P792: a rapid clearance blood pool agent for magnetic resonance imaging: preliminary results

An original MRI contrast agent, called P792, is described. P792 is a gadolinium macrocyclic compound based on a Gd-DOTA structure substituted by hydrophilic arms. The chemical structure of P792 has been optimized in order to provide (1) a high r₁ relaxivity in the clinical field for MRI: 29 mM⁻¹ x s⁻¹ at 60 MHz. (2) a high biocompatibility profile and (3) a high molecular volume: the apparent hydrodynamic volume of P792 is 125 times greater than that of Gd-DOTA. As a result of this high molecular volume, P792 presents an unusual pharmacokinetic profile, as it is a Rapid Clearance Blood Pool Agent (RCBPA) characterized by limited diffusion across the normal endothelium. The original pharmacokinetic properties of this RCBPA are expected to be well suited to MR coronary angiography, angiography, perfusion imaging (stress and rest), and permeability imaging (detection of ischemia and tumor grading). Further experimental imaging studies are ongoing to define the clinical value of this compound.     

Gadolinium-containing copolymeric chelates—a new potential MR contrast agent

Rationale and objectives: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents.Methods: Various copolymeric chelates of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium-DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd-copolymers.Results: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. Ther ₁ (1/T1, mM⁻¹ s⁻¹) for Gd-DTPA=4.1. Ther ₁ values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowestr ₁ for the polymer prepared with the lowest-molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd-DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement—a reflection of distribution into extravascular fluid space—was observed.Conclusions: Relative to Gd-DTPA monomers, PEG-containing Gd-DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase inr ₁ relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd-copolymers are promising agents that merit additional study.     

Relationship between carotid plaque surface morphology and perfusion: a 3D DCE-MRI study

Objective

This study aims to explore the relationship between plaque surface morphology and neovascularization using a high temporal and spatial resolution 4D contrast-enhanced MRI/MRA sequence.

Materials and methods

Twenty one patients with either recent symptoms or a carotid artery stenosis ≥40% were recruited in this study. Plaque surface morphology and luminal stenosis were determined from the arterial phase MRA images. Carotid neovascularization was evaluated by a previously validated pharmacokinetic (PK) modeling approach. K ^trans (transfer constant) and v _p (partial plasma volume) were calculated in both the adventitia and plaque.

Results

Image acquisition and analysis was successfully performed in 28 arteries. Mean luminal stenosis was 44% (range 11–82%). Both adventitial and plaque K ^trans in ulcerated/irregular plaques were significantly higher than smooth plaques (0.079 ± 0.018 vs. 0.064 ± 0.011 min^?1, p = 0.02; 0.065 ± 0.013 vs. 0.055 ± 0.010 min^?1, p = 0.03, respectively). Positive correlations between adventitial K ^trans and v _p against stenosis were observed (r = 0.44, p = 0.02; r = 0.55, p = 0.01, respectively).

Conclusion

This study demonstrates the feasibility of using a single sequence to acquire both high resolution 4D CE-MRA and DCE-MRI to evaluate both plaque surface morphology and function. The results demonstrate significant relationships between lumen surface morphology and neovascularization.

     

Fast chemical shift mapping with multiecho balanced SSFP

Object: A method is proposed that provides spectroscopic images with high spatial resolution and moderate spectral resolution at very short total data acquisition times. Materials and methods: Balanced steady-state free precession (bSSFP, TrueFISP, FIESTA, b-FFE) is combined with a multiecho readout gradient and frequency-sensitive reconstruction such as Fourier reconstruction known from echo-planar spectroscopic imaging (EPSI) or matrix inversion. Balanced SSFP imaging requires short repetition times to minimize banding artefacts, thereby restricting the achievable frequency resolution. Results: Two-dimensional (2D) high-resolution spectroscopic images were produced of three ¹H resonances (water, acetone and fat) on phantoms and water/fat separation in vivo within 1–2 s. Additionally, fast ³¹P spectroscopic images were acquired from a phantom consisting of two resonances within 195 ms. Conclusion: Frequency-sensitive reconstruction of multiecho bSSFP data can provide spectroscopic images with high spatial and temporal resolution while the frequency resolution is moderate at around 100 Hz. The method can also separate more than three resonances, allowing for hetero-nuclei metabolite mapping, for example ¹³C and ³¹P.     

