Dual-tracer Data Research Articles

Hybrid PET- and MR-driven attenuation correction for enhanced 18F-NaF and 18F-FDG quantification in cardiovascular PET/MR imaging

BackgroundThe standard MR Dixon-based attenuation correction (AC) method in positron emission tomography/magnetic resonance (PET/MR) imaging segments only the air, lung, fat and soft-tissues (4-class), thus neglecting the highly attenuating bone tissues and affecting quantification in bones and adjacent vessels. We sought to address this limitation by utilizing the distinctively high bone uptake rate constant Ki expected from 18F-Sodium Fluoride (18F-NaF) to segment bones from PET data and support 5-class hybrid PET/MR-driven AC for 18F-NaF and 18F-Fluorodeoxyglucose (18F-FDG) PET/MR cardiovascular imaging. MethodsWe introduce 5-class Ki/MR-AC for (i) 18F-NaF studies where the bones are segmented from Patlak Ki images and added as the 5th tissue class to the MR Dixon 4-class AC map. Furthermore, we propose two alternative dual-tracer protocols to permit 5-class Ki/MR-AC for (ii) 18F-FDG-only data, with a streamlined simultaneous administration of 18F-FDG and 18F-NaF at 4:1 ratio (R4:1), or (iii) for 18F-FDG-only or both 18F-FDG and 18F-NaF dual-tracer data, by administering 18F-NaF 90 minutes after an equal 18F-FDG dosage (R1:1). The Ki-driven bone segmentation was validated against computed tomography (CT)-based segmentation in rabbits, followed by PET/MR validation on 108 vertebral bone and carotid wall regions in 16 human volunteers with and without prior indication of carotid atherosclerosis disease (CAD). ResultsIn rabbits, we observed similar (< 1.2% mean difference) vertebral bone 18F-NaF SUVmean scores when applying 5-class AC with Ki-segmented bone (5-class Ki/CT-AC) vs CT-segmented bone (5-class CT-AC) tissue. Considering the PET data corrected with continuous CT-AC maps as gold-standard, the percentage SUVmean bias was reduced by 17.6% (18F-NaF) and 15.4% (R4:1) with 5-class Ki/CT-AC vs 4-class CT-AC. In humans without prior CAD indication, we reported 17.7% and 20% higher 18F-NaF target-to-background ratio (TBR) at carotid bifurcations wall and vertebral bones, respectively, with 5- vs 4-class AC. In the R4:1 human cohort, the mean 18F-FDG:18F-NaF TBR increased by 12.2% at carotid bifurcations wall and 19.9% at vertebral bones. For the R1:1 cohort of subjects without CAD indication, mean TBR increased by 15.3% (18F-FDG) and 15.5% (18F-NaF) at carotid bifurcations and 21.6% (18F-FDG) and 22.5% (18F-NaF) at vertebral bones. Similar TBR enhancements were observed when applying the proposed AC method to human subjects with prior CAD indication. ConclusionsKi-driven bone segmentation and 5-class hybrid PET/MR-driven AC is feasible and can significantly enhance 18F-NaF and 18F-FDG contrast and quantification in bone tissues and carotid walls.

Open ocean DMS air/sea fluxes over the eastern South Pacific Ocean

Abstract. Air/sea fluxes of dimethylsulfide (DMS) were measured by eddy correlation over the Eastern South Pacific Ocean during January 2006. The cruise track extended from Manzanillo, Mexico, along 110° W, to Punta Arenas, Chile. Bulk air and surface ocean DMS levels were also measured and gas transfer coefficients (kDMS) were computed. Air and seawater DMS measurements were made using chemical ionization mass spectrometry (API-CIMS) and a gas/liquid membrane equilibrator. Mean surface seawater DMS concentrations were 3.8±2.2 nM and atmospheric mixing ratios were 340±370 ppt. The air/sea flux of DMS was uniformly out of the ocean, with an average value of 12±15 μmol m−2 d−1. Sea surface concentration and flux were highest around 15° S, in a region influenced by shelf waters and lowest around 25° S, in low chlorophyll gyre waters. The DMS gas transfer coefficient exhibited a linear wind speed-dependence over the wind speed range of 1 to 9 m s−1. This relationship is compared with previously measured estimates of k from DMS, CO2, and dual tracer data from the Atlantic and Pacific Ocean, and with the NOAA/COARE gas transfer model. The model generated slope of k vs. wind speed is at the low end of those observed in previous DMS field studies.

