently long decay times to make effective luminescence-decay-time based temperature measurements above 1000 C. This phosphor is therefore an attractive alternative to the much lower luminescence intensity rare-earth-doped thermographic phosphors that are typically utilized at these elevated temperatures. In particular, Cr:GdAlO3 will be preferred over rare-earth-doped phosphors, such as Dy:YAG, at temperatures up to 1200 C for intensity-starved situations when the much lower emission intensity from rare-earth-doped phosphors is insufficient for accurate temperature measurements in the presence of significant radiation background. While transition-metal-doped phosphors such as Cr:Al2O3 (ruby) are known to exhibit high luminescence intensity at low dopant concentrations, quenching due to nonradiative decay pathways competing with the (sup 2)E to (sup 4)A(sub 2) radiative transition (R line) has typically restricted their use for temperature sensing to below 600 C. Thermal quenching of the broadband (sup 4)T(sub 2) to (sup 4)A(sub 2) radiative transition from Cr:GdAlO3, however, is delayed until much higher temperatures (above 1000 C). This spin-allowed broadband emission persists to high temperatures because the lower-lying (sup 2)E energy level acts as a reservoir to thermally populate the higher shorter-lived (sup 4)T(sub 2) energy level and because the activation energy for nonradiative crossover relaxation from the (sup 4)T(sub 2) level to the (sup 4)A(sub 2) ground state is high. The strong crystal field associated with the tight bonding of the AlO6 octahedra in the GdAlO3 perovskite structure is responsible for this behavior.

Synthesis of DTPA analogues derived from piperidine and azepane: potential contrast enhancement agents for magnetic resonance imaging.

PubMed

Chong, H S; Garmestani, K; Bryant, L H; Brechbiel, M W

2001-11-16

Two DTPA derivatives (PIP-DTPA and AZEP-DTPA) as potential contrast enhancement agents in MRI are synthesized. The T1 and T2 relaxivities of their corresponding Gd(III) complexes are reported. At clinically relevant field strengths, the relaxivities of the complexes are comparable to that of the contrast agent, Gd(DTPA) which is in clinical use. The serum stability of the (153)Gd-labeled complexes is assessed by measuring the release of (153)Gd from the ligands. The radiolabeled Gd chelates are found to be kinetically stable in human serum for up to at least 14 days without any measurable loss of radioactivity.

A novel contrast agent with rare earth-doped up-conversion luminescence and Gd-DTPA magnetic resonance properties

NASA Astrophysics Data System (ADS)

Lu, Qing; Wei, Daixu; Cheng, Jiejun; Xu, Jianrong; Zhu, Jun

2012-08-01

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 T1-weighted maps of the obtained nanoparticles were carried out by 980 nm 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.

Patellar cartilage lesions: comparison of magnetic resonance imaging and T2 relaxation-time mapping.

PubMed

Hannila, I; Nieminen, M T; Rauvala, E; Tervonen, O; Ojala, R

2007-05-01

To evaluate the detection and the size of focal patellar cartilage lesions in T2 mapping as compared to standard clinical magnetic resonance imaging (MRI) at 1.5T. Fifty-five consecutive clinical patients referred to knee MRI were imaged both with a standard knee MRI protocol (proton-density-weighted sagittal and axial series, T2-weighted sagittal and coronal series, and T1-weighted coronal series) and with an axial multislice multi-echo spin-echo measurement to determine the T2 relaxation time of the patellar cartilage. MR images and T2 maps of patellar cartilage were evaluated for focal lesions. The lesions were evaluated for lesion width (mm), lesion depth (1/3, 2/3, or 3/3 of cartilage thickness), and T2 value (20-40 ms, 40-60 ms, or 60-80 ms) based on visual evaluation. Altogether, 36 focal patellar cartilage lesions were detected from 20 human subjects (11 male, nine female, mean age 40+/-15 years). Twenty-eight lesions were detected both on MRI and T2 maps, while eight lesions were only visible on T2 maps. Cartilage lesions were significantly wider (P = 0.001) and thicker (P<0.001) on T2 maps as compared to standard knee MRI. Most lesions 27 had moderately (T2 40-60 ms) increased T2 values, while two lesions had slightly (T2 20-40 ms) and seven lesions remarkably (T2 60-80 ms) increased T2 relaxation times. T2 mapping of articular cartilage is feasible in the clinical setting and may reveal early cartilage lesions not visible with standard clinical MRI.

GD3- and O-acetylated GD3-gangliosides in the GM2 synthase-deficient mouse brain and their immunohistochemical localization

PubMed Central

Matsuda, Junko; Vanier, Marie T.; Popa, Iuliana; Portoukalian, Jacques; Suzuki, Kunihiko

2006-01-01

Gangliosides in the brain of the knockout mouse deficient in the activity of β1,4 N-acetylgalactosaminyl transferase (β1,4 GalNAc-T)(GM2 synthase) consisted of nearly exclusively of GM3- and GD3-gangliosides as expected from the known substrate specificity of the enzyme and in confirmation of the initial reports from two laboratories that generated the mutant mouse experimentally. The total molar amount of gangliosides was approximately 30% higher in the mutant mouse brain than that in the wild-type brain. However, contrary to the initial reports, one-fourth of total GD3-ganglioside was O-acetylated. It reacted positively with an anti-O-acetylated GD3 monoclonal antibody and disappeared with a corresponding increase in GD3-ganglioside after mild alkaline treatment. The absence of O-acetylated GD3 in the initial reports can be explained by the saponification step included in their analytical procedures. Although quantitatively much less and identification tentative, we also detected GT3 and O-acetylated GT3. Anti-GD3 and anti-O-acetylated GD3 monoclonal antibodies gave positive reactions in the brain of mutant mouse as expected from the analytical results. Either antibody barely stained wild-type brain except for immunoreactivity of GD3 in the cerebellar Purkinje cells. The distributions of GD3 and O-acetylated GD3 in the brain of mutant mouse were similar but differential localization was noted in the cerebellar Purkinje cells and cerebral cortex. PMID:25792782

Inorganic photosensitizer coupled Gd-based upconversion luminescent nanocomposites for in vivo magnetic resonance imaging and near-infrared-responsive photodynamic therapy in cancers.

