Radiotracer dose reduction in integrated PET/MR: implications from national electrical manufacturers association phantom studies.

UNLABELLED: 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 signal-to-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 +7%), 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.

Image-guided PO2 probe measurements correlated with parametric images derived from 18F-fluoromisonidazole small-animal PET data in rats.

UNLABELLED: (18)F-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 (18)F-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 (18)F-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 (Po(2)). The dynamic (18)F-fluoromisonidazole uptake data were fitted with 2 variants of a 2-compartment, 3-rate-constant model, one constrained to have K(1) equal to k(2) and the other unconstrained. Parametric images of the rate constants were generated. The Po(2) 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, k(3), of the constrained model provided a better discrimination of low Po(2) than the tissue-to-plasma ratio or the k(3) 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, k(3), without introducing significant bias, is to constrain K(1) equal to k(2) during the fitting process.

Pharmacokinetic analysis of hypoxia (18)F-fluoromisonidazole dynamic PET in head and neck cancer.

UNLABELLED: 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)), tumor-to-blood ratio (T/B) in the late-time image, plasma-to-tissue transport rate (k(1)), and local vascular volume fraction (beta) 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), beta) 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 beta. 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 beta and K(i), but no correlation between beta and k(1).

Evaluation of a compartmental model for estimating tumor hypoxia via FMISO dynamic PET imaging.

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 three 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 nine 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.

Effects of low energy protons on clonogenic survival, DSB repair and cell cycle in human glioblastoma cells and B14 fibroblasts.

BACKGROUND AND PURPOSE: The reaction of human tumor cells and mammalian normal tissue to irradiation with low energy protons and X-rays was examined. MATERIAL AND METHODS: An irradiation facility with a vertical proton beam was set up at the Tandem accelerator at the University of Erlangen. U-138MG human glioblastoma cells and B14 hamster fibroblasts were irradiated with 5.7 and 7.0 MeV protons (LET 7.27 and 6.23 keV/microm) and with 120 kV X-rays. The inactivation was measured by the colony forming assay, induction and repair of DNA double strand breaks (DSB) by constant field gel electrophoresis and cell cycle control by image cytometry. RESULTS: An obvious reduction of the shoulder of the dose effect curve was determined. This effect was more pronounced for the glioblastoma cell line. The RBE at 10% survival was measured as 1.78 +/- 0.09 for glioblastoma cells and 1.18 +/- 0.06 for B14 fibroblasts. The induction of DNA DSB in glioblastoma cells showed an RBE of 0.96 +/- 0.06, after 24h repair time an RBE of 2.63 +/- 0.07 was calculated. Protons had a larger and enduring effect on G2 arrest of cell cycle than X-rays, 72 hours after irradiation with 10 Gy an RBE of 1.57 +/- 0.05 was calculated. CONCLUSIONS: The effect of higher LET irradiation was more distinct for tumor cells than for normal tissue. Both cell lines showed a higher RBE for cell survival than the value of 1.1 normally used for proton therapy. Repair capacity of DNA DSB was reduced following low energy proton irradiation and G2 arrest was induced to a larger degree. Further experiments are needed to elucidate if this could be a reason for lower cell survival.