Electrical properties of ultrathin HfO2 gate dielectrics on partially strain compensated SiGeC/Si heterostructures

Ultrathin HfO₂ gate dielectrics have been deposited on strained Si_0.69Ge_0.3C_0.01 layers by rf magnetron sputtering. The polycrystalline HfO₂ film with a physical thickness of ∼6.5 nm and an amorphous interfacial layer with a physical thickness of ∼2.5 nm have been observed by high resolution transmission electron microscopy (HRTEM). The electrical properties have been studied using metal-oxide-semiconductor (MOS) structures. The fabricated MOS capacitors on Si_0.69 Ge_0.3C_0.01 show an equivalent oxide thickness (EOT) of 2.9 nm, with a low leakage current density of ∼4.5 × 10 ^{− 7} A/cm² at a gate voltage of –1.0 V. The fixed oxide charge and interface state densities are calculated to be 1.9 × 10¹² cm^{− 2} and 3.3 × 10 ¹¹ cm^{− 2}eV⁻¹, respectively. The temperature dependent gate leakage characteristics has been studied to establish the current transport mechanism in high-k HfO₂ gate dielectric to be Poole–Frenkel one. An improvement in electrical properties of HfO₂ gate dielectrics has been observed after post deposition annealing in O₂ and N₂ environments.     

Oxygen permeation properties and surface modification of acceptor-doped CeO2/MnFe2O4 composites

The preparation and oxygen permeation properties of the (Ce_0.8Pr_0.2)O_2−δ − x vol% MnFe₂O₄ composites, where x = 0 to 35, have been investigated. The samples were prepared by the Pechini method. In the case of Ce_0.8Pr_0.2O_2−δ, an oxygen flux density of 6 μmol⋅cm⁻²⋅s⁻¹ (L = 0.0247 cm) and the maximum methane conversion of 50% were attained at 1000^∘C. Unlike composites consisting of Gd-doped CeO₂ and MnFe₂O₄, the oxygen permeability of the (Ce_0.8Pr_0.2)O_2−δ – x vol% MnFe₂O₄ composites was almost constant regardless of the volume fraction of MnFe₂O₄; however, the optimum volume fraction of MnFe₂O₄ was determined to be 5 to 25 in the context of the chemical and mechanical stabilities under methane conversion atmosphere. In addition, the surface modification of the (Ce_0.8Gd_0.2)O_2−δ – 15 vol% MnFe₂O₄ composite was performed by using the FePt nanoparticles. The catalyst loading of 2.8 mg/cm² on the both side of the 0.3 mm-thick (Ce_0.8Gd_0.2)O_2−δ – 15vol% MnFe₂O₄ composite increased the oxygen flux density from 0.30 to 0.76 μmol⋅cm⁻²⋅s⁻¹ in the case of He/air gradients; however, the effect seems to be reduced in the case of high oxygen flux density caused by a large pO₂ gradient. Moreover, the Langmuir-Blodgett film of the FePt nanoparticles were successfully prepared on the tape-cast (Ce_0.8Gd_0.2)O_2−δ – 15vol% MnFe₂O₄ composite. Hydrophobic treatments for the surface of the composite were crucial to achieve high transfer ratio for the deposition of the LB film.     