PubMed

Zhang, Ling'e; Zeng, Leyong; Pan, Yuanwei; Luo, Song; Ren, Wenzhi; Gong, An; Ma, Xuehua; Liang, Hongze; Lu, Guangming; Wu, Aiguo

2015-03-01

Inorganic photosensitizer coupled Gd-based upconversion luminescent (UCL) nanocomposites have potential application for both magnetic resonance imaging (MRI) and photodynamic therapy (PDT) of cancers using the light stability and biocompatibility of TiO2 inorganic photosensitizer. However, TiO2 inorganic photosensitizer could only be excited by ultraviolet (UV) light, which was harmful and weakly penetrable in tissues. In this work, folic acid (FA)-targeted NaGdF4:Yb/Tm@SiO2@TiO2 nanocomposites (FA-Gd-Si-Ti NPs) were constructed and synthesized for both in vivo MRI and near infrared (NIR)-responsive inorganic PDT, in which TiO2 component could be excited by NIR light due to the UCL performance of NaGdF4:Yb/Tm component converting NIR to UV light. The results showed the as-prepared FA-Gd-Si-Ti NPs had good biocompatibility in vitro and in vivo. Moreover, MR study indicated that FA-Gd-Si-Ti NPs were good T1-weighted MRI contrast agents with high longitudinal relaxivity (r1) of 4.53 mm(-1) s(-1), also in vivo MRI of nude mice showed "bright" signal in MCF-7 tumor. Under the irradiation of 980 nm laser at the power density of 0.6 W/cm(2) for 20 min, the viability of HeLa and MCF-7 cells incubated with FA-Gd-Si-Ti NPs could decrease from about 90 % to 35 % and 31%, respectively. Furthermore, in vivo PDT of MCF-7 tumor-bearing nude mice model showed that the inhibition ratio of tumors injected with FA-Gd-Si-Ti NPs reached up to 88.6% after 2-week treatment, compared with that of nude mice in control group. Based on the deep penetration of NIR light and the good biocompatibility of TiO2 inorganic photosensitizer, the as-prepared FA-Gd-Si-Ti NPs could have potential applications in both MRI and NIR-responsive PDT of cancers in deep tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Ji-Ae, E-mail: jpark@kirams.re.kr; Lee, Yong Jin; Ko, In Ok

2014-12-12

Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyKmore » peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.« less

Preparation of Gd Loaded Liquid Scintillator for Daya Bay Neutrino Experiment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding Yayun; Zhang Zhiyong

2010-05-12

Gadolinium loaded liquid scintillator (Gd-LS) is an excellent target material for reactor antineutrino experiments. Ideal Gd-LS should have long attenuation length, high light yield, long term stability, low toxicity, and should be compatible with the material used to build the detector. We have developed a new Gd-LS recipe in which carboxylic acid 3,5,5-trimethylhexanoic acid is used as the complexing ligand to gadolinium, 2,5-diphenyloxazole (PPO) and 1,4-bis[2-methylstyryl]benzene (bis-MSB) are used as primary fluor and wavelength shifter, respectively. The scintillator base is linear alkyl benzene (LAB). Eight hundred liters of Gd-LS has been synthesized and tested in a prototype detector. Results showmore » that the Gd-LS has high quality and is suitable for underground experiments in large quantity. Large scale production facility has been built. A full batch production of 4 t Gd-LS has been produced and monitored for several months. The production of 180 t Gd-LS will be carried out in the near future.« less

Preparation of Gd Loaded Liquid Scintillator for Daya Bay Neutrino Experiment

NASA Astrophysics Data System (ADS)

Ya-yun, Ding; Zhi-yong, Zhang

2010-05-01

Gadolinium loaded liquid scintillator (Gd-LS) is an excellent target material for reactor antineutrino experiments. Ideal Gd-LS should have long attenuation length, high light yield, long term stability, low toxicity, and should be compatible with the material used to build the detector. We have developed a new Gd-LS recipe in which carboxylic acid 3,5,5-trimethylhexanoic acid is used as the complexing ligand to gadolinium, 2,5-diphenyloxazole (PPO) and 1,4-bis[2-methylstyryl]benzene (bis-MSB) are used as primary fluor and wavelength shifter, respectively. The scintillator base is linear alkyl benzene (LAB). Eight hundred liters of Gd-LS has been synthesized and tested in a prototype detector. Results show that the Gd-LS has high quality and is suitable for underground experiments in large quantity. Large scale production facility has been built. A full batch production of 4 t Gd-LS has been produced and monitored for several months. The production of 180 t Gd-LS will be carried out in the near future.

Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features

PubMed Central

Seo, Mirinae; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

2017-01-01

Objective The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Materials and Methods Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Results Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). Conclusion The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer. PMID:28096732

Diagnostic value of Gd-EOB-DTPA-enhanced MR cholangiography in non-invasive detection of postoperative bile leakage.

PubMed

Kul, Melahat; Erden, Ayşe; Düşünceli Atman, Ebru

2017-04-01

To assess the diagnostic value of dynamic T 1 weighted (T1w) gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA)-enhanced MR cholangiography (MRC) for the detection of active bile leaks. A total of 28 patients with suspected biliary leakage who underwent routine T 2 weighted (T2w) MRC and T1w GD-EOB-DTPA-enhanced MRC at our institution from February 2013 to June 2016 were included in this study. The image sets were retrospectively analyzed in consensus by three radiologists. T1w Gd-EOB-DTPA-enhanced MRC findings were correlated with clinical data, follow-up examinations and findings of invasive/surgical procedures. Patients with positive bile leak findings in Gd-EOB-DTPA-enhanced MRC were divided into hepatobiliary phase (HBP) (20-30 min) and delayed phase (DP) (60-390 min) group according to elapsed time between Gd-EOB-DTPA injection and initial bile leak findings in MRC images. These groups were compared in terms of laboratory test results (total bilirubin, liver enzymes) and the presence of bile duct dilatation in T2w MRC images. In each patient, visualization of bile ducts was sufficient in the HBP. The accuracy, sensitivity and specificity of dynamic Gd-EOB-DTPA-enhanced T1w MRC in the detection of biliary leaks were 92.9%, 90.5% and 100%, respectively (p < 0.001). 19 of 28 patients had bile leak findings in T1w Gd-EOB-DTPA-enhanced MRC [HBP group: N = 7 (36.8%), DP group: N = 12 (63.2%)]. There was no statistically significant difference in terms of laboratory test results and the presence of bile duct dilatation between HBP and DP group (p > 0.05). Three patients, each of them in DP group, showed normal laboratory test results and bile duct diameters. Dynamic T1w Gd-EOB-DTPA-enhanced MRC is a useful non-invasive diagnostic tool to detect bile leak. Advances in knowledge: Prolonged DP imaging may be required for bile leak detection even if visualization of biliary tree is sufficient in HBP and liver function tests

Synthesis of a novel 'smart' bifunctional chelating agent 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and its Gd(III) complex.

