Access to metabolic information in vivo using magnetic resonance (MR) technologies has generally been the niche of MR spectroscopy (MRS) and spectroscopic imaging (MRSI). Metabolic fluxes can be ...studied using the infusion of substrates labeled with magnetic isotopes, with the use of hyperpolarization especially powerful. Unfortunately, these promising methods are not yet accepted clinically, where fast, simple, and reliable measurement and diagnosis are key. Recent advances in functional MRI and chemical exchange saturation transfer (CEST) MRI allow the use of water imaging to study oxygen metabolism and tissue metabolite levels. These, together with the use of novel data analysis approaches such as machine learning for all of these metabolic MR approaches, are increasing the likelihood of their clinical translation.
With the purpose of controlling the steady state of a dielectric nanosphere levitated within an optical cavity, we study its conditional dynamics under simultaneous sideband cooling and additional ...time-continuous measurement of either the output cavity mode or the nanosphere's position. We find that the average phonon number, purity and quantum squeezing of the steady-states can all be made more non-classical through the addition of time-continuous measurement. We predict that the continuous monitoring of the system, together with Markovian feedback, allows one to stabilize the dynamics for any value of the laser frequency driving the cavity. By considering state of the art values of the experimental parameters, we prove that one can in principle obtain a non-classical (squeezed) steady-state with an average phonon number .
Scalar couplings provide important information regarding molecular structure and dynamics. The measurement of scalar coupling constants constitutes a topic of interest and significance in NMR ...spectroscopy. However, the measurement of J values is often not straightforward because of complex signal splitting patterns and signal overlap. Many methods have been proposed for the measurement of scalar coupling constants, both for homonuclear and heteronuclear cases. Different approaches to the measurement of scalar coupling constants are reviewed here with several applications presented. The accurate measurement of scalar coupling constants can greatly facilitate molecular structure elucidation and the study of molecule dynamics.
The Scotia Sea and surrounding Scotia Arc have evolved over the past 40 Ma, by extension behind an east-migrating subduction zone, at the boundary between the South American (SAM) and Antarctic (ANT) ...plates. The considerable data set now available (regional geology and geophysics, earthquake seismology, satellite altimetry, global plate analyses) suggest why east-migrating subduction began, what has been the driving force that has sustained it, and what other processes have controlled the mode of back-arc extension in the Scotia Sea. A suite of six reconstructions has been developed, based on this data set. The reconstruction to 40 Ma creates a compact, cuspate continental connection between South America and the Antarctic Peninsula at the subducting Pacific margin, with fragments (now dispersed around the Scotia Arc) occupying positions within it compatible with their known geology. The driving force has been subduction of South American ocean floor, which began as a result of southward migration of the pole of South American–Antarctic plate rotation, and a key modulator of back-arc extension has been collision of ridge crest sections of the South American–Antarctic plate boundary with the east-advancing trench. Cenozoic regional tectonic evolution has two other likely consequences which greatly increase its importance. Firstly, this region saw the tectonic disruption of the final barrier to complete circum-Antarctic deep water flow, that may have had a profound effect on palaeoclimate. Secondly, it is possible that the rapid roll-back of the hinge of subduction is related to shallow eastward flow in the sub-lithospheric mantle. Both of these consequences are explored. The reconstructions show that rapid roll-back of the subduction hinge (averaging 50 mm/a over the last 40 Ma with respect to the South American plate) has been a feature of all of Scotia Sea evolution, and provide a history of motion of several oceanic microplates, most of which are now welded together within the Scotia Sea. This will guide the location of seismometers and/or dredge hauls to test the hypothesis of shallow mantle flow, and help interpret the results. The reconstructions also allow an assessment of the creation of deep-water pathways that would have permitted the development of the present-day Antarctic Circumpolar Current (ACC). An early Miocene onset (within the period 22–17 Ma) seems likely for the ACC, depending on the structure and palaeo-elevation of Davis Bank and Aurora Bank, sections of the North Scotia Ridge. However, the study shows there was a delay (of one or more million years) between initial provision of a deep-water pathway and the major mid-Miocene change in global climate (involving the general level of Antarctic glaciation) that may have been related. If these changes were related, then the delay suggests that other factors, possibly rough elevated ocean floor but also non-tectonic factors (such as atmospheric CO
2), were important in determining palaeoclimate.
Pathological assessment using World Health Organization (WHO) criteria is the gold standard for diagnosis of gliomas. However, the accuracy of diagnosis is limited by tissue sampling, particularly ...for infiltrating, heterogeneous tumours. We assessed the accuracy of amide proton transfer-weighted (APTw) magnetic resonance imaging (MRI)-guided tissue sampling to identify regions of high-grade glioma via radiographic-histopathologic correlation in patients with newly suspected glioma.