Evaluation of rapid dual-tracer 62Cu-PTSM + 62Cu-ATSM PET in dogs with spontaneously occurring tumors

We are developing methods for imaging multiple PET tracers in a single scan with staggered injections, where imaging measures for each tracer are separated and recovered using differences in tracer kinetics and radioactive decay. In this work, signal separation performance for rapid dual-tracer 62Cu-PTSM (blood flow) + 62Cu-ATSM (hypoxia) tumor imaging was evaluated in a large animal model. Four dogs with pre-existing tumors received a series of dynamic PET scans with 62Cu-PTSM and 62Cu-ATSM, permitting evaluation of a rapid dual-tracer protocol designed by previous simulation work. Several imaging measures were computed from the dual-tracer data and compared with those from separate, single-tracer imaging. Static imaging measures (e.g. SUV) for each tracer were accurately recovered from dual-tracer data. The wash-in (k1) and wash-out (k2) rate parameters for both tracers were likewise well recovered (r = 0.87–0.99), but k3 was not accurately recovered for PTSM (r = 0.19) and moderately well recovered for ATSM (r = 0.70). Some degree of bias was noted, however, which may potentially be overcome through further refinement of the signal separation algorithms. This work demonstrates that complementary information regarding tumor blood flow and hypoxia can be acquired by a single dual-tracer PET scan, and also that the signal separation procedure works effectively for real physiologic data with realistic levels of kinetic model mismatch. Rapid multi-tracer PET has the potential to improve tumor assessment for image-guide therapy and monitoring, and further investigation with these and other tracers is warranted.

Feasibility of rapid multitracer PET tumor imaging

Positron emission tomography (PET) can characterize different aspects of tumor physiology using various tracers. PET scans are usually performed using only one tracer since there is no explicit signal for distinguishing multiple tracers. We tested the feasibility of rapidly imaging multiple PET tracers using dynamic imaging techniques, where the signals from each tracer are separated based upon differences in tracer half-life, kinetics, and distribution. Time-activity curve populations for FDG, acetate, ATSM, and PTSM were simulated using appropriate compartment models, and noisy dual-tracer curves were computed by shifting and adding the single-tracer curves. Single-tracer components were then estimated from dual-tracer data using two methods: principal component analysis (PCA)-based fits of single-tracer components to multitracer data, and parallel multitracer compartment models estimating single-tracer rate parameters from multitracer time-activity curves. The PCA analysis found that there is information content present for separating multitracer data, and that tracer separability depends upon tracer kinetics, injection order and timing. Multitracer compartment modeling recovered rate parameters for individual tracers with good accuracy but somewhat higher statistical uncertainty than single-tracer results when the injection delay was >10 min. These approaches to processing rapid multitracer PET data may potentially provide a new tool for characterizing multiple aspects of tumor physiology in vivo.

Use of a novel triple-tracer approach to assess postprandial glucose metabolism.

Numerous studies have used the dual-tracer method to assess postprandial glucose metabolism. The present experiments were undertaken to determine whether the marked tracer nonsteady state that occurs with the dual-tracer approach after food ingestion introduces error when it is used to simultaneously measure both meal glucose appearance (R(a meal)) and endogenous glucose production (EGP). To do so, a novel triple-tracer approach was designed: 12 subjects ingested a mixed meal containing [1-(13)C]glucose while [6-(3)H]glucose and [6,6-(2)H(2)]glucose were infused intravenously in patterns that minimized the change in the plasma ratios of [6-(3)H]glucose to [1-(13)C]glucose and of [6,6-(2)H(2)]glucose to endogenous glucose, respectively. R(a meal) and EGP measured with this approach were essentially model independent, since non-steady-state error was minimized by the protocol. Initial splanchnic glucose extraction (ISE) was 12.9% +/- 3.4%, and suppression of EGP (EGPS) was 40.3% +/- 4.1%. In contrast, when calculated with the dual-tracer one-compartment model, ISE was higher (P < 0.05) and EGPS was lower (P < 0.005) than observed with the triple-tracer approach. These errors could only be prevented by using time-varying volumes different for R(a meal) and EGP. Analysis of the dual-tracer data with a two-compartment model reduced but did not totally avoid the problems associated with marked postprandial changes in the tracer-to-tracee ratios. We conclude that results from previous studies that have used the dual-tracer one-compartment model to measure postprandial carbohydrate metabolism need to be reevaluated and that the triple-tracer technique may provide a useful approach for doing so.

