Cerebral oxygen extraction fraction (OEF): Comparison of challenge-free gradient echo QSM+qBOLD (QQ) with 15O PET in healthy adults.

We aimed to validate oxygen extraction fraction (OEF) estimations by quantitative susceptibility mapping plus quantitative blood oxygen-level dependence (QSM+qBOLD, or QQ) using 15O-PET. In ten healthy adult brains, PET and MRI were acquired simultaneously on a PET/MR scanner. PET was acquired using C[15O], O[15O], and H2[15O]. Image-derived arterial input functions and standard models of oxygen metabolism provided quantification of PET. MRI included T1-weighted imaging, time-of-flight angiography, and multi-echo gradient-echo imaging that was processed for QQ. Region of interest (ROI) analyses compared PET OEF and QQ OEF. In ROI analyses, the averaged OEF differences between PET and QQ were generally small and statistically insignificant. For whole brains, the average and standard deviation of OEF was 32.8 ± 6.7% for PET; OEF was 34.2 ± 2.6% for QQ. Bland-Altman plots quantified agreement between PET OEF and QQ OEF. The interval between the 95% limits of agreement was 16.9 ± 4.0% for whole brains. Our validation study suggests that respiratory challenge-free QQ-OEF mapping may be useful for non-invasive clinical assessment of regional OEF impairment.

An integrated assessment of nitrogen source, transformation and fate within an intensive dairy system to inform management change.

From an environmental perspective optimised dairy systems, which follow current regulations, still have low nitrogen (N) use efficiency, high N surplus (kg N ha-1) and enable ad-hoc delivery of direct and indirect reactive N losses to water and the atmosphere. The objective of the present study was to divide an intensive dairy farm into N attenuation capacity areas based on this ad-hoc delivery. Historical and current spatial and temporal multi-level datasets (stable isotope and dissolved gas) were combined and interpreted. Results showed that the farm had four distinct attenuation areas: high N attenuation: characterised by ammonium-N (NH4+-N) below 0.23 mg NH4+-N l-1 and nitrate (NO3--N) below 5.65 mg NO3--N l-1 in surface, drainage and groundwater, located on imperfectly to moderately-well drained soils with high denitrification potential and low nitrous oxide (N2O) emissions (av. 0.0032 mg N2O-N l-1); moderate N attenuation: characterised by low NO3--N concentration in drainage water but high N2O production (0.0317 mg N2O-N l-1) and denitrification potential lower than group 1 (av. δ15N-NO3-: 16.4‰, av. δ18O-NO3-: 9.2‰), on well to moderately drained soils; low N attenuation-area 1: characterised by high NO3--N (av. 6.90 mg NO3--N l-1) in drainage water from well to moderately-well drained soils, with low denitrification potential (av. δ15N-NO3-: 9.5‰, av. δ18O-NO3-: 5.9‰) and high N2O emissions (0.0319 mg N2O l-1); and low N attenuation-area 2: characterised by high NH4+-N (av. 3.93 mg NH4+-N l-1 and high N2O emissions (av. 0.0521 mg N2O l-1) from well to imperfectly drained soil. N loads on site should be moved away from low attenuation areas and emissions to air and water should be assessed.

Range verification of radioactive ion beams of 11C and 15O using in-beam PET imaging.

In advanced ion therapy, the visualization of the range of incident ions in a patient's body is important for exploiting the advantages of this type of therapy. It is ideal to use radioactive ion beams for in-beam positron emission tomography (PET) imaging in particle therapy due to the high quality of PET images caused by the high signal-to-noise ratio. We have shown the feasibility of this idea through an in-beam PET study for 11C and 15O ion beams using the dedicated OpenPET system. In this work, we investigate the potential difference between the Bragg peak position and the position of the maximum detected positron-emitting fragments by a PET system for the radioactive beams of 11C and 15O. For this purpose, we measured the depth dose in a water phantom and performed PET scans of an irradiated PMMA phantom for the available beams of 11C and 15O at the Heavy Ion Medical Accelerator in Chiba (HIMAC). Then, we simulated the depth dose profiles in the water phantom and the yield of the positron-emitting fragments in a PMMA phantom for both available beams using the Monte Carlo code PHITS. The positions of the Bragg peak and maximum positron-emitting fragments from the measurements were well reproduced by simulation. The effect of beam energy broadening on the positional differences between two peaks was studied by simulating an irradiated PMMA phantom. The differences in position between the Bragg peak and the maximum positron-emitting fragments increased when the beam energy spread was broadened, although the differences were zero for the ideal mono-energetic beams. Greater differences were observed for 11C ion beams compared to 15O ion beams, although both beams had the same range in water, and the higher energy corresponded to a larger difference. For the known energy spread of the beams, the predicted differences between two peaks from the simulation were consistent with the measured data within submillimetre agreement.