PubMed

Wardle, Nick J; Herlihy, Amy H; So, Po-Wah; Bell, Jimmy D; Bligh, S W Annie

2007-07-15

A new synthetic pathway to 1-(2-[beta,D-galactopyranosyloxy]ethyl)-7-(1-carboxy-3-[4-aminophenyl]propyl)-4,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (Gal-PA-DO3A-NH2) and 1-(2-[beta,D-galactopyranosyloxy]ethyl)-4,7,10-tris(carboxymethyl)-1, 4,7,10-tetraazacyclododecane (Gal-DO3A) chelating agents was developed involving full hydroxyl- and carboxyl-group protection in precursors to product. Two sequences of cyclen-N-functionalisation were subsequently investigated, one successfully, towards synthesis of the novel 'smart' bifunctional Gal-PA-DO3A-NH2 chelate. The longitudinal proton relaxivities of the neutral [Gd-(Gal-PA-DO3A-NH2)] and [Gd-(Gal-DO3A)] complexes were increased by 28% and 37% in the presence of beta-galactosidase, respectively.

A novel contrast agent with rare earth-doped up-conversion luminescence and Gd-DTPA magnetic resonance properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu Qing; Wei Daixu; Cheng Jiejun

2012-08-15

The magnetic-luminescent multifunctional nanoparticles based on Gd-DTPA and NaYF{sub 4}:Yb, Er were successfully synthesized by the conjugation of activated DTPA and silica-coated/surface-aminolated NaYF{sub 4}: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{sub 1}-weighted maps of the obtained nanoparticles were carried out by 980 nm 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 bothmore » high MR relaxivities and upconversion luminescence may have potential usage for MR imaging in future. - Graphical abstract: We have synthesized magnetic-luminescent multifunctional nanoparticles based on Gd-DTPA and NaYF4:Yb, Er by the conjugation of activated DTPA and silica-coated/surface-aminolated NaYF4:Yb, Er nanoparticles through EDC/NHS coupling chemistry. Highlights: Black-Right-Pointing-Pointer A novel magnetic-luminescent multifunctional nanoparticles are synthesized. Black-Right-Pointing-Pointer The nanoparticles are highly efficient for luminescence and T{sub 1}-weighted MR imaging. Black-Right-Pointing-Pointer The nanoparticles are small in size and highly solubility in water. Black-Right-Pointing-Pointer The nanoparticles hold great potential usage for future biomedical engineering.« less

Efficacy of progressive aquatic resistance training for tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis: a randomised controlled trial.

PubMed

Munukka, M; Waller, B; Rantalainen, T; Häkkinen, A; Nieminen, M T; Lammentausta, E; Kujala, U M; Paloneva, J; Sipilä, S; Peuna, A; Kautiainen, H; Selänne, H; Kiviranta, I; Heinonen, A

2016-10-01

To study the efficacy of aquatic resistance training on biochemical composition of tibiofemoral cartilage in postmenopausal women with mild knee osteoarthritis (OA). Eighty seven volunteer postmenopausal women, aged 60-68 years, with mild knee OA (Kellgren-Lawrence grades I/II and knee pain) were recruited and randomly assigned to an intervention (n = 43) and control (n = 44) group. The intervention group participated in 48 supervised aquatic resistance training sessions over 16 weeks while the control group maintained usual level of physical activity. The biochemical composition of the medial and lateral tibiofemoral cartilage was estimated using single-slice transverse relaxation time (T2) mapping and delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC index). Secondary outcomes were cardiorespiratory fitness, isometric knee extension and flexion force and knee injury and OA outcome (KOOS) questionnaire. After 4-months aquatic training, there was a significant decrease in both T2 -1.2 ms (95% confidence interval (CI): -2.3 to -0.1, P = 0.021) and dGEMRIC index -23 ms (-43 to -3, P = 0.016) in the training group compared to controls in the full thickness posterior region of interest (ROI) of the medial femoral cartilage. Cardiorespiratory fitness significantly improved in the intervention group by 9.8% (P = 0.010). Our results suggest that, in postmenopausal women with mild knee OA, the integrity of the collagen-interstitial water environment (T2) of the tibiofemoral cartilage may be responsive to low shear and compressive forces during aquatic resistance training. More research is required to understand the exact nature of acute responses in dGEMRIC index to this type of loading. Further, aquatic resistance training improves cardiorespiratory fitness. ISRCTN65346593. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

X-ray absorption spectroscopy study of Gd3+-loaded ultra-short carbon nanotubes

NASA Astrophysics Data System (ADS)

Ma, Q.; Jebb, M.; Tweedle, M. F.; Wilson, L. J.

2013-04-01

We present an x-ray absorption spectroscopy study of the local structure around the Gd3+ion loaded in ultra short (20-100 nm) carbon nanotubes (GNTs). X-ray Gd L3 absorption near edge structure data shows that the 31.2-μM GNT suspension exhibits a clear characteristic of hydration at the [GdOn] cluster. Extended x-ray absorption fine structure data show that the Gd3+ ion is coordinated by about 9 oxygen ions and that this first coordination shell exhibits an asymmetry similar to that found in triclinic Gd-acetate or Gd[C2H3O2]3·4H2O or GdAc. After correction for the asymmetry using the cumulant of the third order, the Gd-O bond distance is found to be 2.345 Å, instead of 2.406 Å for a symmetrical (or Gaussian) distribution. It is shorter than that in the Gd-containing MRI contrast agents currently in clinical uses. This may account in part for high proton relaxivity observed for the GNT suspension.

Multi-Component T2 Relaxation Studies of the Avian Egg

PubMed Central

Mitsouras, Dimitris; Mulkern, Robert V.; Maier, Stephan E.

