Stephen J. Lokitz

Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine

Tobacco smoking is a chronic, relapsing disorder that constitutes one of the primary preventable causes of death in developed countries. Two of the popular hypotheses to explain the development and maintenance of strong nicotine dependence in cigarette smokers posit (i) a rapid brain nicotine accumulation during cigarette smoking and/or (ii) puff-associated spikes in brain nicotine concentration. To address these hypotheses, we investigated the dynamics of nicotine accumulation in the smokers brain during actual cigarette smoking using PET with 3-s temporal resolution and 11C-nicotine loaded into cigarettes. The results of the study, performed in 13 dependent smokers (DS) and 10 nondependent smokers (NDS), suggest that puff-associated spikes in the brain nicotine concentration do not occur during habitual cigarette smoking. Despite the presence of a puff-associated oscillation in the rate of nicotine accumulation, brain nicotine concentration gradually increases during cigarette smoking. The results further suggest that DS have a slower process of brain nicotine accumulation than NDS because they have slower nicotine washout from the lungs and that DS have a tendency to compensate for their slower rate of brain nicotine accumulation compared with NDS by inhaling a larger volume of smoke. For these reasons, smokers’ dependence on cigarette smoking, or the resistance of NDS to becoming dependent, cannot be explained solely by a faster brain nicotine accumulation.

Development of a fillable, tapered PET/CT phantom

PET system performance and image quality are degraded as body size increases; as size increases so do scatter fractions, random fractions, and attenuation. Based on simulated and acquired data, a fillable, tapering phantom is being developed to measure PET scanner performance and image quality as a function of body size over a wide range of sizes. Design constraints included shape, cross-sectional dimensions, material, wall thickness, and taper angle. For fixed end sizes (large at one end, small at the other) a narrow taper leads to a long, heavy phantom. A steep taper (where the diameter changes greatly within the scanner field of view) may not represent any particular cross section very well. Monte Carlo simulations were performed to determine an acceptable taper angle that balances the pros and cons of steep and narrow taper rates. The simulations were validated with measurements on existing physical phantoms. Then, tapering phantoms with different taper angles and phantoms with constant cross-sectional dimensions were simulated at different positions in the axial field of view to investigate properties of different taper rates. Scatter fractions of simulated taper phantoms and phantoms with constant cross-sectional dimensions were compared. Of the different taper angles simulated, it was determined that a 25° taper will yield a phantom that can represent a continuum of cross-sectional dimensions while still being a practical size. The final design parameters for this phantom include the 25° taper, an oval cross section ranging from 38.5 × 49.5 cm to 6.8 × 17.8 cm, a length of 51.1 cm, a mass of 6 kg (empty), a mass of 42 kg (water filled), and acrylic walls 1.25 cm thick.

Ultra low dose CT for attenuation correction in PET/CT

In this paper, we present an ultra low-dose CT acquisition and reconstruction technique that provides sufficient image quality for PET attenuation correction while keeping the CT dose to a minimum. With PET/CT, CT is used instead of radioactive transmission sources to acquire data for attenuation correction. While this results in higher radiation dose to the patient, the CT images are also viewed with the PET images and provide an anatomical reference to aid the physician in localizing tumors. We found that using low tube voltage and current results in severe shading and CT number shifts and causes artifacts and quantitative errors in PET images. By adding a simple low pass filter to CT reconstruction prior to the logarithmic step, shading and CT number shifts are reduced substantially. The resulting CT number accuracy and uniformity of the images with the proposed approach makes them acceptable for PET attenuation correction.

Development of a Fillable, Tapered PET/CT Phantom

PET performance and image quality are degraded as body size increases; as size increases so do attenuation and background fractions. Based on simulated and acquired data, a fillable, tapered phantom was developed to measure PET scanner performance and image quality as a function of body size over a wide range of sizes. Design constraints included shape, cross-sectional dimensions, material, wall thickness, and taper angle. For fixed end sizes (as large as possible at one end and small at the other) a lower taper (narrow) leads to a long, heavy phantom. A higher taper (steep so that the diameter changes greatly within the scanner field of view) may not represent any particular cross section well. Monte Carlo simulations were performed to determine an acceptable taper angle that balanced the benefits and drawbacks of lower and higher taper rates. The simulations were validated with measurements on existing physical phantoms. Then, tapered phantoms with different angles and non-tapered phantoms, which had dimensions similar to the tapered phantoms, were simulated at different positions in the PET axial field of view to investigate properties of different taper angles. Scatter fractions of simulated tapered and non-tapered phantoms were compared. Of the different angles simulated, the results indicated that a 25° taper would yield a phantom that represents a continuum of cross-sectional dimensions while still being a practical size. The 25 ° tapered phantom was machined with an oval cross-section ranging from 38.5 cm × 49.5 cm to 6.8 cm × 17.8 cm, a length of 51.1 cm, a mass of 6 kg (empty) or 42 kg (water filled), and acrylic walls 1.25-cm thick. Initial PET/CT images were acquired.