Hybrid PET/MRI imaging in healthy unsedated newborn infants with quantitative rCBF measurements using 15O-water PET.

In this study, a new hybrid PET/MRI method for quantitative regional cerebral blood flow (rCBF) measurements in healthy newborn infants was assessed and the low values of rCBF in white matter previously obtained by arterial spin labeling (ASL) were tested. Four healthy full-term newborn subjects were scanned in a PET/MRI scanner during natural sleep after median intravenous injection of 14 MBq 15O-water. Regional CBF was quantified using a one-tissue-compartment model employing an image-derived input function (IDIF) from the left ventricle. PET rCBF showed the highest values in the thalami, mesencephalon and brain stem and the lowest in cortex and unmyelinated white matter. The average global CBF was 17.8 ml/100 g/min. The average frontal and occipital unmyelinated white matter CBF was 10.3 ml/100 g/min and average thalamic CBF 31.3 ml/100 g/min. The average white matter/thalamic ratio CBF was 0.36, significantly higher than previous ASL data. The rCBF ASL measurements were all unsuccessful primarily owing to subject movement. In this study, we demonstrated for the first time, a minimally invasive PET/MRI method using low activity 15O-water PET for quantitative rCBF assessment in unsedated healthy newborn infants and found a white/grey matter CBF ratio similar to that of the adult human brain.

Experimental validation of estimated spatially variant radioisotope-specific point spread functions using published positron range simulations and fluorine-18 measurements.

In this work we compare spatially variant radioisotope-specific point spread functions (PSFs) derived from published positron range data with measured data using a high resolution research tomograph (HRRT). Spatially variant PSFs were measured on a HRRT for fluorine-18, carbon-11 and gallium-68 using an array of printed point sources. For gallium-68, this required modification of the original design to handle its longer positron range. Using the fluorine-18 measurements and previously published data from Monte-Carlo simulations of positron range, estimated PSFs for carbon-11 and gallium-68 were calculated and compared with experimental data. A double 3D Gaussian function was fitted to the estimated and measured data and used to model the spatially varying PSFs over the scanner field of view (FOV). Differences between the measured and estimated PSFs were quantified using the full-width-at-half-maximum (FWHM) and full-width-at-tenth-maximum (FWTM) in the tangential, radial and axial directions. While estimated PSFs were generally in agreement with the measured PSFs over the entire FOV better agreement was observed (FWHM and FWTM differences of less than 10%) when using one of the two sets of positron range simulations, especially for gallium-68 and for the FWTM. Spatially variant radioisotope specific PSFs can be accurately estimated from fluorine-18 measurements and published positron range data. We have experimentally validated this approach for carbon-11 and gallium-68, and such an approach may be applicable to other radioisotopes such as oxygen-15 for which measurements are not practical.

Earliest isotopic evidence in the Maya region for animal management and long-distance trade at the site of Ceibal, Guatemala.

This study uses a multiisotope (carbon, nitrogen, oxygen, and strontium) approach to examine early animal management in the Maya region. An analysis of faunal specimens across almost 2,000 years (1000 BC to AD 950) at the site of Ceibal, Guatemala, reveals the earliest evidence for live-traded dogs and possible captive-reared taxa in the Americas. These animals may have been procured for ceremonial functions based on their location in the monumental site core, suggesting that animal management and trade began in the Maya area to promote special events, activities that were critical in the development of state society. Isotopic evidence for animal captivity at Ceibal reveals that animal management played a greater role in Maya communities than previously believed.

Timber isoscapes. A case study in a mountain area in the Italian Alps.

