The International Atomic Energy Agency International Doubly Labelled Water Database: Aims, Scope and Procedures.

BACKGROUND: The doubly labelled water (DLW) method is an isotope-based technique that quantifies total energy expenditure (TEE) over periods of 1-3 weeks from the differential elimination of stable isotopes of oxygen and hydrogen. The method was invented in the 1950s, but limited ability to measure low isotope enrichments combined with the high cost of isotopes meant it only became feasible to use in humans in the 1980s. It is still relatively expensive to use, and alone small samples are unable to tackle some of the important questions surrounding energy balance such as how have expenditures changed over time and how do expenditures differ with age, between sexes and in different environments? SUMMARY: By combining information across studies, answers to such questions may be possible. The International Atomic Energy Agency (IAEA) DLW database was established to pool DLW data across multiple studies. It was initiated by the main labs currently using the method and is hosted by the IAEA. At present, the database contains 6,621 measures of TEE by DLW from individuals in 23 countries, along with various additional data on the study participants. Key Messages: The IAEA DLW database is a key resource enabling future studies of energy demands.

Strengthened Data Systems to Mitigate the Double Burden of Malnutrition: The Role of Stable Isotope Technique-Derived Nutrition Indicators.

Indicators reflecting the double burden of malnutrition are rarely measured in nutrition surveys and are needed to strengthen national data systems. Indicators such as body composition reflect both metabolic response to undernutrition and obesity risk and nutrition-related noncommunicable diseases. Stable isotope techniques (SITs) provide accurate data on body composition, exclusive breastfeeding and vitamin A status that are otherwise problematic with routine methods. Integration of SIT-derived nutrition indicators in data systems could improve the design and evaluation of programmes focused on obesity prevention, food fortification and infant and young child feeding practices. The Working Group at the symposium considered "how SIT-derived nutrition indicators may be integrated into surveillance systems to strengthen data availability and capacity at national and regional levels". Practical considerations for the use of SITs include cost, sample size, rigorous training and logistics. It was concluded that SITs are best suited, at present, for use in sub-samples of population surveys and for validating tools that can be scaled-up more easily in population surveys. In the long term, SITs could be applied to larger surveys following potential innovations in more affordable, hand-held devices for analysis of stable isotope enrichment in the field and simpler specimen collection protocols.

The Assessment of Total Energy Expenditure During a 14-Day In-Season Period of Professional Rugby League Players Using the Doubly Labelled Water Method.

Rugby League is a high-intensity collision sport competed over 80 min. Training loads are monitored to maximize recovery and assist in the design of nutritional strategies although no data are available on the total energy expenditure (TEE) of players. We therefore assessed resting metabolic rate (RMR) and TEE in six Super League players over 2 consecutive weeks in-season including one game per week. Fasted RMR was assessed followed by a baseline urine sample before oral administration of a bolus dose of hydrogen (deuterium 2H) and oxygen (18O) stable isotopes in the form of water (2H218O). Every 24 hr thereafter, players provided urine for analysis of TEE via DLW method. Individual training load was quantified using session rating of perceived exertion (sRPE) and data were analyzed using magnitude-based inferences. There were unclear differences in RMR between forwards and backs (7.7 ± 0.5 cf. 8.0 ± 0.3 MJ, respectively). Indirect calorimetry produced RMR values most likely lower than predictive equations (7.9 ± 0.4 cf. 9.2 ± 0.4 MJ, respectively). A most likely increase in TEE from Week 1 to 2 was observed (17.9 ± 2.1 cf. 24.2 ± 3.4 MJ) explained by a most likelyincrease in weekly sRPE (432 ± 19 cf. 555 ± 22 AU), respectively. The difference in TEE between forward and backs was unclear (21.6 ± 4.2 cf. 20.5 ± 4.9 MJ, respectively). We report greater TEE than previously reported in rugby that could be explained by the ability of DLW to account for all match and training-related activities that contributes to TEE.

Comparison of velocity- and acceleration-selective arterial spin labeling with [15O]H2O positron emission tomography.

In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [(15)O]H2O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7 ± 4.1 versus 47.1 ± 6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [(15)O]H2O PET.

Direct (17)O MRI with partial volume correction: first experiences in a glioblastoma patient.