Thermoelectric properties of Bi and Cu co-doped Ca3Co2O6single crystals

Single crystals of Bi and Cu-doped Ca₃Co₂O₆were synthesized in a molten K₂CO₃flux. Using an obtained single crystal of (Ca_0.985(5)Bi_0.015(5))₃(Co_0.990(3)Cu_0.010(3))₂O₆elongated to the c-axis direction of the crystal structure, the electric resistivity (ρ) and Seebeck coefficient (S) were measured from room temperature to over 1000 K in air. The single crystal showed p-type semiconducting behavior with ρ values of 1.8 Ω cm at 303 K and 0.017 Ω cm at 1000 K. The S values were +254 μ VK^{− 1} at 325 K, +360 μ VK^{− 1} at 420 K, and +214 μ VK^{− 1} at 1000 K. The power factor (S ² ρ ^{− 1}) increased with an increase of temperature and attained 2.70 × 10^{− 4} Wm^{− 1}K^{− 2} at 1000 K.     

Effects of sputtering pressure on the characteristics of lithium ion conductive lithium phosphorous oxynitride thin film

Lithium phosphorous oxynitride(Lipon) thin films as a lithium ion conductive electrolyte were prepared by radio frequency reactive sputtering in N₂ plasma. The properties of the amorphous Lipon solid electrolyte were investigated as a function of N₂ pressure during reactive sputtering. The ionic conductivity and the electrochemical stability of Lipon thin films improved drastically as the N₂ pressure decreased. The ionic conductivity closed to 10⁻⁶ S cm⁻¹ and obtained a stability window of 1.0–5.0 V with an N₂ pressure of 5 mTorr, where the number of nitrogen bonds between the phosphate groups were more than those formed at higher pressure. It was possible to fabricate the Li//LiCoO₂ complete thin film battery using this Lipon solid electrolyte, which exhibited excellent discharge characteristics close to the theoretical capacity (ca. 69 uAhcm⁻²−um⁻¹) and showed a considerably high rate capability.     

Effect of Concentration of SH U 555A Labeled Human Melanoma Cells on MR Spin Echo and Gradient Echo Signal Decay at 0.2, 1.5, and 3T

In the current study the effect of increasing concentrations of superparamagnetic iron oxide labeled cells on the MRI signal decay at magnetic field strengths of 0.2, 1.5, and 3 T was evaluated. The spin echo and gradient echo cellular transverse relaxivity was systematically studied for various concentrations (N = 1, 5, 10, 20, 40, and 80 cells/μl_gel) of homogeneously suspended SH U 555A labeled SK-Mel28 human melanoma cells. For all field strengths investigated a linear relationship between cellular transverse relaxation enhancement and cell concentration was found. In the spin echo case, the cellular relaxivities [i.e., d(ΔR ₂)/dN] were determined to 0.12 s⁻¹ (cell/μl)⁻¹ at 0.2 T, 0.16 s⁻¹ (cell/μl)⁻¹ at 1.5 T, and 0.17 s⁻¹ (cell/μl) at 3 T. In the gradient echo case, the calculated cellular relaxivities (i.e., d(ΔR ₂ ^* )/dN) were 0.51 s⁻¹ (cell/μl)⁻¹ at 0.2 T, 0.69 s⁻¹ (cell/μl)⁻¹ at 1.5 T, and 0.71 s⁻¹ (cell/μl)⁻¹ at 3 T. The proposed preparation technique has proven to be a simple and reliable approach to quantify effects of magnetically labeled cells in vitro. On the basis of this quantification well suited tissue specific models can be derived.     

Is absolute noninvasive temperature measurement by the Pr[MOE-DO3A] complex feasible