2015-01-01

Purpose To investigate the tissue-like multiexponential T2 signal decays in avian eggs. Methods Transverse relaxation studies of raw, soft-boiled and hard-boiled eggs were performed at 3 Tesla using a 3D Carr-Purcell-Meiboom-Gill (CPMG) imaging sequence. Signal decays over a TE range of 11 to 354 ms were fitted assuming single- and multi-component signal decays with up to three separately decaying components. Fat saturation was used to facilitate spectral assignment of observed decay components. Results Egg white, yolk and the centrally located latebra all demonstrate nonmonoexponential T2 decays. Specifically, egg white exhibits two-component decays with intermediate and long T2 times. Meanwhile, yolk and latebra are generally best characterized with triexponential decays, with short, intermediate and very long T2 decay times. Fat saturation revealed that the intermediate component of yolk could be attributed to lipids. Cooking of the egg profoundly altered the decay curves. Conclusion Avian egg T2 decay curves cover a wide range of decay times. Observed T2 components in yolk and latebra as short as 10 ms, may prove valuable for testing clinical sequences designed to measure short T2 components, such as myelin-associated water in the brain. Thus we propose that the egg can be a versatile and widely available MR transverse relaxation phantom. PMID:26037128

Cartilage and meniscal T2 relaxation time as non-invasive biomarker for knee osteoarthritis and cartilage repair procedures

PubMed Central

Baum, T.; Joseph, G.B.; Karampinos, D.C.; Jungmann, P.M.; Link, T.M.; Bauer, J.S.

2014-01-01

SUMMARY Objective The purpose of this work was to review the current literature on cartilage and meniscal T2 relaxation time. Methods Electronic searches in PubMed were performed to identify relevant studies about T2 relaxation time measurements as non-invasive biomarker for knee osteoarthritis (OA) and cartilage repair procedures. Results Initial osteoarthritic changes include proteoglycan loss, deterioration of the collagen network, and increased water content within the articular cartilage and menisci. T2 relaxation time measurements are affected by these pathophysiological processes. It was demonstrated that cartilage and meniscal T2 relaxation time values were significantly increased in subjects with compared to those without radiographic OA and focal knee lesions, respectively. Subjects with OA risk factors such as overweight/obesity showed significantly greater cartilage T2 values than normal controls. Elevated cartilage and meniscal T2 relaxation times were found in subjects with vs without knee pain. Increased cartilage T2 at baseline predicted morphologic degeneration in the cartilage, meniscus, and bone marrow over 3 years. Furthermore, cartilage repair tissue could be non-invasively assessed by using T2 mapping. Reproducibility errors for T2 measurements were reported to be smaller than the T2 differences in healthy and diseased cartilage indicating that T2 relaxation time may be a reliable discriminatory biomarker. Conclusions Cartilage and meniscal T2 mapping may be suitable as non-invasive biomarker to diagnose early stages of knee OA and to monitor therapy of OA. PMID:23896316

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer.

PubMed

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J; Liu, Xuewu; Decuzzi, Paolo

2014-09-28

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1000×400nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities - small pore (SP: ∼5nm) and huge pore (HP: ∼40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ∼17 (mMs)(-)(1), which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Impaired hepatic Gd-EOB-DTPA enhancement after radioembolisation of liver malignancies.

PubMed

Powerski, Maciej Janusz; Scheurig-Münkler, Christian; Hamm, Bernd; Gebauer, Bernhard

2014-08-01

To evaluate the uptake of the liver-specific magnetic resonance imaging (MRI) contrast agent gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) by functional liver parenchyma after radioembolisation (RE) of hepatic malignancies. Uptake of Gd-EOB-DTPA prior to RE versus 60+/-24d and 126+/-32d after RE was compared in a group of 33 patients with primary or secondary hepatic malignancies. In patients who underwent single-lobe treatment, left and right lobes were compared 59+/-24 days after RE. Gd-EOB-DTPA uptake was determined as follows: ratio of mean signal intensity in liver parenchyma to muscle in Gd-EOB-DTPA-enhanced T1-weighted MRI was subtracted from ratio of mean intensity in liver parenchyma to muscle in unenhanced T1-weighted MRI. Gd-EOB-DTPA uptake in liver parenchyma was 0.845+/-0.29 before RE, 0.615+/-0.38 (P = 0.0022) at day 60+/-24, and 0.739+/-0.30 at day 126+/-32 after RE. In cases of single-lobe treatment, Gd-EOB-DTPA uptake was 0.581+/-0.256 for treated and 0.828+/-0.32 (P = 0.0164) for untreated hepatic lobes. Uptake of Gd-EOB-DTPA by liver parenchyma is impaired after RE, indicating dysfunction of the local hepatic system. These findings suggest that Gd-EOB-DTPA-enhanced MRI has the potential to be used for monitoring liver damage after RE. © 2014 The Royal Australian and New Zealand College of Radiologists.

Silica-F127 nanohybrid-encapsulated manganese oxide nanoparticles for optimized T1 magnetic resonance relaxivity

NASA Astrophysics Data System (ADS)

Wei Hsu, Benedict You; Wang, Miao; Zhang, Yu; Vijayaragavan, Vimalan; Wong, Siew Yee; Yuang-Chi Chang, Alex; Bhakoo, Kishore Kumar; Li, Xu; Wang, John

2013-12-01

To properly engineer MnO nanoparticles (MONPs) of high r1 relaxivity, a nanohybrid coating consisting of silica and F127 (PEO106PPO70PEO106) is designed to encapsulate MONPs. Achieved by an interfacial templating scheme, the nanohybrid encapsulating layer is highly permeable and hydrophilic to allow for an optimal access of water molecules to the encapsulated manganese oxide core. Hence, the efficacy of MONPs as MRI contrast agents is significantly improved, as demonstrated by an enhancement of the MR signal measured with a pre-clinical 7.0 T MRI scanner. The nanohybrid encapsulation strategy also confers high colloidal stability to the hydrophobic MONPs by the surface decoration of PEO chains and a small overall diameter (<100 nm) of the PEO-SiO2 nanohybrid-encapsulated MONPs (PEOMSNs). The PEOMSNs are not susceptible to Mn-ion leaching, and their biocompatibility is affirmed by a low toxicity profile. Moreover, these hybrid nanocapsules exhibit a nano-rattle structure, which would favor the facile loading of various therapeutic reagents for theranostic applications.To properly engineer MnO nanoparticles (MONPs) of high r1 relaxivity, a nanohybrid coating consisting of silica and F127 (PEO106PPO70PEO106) is designed to encapsulate MONPs. Achieved by an interfacial templating scheme, the nanohybrid encapsulating layer is highly permeable and hydrophilic to allow for an optimal access of water molecules to the encapsulated manganese oxide core. Hence, the efficacy of MONPs as MRI contrast agents is significantly improved, as demonstrated by an enhancement of the MR signal measured with a pre-clinical 7.0 T MRI scanner. The nanohybrid encapsulation strategy also confers high colloidal stability to the hydrophobic MONPs by the surface decoration of PEO chains and a small overall diameter (<100 nm) of the PEO-SiO2 nanohybrid-encapsulated MONPs (PEOMSNs). The PEOMSNs are not susceptible to Mn-ion leaching, and their biocompatibility is affirmed by a low toxicity profile

GdPtPb: A noncollinear antiferromagnet with distorted kagome lattice

DOE PAGES

Manni, S.; Bud'ko, Sergey L.; Canfield, Paul C.