Development of a phantom to simulate a wide range of body sizes

X-ray image quality is highly dependent on object size. Diagnostic image quality can be maintained while controlling dose to a patient with tube current modulation schemes. For PET attenuation correction, much lower requirements are placed on CT image quality, but the minimum technique is still likely to be body size dependent. To investigate tube current modulation and non-diagnostic CT image quality effects on PET attenuation correction, and to aid in the development of new body-size dependent CT protocols for CT and PET/CT, we have developed a water-equivalent phantom that simulates a wide range of body sizes. Design criteria for the phantom include cross-sectional dimensions, shape, taper rate and material. Cross sectional dimensions and shape were desired to closely resemble different sized human torsos. Taper rate was important to achieve a smooth edge to reduce edge artifacts and to prevent partial volume effects. The phantom material needed to be easily machined, but still be tissue equivalent for CT imaging. The finished phantom was made of cast acrylic. Twelve one-inch plates of acrylic were machined into ovals with continuously tapered edges. After fabrication, the plates were stacked and secured together. The tolerance between plate diameters is less than 1.0 mm. The final dimensions are 12.3 x 22.4 cm at the small end and 38.8 x 49.0 cm at the large end. The phantom has an overall length of 29.0 cm and a mass of 23.2 kg. Initial results from this phantom include evaluation of image quality when using tube current modulation and evaluation of low-dose CT techniques for accuracy in PET attenuation correction.

Biodistribution and Radiation Dosimetry of C-11 Nicotine from Whole Body PET Imaging in Humans

This study assessed the in vivo distribution of 11C-nicotine and the absorbed radiation dose from whole-body 11C-nicotine PET imaging of 11 healthy (5 male and 6 female) subjects. Methods: After an initial CT attenuation scan, 11C-nicotine was administered via intravenous injection. A dynamic PET scan was acquired for 90 s with the brain in the field of view, followed by a series of 13 whole-body PET scans acquired over a 90-min period. Regions of interest were drawn over organs visible in the reconstructed PET images. Time–activity curves were generated, and the residence times were calculated. The absorbed radiation dose for the whole body was calculated by entering the residence time in OLINDA/EXM 1.0 software to model the equivalent organ dose and the effective dose for a 70-kg man. Results: The mean residence times for 11C-nicotine in the liver, red marrow, brain, and lungs were 0.048 ± 0.010, 0.031 ± 0.005, 0.021 ± 0.004, and 0.020 ± 0.005 h, respectively. The mean effective dose for 11C-nicotine was 5.44 ± 0.67 μSv/MBq. The organs receiving the highest absorbed dose from the 11C-nicotine injection were the urinary bladder wall (14.68 ± 8.70 μSv/MBq), kidneys (9.56 ± 2.46 μSv/MBq), liver (8.94 ± 1.67 μSv/MBq), and spleen (9.49 ± 3.89 μSv/MBq). The renal and hepatobiliary systems were the major clearance and excretion routes for radioactivity. Conclusion: The estimated radiation dose from 11C-nicotine administration is relatively modest and would allow for multiple PET examinations on the same subject.

