On the recording of sample times and parameter estimation from repeated measures pharmacokinetic data

A pharmacokinetic screen has been advocated for the characterization of the population pharmacokinetics of drugs during Phase 3 clinical trials. A common perception encountered in the collection of such data is that the accuracy of sampling times relative to dose is inadequate. A prospective simulation study was carried out to evaluate the effect of error in the recording of sampling times on the accuracy and precision of population parameter estimates from repeated measures pharmacokinetic data. A two-compartment model with intravenous bolus input(s) (single and multiple doses) was assumed. Random and systematic error in sampling times ranging from 5-50% using profile (block) randomized design were introduced. Sampling times were simulated in EXCEL while concentration data simulation and analysis were done in NONMEM. The effect of error in sampling times was studied at levels of variability ranging from 15-45% for a drug assumed to be dosed at its elimination half-life. One hundred replicate data sets of 100 subjects each were simulated for each case. Although estimates of clearance (CL) and variability in clearance were robust for most of the sampling time errors, there was an increase in bias and imprecision in overall parameter estimation as intersubject variability was increased. If there is interest in parameters other than CL, then the design of prospective population studies should include procedures for minimizing the error in the recording of sample times relative to dosing history.     

Acute vision loss resulting from complications of ethanol abuse

A dynamic digital brain phantom was created from the MRI to evaluate visually the relationship between the noise and the error in the parameter estimates in the PET kinetic analysis. This phantom incorporates the noise level depending on administration dose, camera efficiency and the data acquisition schedule. We simulated a serial dynamic scan with 18F-FDG or 11C-flumazenil, assuming 2-tissue 3-parameter model and 1-tissue 2-parameter model, respectively, and the sampling schedule was determined according to the clinical examination. The noise in the tissue time activity curve in FDG had a peak in the first minute and decreased thereafter, whereas the noise increased gradually in the flumazenil study after the initial peak due to radioactivity decay. We examined the relationship between the noise level and the error in the parameter estimates. Both mean absolute differences between true and estimated values and standard deviation became large, and the quality of the parametric images became poor with increasing noise level. This simulation was compared with human tissue time activity curves and parametric images, which were obtained with 100 MBq administration dose in FDG study and 430 MBq in flumazenil study. We inferred that the noise level in the human study was 10-20% in FDG, and 20-40% in flumazenil, and the error in the estimated parameter of K-complex in FDG study was about 20%, that of DV in flumazenil study was 2%.     

Assessment of the biodistribution and metabolism of 5-fluorouracil as monitored by 18F PET and 19F MRI: a comparative animal study

The effective clinical use of the anticancer drug 5-fluorouracil (5-FU) requires the non-invasive assessment of its transport and metabolism, particularly in the tumor and the liver, where the drug is catabolized to alpha-fluoro-beta-alanine (FBAL). In this study, the potentials and limitations of dynamic 18F PET and metabolic 19F MRI examinations for noninvasive 5-FU monitoring were investigated in ACI and Buffalo rats with transplanted MH3924A and TC5123 Morris hepatomas, respectively. Selective 5-[19F]FU and [19F]FBAL MR images were acquired 5 and 70 min after 5-FU injection using a CHESS MRI sequence. After administration of 5-[18F]FU, the kinetics of the regional 5-[18F]FU uptake were measured by dynamic PET scanning over 120 min. To allow a comparison between PET and MRI data, standardized uptake values (SUV) were computed at the same points in time. The TC5123 hepatoma showed a significantly (p < 0.002) higher mean SUV at 5 and 70 min post-5-FU injection than the MH3924A cell lines, whereas there were no significant differences between the mean SUV measured in the liver of both animal populations. In contrast to the PET data, no significant differences in the mean 5-[19F]FU and [19F]FBAL MR signal values in the tumor of both models were observed. The MR images, however, yielded the additional information that 5-FU is converted to FBAL only in the liver and not in the hepatomas.     

Construction of a food-grade multiple-copy integration system for Lactococcus lactis

We present a clinical evaluation of the quantitative bias which is introduced during simultaneous emission/transmission (SET) acquisition for the application of whole-body positron emission tomography (PET) with fluorine-18 2-fluoro-2-deoxy-d-glucose. The quantitative accuracy of the SET technique was assessed by means of a clinical study involving 28 patients and a realistic phantom experiment. In the clinical study, SET overestimated the activity concentration in the tumours by a factor of approximately 1.10, but in the phantom study, where the tumours were smaller, the bias was found to increase to a value of 1.39. The bias in the soft tissue regions of the patient studies varied between 1.03 and 1.36, and close agreement was observed with the corresponding phantom results. The extent of the bias increased as the local activity concentration decreased and we attribute the effect to scattered photons from the transmission source which are detected in the emission window during SET.     