2017-08-24

In the spirit of searching for Gd-based, frustrated, rare earth magnets, we have found antiferomagnetism (AF) in GdPtPb, which crystallizes in the ZrNiAl-type structure that has a distorted kagome lattice of Gd triangles. Single crystals were grown and investigated using structural, magnetic, transport, and thermodynamic measurements. GdPtPb orders antiferromagnetically at 15.5 K, arguably with a planar, noncollinear structure. The high temperature magnetic susceptibility data reveal an “anti-frustration” behavior having a frustration parameter, |f| = |Θ|/T N = 0.25, which can be explained by mean field theory within a two-sublattice model. Here, the study of the magnetic phase diagram down tomore » T = 1.8K reveals a change of magnetic structure through a metamagnetic transition at around 20 kOe and the disappearance of the AF ordering near 140 kOe. In total, our work indicates that GdPtPb can serve as an example of a planar, noncollinear AF with a distorted kagome magnetic sublattice.« less

Magnetocaloric effect in Gd1-x Ndx Zn2

NASA Astrophysics Data System (ADS)

Matsumoto, Keisuke T.; Hiraoka, Koichi

2017-09-01

The magnetization of Gd1-xNdxZn2 (0 < x ⩽ 1) was measured to study the effect of Nd substitution in GdZn2 with a Curie temperature of 85 K and a spin-reorientation transition temperature of 58 K on the magnetocaloric effect. The Nd counterpart NdZn2 shows antiferromagnetic order at 23 K. Samples of Gd1-xNdxZn2 (0 < x ⩽ 1) were prepared by the melt-growth method. In Nd-substituted systems, the anomaly due to spin-reorientation disappeared. For x ⩾ 0.6 , field-induced metamagnetic transitions were observed, indicating an antiferromagnetic ground state. This complex magnetism may originate from competition between ferromagnetic and antiferromagnetic interactions. Magnetic entropy change ΔSm was calculated based on the magnetization measurements. ΔSm was suppressed by Nd substitution for x values up to 0.6. For x = 1 (NdZn2), the maximum value of ΔSm was -9 J/K kg, which is almost the same as those of other Nd-based magnetocaloric materials.

Multivalent Protein Polymer MRI Contrast Agents: Controlling Relaxivity via Modulation of Amino Acid Sequence

PubMed Central

Karfeld-Sulzer, Lindsay S.; Waters, Emily A.; Davis, Nicolynn E.; Meade, Thomas J.; Barron, Annelise E.

2010-01-01

Magnetic Resonance Imaging (MRI) is a noninvasive imaging modality with high spatial and temporal resolution. Contrast agents (CAs) are frequently used to increase the contrast between tissues of interest. To increase the effectiveness of MR agents, small molecule CAs have been attached to macromolecules. We have created a family of biodegradable, macromolecular CAs based on protein polymers, allowing control over the CA properties. The protein polymers are monodisperse, random coil, and contain evenly spaced lysines that serve as reactive sites for Gd(III) chelates. The exact sequence and length of the protein can be specified, enabling controlled variation in lysine spacing and molecular weight. Relaxivity could be modulated by changing protein polymer length and lysine spacing. Relaxivities of up to ∼14 mM-1s-1 per Gd(III) and ∼461 mM-1s-1 per conjugate were observed. These CAs are biodegradable by incubation with plasmin, such that they can be easily excreted after use. They do not reduce cell viability, a prerequisite for future in vivo studies. The protein polymer CAs can be customized for different clinical diagnostic applications, including biomaterial tracking, as a balanced agent with high relaxivity and appropriate molar mass. PMID:20420441

Preclinical evaluation of severely defective manganese-based nanocrystal as a liver-specific contrast media for MR imaging: comparison with Gd-EOB-DTPA and MnDPDP

NASA Astrophysics Data System (ADS)

Zhang, Yu; Xiao, Xiao-ping; Shu, Ting; Cai, Jing; Xiao, Xin-lan; Li, Yan-shu; Zhang, Zhong-wei; Tang, Qun

2018-06-01

Manganese-based (chemically formulated of KMnF3) nanocrystal was evaluated as a liver-specific contrast agent for MR imaging and its imaging performance was also compared with those of two commercial hepatobiliary contrast media (Gd-EOB-DTPA and MnDPDP). KMnF3 nanocrystal was post-treated using a plasma technique to cause severe defects, leading to appropriate water dispersibility and high relaxivity. Severely defective KMnF3 nanocrystal (SD-KMnF3) has characteristic high tolerance, as evidenced by cytotoxicity on the macrophage cell, and acute and subchronic toxicity on the healthy mouse. SD-KMnF3 showed better hepatic MR imaging as the T 1 relaxation time of the liver decreased to only 17% of the control group, compared to 22% of the control group for Gd-EOB-DTPA (P < 0.01) and 42% of the control group for MnDPDP (P < 0.001). As applied to MR imaging of the allograft orthotopic model of liver cancer, statistical studies demonstrated that SD-KMnF3 significantly improved the tumor’s contrast-to-noise ratio, compared with Gd-EOB-DTPA (P < 0.01) and MnDPDP (P < 0.01) by spin-echo pulse sequence, and even better performance (P < 0.001) by gradient-echo sequence. Our findings indicate that SD-KMnF3 could serve as a hepatic contrast agent for imaging liver cancer such as hepatocarcinoma or metastatic lesions.

Preclinical evaluation of severely defective manganese-based nanocrystal as a liver-specific contrast media for MR imaging: comparison with Gd-EOB-DTPA and MnDPDP.