CT Based Attenuation Correction for PET Brain Imaging

For research and clinical PET brain studies performed on PET/CT systems, the CT image is often of little benefit beyond attenuation correction. The goal of this work is both to investigate the quantitative accuracy of CT-based attenuation correction (CTAC) for PET brain studies and to determine the lowest-dose protocol that performs adequately. Measurements were performed on a GE Discovery ST PET/CT scanner using the GE kVp-dependent CTAC algorithm. The effects of pitch on CT images were investigated by acquiring CT images of a Defrise disk phantom. The effects of pitch and X-ray tube voltage and current were investigated using a human skull phantom encased in plastic filled with F-18 radioactivity. This phantom was imaged and CT-based attenuation correction factors (CTACF) were created for several permutations of pitch (0.562:1, 0.938:1, 1.375:1, 1.75:1), voltage (80, 100, 120, 140 kVp) and current (10, 100mA). Emission images were acquired and reconstructed using the 3-D reprojection algorithm with the various CTACFs. The measured mean activity concentration is independent of pitch, kVp, and mA and accurate on an absolute scale to ~5%. Anatomically sized regional differences in the brain region indicate that tube voltages less than 100 kVp may not perform adequately (10% of values have a discrepancy greater than 5%). Results indicate that the higher pitch, lower current, and tube voltages down to 100 kVp perform equivalently to higher-dose configurations.

Pancreatic uptake and radiation dosimetry of 6-[18F]fluoro-L-DOPA from PET imaging studies in infants with congenital hyperinsulinism

The aim of this study is to assess the radiation absorbed dose of 18F-Fluoro-L-DOPA derived from the Positron Emission Tomography (PET) images of infants age ranging from 2 weeks– 32 weeks and a median age of 4.84 weeks (Mean 10.0 ± 10.3 weeks) with congenital hyperinsulinism. Methods After injecting 25.6 ± 8.8 MBq (0.7 ± 0.2 mCi) of 18F-Fluoro-L-DOPA intravenously, three static PET scans were acquired at 20, 30, and 40 min post injection in 3-D mode on 10 patients (6 male, 4 female) with congenital hyperinsulinism. Regions of interest (ROIs) were drawn over several organs visible in the reconstructed PET/CT images and time activity curves (TACs) were generated. Residence times were calculated using the TAC data. The radiation absorbed dose for the whole body was calculated by entering the residence times in the OLINDA/EXM 1.0 software. Results The mean residence times for the 18F-Fluoro-L-DOPA in the liver, lungs, kidneys, muscles, and pancreas were 11.54 ± 2.84, 1.25 ± 0.38, 4.65 ± 0.97, 17.13 ± 2.62, and 0.89 ± 0.34 min, respectively. The mean effective dose equivalent for 18F-Fluoro-L-DOPA was 0.40 ± 0.04 mSv/MBq. The CT scan used for attenuation correction delivered an additional radiation dose of 5.7 mSv. The organs receiving the highest radiation absorbed dose from 18F-Fluoro-L-DOPA were the urinary bladder wall (2.76 ± 0.95 mGy/MBq), pancreas (0.87 ± 0.30 mGy/MBq), liver (0.34 ± 0.07 mGy/MBq), and kidneys (0.61 ± 0.11 mGy/MBq). The renal system was the primary route for the radioactivity clearance and excretion. Conclusions The estimated radiation dose burden from 18F-Fluoro-L-DOPA is relatively modest to newborns.

Mixed isotope effects: Image quality in multimodality PET/SPECT preclinical imaging

The recent availability of pre-clinical PET/SPECT/CT tri-modality systems provides an opportunity to image animals injected with mixed modality (PET/SPECT) isotopes. However, before these procedures can be truly useful, some understanding of the effect of different modality radiotracers on image quality and the resulting noise characteristics must be investigated. Our goal in this study was to characterize effects on image resolution that might arise in one modality because of the presence of another (different modality) isotope. A phantom, consisting of a set of side-by-side micro-capillary tubes, were imaged on a trimodality (SPECT/PET/CT) pre-clinical scanner. Each tube was filled with a SPECT isotope and imaged while varying acquisition time, amount of activity, and distance between line sources. Images were evaluated to determine the visualization threshold at which objects became apparent in cross-sectional and MIP images (both that the objects were line sources and that the lines were two separate objects). These experiments were repeated in the presence of a PET isotope. After re-evaluating resolution, the signal to noise characteristics of the image as a whole were assessed and related to amounts of each isotope as well as total activity in the field of view. PET acquisition in the presence of SPECT isotopes was investigated using a contrast phantom with spheres filled with PET, SPECT, and mixed isotopes in backgrounds of mixed SPECT and PET isotopes. The noise properties of the background and spheres were measured as well as the visibility of the spheres. Finally, SPECT, PET, and CT images were acquired of a mouse after injection of both a PET and SPECT isotope. Acquisition of SPECT and PET images in the presence of different modality tracers (with careful considerations of the activity and acquisition parameters) seems feasible.