Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolution 31P-CMRS in the mouse

Background Phosphorus cardiovascular magnetic resonance spectroscopy (31P-CMRS) has emerged as an important tool for the preclinical assessment of myocardial energetics in vivo. However, the high rate and diminutive size of the mouse heart is a challenge, resulting in low resolution and poor signal-to-noise. Here we describe a refined high-resolution 31P-CMRS technique and apply it to a novel double transgenic mouse (dTg) with elevated myocardial creatine and creatine kinase (CK) activity. We hypothesised a synergistic effect to augment energetic status, evidenced by an increase in the ratio of phosphocreatine-to-adenosine-triphosphate (PCr/ATP). Methods and results Single transgenic Creatine Transporter overexpressing (CrT-OE, n = 7) and dTg mice (CrT-OE and CK, n = 6) mice were anaesthetised with isoflurane to acquire 31P-CMRS measurements of the left ventricle (LV) utilising a two-dimensional (2D), threefold under-sampled density-weighted chemical shift imaging (2D-CSI) sequence, which provided high-resolution data with nominal voxel size of 8.5 µl within 70 min. (1H-) cine-CMR data for cardiac function assessment were obtained in the same imaging session. Under a separate examination, mice received invasive haemodynamic assessment, after which tissue was collected for biochemical analysis. Myocardial creatine levels were elevated in all mouse hearts, but only dTg exhibited significantly elevated CK activity, resulting in a 51% higher PCr/ATP ratio in heart (3.01 ± 0.96 vs. 2.04 ± 0.57—mean ± SD; dTg vs. CrT-OE), that was absent from adjacent skeletal muscle. No significant differences were observed for any parameters of LV structure and function, confirming that augmentation of CK activity does not have unforeseen consequences for the heart. Conclusions We have developed an improved 31P-CMRS methodology for the in vivo assessment of energetics in the murine heart which enabled high-resolution imaging within acceptable scan times. Mice over-expressing both creatine and CK in the heart exhibited a synergistic elevation in PCr/ATP that can now be tested for therapeutic potential in models of chronic heart failure

Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolution 31P-CMRS in the mouse

Background: Phosphorus cardiovascular magnetic resonance spectroscopy (31P-CMRS) has emerged as an important tool for the preclinical assessment of myocardial energetics in vivo. However, the high rate and diminutive size of the mouse heart is a challenge, resulting in low resolution and poor signal-to-noise. Here we describe a refined high-resolution 31P-CMRS technique and apply it to a novel double transgenic mouse (dTg) with elevated myocardial creatine and creatine kinase (CK) activity. We hypothesised a synergistic effect to augment energetic status, evidenced by an increase in the ratio of phosphocreatine-to-adenosine-triphosphate (PCr/ATP). Methods and results: Single transgenic Creatine Transporter overexpressing (CrT-OE, n = 7) and dTg mice (CrT-OE and CK, n = 6) mice were anaesthetised with isoflurane to acquire 31P-CMRS measurements of the left ventricle (LV) utilising a two-dimensional (2D), threefold under-sampled density-weighted chemical shift imaging (2D-CSI) sequence, which provided high-resolution data with nominal voxel size of 8.5 µl within 70 min. (1H-) cine-CMR data for cardiac function assessment were obtained in the same imaging session. Under a separate examination, mice received invasive haemodynamic assessment, after which tissue was collected for biochemical analysis. Myocardial creatine levels were elevated in all mouse hearts, but only dTg exhibited significantly elevated CK activity, resulting in a 51% higher PCr/ATP ratio in heart (3.01 ± 0.96 vs. 2.04 ± 0.57—mean ± SD; dTg vs. CrT-OE), that was absent from adjacent skeletal muscle. No significant differences were observed for any parameters of LV structure and function, confirming that augmentation of CK activity does not have unforeseen consequences for the heart. Conclusions: We have developed an improved 31P-CMRS methodology for the in vivo assessment of energetics in the murine heart which enabled high-resolution imaging within acceptable scan times. Mice over-expressing both creatine and CK in the heart exhibited a synergistic elevation in PCr/ATP that can now be tested for therapeutic potential in models of chronic heart failure

Targeted T1 Magnetic Resonance Imaging Contrast Enhancement with Extraordinarily Small CoFe2O4 Nanoparticles

Extraordinarily small (2.4 nm) cobalt ferrite nanoparticles (ESCIoNs) were synthesized by a one-pot thermal decomposition approach to study their potential as magnetic resonance imaging (MRI) contrast agents. Fine size control was achieved using oleylamine alone, and annular dark-field scanning transmission electron microscopy revealed highly crystalline cubic spinel particles with atomic resolution. Ligand exchange with dimercaptosuccinic acid rendered the particles stable in physiological conditions with a hydrodynamic diameter of 12 nm. The particles displayed superparamagnetic properties and a low r2/r1 ratio suitable for a T1 contrast agent. The particles were functionalized with bile acid, which improved biocompatibility by significant reduction of reactive oxygen species generation and is a first step toward liver-targeted T1 MRI. Our study demonstrates the potential of ESCIoNs as T1 MRI contrast agents

Centrality dependence of pi^[+/-], K^[+/-], p and p-bar production from sqrt(s_NN)=130 GeV Au + Au collisions at RHIC