BACKGROUND: Local timber is still one of the main sources of work and income for mountain communities. However, illegal logging is a major cause of deforestation in many countries and has significant impacts on local communities and biodiversity. Techniques for tracing timber would provide a useful tool to protect local timber industries and contribute to the fight against illegal logging. Although considerable progress has been made in food traceability, timber provenance is still a somewhat neglected research area. Stable isotope ratios in plants are known to reflect geographical variations. This study reports accurate spatial distribution of δ18O and δ2H in timber from north-eastern Italy (Trentino) in order to trace geographical origin. METHODOLOGY AND PRINCIPAL FINDINGS: We tested the accuracy of four kriging methods using an annual resolution of δ18O and δ2H measured in Picea abies. Pearson's correlation coefficients revealed altitude to be the most appropriate covariate for the cokriging model, which has ultimately proved to be the best method due to its low estimation error. CONCLUSIONS: We present regional maps of interpolated δ18O and δ2H in Picea abies wood together with the 95% confidence intervals. The strong spatial structure of the data demonstrates the potential of multivariate spatial interpolation, even in a highly heterogeneous area such as the Alps. We believe that this geospatial approach can be successfully applied on a wider scale in order to combat illegal logging.

In vivo17O MRS imaging - Quantitative assessment of regional oxygen consumption and perfusion rates in living brain.

In the last decade, in vivo oxygen-17 (17O) MRS has evolved into a promising MR technique for noninvasively studying oxygen metabolism and perfusion in aerobic organs with the capability of imaging the regional metabolic rate of oxygen and its changes. In this chapter, we will briefly review the methodology of the in vivo17O MRS technique and its recent development and applications; we will also discuss the advantages of the high/ultrahigh magnetic field for 17O MR detection, as well as the challenges and potential of this unique MRS method for biomedical research of oxygen metabolism, mitochondrial function and tissue energetics in health and disease.

Corrections for the combined effects of decay and dead time in live-timed counting of short-lived radionuclides.

Studies and calibrations of short-lived radionuclides, for example (15)O, are of particular interest in nuclear medicine. Yet counting experiments on such species are vulnerable to an error due to the combined effect of decay and dead time. Separate decay corrections and dead-time corrections do not account for this issue. Usually counting data are decay-corrected to the start time of the count period, or else instead of correcting the count rate, the mid-time of the measurement is used as the reference time. Correction factors are derived for both those methods, considering both extending and non-extending dead time. Series approximations are derived here and the accuracy of those approximations are discussed.

Identification of oxygen-19 during in vivo neutron activation analysis of water phantoms.

Hand bone equivalent phantoms (250 ml) carrying selenium in various amounts were irradiated and counted for in vivo neutron activation analysis (IVNAA) by employing a 4π NaI(TI) based detection system. During the analysis of counting data, a feature at a higher energy than the gamma ray peak from (77m)Se (0.162 MeV) was observed at 0.197 MeV. Further investigations were made by preparing water phantoms containing only de-ionized water in 250 ml and 1034 ml quantities. Neutrons were produced by the (7)Li(p,n)(7)Be reaction using the high beam current Tandetron accelerator. Phantoms were irradiated at a fixed proton energy of 2.3 MeV and proton currents of 400 µA and 550 µA for 30 s and 22 s respectively. The counting data saved using the 4π NaI(TI) detection system for 10 s intervals in anticoincidence, coincidence and singles modes of detection were analyzed. Areas under gamma peaks at energies 0.197 MeV and 1.357 MeV were computed and half-lives from the number of counts for the two peaks were established. It was concluded that during neutron activation of water phantoms, oxygen-18 is activated, producing short-lived radioactive 19O having T(1/2) = 26.9 s. Induced activity from 19O may contribute spectral interference in the gamma ray spectrum. This effect may need to be taken into account by researchers while carrying out IVNAA of biological subjects.

Mapping (15)O production rate for proton therapy verification.

