613 research outputs found
Spectropolarimetry of the Luminous Narrow-Line Seyfert Galaxies IRAS 20181-2244 and IRAS 13224-3809
We observed the narrow-line Seyfert 1 galaxies IRAS 20181-2244 and IRAS
13324-3809 with a new spectropolarimeter on the RC spectrograph at the CTIO 4m
telescope. Previously it had been suggested that IRAS 20181-2244 was a Type 2
QSO and thus might contain an obscured broad-line region which could be
detected by the presence of broad Balmer lines in the polarized flux. We found
the object to be polarized at about 2%, and constant with wavelength, (unlike
most narrow-line Seyfert 1s), but with no evidence of broad Balmer lines in
polarized flux. The spectropolarimetry indicates that the scattering material
is inside the BLR. IRAS 13224-3809, notable for its high variability in X-ray
and UV wavelengths, has a low polarization consistent with a Galactic
interstellar origin.Comment: 19 pages using (AASTEX) aaspp4.sty and 5 postscript figures To be
published in the Astrophysical Journa
P-31 magnetization transfer measurements of P-i -> ATP flux in exercising human muscle
Fundamental criticisms have been made over the use of (31)P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (P(i))→ATP flux (V(Pi-ATP)) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of V(Pi-ATP) is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure V(Pi-ATP) in human exercising muscle for the first time. Steady-state V(Pi-ATP) was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (V(ATP)). We define a surplus P(i)→ATP flux as the difference between V(Pi-ATP) and V(ATP). The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and P(i) in some systems and have been suggested to be responsible for this surplus flux. Surplus V(Pi-ATP) did not change between rest and exercise, even though the concentrations of P(i) and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus P(i)→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the (31)P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and P(i) catalyzed by GAPDH and PGK
Theoretical prediction and experimental measurement of the bile-pigment isomer pattern obtained from degradation of catalase haem
Cardiovascular reactivity patterns and pathways to hypertension: a multivariate cluster analysis
Substantial evidence links exaggerated mental stress induced blood pressure reactivity to future hypertension, but the results for heart rate reactivity are less clear. For this reason multivariate cluster analysis was carried out to examine the relationship between heart rate and blood pressure reactivity patterns and hypertension in a large prospective cohort (age range 55–60 years). Four clusters emerged with statistically different systolic and diastolic blood pressure and heart rate reactivity patterns. Cluster 1 was characterised by a relatively exaggerated blood pressure and heart rate response while the blood pressure and heart rate responses of cluster 2 were relatively modest and in line with the sample mean. Cluster 3 was characterised by blunted cardiovascular stress reactivity across all variables and cluster 4, by an exaggerated blood pressure response and modest heart rate response. Membership to cluster 4 conferred an increased risk of hypertension at 5-year follow-up (hazard ratio=2.98 (95% CI: 1.50–5.90),
Subarcsec emission in Seyfert galaxies: the nuclear component in the L- and M-bands
We present deep L- and M- band imaging with ISAAC on the ESO VLT with
unprecedented spatial resolution of the nearby Seyfert 2 galaxies NGC 7496 and
NGC 7582 and the Seyfert 1 galaxy NGC 7213. The unresolved nuclear component
dominates the emission within the central 90 pc region, while the host galaxy
accounts for up to 50 % of the integrated emission at both wavelengths within
the detected sizes of of 1 kpc in the L-band and 0.5 kpc in the M-band. The
overall morphology of the extended component follows the general isophote
pattern defined by the near-infrared continuum of the galaxies. However, the
central 300 pc regions show much more ordered elliptical isophotes than in the
near-infrared. In particular, emission in the L- and M-bands shows well defined
central point sources in the two Seyfert 2s.Comment: 4 pages, 4 figures. Accepted for publication in ApJ Letter
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Feasibility of metabolic imaging of hyperpolarized 13C-pyruvate in human breast cancer
Introduction
Imaging of the breast with hyperpolarized 13C yields new challenges compared to imaging the prostate [1]. E.g. large anteroposterior B0 gradients [2] require correction and the anatomy and patient positioning need a new, highly optimized RF coil array for achieving sufficient SNR/spatial resolution. As a first step, we have investigated single-breast imaging in the coronal plane.
