ABSTRACT Purpose: To evaluate a pharmacokinetic compartmental model for identifying intra‐tumor h... more ABSTRACT Purpose: To evaluate a pharmacokinetic compartmental model for identifying intra‐tumor hypoxia using dynamic positron‐emission‐tomography (PET) imaging with 18F‐fluoromisonidazole (FMISO) radiotracer. Method and Materials: The compartmental model used for this work is an irreversible generic two‐tissue type implemented within a pharmacokinetic modeling program called Voxulus by Philips Research. A dynamic PET image dataset (spatial and time) was simulated with 3 tissue regions: normoxia, hypoxia and necrosis, and with an image‐based arterial input function. Each voxelized tissue time‐activity‐curve (TAC) simulation used typical kinetic parameters, generalized from 6 head‐and‐neck cancer patient FMISO‐PET data. The dynamic image was first produced without any statistical noise, to ensure that correct kinetic parameters were reproducible by Voxulus. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic image were generated, from which 1000 noisy samples of kinetic parameters were calculated, and used to estimate sample mean and covariance matrix. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude, peak location and tail amplitude of the input TAC, and the bias of various kinetic parameters computed. Results: Without noise, the estimated kinetic parameters matched their true values perfectly. With noise, the hypoxia rate constant k3 had more variation than other parameters. The plasma‐to‐tissue and tissue‐to‐plasma rate constants (k1 and k2) for diffusible compartment, and vascular density β were highly correlated with each other; while k3 had no correlation with others. Voxulus was applied to estimate parametric image maps of hypoxia for 6 head‐and‐neck cancer patients. Conclusion: Mathematical phantom studies have been used to determine the statistical accuracy of Voxulus, which provides us guidance and confidence in clinical dynamic FMISO‐PET data analysis.
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2015
Targeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning ... more Targeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning systems are entering the market. However, some in-house systems are currently developed for a more flexible and customized dosimetry calculation at voxel-level. For this purpose, we developed a novel software, VoxelMed, and performed a comparison with the software STRATOS. The validation of both of them was undertaken using radioactive phantoms with different volume inserts. A cohort of 10 patients was also studied after a therapeutic administration of (177)Lu-labelled radiopeptides. The activity, number of disintegrations, absorbed dose and dose-volume histogram (DVH) were calculated for the phantoms and the kidneys in patients, which were the main critical organs at risk in this study. In phantoms the absorbed doses computed with VoxelMed and STRATOS agree within 5%. In patients at the voxel-level the absorbed dose to kidneys (VoxelMed: mean 0.66 Gy/GBq) showed a limited difference of ...
We consider a model with $\rho\pi\pi$, $\rho KK$, and gauge-invariant $\rho\gamma$ couplings and ... more We consider a model with $\rho\pi\pi$, $\rho KK$, and gauge-invariant $\rho\gamma$ couplings and obtain the pion form factor $F_\pi$ at timelike momentum transfers by resummation of pion and kaon loops. We use a dispersion representation for the loop diagrams and analyse ambiguities related to subtraction constants. The resulting representation for $F_\pi$ is shown to have the form of the conventional vector meson dominance formula with one important distinction - the effective $\rho$-meson decay constant $f^{\rm eff}_\rho$ turns out to depend on the momentum transfer. For the electromagnetic pion form factor we include in addition the $\rho-\omega$ mixing effects. We apply the representations obtained to the analysis of the data on the pion form factors from $e^+e^-$ annihilation and $\tau$ decay and extract the $\rho^-$, $\rho^0$ and $\omega$ masses and coupling constants.
To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of... more To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of the tumour-specific micromilieu of breast cancer and compare them with corresponding values in normal breast tissue. H2(15)O PET and 18F-FDG PET were performed on 10 patients with advanced invasive ductal carcinomas of the breast. Perfusion, distribution coefficient, and glucose metabolism and standardized uptake were quantified and analysed. Mean values based on the regions of interest were 59.2+/-43.9 ml x min(-1) x 100 g(-1) (perfusion), 0.58+/-0.26 ml x g(-1) (distribution coefficient), 7.76+/-6.10 (standardized uptake), and 5.4+/-2.5 mg x min(-1) x 100 g(-1) (glucose metabolism). The corresponding values for normal breast tissue were 22.1+/-13.2 ml x min x 100 g(-1) (perfusion), 0.16+/-0.05 ml x g(-1) (distribution coefficient), 0.33+/-0.07 (standardized uptake), and 0.18+/-0.08 mg x min x 100 g(-1) (glucose metabolism). For each tumour-normal tissue parameter pair, the mean values...