PURPOSE: This work was a proof-of-principle study for the evaluation of oxygen-15 ((15)O) production as an imaging target through the use of positron emission tomography (PET), to improve verification of proton treatment plans and to study the effects of perfusion. METHODS AND MATERIALS: Dynamic PET measurements of irradiation-produced isotopes were made for a phantom and rabbit thigh muscles. The rabbit muscle was irradiated and imaged under both live and dead conditions. A differential equation was fitted to phantom and in vivo data, yielding estimates of (15)O production and clearance rates, which were compared to live versus dead rates for the rabbit and to Monte Carlo predictions. RESULTS: PET clearance rates agreed with decay constants of the dominant radionuclide species in 3 different phantom materials. In 2 oxygen-rich materials, the ratio of (15)O production rates agreed with the expected ratio. In the dead rabbit thighs, the dynamic PET concentration histories were accurately described using (15)O decay constant, whereas the live thigh activity decayed faster. Most importantly, the (15)O production rates agreed within 2% (P>.5) between conditions. CONCLUSIONS: We developed a new method for quantitative measurement of (15)O production and clearance rates in the period immediately following proton therapy. Measurements in the phantom and rabbits were well described in terms of (15)O production and clearance rates, plus a correction for other isotopes. These proof-of-principle results support the feasibility of detailed verification of proton therapy treatment delivery. In addition, (15)O clearance rates may be useful in monitoring permeability changes due to therapy.

Hydrogeochemistry of the drinking water sources of Derebogazi Village (Kahramanmaras) and their effects on human health.

The aim of this study was to investigate the sources of drinking water for Derebogazi Village, Kahramanmaras Province, Turkey, in terms of hydrogeochemistry, isotope geochemistry, and medical geology. Water samples were obtained from seven different water sources in the area, all of which are located within quartzite units of Paleozoic age, and isotopic analyses of (18)O and (2)H (deuterium) were conducted on the samples. Samples were collected from the region for 1 year. Water quality of the samples was assessed in terms of various water quality parameters, such as temperature, pH, conductivity, alkalinity, trace element concentrations, anion-cation measurements, and metal concentrations, using ion chromatography, inductively coupled plasma (ICP) mass spectrometry, ICP-optical emission spectrometry techniques. Regional health surveys had revealed that the heights of local people are significantly below the average for the country. In terms of medical geology, the sampled drinking water from the seven sources was deficient in calcium and magnesium ions, which promote bone development. Bone mineral density screening tests were conducted on ten females using dual energy X-ray absorptiometry to investigate possible developmental disorder(s) and potential for mineral loss in the region. Of these ten women, three had T-scores close to the osteoporosis range (T-score < -2.5).

Antarctic glaciation caused ocean circulation changes at the Eocene-Oligocene transition.

Two main hypotheses compete to explain global cooling and the abrupt growth of the Antarctic ice sheet across the Eocene-Oligocene transition about 34 million years ago: thermal isolation of Antarctica due to southern ocean gateway opening, and declining atmospheric CO2 (refs 5, 6). Increases in ocean thermal stratification and circulation in proxies across the Eocene-Oligocene transition have been interpreted as a unique signature of gateway opening, but at present both mechanisms remain possible. Here, using a coupled ocean-atmosphere model, we show that the rise of Antarctic glaciation, rather than altered palaeogeography, is best able to explain the observed oceanographic changes. We find that growth of the Antarctic ice sheet caused enhanced northward transport of Antarctic intermediate water and invigorated the formation of Antarctic bottom water, fundamentally reorganizing ocean circulation. Conversely, gateway openings had much less impact on ocean thermal stratification and circulation. Our results support available evidence that CO2 drawdown--not gateway opening--caused Antarctic ice sheet growth, and further show that these feedbacks in turn altered ocean circulation. The precise timing and rate of glaciation, and thus its impacts on ocean circulation, reflect the balance between potentially positive feedbacks (increases in sea ice extent and enhanced primary productivity) and negative feedbacks (stronger southward heat transport and localized high-latitude warming). The Antarctic ice sheet had a complex, dynamic role in ocean circulation and heat fluxes during its initiation, and these processes are likely to operate in the future.