PubMed

Zhang, Yu; Xiao, Xiao-Ping; Shu, Ting; Cai, Jing; Xiao, Xin-Lan; Li, Yan-Shu; Zhang, Zhong-Wei; Tang, Qun

2018-06-01

Manganese-based (chemically formulated of KMnF 3 ) nanocrystal was evaluated as a liver-specific contrast agent for MR imaging and its imaging performance was also compared with those of two commercial hepatobiliary contrast media (Gd-EOB-DTPA and MnDPDP). KMnF 3 nanocrystal was post-treated using a plasma technique to cause severe defects, leading to appropriate water dispersibility and high relaxivity. Severely defective KMnF 3 nanocrystal (SD-KMnF 3 ) has characteristic high tolerance, as evidenced by cytotoxicity on the macrophage cell, and acute and subchronic toxicity on the healthy mouse. SD-KMnF 3 showed better hepatic MR imaging as the T 1 relaxation time of the liver decreased to only 17% of the control group, compared to 22% of the control group for Gd-EOB-DTPA (P < 0.01) and 42% of the control group for MnDPDP (P < 0.001). As applied to MR imaging of the allograft orthotopic model of liver cancer, statistical studies demonstrated that SD-KMnF 3 significantly improved the tumor's contrast-to-noise ratio, compared with Gd-EOB-DTPA (P < 0.01) and MnDPDP (P < 0.01) by spin-echo pulse sequence, and even better performance (P < 0.001) by gradient-echo sequence. Our findings indicate that SD-KMnF 3 could serve as a hepatic contrast agent for imaging liver cancer such as hepatocarcinoma or metastatic lesions.

NMR relaxation studies in doped poly-3-methylthiophene

NASA Astrophysics Data System (ADS)

Singh, K. Jugeshwar; Clark, W. G.; Gaidos, G.; Reyes, A. P.; Kuhns, P.; Thompson, J. D.; Menon, R.; Ramesh, K. P.

2015-05-01

NMR relaxation rates (1 /T1 ), magnetic susceptibility, and electrical conductivity studies in doped poly-3-methylthiophene are reported in this paper. The magnetic susceptibility data show the contributions from both Pauli and Curie spins, with the size of the Pauli term depending strongly on the doping level. Proton and fluorine NMR relaxation rates have been studied as a function of temperature (3-300 K) and field (for protons at 0.9, 9.0, 16.4, and 23.4 T, and for fluorine at 9.0 T). The temperature dependence of T1 is classified into three regimes: (a) For T <(g μBB /2 kB ) , the relaxation mechanism follows a modified Korringa relation due to electron-electron interactions and disorder. 1H - T1 is due to the electron-nuclear dipolar interaction in addition to the contact term. (b) For the intermediate temperature range (g μBB /2 kB ) <T T1 is insignificant) the relaxation mechanism is via spin diffusion to the paramagnetic centers. (c) In the high-temperature regime and at low Larmor frequency the relaxation follows the modified Bloembergen, Purcell, and Pound model. T1 data analysis has been carried out in light of these models depending upon the temperature and frequency range of study. Fluorine relaxation data have been analyzed and attributed to the P F6 reorientation. The cross relaxation among the 1H and 19F nuclei has been observed in the entire temperature range suggesting the role of magnetic dipolar interaction modulated by the reorientation of the symmetric molecular subgroups. The data analysis shows that the enhancement in the Korringa ratio is greater in a less conducting sample. Intra- and interchain hopping of charge carriers is found to be a dominant relaxation mechanism at low temperature. Frequency dependence of T1-1 on temperature shows that at low temperature [T <(g μBB /2 kB ) ] the system shows three dimensions and changes to quasi one dimension at

Molecular order and T1-relaxation, cross-relaxation in nitroxide spin labels

NASA Astrophysics Data System (ADS)

Marsh, Derek

2018-05-01

Interpretation of saturation-recovery EPR experiments on nitroxide spin labels whose angular rotation is restricted by the orienting potential of the environment (e.g., membranes) currently concentrates on the influence of rotational rates and not of molecular order. Here, I consider the dependence on molecular ordering of contributions to the rates of electron spin-lattice relaxation and cross relaxation from modulation of N-hyperfine and Zeeman anisotropies. These are determined by the averages and , where θ is the angle between the nitroxide z-axis and the static magnetic field, which in turn depends on the angles that these two directions make with the director of uniaxial ordering. For saturation-recovery EPR at 9 GHz, the recovery rate constant is predicted to decrease with increasing order for the magnetic field oriented parallel to the director, and to increase slightly for the perpendicular field orientation. The latter situation corresponds to the usual experimental protocol and is consistent with the dependence on chain-labelling position in lipid bilayer membranes. An altered dependence on order parameter is predicted for saturation-recovery EPR at high field (94 GHz) that is not entirely consistent with observation. Comparisons with experiment are complicated by contributions from slow-motional components, and an unexplained background recovery rate that most probably is independent of order parameter. In general, this analysis supports the interpretation that recovery rates are determined principally by rotational diffusion rates, but experiments at other spectral positions/field orientations could increase the sensitivity to order parameter.

NOTE: The effects of paramagnetic contrast agents on metabolite protons in aqueous solution

NASA Astrophysics Data System (ADS)

Murphy, Philip S.; Leach, Martin O.; Rowland, Ian J.

2002-03-01

The longitudinal (R1) and transverse (R2) relaxivities of the clinically used contrast agents Gd(DTPA)2-, Gd(DOTA)- and Gd(DTPA-BMA) have been determined in mixed aqueous metabolite solutions for choline, creatine and N-acetylaspartate. Measurements were performed at 1.5 T using a STEAM sequence on 25 mM metabolite solutions at pH = 7.4 and 22 °C. The data showed that for all the contrast agents and metabolites, R1 ~ R2. The largest range of relaxivity values was found for Gd(DTPA)2-, where R2 = 6.8 +/- 0.3 mM-1 s-1 for choline and 1.5 +/- 0.4 mM-1 s-1 for N-acetylaspartate. Variation in relaxivity values was attributed primarily to differences between the charges of the paramagnetic agent and metabolite. The maximum potential influence of the contrast agents on in vivo metabolite signals was calculated using the measured relaxivities.

3.0 Tesla high spatial resolution contrast-enhanced magnetic resonance angiography (CE-MRA) of the pulmonary circulation: initial experience with a 32-channel phased array coil using a high relaxivity contrast agent.