ABSTRACT Purpose: To evaluate a pharmacokinetic compartmental model for identifying intra‐tumor h... more ABSTRACT Purpose: To evaluate a pharmacokinetic compartmental model for identifying intra‐tumor hypoxia using dynamic positron‐emission‐tomography (PET) imaging with 18F‐fluoromisonidazole (FMISO) radiotracer. Method and Materials: The compartmental model used for this work is an irreversible generic two‐tissue type implemented within a pharmacokinetic modeling program called Voxulus by Philips Research. A dynamic PET image dataset (spatial and time) was simulated with 3 tissue regions: normoxia, hypoxia and necrosis, and with an image‐based arterial input function. Each voxelized tissue time‐activity‐curve (TAC) simulation used typical kinetic parameters, generalized from 6 head‐and‐neck cancer patient FMISO‐PET data. The dynamic image was first produced without any statistical noise, to ensure that correct kinetic parameters were reproducible by Voxulus. Next, to investigate the stability of kinetic parameter estimation in the presence of noise, 1000 noisy samples of the dynamic image were generated, from which 1000 noisy samples of kinetic parameters were calculated, and used to estimate sample mean and covariance matrix. To further investigate how bias in the arterial input function affected the kinetic parameter estimation, a shift error was introduced in the peak amplitude, peak location and tail amplitude of the input TAC, and the bias of various kinetic parameters computed. Results: Without noise, the estimated kinetic parameters matched their true values perfectly. With noise, the hypoxia rate constant k3 had more variation than other parameters. The plasma‐to‐tissue and tissue‐to‐plasma rate constants (k1 and k2) for diffusible compartment, and vascular density β were highly correlated with each other; while k3 had no correlation with others. Voxulus was applied to estimate parametric image maps of hypoxia for 6 head‐and‐neck cancer patients. Conclusion: Mathematical phantom studies have been used to determine the statistical accuracy of Voxulus, which provides us guidance and confidence in clinical dynamic FMISO‐PET data analysis.
Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB), 2015
Targeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning ... more Targeted radionuclide therapy is a rapidly growing modality. A few commercial treatment planning systems are entering the market. However, some in-house systems are currently developed for a more flexible and customized dosimetry calculation at voxel-level. For this purpose, we developed a novel software, VoxelMed, and performed a comparison with the software STRATOS. The validation of both of them was undertaken using radioactive phantoms with different volume inserts. A cohort of 10 patients was also studied after a therapeutic administration of (177)Lu-labelled radiopeptides. The activity, number of disintegrations, absorbed dose and dose-volume histogram (DVH) were calculated for the phantoms and the kidneys in patients, which were the main critical organs at risk in this study. In phantoms the absorbed doses computed with VoxelMed and STRATOS agree within 5%. In patients at the voxel-level the absorbed dose to kidneys (VoxelMed: mean 0.66 Gy/GBq) showed a limited difference of ...
We consider a model with $\rho\pi\pi$, $\rho KK$, and gauge-invariant $\rho\gamma$ couplings and ... more We consider a model with $\rho\pi\pi$, $\rho KK$, and gauge-invariant $\rho\gamma$ couplings and obtain the pion form factor $F_\pi$ at timelike momentum transfers by resummation of pion and kaon loops. We use a dispersion representation for the loop diagrams and analyse ambiguities related to subtraction constants. The resulting representation for $F_\pi$ is shown to have the form of the conventional vector meson dominance formula with one important distinction - the effective $\rho$-meson decay constant $f^{\rm eff}_\rho$ turns out to depend on the momentum transfer. For the electromagnetic pion form factor we include in addition the $\rho-\omega$ mixing effects. We apply the representations obtained to the analysis of the data on the pion form factors from $e^+e^-$ annihilation and $\tau$ decay and extract the $\rho^-$, $\rho^0$ and $\omega$ masses and coupling constants.
To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of... more To determine parameters of perfusion, distribution coefficient, and glucose metabolism as part of the tumour-specific micromilieu of breast cancer and compare them with corresponding values in normal breast tissue. H2(15)O PET and 18F-FDG PET were performed on 10 patients with advanced invasive ductal carcinomas of the breast. Perfusion, distribution coefficient, and glucose metabolism and standardized uptake were quantified and analysed. Mean values based on the regions of interest were 59.2+/-43.9 ml x min(-1) x 100 g(-1) (perfusion), 0.58+/-0.26 ml x g(-1) (distribution coefficient), 7.76+/-6.10 (standardized uptake), and 5.4+/-2.5 mg x min(-1) x 100 g(-1) (glucose metabolism). The corresponding values for normal breast tissue were 22.1+/-13.2 ml x min x 100 g(-1) (perfusion), 0.16+/-0.05 ml x g(-1) (distribution coefficient), 0.33+/-0.07 (standardized uptake), and 0.18+/-0.08 mg x min x 100 g(-1) (glucose metabolism). For each tumour-normal tissue parameter pair, the mean values...
Uploads
Papers by Timo Paulus