In situ evaluation of air‐sea gas exchange parameterizations using novel conservative and volatile tracers

Measurements of air‐sea gas exchange rates are reported from two deliberate tracer experiments in the southern North Sea during February 1992 and 1993. A conservative tracer, spores of the bacterium Bacillus globigii var. Niger, was used for the first time in an in situ air‐sea gas exchange experiment. This nonvolatile tracer is used to correct for dispersive dilution of the volatile tracers and allows three estimations of the transfer velocity for the same time period. The first estimation of the power dependence of gas transfer on molecular diffusivity in the marine environment is reported. This allows the impact of bubbles on estimates of the transfer velocity derived from changes in the helium/sulphur hexafluoride ratio to be assessed. Data from earlier dual tracer experiments are reinterpreted, and findings suggest that results from all dual tracer experiments are mutually consistent. The complete data set is used to test published parameterizations of gas transfer with wind speed. A gas ex‐ change relationship that shows a dependence on wind speed intermediate between those ofLiss and Merlivat [1986] and Wanninkhof [1992] is found to be optimal. The dual tracer data are shown to be reasonably consistent with global estimates of gas exchange based on the uptake of natural and bomb‐derived radiocarbon. The degree of scatter in the data when plotted against wind speed suggests that parameters not scaling with wind speed are also influencing gas exchange rates.

A Continuous Fast-Response Dual-Tracer Analyzer for Halogenated Atmospheric Tracer Studies

An apparatus for the simultaneous measurement of two tracers, sulfur hexafluoride (SF6) and a perfluorocarbon compound, is introduced. The new instrument is a modification of a commercially available fast-response, continuous analyzer for single halogenated atmospheric tracer studies. A two-channel flow system was implemented consisting of an alumina cartridge in one channel and a glass beads cartridge of equal flow resistance in the second channel. The alumina passes only sulfur hexafluoride, while the glass beads pass both SF6 and the perfluoroarbon tracer. The SF6 is quantified directly from the electron capture detector (ECD) signal in the alumina channel, and the perfluorocarbon concentration is obtained from the difference of the ECD responses in the two channels. The dual-tracer analyzer is field portable for mobile operations or fixed-location monitoring, has a response time of 1.2 s, and has limits of detection of about 15 pptv for SF6 and 10 pptv for perfluoro-methylcyclohexane, which was the principal perfluorocarbon tracer used in this study. The present instrument configuration, which requires periodic purging of the adsorbent trap, can obtain continuous measurements for a 10-15-min segment in every half hour of operation. Dual-tracer data from a field demonstration test are presented.

An evaluation of Gaussian plume-depletion models with dual-tracer field measurements

To evaluate atmospheric diffusion-deposition models, airborne tracer concentrations were measured during simultaneous releases of depositing (ZnS) and nondepositing (SF 6) tracers. The effective deposition velocity of the ZnS tracer, a polydisperse aerosol, was obtained from the near-surface, crosswind-integrated, dual tracer concentrations, using a method based on the surface depletion model of Horst (1977, Atmospheric Environment 11, 41–46.). These deposition velocities were in good agreement with predictions based on the particle size distribution of the ZnS tracer and on wind tunnel measurements of the deposition velocities of monodisperse aerosols. Four Gaussian plume-depletion models were evaluated with the dual tracer data. Source depletion and constant eddy-diffusivity models were found to overestimate the depositing/nondepositing concentration ratio near the surface, but the estimates of these models were noticeably improved by a profile correction to the source depletion model and a mass-conservation correction to the K model. Of the four models tested, the corrected source depletion model gave the best agreement with the observations.