Recently, the feasibility of the praseodymium complex of 10-(2-methoxyethyl)-1,4,7,10-tetraaza-cyclododecane-1,4,7-triacetate (Pr[MOE-DO3A]) for non-invasive temperature measurement via¹H spectroscopy has been demonstrated. Particularly the suitability of the complex for non-invasive temperature measurements including in vivo spectroscopy without spatial resolution as well as first spectroscopic imaging measurements at low temporal resolution (≥4 min) and high temporal resolution (breath hold, ∼20 s) has been shown. As of today, calibration curves according to the particular experimental conditions are necessary. This work aims to clarify whether the Pr[MOE-DO3A] probe in conjunction with¹H-NMR spectroscopy allows non-invasive absolute temperature measurements with high accuracy. The measurement results from two different representative media, distilled water and human plasma, show a slight but significant dependence of the calibration curves on the surrounding medium. Calibration curves in water and plasma were derived for the temperature dependence of the chemical shift difference (F) between Pr[MOE-DO3A]'s OCH₃ and water withF=−(27.53±0.04)+(0.125±0.001)^* T andF=−(27.61±0.02)+(0.129±0.001)^* T. respectivel, withF in ppm andT in °C. However, the differences are minuscule even for the highest spectral resolution of 0.001 ppm/pt, so that they are indistinguishable under practical conditions. The estimated temperature errors are ±0.18°C for water and ±0.14°C for plasma and with that only slightly worse than the measurement accuracy of the fiber-optical temperature probe (±0.1°C). It can be concluded that the results obtained indicate the feasibility of the¹H spectroscopy method in conjunction with the Pr[MOE-DO3A] probe for absolute temperature measurements, with a maximum accuracy of ±0.2°C.     

The development of novel trivalent ion conducting solids and their application for gas sensors

An exceptionally high Al³⁺ ion conducting polycrystalline solid based on the NASICON type structure was successfully realized within the system (Al_xZr_1−x)_4/(4−x)Nb(PO₄)₃. The partial substitution of the smaller higher valent Nb⁵⁺ ion for Zr⁴⁺ helped stabilize and accommodate the mobile Al³⁺ ion into the NASICON like structure. The addition of boron oxide to the Al³⁺ ion conducting solid electrolyte, as a sintering additive, aided in the achievement of satisfactory mechanical strength and density for practical use. Environmental gas sensors were fabricated by combining the (Al_xZr_1−x)_4/(4−x)Nb(PO₄)₃ solid electrolyte with yttria stabilized zirconia (YSZ) and appropriate auxiliary electrodes. The Nernst-like electrochemical sensors demonstrated rapid and reproducible response to CO₂ and NOx, thereby promising excellent potential for environmental monitoring applications.     

Characterization and dielectric properties of Ba5LnNiTa9O30 (Ln = La, Nd and Sm) ceramics

Three novel Ba₅LnNiTa₉O₃₀ (Ln = La, Nd and Sm) ceramics were prepared and characterized in the BaO-Ln₂O₃-NiO-Ta₂O₅ system. All three compounds adopted the filled tetragonal tungsten bronze (TB) structure at room temperature. The present ceramics exhibited relaxor behavior, and the Curie temperature (at 10kHz) were −130, −80 and −45°C for Ba₅LaNiTa₉O₃₀, Ba₅NdNiTa₉O₃₀, and Ba₅SmNiTa₉O₃₀ respectively. At room temperature, Ba₅LnNiTa₉O₃₀ ceramics have a high dielectric constants in the range 102∼118, a low dielectric loss in range 0.0019∼0.0036, and the temperature coefficients of the dielectric constant (τ_ɛ) in the range −320∼−460 ppm°C⁻¹ (at 1 MHz).     

Conductivity and expansion at high temperature in Sr0.7La0.3TiO3−α prepared under reducing atmosphere

Sr_0.7La_0.3TiO_3−α specimens were prepared in reducing atmosphere, and the structural and electrical properties were studied. The lattice parameter of Sr_0.7La_0.3TiO_3−α at room temperature was larger than that expected from Vegard’s law between SrTiO₃ and LaTiO₃ due to the reductive expansion. The conductivity of this specimen was 100 S cm⁻¹ at 1000°C, p_O2 = 10⁻¹³ Pa. However, the conductivity was not preserved after an oxidation-reduction cycle. Over p_O2 = 10² Pa, the conductivity drastically dropped with increasing p_O2. The thermal expansion coefficient of Sr_0.7La_0.3TiO_3−α was 11.8 × 10⁻⁶ K⁻¹ in 9% H₂/N₂ (room temperature – 1000°C). In this Sr_0.7La_0.3TiO_3−α, the chemical expansion on oxidation reached Δl/l_o = 0.51%, when changing p_O2 from 10⁻¹¹ Pa to 2 × 10⁴ Pa (air) at 1000°C.     