Identified pi^[+/-] K^[+/-], p and p-bar transverse momentum spectra at mid-rapidity in sqrt(s_NN)=130 GeV Au-Au collisions were measured by the PHENIX experiment at RHIC as a function of collision centrality. Average transverse momenta increase with the number of participating nucleons in a similar way for all particle species. The multiplicity densities scale faster than the number of participating nucleons. Kaon and nucleon yields per participant increase faster than the pion yields. In central collisions at high transverse momenta (p_T greater than 2 GeV/c), anti-proton and proton yields are comparable to the pion yields.Comment: 6 pages, 3 figures, 1 table, 307 authors, accepted by Phys. Rev. Lett. on 9 April 2002. This version has minor changes made in response to referee Comments. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Net Charge Fluctuations in Au + Au Interactions at sqrt(s_NN) = 130 GeV

Data from Au + Au interactions at sqrt(s_NN) = 130 GeV, obtained with the PHENIX detector at RHIC, are used to investigate local net charge fluctuations among particles produced near mid-rapidity. According to recent suggestions, such fluctuations may carry information from the Quark Gluon Plasma. This analysis shows that the fluctuations are dominated by a stochastic distribution of particles, but are also sensitive to other effects, like global charge conservation and resonance decays.Comment: 6 pages, RevTeX 3, 3 figures, 307 authors, submitted to Phys. Rev. Lett. on 21 March, 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Flow Measurements via Two-particle Azimuthal Correlations in Au + Au Collisions at sqrt(s_NN) = 130 GeV

Two particle azimuthal correlation functions are presented for charged hadrons produced in Au + Au collisions at RHIC sqrt(s_NN) = 130 GeV. The measurements permit determination of elliptic flow without event-by-event estimation of the reaction plane. The extracted elliptic flow values v_2 show significant sensitivity to both the collision centrality and the transverse momenta of emitted hadrons, suggesting rapid thermalization and relatively strong velocity fields. When scaled by the eccentricity of the collision zone, epsilon, the scaled elliptic flow shows little or no dependence on centrality for charged hadrons with relatively low p_T. A breakdown of this epsilon scaling is observed for charged hadrons with p_T > 1.0 GeV/c for the most central collisions.Comment: 6 pages, RevTeX 3, 4 figures, 307 authors, submitted to Phys. Rev. Lett. on 11 April 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Centrality Dependence of Charged Particle Multiplicity in Au-Au Collisions at sqrt(s_NN)=130 GeV

We present results for the charged-particle multiplicity distribution at mid-rapidity in Au - Au collisions at sqrt(s_NN)=130 GeV measured with the PHENIX detector at RHIC. For the 5% most central collisions we find $dN_{ch}/d\eta_{|\eta=0} = 622 \pm 1 (stat) \pm 41 (syst)$. The results, analyzed as a function of centrality, show a steady rise of the particle density per participating nucleon with centrality.Comment: 307 authors, 43 institutions, 6 pages, 4 figures, 1 table Minor changes to figure labels and text to meet PRL requirements. One author added: M. Hibino of Waseda Universit

Measurement of the mid-rapidity transverse energy distribution from sNN=130\sqrt{s_{NN}}=130 GeV Au+Au collisions at RHIC

The first measurement of energy produced transverse to the beam direction at RHIC is presented. The mid-rapidity transverse energy density per participating nucleon rises steadily with the number of participants, closely paralleling the rise in charged-particle density, such that E_T / N_ch remains relatively constant as a function of centrality. The energy density calculated via Bjorken's prescription for the 2% most central Au+Au collisions at sqrt(s_NN)=130 GeV is at least epsilon_Bj = 4.6 GeV/fm^3 which is a factor of 1.6 larger than found at sqrt(s_NN)=17.2 GeV (Pb+Pb at CERN).Comment: 307 authors, 6 pages, 4 figures, 1 table, submitted to PRL 4/18/2001; revised version submitted to PRL 5/24/200

Event-by-event fluctuations in Mean pTp_T and Mean eTe_T in sqrt(s_NN) = 130 GeV Au+Au Collisions

Distributions of event-by-event fluctuations of the mean transverse momentum and mean transverse energy near mid-rapidity have been measured in Au+Au collisions at sqrt(s_NN) = 130 GeV at RHIC. By comparing the distributions to what is expected for statistically independent particle emission, the magnitude of non-statistical fluctuations in mean transverse momentum is determined to be consistent with zero. Also, no significant non-random fluctuations in mean transverse energy are observed. By constructing a fluctuation model with two event classes that preserve the mean and variance of the semi-inclusive p_T or e_T spectra, we exclude a region of fluctuations in sqrt(s_NN) = 130 GeV Au+Au collisions.Comment: 10 pages, RevTeX 3, 7 figures, 4 tables, 307 authors, submitted to Phys. Rev. C on 22 March 2002. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (will be made) publicly available at http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm

Proximity effect at superconducting Sn-Bi2Se3 interface

We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions down to 250 mK and in different magnetic fields. A number of conductance anomalies were observed below the superconducting transition temperature of Sn, including a small gap different from that of Sn, and a zero-bias conductance peak growing up at lower temperatures. We discussed the possible origins of the smaller gap and the zero-bias conductance peak. These phenomena support that a proximity-effect-induced chiral superconducting phase is formed at the interface between the superconducting Sn and the strong spin-orbit coupling material Bi2Se3.Comment: 7 pages, 8 figure