Quantitative proteomics by 2-DE, 16O/18O labelling and linear ion trap mass spectrometry analysis of lymph nodes from piglets inoculated by porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) has been identified as the essential causal agent of postweaning multisystemic wasting syndrome. However, little is known regarding the mechanism(s) underlying the pathogenesis of PCV2-induced disease and the interaction of the virus with the host immune system. Here, we present a proteomics study on inguinal lymph nodes of piglets inoculated with PCV2, in order to better understand the pathogenesis of postweaning multisystemic wasting syndrome and the pathways might be affected after infection. We used two proteomics strategies, 2-DE and 1-DE followed by (16)O/(18)O peptide labelling and peptide identification and quantification by MS. More than 100 proteins were found to be differentially regulated and the results obtained by the two strategies were fairly concordant but also complementary, the (18)O labelling approach being a more robust alternative. Analysis of these proteins by systems biology tools revealed the implication of acute phase response and NrF2-mediated oxidative stress, suggesting a putative role for these pathways in the pig immune response. Besides, CD81 was found to be up-regulated, suggesting a possible role in the internalization of the virus. The use of proteomics technologies together with biology analysis systems opens up the way to gain more exhaustive and systematic knowledge of virus-pathogen interactions.

Magnetic field-cycling NMR and (14)N, (17)O quadrupole resonance in the explosive pentaerythritol tetranitrate (PETN).

The explosive pentaerythritol tetranitrate (PETN) C(CH(2)-O-NO(2))(4) has been studied by (1)H NMR and (14)N NQR. The (14)N NQR frequency and spin-lattice relaxation time T(1Q) for the nu(+) line have been measured at temperatures from 255 to 325K. The (1)H NMR spin-lattice relaxation time T(1) has been measured at frequencies from 1.8kHz to 40MHz and at temperatures from 250 to 390K. The observed variations are interpreted as due to hindered rotation of the NO(2) group about the bond to the oxygen atom of the CH(2)-O group, which produces a transient change in the dipolar coupling of the CH(2) protons, generating a step in the (1)H T(1) at frequencies between 2 and 100kHz. The same mechanism could also explain the two minima observed in the temperature variation of the (14)N NQR T(1Q) near 284 and 316K, due in this case to the transient change in the (14)N...(1)H dipolar interaction, the first attributed to hindered rotation of the NO(2) group and the second to an increase in torsional amplitude of the NO(2) group due to molecular distortion of the flexible CH(2)-O-NO(2) chain which produces a 15% increase in the oscillational amplitude of the CH(2) group. The correlation times governing the (1)H T(1) values are approximately 25 times longer than those governing the (14)N NQR T(1Q), explained by the slow spin-lattice cross-coupling between the two spin systems. At higher frequencies, the (1)H T(1) dispersion results show well-resolved dips between 200 and 904kHz assigned to level crossing with (14)N and weaker features between 3 and 5MHz tentatively assigned to level crossing with (17)O.

2H NMR and 13C-IRMS analyses of acetic acid from vinegar, 18O-IRMS analysis of water in vinegar: international collaborative study report.

An international collaborative study of isotopic methods applied to control the authenticity of vinegar was organized in order to support the recognition of these procedures as official methods. The determination of the 2H/1H ratio of the methyl site of acetic acid by SNIF-NMR (site-specific natural isotopic fractionation-nuclear magnetic resonance) and the determination of the 13C/12C ratio, by IRMS (isotope ratio mass spectrometry) provide complementary information to characterize the botanical origin of acetic acid and to detect adulterations of vinegar using synthetic acetic acid. Both methods use the same initial steps to recover pure acetic acid from vinegar. In the case of wine vinegar, the determination of the 18O/16O ratio of water by IRMS allows to differentiate wine vinegar from vinegars made from dried grapes. The same set of vinegar samples was used to validate these three determinations. The precision parameters of the method for measuring delta13C (carbon isotopic deviation) were found to be similar to the values previously obtained for similar methods applied to wine ethanol or sugars extracted from fruit juices: the average repeatability (r) was 0.45 per thousand, and the average reproducibility (R) was 0.91 per thousand. As expected from previous in-house study of the uncertainties, the precision parameters of the method for measuring the 2H/1H ratio of the methyl site were found to be slightly higher than the values previously obtained for similar methods applied to wine ethanol or fermentation ethanol in fruit juices: the average repeatability was 1.34 ppm, and the average reproducibility was 1.62 ppm. This precision is still significantly smaller than the differences between various acetic acid sources (delta13C and delta18O) and allows a satisfactory discrimination of vinegar types. The precision parameters of the method for measuring delta18O were found to be similar to the values previously obtained for other methods applied to wine and fruit juices: the average repeatability was 0.15 per thousand, and the average reproducibility was 0.59 per thousand. The above values are proposed as repeatability and reproducibility limits in the current state of the art. On the basis of this satisfactory inter-laboratory precision and on the accuracy demonstrated by a spiking experiment, the authors recommend the adoption of the three isotopic determinations included in this study as official methods for controlling the authenticity of vinegar.