Methods
A BRCA gene carrier with a 38-mm diameter grade 3 triple-negative invasive ductal carcinoma was studied on a 3T MRI (GE Healthcare) using a prototype 8-channel 13C breast coil (Rapid Biomedical), containing 2 transmit/receive coils and 6 receive-only covering both breasts in a prone position. 1H imaging was performed with the body coil. Following injection of 40ml of 250mM 13C-pyruvate, polarized to c. 25%, a 1-minute time series of spirals with IDEAL encoding (3) was collected (flip angle 10°, TR=260ms, 8-step cycle, time resolution 2.08s, 3 x 3-cm thick slices, 3mm gap, 40-pt spiral, 24cm coronal FOV, real pixel size 12 x 12 x 30mm). IDEAL reconstruction of images was optimized separately for each slice to enable independent frequency offsets to be applied. Kinetic modelling was performed in MATLAB, with automated tumour segmentation.
Results
Tumour pixels were identified by the segmentation algorithm only in the tumour-containing slice 2, and the average estimated flux from pyruvate to lactate kPL within this ROI was 0.022 s-1 (Fig. 1). The frequency shift of pyruvate relative to slice 2 was +6 Hz in slice 3 and -34 Hz in slice 1, confirming a sharp gradient in B0 approaching the nipple, which was corrected by optimizing slices separately (Fig 2). Images of lactate and pyruvate summed over the time course (Fig 3) showed strong signal of both metabolites over the tumour in slice 2, lower pyruvate in the slice toward the chest wall, and no consistent signal in slice 1.
Conclusion
This first-in-Europe study in breast cancer established the feasibility of obtaining metabolite images with high temporal and moderate spatial resolution in humans in vivo following administration of hyperpolarized 13C-pyruvate. Coronal image orientation allowed application of significant corrections for a known limitation, the anteroposterior B0 gradient, as well as a small FOV to improve spatial resolution. Kinetic rate constants within the tumour were found to be consistent with previous reports in human prostate cancer (1).
References
1) Nelson SJ et al. Sci Transl Med 5, 198ra108 (2013). 2) Maril N, et al. Magn. Reson. Med. 2005; 54:1139-1145. 3) Wiesinger F, et al. Magn Reson Med 2012; 68:8-16
Low-field thermal mixing in [1-13C] pyruvic acid for brute-force hyperpolarization
We detail the process of low-field thermal mixing (LFTM) between 1H and 13C nuclei in neat [1-13C] pyruvic acid at cryogenic temperatures (4–15 K). Using fast-field-cycling NMR, 1H nuclei in the molecule were polarized at modest high field (2 T) and then equilibrated with 13C nuclei by fast cycling (∼300–400 ms) to a low field (0–300 G) that activates thermal mixing. The 13C NMR spectrum was recorded after fast cycling back to 2 T. The 13C signal derives from 1H polarization via LFTM, in which the polarized (‘cold’) proton bath contacts the unpolarised (‘hot’) 13C bath at a field so low that Zeeman and dipolar interactions are similar-sized and fluctuations in the latter drive 1H–13C equilibration. By varying mixing time (tmix) and field (Bmix), we determined field-dependent rates of polarization transfer (1/τ) and decay (1/T1m) during mixing. This defines conditions for effective mixing, as utilized in ‘brute-force’ hyperpolarization of low-γ nuclei like 13C using Boltzmann polarization from nearby protons. For neat pyruvic acid, near-optimum mixing occurs for tmix ∼ 100–300 ms and Bmix ∼ 30–60 G. Three forms of frozen neat pyruvic acid were tested: two glassy samples, (one well-deoxygenated, the other O2-exposed) and one sample pre-treated by annealing (also well-deoxygenated). Both annealing and the presence of O2 are known to dramatically alter high-field longitudinal relaxation (T1) of 1H and 13C (up to 102–103-fold effects). Here, we found smaller, but still critical factors of ∼(2–5)× on both τ and T1m. Annealed, well-deoxygenated samples exhibit the longest time constants, e.g., τ ∼ 30–70 ms and T1m ∼ 1–20 s, each growing vs. Bmix. Mixing ‘turns off’ for Bmix > ∼100 G. That T1m ≫ τ is consistent with earlier success with polarization transfer from 1H to 13C by LFTM
Dual-modality gene reporter for in vivo imaging