OBJECT: In tumor cells the energy production is shifted from aerobic to anaerobic metabolization of glucose, which makes the cerebral metabolic rate of oxygen consumption (CMRO2) a diagnostic parameter for tissue viability. Direct oxygen-17 ((17)O) MRI during inhalation of (17)O gas allows for a non-invasive determination of the CMRO2. However, the low spatial resolution and the fast transverse relaxation of (17)O lead to partial volume effects that severely bias the quantification of signal intensities. The aim of this work was to determine the CMRO2 in a tumor patient by (17)O MRI in combination with a partial volume correction (PVC) scheme. MATERIALS AND METHODS: Direct (17)O MRI was performed in a glioblastoma patient (F, 51 years) prior to surgery at 7 T. The 'geometric transfer matrix' algorithm for volume of interest based PVC was adapted to (17)O MRI to recover the true signal intensities. We determined the CMRO2 values of gray matter (GM), white matter (WM), cerebrospinal fluid (CSF) and the tumor areas of the contrast enhancing rim (CE), the necrotic center (NE), and the perifocal edema (PE) using a three-phase metabolic model. RESULTS: Large differences in the signal increase during (17)O2 inhalation were obtained ranging from less than 2% in the tumor center up to more than 20% in GM areas. After PVC of the signal time curves, we determined CMRO2 values of 0.67 ± 0.08 µmol/g/min (WM), 3.57 ± 0.67 µmol/g/min (GM), 0.35 ± 0.09 µmol/g/min (CE), and 0.42 ± 0.05 µmol/g/min (PE). In CSF and NE no oxygen uptake (i.e. CMRO2 = 0) was determined from the corrected signals, well in accordance with the underlying physiology in these regions. CONCLUSION: The results show that PVC has a strong effect on the resulting CMRO2 values obtained by (17)O MRI. We found substantial differences-especially in GM tissue-between corrected and non-corrected CMRO2 values. Additionally, we demonstrated the feasibility of CMRO2 assessment in a glioblastoma patient by (17)O MRI.

[Modification of the cytogenetic effects of irradiation by water with the reduced content of deuterium and heavy isotopes of oxygen].

The influence of light water with the reduced content of heavy stable isotopes of oxygen and hydrogen (deuterium) on the cytogenetic status of irradiated animals was investigated. In mice, hybrids of the first generation (CBA x C57B1) F1, the increase in the output (two-fold at the dose of 2 Gy) of aberrant mitoses in the cells of bone marrow and the decrease in the duration of the mitotic index of the first cellular cycle occurred under the influence of the two week maintenance before the irradiation on light water with ppm 35 obtained by the method of rectification as compared with the irradiated animals that were kept on the distilled water. It has been discovered that 24 h after irradiation the number of leukocytes in the group which consumed light water is lower than that in the animals that were contained on the distilled water. Moreover, the cellularity of the bone marrow in the group which consumed light water was higher than that in the animals that were contained on distilled water. The prolonged application of light water before irradiation (for 14 days) led to an increase in the sensitivity of the chromosomal apparatus of mice to γ-irradiation against the background of an increase in the mitotic activity of cells.

Administering labelled water to exclusively breast-fed infants in studies involving stable isotope dilution techniques.

Stable isotope techniques using deuterium or (18)O are reference methods for assessing total body water (TBW) for body composition. In combination, they provide total energy expenditure and human milk intake in exclusively breast-fed (EBF) infants. These techniques require an oral administration of an accurately quantified dose of labelled water to infants, who often have no prior experience of consuming water. In the present study, (18)O labelled water was administered to 47 EBF infants at two time points. Route of administration, duration of dosing and spills were quantified and recorded. Eighty-seven out of 94 (92.6%) dose administrations were successful. In two-thirds of dose administrations, >90% of the prepared dose was consumed. Spills ranged from 0.2% to 57%. Approaches to correct for spills can introduce bias in the calculation of TBW. Minimising and recording all dose spills is an important issue for the accuracy and precision of stable isotope techniques, when applied to EBF infants.

A measurement setup for direct 17O MRI at 7 T.

