This paper systematically evaluates a pharmacokinetic compartmental model for identifying tumor hypoxia using dynamic positron-emission-tomography (PET) imaging with 18F-fluoromisonidazole (FMISO). A generic irreversible one-plasma two-tissue compartmental model was used. A dynamic PET image dataset was simulated with 3 tumor regions -- normoxic, hypoxic and necrotic, embedded in a normal-tissue background, and with an image-based arterial input function. Each voxelized tissue’s time-activity-curve (TAC) was simulated with typical values of kinetic parameters, as deduced from FMISO-PET data from 9 head-and-neck cancer patients. The dynamic dataset was first produced without any statistical noise to ensure that correct kinetic parameters were reproducible. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic dataset were generated, from which 1000 noisy estimates of kinetic parameters were calculated and used to estimate the sample mean and covariance matrix. It is found that a more peaked input function gave less variation in various kinetic parameters, and the variation of kinetic parameters could also be reduced by two region-of-interest averaging techniques. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak-amplitude and peak-location of the input TAC, and the bias of various kinetic parameters calculated. In summary, mathematical phantom studies have been used to determine the statistical accuracy and precision of model-based kinetic analysis, which helps to validate this analysis and provides guidance in planning clinical dynamic FMISO-PET studies.

This study used pharmacokinetic analysis of 18 F-labeled fluoromisonidazole ( 18 F-FMISO) dynamic PET to assist the identification of regional tumor hypoxia and to investigate the relationship among a potential tumor hypoxia index (K i ), tumorto-blood ratio (T/B) in the late-time image, plasma-to-tissue transport rate (k 1 ), and local vascular volume fraction (b) for head and neck cancer patients. Methods: Newly diagnosed patients underwent a dynamic 18 F-FMISO PET scan before chemotherapy or radiotherapy. The data were acquired in 3 consecutive PET/CT dynamic scan segments, registered with each other and analyzed using pharmacokinetics software. The (K i , k 1 , b) kinetic parameter images were derived for each patient. Results: Nine patients' data were analyzed. Representative images of 18 F-FDG PET (of the tumor), CT (of the anatomy), and late-time 18 F-FMISO PET (of the T/B) and parametric images of K i (potentially representing tumor hypoxia) are shown. The patient image data could be classified into 3 types: with good concordance between the parametric hypoxia map K i and high T/B, with concordant findings between the parametric hypoxia map and low T/B, and with ambiguity between parametric hypoxia map and T/B. Correlation coefficients are computed between each pair of T/ B, K i , k 1 , and b. Data are also presented for other potential hypoxia surrogate measures, for example, k 3 and k 1 /k 2 . Conclusion: There is a positive correlation of 0.86 between the average T/B and average hypoxia index K i of the region of interest. However, because of the statistical photon counting noise in PET and the amplification of noise in kinetic analysis, the direct correlation between the T/B and hypoxia of the individual pixel is not obvious. For a tumor region of interest, there is a slight negative correlation between k 1 and K i , moderate positive correlation between b and K i , but no correlation between b and k 1 .

18F-fluoromisonidazole PET, a noninvasive means of identifying hypoxia in tumors, has been widely applied but with mixed results, raising concerns about its accuracy. The objective of this study was to determine whether kinetic analysis of dynamic 18F-fluoromisonidazole data provides better discrimination of tumor hypoxia than methods based on a simple tissue-to-plasma ratio. Methods Eleven Dunning R3327-AT prostate tumor-bearing nude rats were immobilized in custom-fabricated whole-body molds, injected intravenously with 18F-fluoromisonidazole, and imaged dynamically for 105 min. They were then transferred to a robotic system for image-guided measurement of intratumoral partial pressure of oxygen (PO2). The dynamic 18F-fluoromisonidazole uptake data were fitted with 2 variants of a 2-compartment, 3-rate-constant model, one constrained to have K1 equal to k2 and the other unconstrained. Parametric images of the rate constants were generated. The PO2 measurements were compared with spatially registered maps of kinetic rate constants and tumor-to-plasma ratios. Results The constrained pharmacokinetic model variant was shown to provide fits similar to that of the unconstrained model and did not introduce significant bias in the results. The trapping rate constant, k3, of the constrained model provided a better discrimination of low PO2 than the tissue-to-plasma ratio or the k3 of the unconstrained model. Conclusion The use of kinetic modeling on a voxelwise basis can identify tumor hypoxia with improved accuracy over simple tumor-to-plasma ratios. An effective means of controlling noise in the trapping rate constant, k3, without introducing significant bias, is to constrain K1 equal to k2 during the fitting process.

The cross section for the production of ω mesons in proton-proton collisions has been measured in a previously unexplored region of incident energies. Cross sections of σ = (7.5 ± 1.9) µb and σ = (30.8 ± 3.4) µb (with 20% systematic uncertainties) were extracted at ǫ = 92 MeV and 173 MeV excess energy above the ω threshold, respectively. The angular distribution of the ω at ǫ = 173 MeV is strongly anisotropic,

With the replacement of ionizing CT by MR imaging, integrated PET/MR in selected clinical applications may reduce the overall patient radiation dose when compared with PET/CT. Further potential for radiotracer dose reduction, while maintaining PET image quality (IQ) in integrated PET/MR, may be achieved by increasing the PET acquisition duration to match the longer time needed for MR data acquisition. To systematically verify this hypothesis under controlled conditions, this dose-reduction study was performed using a standardized phantom following the National Electrical Manufacturers Association (NEMA) IQ protocol. Methods: All measurements were performed on an integrated PET/MR whole-body hybrid system. The NEMA IQ phantom was filled with water and a total activity of 50.35 MBq of 18 F-FDG. The sphere-to-background activity ratio was 8:1. Multiple PET data blocks of 20-min acquisition time were acquired in list-mode format and were started periodically at multiples of the 18 F-FDG half-lives. Different sinograms (2, 4, 8, and 16 min in duration) were reconstructed. Attenuation correction of the filled NEMA phantom was performed using a CT-based attenuation map template. The attenuation-corrected PET images were then quantitatively evaluated following the NEMA IQ protocol, investigating contrast recovery, background variability, and signalto-noise ratio. Image groups with half the activity and twice the acquisition time were evaluated. For better statistics, the experiment was repeated 3 times. Results: Contrast recovery, background variability, and signal-to-noise ratio remained almost constant over 3 half-life periods when the decreasing radiotracer activity (100%, 50%, 25%, and 12.5%) was compensated by increasing acquisition time (2, 4, 8, and 16 min). The variation of contrast recovery over 3 half-life periods was small (−6% to 17%), with a mean variation of 2%, compared with the reference setting (100%, 2 min). The signal-to-noise ratio of the hot spheres showed only minor variations over 3 half-life periods (5%). Image readers could not distinguish subjective IQ between the different PET acquisition setups. Conclusion: An approach to reduce the injected radiotracer activity in integrated PET/MR imaging, while maintaining PET IQ, was presented and verified under idealized experimental conditions. This experiment may serve as a basis for further clinical PET/MR studies using reduced radiotracer dose as compared with conventional PET/CT studies.