Isotopes and sustainability of ground water resources, North China Plain.

Ground water in deep confined aquifers is one of the major water resources for agricultural, industrial, and domestic uses in the North China Plain. Detailed information on ground water age and recharge is vital for the proper management of these water resources, and to this end, we used carbon 14 of dissolved inorganic carbon and tritium in water to measure the age and determine the recharge areas of ground water in the North China Plain. These isotopic data suggest that most ground water in the piedmont part of the North China Plain is <40 years old and is recharged locally. In contrast, ground water in the central and littoral portions of the North China Plain is 10,000 to 25,000 years old. The delta18O (deltaD) values of this ground water are 1.7 per thousand (11 per thousand) less than that in the piedmont plain ground water and possibly reflect water recharged during a cooler climate during the last glaciation. The temperature of this recharge, based on delta18O values, ranges from 3.7 degrees C to 8.4 degrees C, compared to 12 degrees C to 13 degrees C of modern recharge water. The isotopic data set combined indicates that ground water in the central and littoral part of the North China Plain is being mined under non-steady state conditions.

Determination of sites citrullinated by peptidylarginine deiminase using 18O stable isotope labeling and mass spectrometry.

Peptidylarginine deiminase (PADI) is an enzyme which catalyzes conversion of arginine residues into citrulline residues in proteins. Citrullination is known to be related to autoimmune diseases including rheumatoid arthritis. Previous work in this laboratory succeeded in identifying citrullinated sites of human fibrinogen by mass spectrometry, but discrimination between citrullination and deamidation of asparagines and glutamine required time-consuming and labor-intensive inspection of tandem mass spectra. In this work a stable isotope is utilized to improve on a previous method for the determination of citrullinated sites by mass spectrometry. Since an oxygen atom is incorporated into the citrulline residue from H(2)O in citrullination by PADI, peptides citrullinated in 50% H(2)(18)O would show a characteristic isotope distribution different from natural abundance, and thus determination of citrullinated sites is expected to be much easier. To verify the utility of this new method, the sites of citrullination of human fibrinogen by human PADI4 were investigated using 50% H(2)(18)O. Compared with the previous method, this new method identified citrullinated sites more easily and effectively, while both the determined citrullinated sites and protein sequence coverage were unaltered.

Formation of short-lived positron emitters in reactions of protons of energies up to 200 MeV with the target elements carbon, nitrogen and oxygen.

Excitation functions were measured by the stacked-foil technique for proton induced reactions on carbon, nitrogen and oxygen leading to the formation of the short-lived positron emitters (11)C (T(1/2) = 20.38 min) and (13)N (T(1/2) = 9.96 min). The energy region covered extended up to 200 MeV. The product activity was measured non-destructively via gamma-ray spectrometry. A careful decay curve analysis of the positron annihilation radiation was invariably performed. The experimental results were compared with theoretical data obtained using the modified hybrid nuclear model code ALICE-IPPE for intermediate energies. The agreement was found to be generally satisfactory. The data are of importance in proton therapy.

A simple effective method for estimating the [18O] enrichment of water mixtures.

Isotopically enriched water, [18O] H(2)O, recovered from the synthesis of [18F] fluorine-labelled PET radiopharmaceuticals, is frequently diluted with natural water, [16O] H(2)O. The extent of isotope dilution limits the usefulness of the recovered water. A simple method for determining the [18O] enrichment of water mixtures could aid PET cyclotron facilities to calculate the [18F] yields to be expected when the recovered [18O] H(2)O is reused. A gravimetric method (repeatability for high enrichment +/-0.3% [18O], detection limit approximately 2% [18O] enrichment) is described.