PubMed

Nael, Kambiz; Fenchel, Michael; Krishnam, Mayil; Finn, J Paul; Laub, Gerhard; Ruehm, Stefan G

2007-06-01

To evaluate the technical feasibility of high spatial resolution contrast-enhanced magnetic resonance angiography (CE-MRA) with highly accelerated parallel acquisition at 3.0 T using a 32-channel phased array coil, and a high relaxivity contrast agent. Ten adult healthy volunteers (5 men, 5 women, aged 21-66 years) underwent high spatial resolution CE-MRA of the pulmonary circulation. Imaging was performed at 3 T using a 32-channel phase array coil. After intravenous injection of 1 mL of gadobenate dimeglumine (Gd-BOPTA) at 1.5 mL/s, a timing bolus was used to measure the transit time from the arm vein to the main pulmonary artery. Subsequently following intravenous injection of 0.1 mmol/kg of Gd-BOPTA at the same rate, isotropic high spatial resolution data sets (1 x 1 x 1 mm3) CE-MRA of the entire pulmonary circulation were acquired using a fast gradient-recalled echo sequence (TR/TE 3/1.2 milliseconds, FA 18 degrees) and highly accelerated parallel acquisition (GRAPPA x 6) during a 20-second breath hold. The presence of artifact, noise, and image quality of the pulmonary arterial segments were evaluated independently by 2 radiologists. Phantom measurements were performed to assess the signal-to-noise ratio (SNR). Statistical analysis of data was performed by using Wilcoxon rank sum test and 2-sample Student t test. The interobserver variability was tested by kappa coefficient. All studies were of diagnostic quality as determined by both observers. The pulmonary arteries were routinely identified up to fifth-order branches, with definition in the diagnostic range and excellent interobserver agreement (kappa = 0.84, 95% confidence interval 0.77-0.90). Phantom measurements showed significantly lower SNR (P < 0.01) using GRAPPA (17.3 +/- 18.8) compared with measurements without parallel acquisition (58 +/- 49.4). The described 3 T CE-MRA protocol in addition to high T1 relaxivity of Gd-BOPTA provides sufficient SNR to support highly accelerated parallel acquisition

A study of spin-lattice relaxation rates of glucose, fructose, sucrose and cherries using high-T c SQUID-based NMR in ultralow magnetic fields

NASA Astrophysics Data System (ADS)

Liao, Shu-Hsien; Wu, Pei-Che

2017-08-01

We study the concentration dependence of spin-lattice relaxation rates, T 1 -1, of glucose, fructose, sucrose and cherries by using high-T c SQUID-based NMR at magnetic fields of ˜97 μT. The detected NMR signal, Sy (T Bp), is fitted to [1 - exp(-T Bp/T 1)] to derive T 1 -1, where Sy (T Bp) is the strength of the NMR signal, T Bp is the duration of pre-polarization and T 1 -1 is the spin-lattice relaxation rate. It was found that T 1 -1 increases as the sugar concentrations increase. The increased T 1 -1 is due to the presence of more molecules in the surroundings, which increases the spin-lattice interaction and in turn enhances T 1 -1. The T 1 -1 versus degrees Brix curve provides a basis for determining unknown Brix values for cherries as well as other fruits.

Thermodynamic scaling of α-relaxation time and viscosity stems from the Johari-Goldstein β-relaxation or the primitive relaxation of the coupling model.

PubMed

Ngai, K L; Habasaki, J; Prevosto, D; Capaccioli, S; Paluch, Marian

2012-07-21

By now it is well established that the structural α-relaxation time, τ(α), of non-associated small molecular and polymeric glass-formers obey thermodynamic scaling. In other words, τ(α) is a function Φ of the product variable, ρ(γ)/T, where ρ is the density and T the temperature. The constant γ as well as the function, τ(α) = Φ(ρ(γ)/T), is material dependent. Actually this dependence of τ(α) on ρ(γ)/T originates from the dependence on the same product variable of the Johari-Goldstein β-relaxation time, τ(β), or the primitive relaxation time, τ(0), of the coupling model. To support this assertion, we give evidences from various sources itemized as follows. (1) The invariance of the relation between τ(α) and τ(β) or τ(0) to widely different combinations of pressure and temperature. (2) Experimental dielectric and viscosity data of glass-forming van der Waals liquids and polymer. (3) Molecular dynamics simulations of binary Lennard-Jones (LJ) models, the Lewis-Wahnström model of ortho-terphenyl, 1,4 polybutadiene, a room temperature ionic liquid, 1-ethyl-3-methylimidazolium nitrate, and a molten salt 2Ca(NO(3))(2)·3KNO(3) (CKN). (4) Both diffusivity and structural relaxation time, as well as the breakdown of Stokes-Einstein relation in CKN obey thermodynamic scaling by ρ(γ)/T with the same γ. (5) In polymers, the chain normal mode relaxation time, τ(N), is another function of ρ(γ)/T with the same γ as segmental relaxation time τ(α). (6) While the data of τ(α) from simulations for the full LJ binary mixture obey very well the thermodynamic scaling, it is strongly violated when the LJ interaction potential is truncated beyond typical inter-particle distance, although in both cases the repulsive pair potentials coincide for some distances.

Preparation, spectroscopic and high field NMR relaxometry studies of gadolinium(III) complexes with the asymmetric tetraamine 1,4,7,11-tetraazaundecane

NASA Astrophysics Data System (ADS)

Hatzipanayioti, Despina; Veneris, Antonis

2009-10-01

The reaction of Gd(III) with asymmetric tetramine 1,4,7,11-tetraazaundecane (2,2,3-tet, L1) ligand has been studied via NMR spectroscopy. The ligand proton longitudinal relaxation rates ( R1) have been used to estimate the distances of these protons from the Gd(III) center, in Gd(III)- L1 reaction solutions, in H 2O/D 2O 5/1 mixtures. Two Gd(III) complexes [Gd(III)( L1)(NH 3)(H 2O) 4](CH 3COO) 3·2H 2O ( 1) and [Gd(III)( L1)(NH 3)(H 2O) 2]Cl 3·EtOH ( 2) have been isolated and characterized by elemental analyses, TGA, IR, NMR and relaxometry measurements. The NMR relaxation measurements of 2 in aqueous solutions have been performed, under various temperature or concentration conditions, and compared with those of the commercial contrast agents Gd(III)-DTPA and Gd(III)-DTPA-BMA. It has also been studied the influence of (i) the Gd(III) inner-sphere water molecule number ( q) alteration and (ii) the steric constraint enhancement on the metal site, over the relaxation rate values of the parent aqueous solution of Gd(III)-2,2,3-tet, and of the aqueous solutions of 2.

A Rare Form of Guillan Barre Syndrome: A Child Diagnosed with Anti-GD1a and Anti-GD1b Positive Pharyngeal-Cervical-Brachial Variant.