Defects and transport in Gd-doped BaPrO3

The electrical conductivity of BaPr_1−x Gd_xO_3−δ has been characterized by means of the four-point van der Pauw technique at 200–1100 °C as a function of pO₂ and pH₂O. The contributions from ionic charge carriers were investigated by the EMF of concentration cells and the H⁺/D⁺ isotope effect on the total conductivity. BaPr_1−x Gd _x O_3−δ is predominately a p-type electronic conductor under oxidizing conditions, while ionic conduction is barely measurable. Gd(III) substituted for Pr(IV) is charge compensated mainly by electron holes, with protons and oxygen vacancies contributing significantly but as minority defects only at low temperatures (wet conditions) and at high temperatures, respectively. The conductivity behaviour has been modelled under these assumptions to extract thermodynamic parameters for the defect reactions at play. The practical use of this material is limited by its poor chemical stability.     

Electrical conductivity of the Al-stabilized La<Subscript>2/3</Subscript>TiO<Subscript>3</Subscript>

A-site deficient lanthanum titanate (La_2/3TiO₃) materials with perovskite structure are attractive due to their electrical applications such as ion conductors and dielectrics. However, its stability at room temperature in air is obtained only if Na or Li etc. is incorporated into La site or Al into Ti site. In this study, the electrical conductivities of La_0.683(Ti_0.95Al_0.05)O₃ have been measured in oxygen partial pressure (Po₂) between 1 and 10⁻¹⁸ atm at 1000~1400°C. The electrical conductivity exhibited −1/4, −1/6 and −1/5 dependence (log σ ∝ log , n = −1/4, −1/6, −1/5) depending upon temperature and Po₂. The defect model explaining the observation was proposed and discussed. The chemical diffusion coefficient was estimated from the electrical conductivity relaxation.     

Praseodymium-cerium oxide thin film cathodes: Study of oxygen reduction reaction kinetics

Praseodymium-Cerium Oxide (Pr_xCe_1-xO_2−δ; PCO), a potential three way catalyst oxygen storage material and solid oxide fuel cell (SOFC) cathode, exhibits surprisingly high levels of oxygen nonstoichiometry, even under oxidizing (e.g. air) conditions, resulting in mixed ionic electronic conductivity (MIEC). In this study we examine the redox kinetics of dense PCO thin films using impedance spectroscopy, for x = 0.01, 0.10 and 0.20, over the temperature range of 550 to 670°C, and the oxygen partial pressure range of 10⁻⁴ to 1 atm O₂. The electrode impedance was observed to be independent of electrode thickness and inversely proportional to electrode area, pointing to surface exchange rather than bulk diffusion limited kinetics. The large electrode capacitance (10⁻²F) was found to be consistent with an expected large electrochemically induced change in stoichiometry for x = 0.1 and x = 0.2 PCO. The PCO films showed surprisingly rapid oxygen exchange kinetics, comparable to other high performance SOFC cathode materials, from which values for the surface exchange coefficient, k ^q , were calculated. This study confirms the suitability of PCO as a model MIEC cathode material compatible with both zirconia and ceria based solid oxide electrolytes.     

Determination of in vivo rat muscle Gd-DTPA relaxivity at 6.3 T

For the in vivo relaxivity of Gd-DTPA at 6.3 T in rat muscle a value of 2.7±0.5 (mM s)⁻¹ was found, and for the in vitro value in water 3.00±0.56 (mM s)⁻¹ at 37°C. The temperature dependence of the in vitro relaxivity was −0.087 (mM s °C)⁻¹. The relation between1/T ₁ and the tissue Gd-DTPA concentration is linear for the normally used in vivo Gd-DTPA concentration range     