An efficient breathing system was designed for direct (17)O MRI to perform oxygen metabolism studies of the human brain. The breathing system consists of a demand oxygen delivery device for (17)O(2) supply and a custom-built re-breathing circuit with pneumatic switching valve. To efficiently deliver the (17)O gas to the alveoli of the lungs, the system applies short gas pulses upon an inspiration trigger via a nasal cannula. During and after (17)O(2) administration, the exhaled gas volumes are stored and filtered in the re-breathing section to make the most efficient use of the rare (17)O gas. In an inhalation experiment, 2.2 ± 0.1 L of 70%-enriched (17)O(2) were administered to a healthy volunteer and direct (17)O MRI was performed for a total imaging time of 38 min with a temporal resolution of 50 s per 3D data set. Mapping of the maximum signal increase was carried out showing regional variations of oxygen concentration of up to 30% over the natural abundance of (17)O water.

[Radioprotective effect of "light" water: doubtful validity].

Several publications have reported a radioprotective and immunopotentiating action of "light" water with low content of such stable isotopes as deuterium and 18O. Validity of these statements is the subject of the Letter to editors. Investigations of "light" water compare with that of water purified of a microelement. Prolonged consumption of this water may result in deficiency of the microelement, whereas the positive effect of absence in water of a natural microcomponent is impossible or very unlikely.

Estimation of the regional cerebral metabolic rate of oxygen consumption with proton detected 17O MRI during precision 17O2 inhalation in swine.

Despite the importance of metabolic disturbances in many diseases, there are currently no clinically used methods for the detection of oxidative metabolism in vivo. To address this deficiency, (17)O MRI techniques are scaled from small animals to swine as a large animal model of human inhalation and circulation. The hemispheric cerebral metabolic rate of oxygen consumption (CMRO(2)) is estimated in swine by detection of metabolically produced H(2)(17)O by rapid T(1rho)-weighted proton magnetic resonance imaging on a 1.5T clinical scanner. The (17)O is delivered as oxygen gas by a custom, minimal-loss, precision delivery breathing circuit and converted to H(2)(17)O by oxidative metabolism. A model for gas arterial input is presented for the deeply breathing large animal. The arterial input function for recirculation of metabolic water is measured by arterial blood sampling and high field (17)O spectroscopy. It is found that minimal metabolic water "wash-in" occurs before 60s. A high temporal resolution pulse sequence is employed to measure CMRO(2) during those 60s after delivery begins. Only about one tidal volume of (17)O enriched oxygen gas is used per measurement. Proton measurements of signal change due to metabolically produced water are correlated with (17)O in vivo spectroscopy. Using these techniques, the hemispheric CMRO(2) in swine is estimated to be 1.23+/-.26 micromol/g/min, consistent with existing literature values. All of the technology used to perform these CMRO(2) estimates can easily be adapted to clinical MR scanners, and it is hoped that this work will lead to future studies of human disease.

Centile reference charts for total energy expenditure in infants from 1 to 12 months.

BACKGROUND: A knowledge of energy expenditure in infancy is required for the estimation of recommended daily amounts of food energy, for designing artificial infant feeds, and as a reference standard for studies of energy metabolism in disease states. OBJECTIVES: The objectives of this study were to construct centile reference charts for total energy expenditure (TEE) in infants across the first year of life. METHODS: Repeated measures of TEE using the doubly labeled water technique were made in 162 infants at 1.5, 3, 6, 9 and 12 months. In total, 322 TEE measurements were obtained. The LMS method with maximum penalized likelihood was used to construct the centile reference charts. Centiles were constructed for TEE expressed as MJ/day and also expressed relative to body weight (BW) and fat-free mass (FFM). RESULTS: TEE increased with age and was 1.40,1.86, 2.64, 3.07 and 3.65 MJ/day at 1.5, 3, 6, 9 and 12 months, respectively. The standard deviations were 0.43, 0.47, 0.52,0.66 and 0.88, respectively. TEE in MJ/kg increased from 0.29 to 0.36 and in MJ/day/kg FFM from 0.36 to 0.48. CONCLUSIONS: We have presented centile reference charts for TEE expressed as MJ/day and expressed relative to BW and FFM in infants across the first year of life. There was a wide variation or biological scatter in TEE values seen at all ages. We suggest that these centile charts may be used to assess and possibly quantify abnormal energy metabolism in disease states in infants.