PubMed

Uysalol, Metin; Tatlı, Burak; Uzel, Nedret; Cıtak, Agop; Aygün, Erhan; Kayaoğlu, Semra

2013-09-01

Pharyngeal-cervical-brachial (PCB) variant is a rare form of Guillan-Barre Syndrome (GBS). Antibodies against other membrane proteins like GM1b and GD1a have been found only in a small number of patients with Guillan Barre syndrome variant. Here, we report a 5.5 year-old boy diagnosed early with positive GD1a and GD1b gangliosides of Guillan-Barre syndrome pharyngeal cervical-Brachial variant, who improved and recovered fully in a short period. This is in contrast to those whose recovery period prolongs in spite of early diagnosis and appropriate treatment and/or those who experience incomplete recovery. In summary, diagnosis of PCB variant of GBS should be considered in infants with sudden onset bulbar symptoms and muscle weakness, and it should be kept in mind that early diagnosis and appropriate treatment can give successful outcomes.

Development of Gd3N@C80 encapsulated redox nanoparticles for high-performance magnetic resonance imaging.

PubMed

Gao, Zhenyu; Nakanishi, Yusuke; Noda, Shoko; Omachi, Haruka; Shinohara, Hisanori; Kimura, Hiroyuki; Nagasaki, Yukio

As novel magnetic resonance imaging (MRI) contrast agent, gadofullerene encapsulated redox nanoparticles (Gd 3 NPs) were prepared by encapsulation of Gd 3 N@C 80 in the core of core-shell-type polymer micelles composed of original polyamine with a reactive oxygen species (ROS)-scavenging ability. Because Gd 3 NPs possess biocompatible PEG shell with a smaller size (ca. 50 nm), they had high colloidal stability in a physiological environment, and showed low cytotoxicity. Specific accumulation of Gd 3 NPs in a tumor was confirmed in tumor-bearing mice after systemic administration. The tumor/muscle (T/M) ratio of the Gd ion reached five at 7.5 h after the administration. T 1 -weighted MRI signal enhancement of the T/M ratio increased by 8% at 6 h postinjection of Gd 3 NPs (Gd dose:14.35 μmol/kg). Although Gd 3 NPs showed a tendency for extended blood circulation, they did not have severe adverse effects, probably due to the confinement of Gd in a hydrophobic fullerene in addition to the ROS-scavenging capacity of these nanoparticles. In sharp contrast, systemic administration of Gd-chelate nanoparticles (GdCNPs) to mice disrupts liver function, increases leukocyte counts, and destroys spleen and skin tissues. Leaking of Gd ions from GdCNPs may cause such adverse effects. Based on these results, we expect that Gd 3 NPs is high-performance MRI contrast agents for tumor diagnosis.

Off-resonance R1rho relaxation outside of the fast exchange limit: an experimental study of a cavity mutant of T4 lysozyme.

PubMed

Korzhnev, Dmitry M; Orekhov, Vladislav Yu; Dahlquist, Frederick W; Kay, Lewis E

2003-05-01

An (15)N off-resonance R(1rho) spin relaxation study of an L99A point mutant of T4 lysozyme is presented. Previous CPMG-based relaxation dispersion studies of exchange in this protein have established that the molecule interconverts between a populated ground state and an excited state (3.4%) with an exchange rate constant of 1450 s(-1) at 25 degrees C. It is shown that for the majority of residues in this protein the offset dependence of the R(1rho) relaxation rates cannot be well fit using models which are only valid in the fast exchange regime. In contrast, a recently derived expression by Trott and Palmer (J. Magn. Reson., 154, 157-160, 2002) which is valid over a wider window of exchange than other relations, is shown to fit the data well. Values of (signed) chemical shift differences between exchanging sites have been extracted and are in reasonable agreement with shift differences measured using CPMG methods. A set of simulations is presented which help establish the exchange regimes that are best suited to analysis by off-resonance R(1rho) techniques.

Gd-EOB-DTPA-enhanced T1ρ imaging vs diffusion metrics for assessment liver inflammation and early stage fibrosis of nonalcoholic steatohepatitis in rabbits.

PubMed

Xie, Yuanliang; Zhang, Hongfeng; Jin, Chaoling; Wang, Xiang; Wang, Xiaoqi; Chen, Jingting; Xu, Yikai

2018-05-01

To assess the value of T1ρ,T1ρ on hepatobiliary phase (HBP) and diffusion metrics in staging of Non-alcoholic fatty liver disease (NAFLD) activity scores, inflammation, fibrosis in NASH rabbits model. Non-alcoholic steatohepatitis (NASH) rabbits model was induced by feeding a varied duration of high-fat, high-cholesterol diet. T1ρ,T1ρ (HBP) 20min after administration of Gd-EOB-DTPA, and Intravoxel incoherent motion imaging (IVIM) diffusion-weighted imaging were performed on a 3.0T magnetic resonance (MR) imaging unit. The diagnostic value of each parameter for NAS, inflammation and fibrosis severity were determined. T1ρ (r=0.658) and T1ρ (HBP) (r=0.750) have strong association with NASH overall activity, T1ρ (HBP) is strongly relevant to inflammation stage (r=0.812). There was negative association between f and inflammation (r=-0.480), whilst no significant relation between other three parameters (apparent diffusion coefficient (ADC), pseudo-diffusion coefficient (D*) and true diffusion coefficient (D)) and inflammation or overall activity. The areas under the receiver operating characteristic curves (AUCs) of f, ADC, T1ρ and T1ρ-HBP were 0.871, 0.728, 0.849 and 0.949 for differentiating NASH; 0.731, 0.552, 0.925 and 0.922 for G2-3 inflammation; and 0.767, 0.625, 0.816, and 0.882 for S1-2 fibrosis. Comparison of ROC curve showed T1ρ (HBP) had an optimal diagnostic performance for NASH [T1ρ (HBP) vs ADC, AUC:0.949 vs 0.728, P=0.043], inflammation [T1ρ (HBP) vs ADC, AUC:0.922 vs 0.552, P=0.003], fibrosis [T1ρ (HBP) vs ADC, AUC:0.882 vs 0.625, P=0.046]. The combination of T1ρ (HBP)+perfusion fraction (f) showed highest diagnostic value for NASH (AUC:0.971), inflammation (AUC:0.935). Among T1ρ imaging and IVIM diffusion metrics, combination of T1rho (HBP)+f was found to be superior noninvasive imaging biomarker for NASH activity assessment. Copyright © 2017 Elsevier Inc. All rights reserved.