Diffusion-weighted imaging of the spine using radialk-space trajectories

Introduction Diffusion-weighted MR imaging (DWI) of the spine requires robust imaging methods, that are insensitive to susceptibility effects caused by the transition from bone to soft tissue and motion artifacts due to breathing, swallowing, and cardiac motion. The purpose of this study was to develop a robust imaging method suitable for DWI of the spine. Methods and subjects A radialk-space spin echo sequence has been implemented, which is sell-navigating because each acquisition line passes through the origin ofk-space. Influence of cardiac motion and associated flow of cerebrospinal fluid is minimized by cardiac gating with a finger photoplethysmograph. The sequence has been tested on a 1.5T system. Diffusion-weighted images of six normal volunteers were acquired in the sagittal plane with 4b values between 50 and 500 s mm⁻². Because of the symmetries of the cord, diffusion measurements in the head-foot (HF) or left-right (LR) directions were sufficient to measure the dominant effects of anisotropy. Results The apparent diffusion coefficients (ADCs) measured, respectively, in the LR and HF directions were (0.699 ± 0.050) × 10⁻³ and (1.805 ± 0.086) × 10⁻³ mm² s⁻¹ in the spinal cord. (1.588 ± 0.082) × 10⁻³ and (1.528 ± 0.052) × 10⁻³ mm² s⁻¹ in the intervertebral disks, and (0.346 ± 0.047) × 10⁻³ and (0.306 ± 0.035) × 10⁻³ mm² s⁻¹ in the vertebrae of the cervicothoraeic spine. Conclusion Diffusion-weighted spin echo sequences with radial trajectories ink-space provide a means of achieving robust, high quality diffusion-weighted imaging and measuring ADCs in the spine. The application of the diffusion-weighting gradients in different directions allows diffusion anisotropy to be measured.     

The effect of alumina addition on the electrical conductivity of Gd-doped ceria

Acceptor doped-ceria is a possible electrolyte material for the IT-SOFC (intermediate temperature solid oxide fuel cell) due to its high oxygen-ion conductivity. However, its use has been limited by its mechanical weakness and the appearance of electronic conductivity in reducing condition. In this study, alumina was selected as an additive in the doped-ceria to see if it increases the oxygen-ion conductivity and mechanical strength. Effects of alumina addition in doped ceria were studied as a function of alumina content and acceptor (Gd) content. The electrical conductivity of (Ce_1−x Gd _x O_2−δ)_1−y + (Al₂O₃) _y (x = 0–0.35, y = 0–0.10) was measured by using impedance spectroscopy. The grain conductivity of Ce_0.8Gd_0.2O_2-δ (GDC20) with 5 mol% alumina increased ∼3 times from that of GDC20 at 300^∘C. The grain conductivity was even ∼2 times higher than that of Ce_0.9Gd_0.1O_2−δ (GDC10) at 300^∘C. The electrical conductivity of GDC20 without alumina addition, measured at 500^∘C in air, rapidly decreased after exposure to reducing condition (Po₂∼10⁻²² atm) at 800^∘C. However, the decrease was much slower in GDC20 with alumina addition, indicating the improved mechanical strength. Among the examined compositions, (Ce_0.75Gd_0.25 O_2-δ)_0.95 + (Al₂O₃)_0.05 (GDC25A5) showed the highest conductivity at most temperatures.     

Oxygen exchange and transport properties of yttria-stabilized zirconia coated with LaCrO3

The oxygen permeation flux through YSZ (Yttria-Stabilized Zirconia) in reducing Po ₂ is mostly controlled by the surface-exchange kinetics in spite of very high temperature [1]. In order to study the kinetics, the YSZ surface was coated with LaCrO₃ on feed side, permeate side, or two sides, and the oxygen fluxes were measured under controlled Po ₂ gradient generated by different CO/CO₂ mixtures (permeate side: ∼3 × 10⁻¹² atm, feed side: 2 × 10⁻¹⁰∼2 × 10⁻⁸ atm) at 1600^∘C. The oxygen flux was determined by measuring the change in CO₂ content of the permeate-side gas. When both feed and permeate surfaces were coated, the oxygen flux increased by ∼6 times. For either permeate- or feed-side coating, the increases were ∼4 times and ∼1.5 times, respectively. A model was proposed in order to estimate the surface-exchange coefficient ( ) of feed and permeate side with or without coating.