Twenty-four patients with previously undiagnosed gliomas underwent a volumetric APTw MRI prior to their first neurosurgical procedure. A total of 70 specimens were collected via APTw image-directed stereotactic biopsy. Cellularity, necrosis, proliferation and glioma WHO grade were analysed for all specimens and correlated with corresponding APTw signal intensities.
Thirty-three specimens displayed grade-II pathology, 14 grade-III, 15 grade-IV, and eight specimens revealed only peritumoural oedema. Multiple glioma grades were found within a single lesion in six patients. APTw signal intensities of the biopsied sites and the maximum APTw values across all biopsied sites in each patient were significantly higher for high-grade versus low-grade specimens. APTw signal intensities were significantly positively correlated with cellularity (R = 0.757) and proliferation (R = 0.538). Multiple linear regression analysis showed that tumour cellularity and proliferation index were the best predictors of APTw signal intensities.
APTw imaging identified tumour areas of higher cellularity and proliferation, allowing identification of high-grade regions within heterogeneous gliomas. APTw imaging can be readily translated for more widespread use and can assist diagnostic neurosurgical procedures by increasing the accuracy of tumour sampling in patients with infiltrating gliomas.
•APTw images were used to guide diagnostic neurosurgical procedures.•APTw MRI guidance found multiple WHO grades within the same lesion in 25% patients.•APTw hyperintensity identified tumour areas of higher cellularity and proliferation.•Maximum APTw intensity correlated with the histological grade of the tumour.
Involvement of oxidative stress in the pathophysiology of schizophrenia (SZ) is suggested by studies of peripheral tissue. Nonetheless, it is unclear how such biological changes are linked to ...relevant, pathological neurochemistry, and brain function. We designed a multi-faceted study by combining biochemistry, neuroimaging, and neuropsychology to test how peripheral changes in a key marker for oxidative stress, glutathione (GSH), may associate with central neurochemicals or neuropsychological performance in health and in SZ. GSH in dorsal anterior cingulate cortex (dACC) was acquired as a secondary 3T
H-MRS outcome using a MEGA-PRESS sequence. Fifty healthy controls and 46 patients with SZ were studied cross-sectionally, and analyses were adjusted for effects of confounding variables. We observed lower peripheral total GSH in SZ compared to controls in extracellular (plasma) and intracellular (lymphoblast) pools. Total GSH levels in plasma positively correlated with composite neuropsychological performance across the total population and within patients. Total plasma GSH levels were also positively correlated with the levels of Glx in the dACC across the total population, as well as within each individual group (controls, patients). Furthermore, the levels of dACC Glx and dACC GSH positively correlated with composite neuropsychological performance in the patient group. Exploring the relationship between systemic oxidative stress (in particular GSH), central glutamate, and cognition in SZ will benefit further from assessment of patients with more varied neuropsychological performance.
The current study aims to assign and estimate the total creatine (tCr) signal contribution to the Z‐spectrum in mouse brain at 11.7 T. Creatine (Cr), phosphocreatine (PCr) and protein phantoms were ...used to confirm the presence of a guanidinium resonance at this field strength. Wild‐type (WT) and knockout mice with guanidinoacetate N‐methyltransferase deficiency (GAMT−/−), which have low Cr and PCr concentrations in the brain, were used to assign the tCr contribution to the Z‐spectrum. To estimate the total guanidinium concentrations, two pools for the Z‐spectrum around 2 ppm were assumed: (i) a Lorentzian function representing the guanidinium chemical exchange saturation transfer (CEST) at 1.95 ppm in the 11.7‐T Z‐spectrum; and (ii) a background signal that can be fitted by a polynomial function. Comparison between the WT and GAMT−/− mice provided strong evidence for three types of contribution to the peak in the Z‐spectrum at 1.95 ppm, namely proteins, Cr and PCr, the latter fitted as tCr. A ratio of 20 ± 7% (protein) and 80 ± 7% tCr was found in brain at 2 μT and 2 s saturation. Based on phantom experiments, the tCr peak was estimated to consist of about 83 ± 5% Cr and 17 ± 5% PCr. Maps for tCr of mouse brain were generated based on the peak at 1.95 ppm after concentration calibration with in vivo magnetic resonance spectroscopy.
Comparison between the chemical exchange saturation transfer (CEST) Z‐spectra recorded in wild‐type (WT) mice and a knockout mouse model (guanidinoacetate N‐methyltransferase deficiency, GAMT−/−), which has low creatine (Cr) and phosphocreatine (PCr) concentrations in the brain, provided strong evidence for three types of contribution to the peak in the Z‐spectrum at 1.95 ppm, namely proteins, Cr and PCr.
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