The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer variously from limited depth penetration, spatial resolution, and sensitivity. We describe here a gene reporter, based on the organic anion transporting protein Oatp1a1, which mediates uptake of a clinically approved, Gd(3+)-based, hepatotrophic contrast agent (gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid). Cells expressing the reporter showed readily reversible, intense, and positive contrast (up to 7.8-fold signal enhancement) in T1-weighted magnetic resonance images acquired in vivo. The maximum signal enhancement obtained so far is more than double that produced by MRI gene reporters described previously. Exchanging the Gd(3+) ion for the radionuclide, (111)In, also allowed detection by single-photon emission computed tomography, thus combining the spatial resolution of MRI with the sensitivity of radionuclide imaging
Hyperpolarized13c mri of tumor metabolism demonstrates early metabolic response to neoadjuvant chemotherapy in breast cancer
Purpose: To compare hyperpolarized carbon 13 (13C) MRI with dynamic contrast material–enhanced (DCE) MRI in the detection of early treatment response in breast cancer. Materials and Methods: In this institutional review board–approved prospective study, a woman with triple-negative breast cancer (age, 49 years) underwent13C MRI after injection of hyperpolarized [1–carbon 13 {13C}]-pyruvate and DCE MRI at 3 T at baseline and after one cycle of neoadjuvant therapy. The13C-labeled lactate-to-pyruvate ratio derived from hyperpolarized13C MRI and the pharmacokinetic parameters transfer constant (Ktrans) and washout parameter (kep ) derived from DCE MRI were compared before and after treatment. Results: Exchange of the13C label between injected hyperpolarized [1-13C]-pyruvate and the endogenous lactate pool was observed, catalyzed by the enzyme lactate dehydrogenase. After one cycle of neoadjuvant chemotherapy, a 34% reduction in the13C-labeled lactate-to-pyruvate ratio resulted in correct identification of the patient as a responder to therapy, which was subsequently confirmed via a complete pathologic response. However, DCE MRI showed an increase in mean Ktrans (132%) and mean kep (31%), which could be incorrectly interpreted as a poor response to treatment. Conclusion: Hyperpolarized13C MRI enabled successful identification of breast cancer response after one cycle of neoadjuvant chemotherapy and may improve response prediction when used in conjunction with multiparametric proton MRI
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ST measurements of Pi->ATP flux in exercising human muscle
Fundamental criticisms have been made over the use of (31)P magnetic resonance spectroscopy (MRS) magnetization transfer estimates of inorganic phosphate (Pi)→ATP flux (VPi-ATP) in human resting skeletal muscle for assessing mitochondrial function. Although the discrepancy in the magnitude of VPi-ATP is now acknowledged, little is known about its metabolic determinants. Here we use a novel protocol to measure VPi-ATP in human exercising muscle for the first time. Steady-state VPi-ATP was measured at rest and over a range of exercise intensities and compared with suprabasal oxidative ATP synthesis rates estimated from the initial rates of postexercise phosphocreatine resynthesis (VATP). We define a surplus Pi→ATP flux as the difference between VPi-ATP and VATP. The coupled reactions catalyzed by the glycolytic enzymes GAPDH and phosphoglycerate kinase (PGK) have been shown to catalyze measurable exchange between ATP and Pi in some systems and have been suggested to be responsible for this surplus flux. Surplus VPi-ATP did not change between rest and exercise, even though the concentrations of Pi and ADP, which are substrates for GAPDH and PGK, respectively, increased as expected. However, involvement of these enzymes is suggested by correlations between absolute and surplus Pi→ATP flux, both at rest and during exercise, and the intensity of the phosphomonoester peak in the (31)P NMR spectrum. This peak includes contributions from sugar phosphates in the glycolytic pathway, and changes in its intensity may indicate changes in downstream glycolytic intermediates, including 3-phosphoglycerate, which has been shown to influence the exchange between ATP and Pi catalyzed by GAPDH and PGK.This work was funded by the Clinical Research Infrastructure Grant and the Siemens MAGNETOM 3T Verio scanner is funded by the NIHR via an award to the Cambridge NIHR/Wellcome Trust Clinical Research Facility. D.B. Savage is supported by the Wellcome Trust (091551)
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