Evaluation of the detectability of breast cancer lesions using a modified anthropomorphic phantom

During the development and characterization of imaging technology or new imaging protocols, it is usually instructive to perform phantom experiments. Often, very simplified forms of the realistic patient anatomy are used that may be acceptable under certain conditions; however, the implications for patient studies can be misleading. This is particularly true in breast and axillary node imaging. The complexities presented by the anatomy, variable object scatter, attenuation and inhomogeneous distribution of activity in this upper thoracic region provide a significant challenge to the imaging task. METHODS: A tissue-equivalent anthropomorphic phantom of the thorax (Radiology Support Devices, Inc., Long Beach, CA) containing fillable cavities and organs was modified for the studies. The phantom was filled with realistic levels of FDG activity and scanned on a Siemens ECAT HR+ whole-body PET scanner. Breast attachments containing 2.0- and 2.55-cc lesions with lesion-to-background ratios of 5:1 and 7:1, respectively, were imaged. Scatter and attenuation effects were analyzed with various experimental setups. A lymph node experiment and a multibed position whole-phantom scan also were performed to illustrate the extent to which the phantom represents the human thorax. RESULTS: Regions of interest were drawn on the lesions as well as the background breast tissue in all studies. It was found that the signal-to-noise ratio decreased 65% when a more realistic phantom (lesions plus breasts plus thorax, all containing activity) was used, as compared to a simple phantom (lesions plus breasts containing activity; no thorax), due to the effects of increased scatter and attenuation. A 23% decrease in the contrast also was seen from the scan of the more realistic phantom due to surrounding activity from nearby organs such as the heart, as well as an increase in the volume of attenuating media. CONCLUSION: This new phantom allows us to more realistically model the conditions for breast and lymph node imaging, leading to preclinical testing that will produce results that better approximate those that will be found in vivo. The phantom will be a valuable tool in comparing different imaging technologies, data collection strategies and image reconstruction algorithms for applications in breast cancer using PET, SPECT or scintimammography systems.     

Correction for partial volume effects in PET: principle and validation

The accuracy of PET for measuring regional radiotracer concentrations in the human brain is limited by the finite resolution capability of the scanner and the resulting partial volume effects (PVEs). We designed a new algorithm to correct for PVEs by characterizing the geometric interaction between the PET system and the brain activity distribution. METHODS: The partial volume correction (PVC) algorithm uses high-resolution volumetric MR images correlated with the PET volume. We used a PET simulator to calculate recovery and cross-contamination factors of identified tissue components in the brain model. These geometry-dependent transfer coefficients form a matrix representing the fraction of true activity from each distinct brain region observed in any given set of regions of interest. This matrix can be inverted to correct for PVEs, independent of the tracer concentrations in each tissue component. A sphere phantom was used to validate the simulated point-spread function of the PET scanner. Accuracy and precision of the PVC method were assessed using a human basal ganglia phantom. A constant contrast experiment was performed to explore the recovery capability and statistic error propagation of PVC in various noise conditions. In addition, a dual-isotope experiment was used to evaluate the ability of the PVC algorithm to recover activity concentrations in small structures surrounded by background activity with a different radioactive half-life. This models the time-variable contrast between regions that is often seen in neuroreceptor studies. RESULTS: Data from the three-dimensional brain phantom demonstrated a full recovery capability of PVC with less than 10% root mean-square error in terms of absolute values, which decreased to less than 2% when results from four PET slices were averaged. Inaccuracy in the estimation of 18F tracer half-life in the presence of 11C background activity was in the range of 25%-50% before PVC and 0%-6% after PVC, for resolution varying from 6 to 14 mm FWHM. In terms of noise propagation, the degradation of the coefficient of variation after PVC was found to be easily predictable and typically on the order of 25%. CONCLUSION: The PVC algorithm allows the correction for PVEs simultaneously in all identified brain regions, independent of tracer levels.     

Test-retest variability of serotonin 5-HT2A receptor binding measured with positron emission tomography and [18F]altanserin in the human brain

The role of serotonin in CNS function and in many neuropsychiatric diseases (e.g., schizophrenia, affective disorders, degenerative dementias) support the development of a reliable measure of serotonin receptor binding in vivo in human subjects. To this end, the regional distribution and intrasubject test-retest variability of the binding of [18F]altanserin were measured as important steps in the further development of [18F]altanserin as a radiotracer for positron emission tomography (PET) studies of the serotonin 5-HT2A receptor. Two high specific activity [18F]altanserin PET studies were performed in normal control subjects (n = 8) on two separate days (2-16 days apart). Regional specific binding was assessed by distribution volume (DV), estimates that were derived using a conventional four compartment (4C) model, and the Logan graphical analysis method. For both analysis methods, levels of [18F]altanserin binding were highest in cortical areas, lower in the striatum and thalamus, and lowest in the cerebellum. Similar average differences of 13% or less were observed for the 4C model DV determined in regions with high receptor concentrations with greater variability in regions with low concentrations (16-20%). For all regions, the absolute value of the test-retest differences in the Logan DV values averaged 12% or less. The test-retest differences in the DV ratios (regional DV values normalized to the cerebellar DV) determined by both data analysis methods averaged less than 10%. The regional [18F]altanserin DV values using both of these methods were significantly correlated with literature-based values of the regional concentrations of 5-HT2A receptors determined by postmortem autoradiographic studies (r2 = 0.95, P < 0.001 for the 4C model and r2 = 0.96, P < 0.001 for the Logan method). Brain uptake studies in rats demonstrated that two different radiolabeled metabolites of [18F]altanserin (present at levels of 3-25% of the total radioactivity in human plasma 10-120 min postinjection) were able to penetrate the blood-brain barrier. However, neither of these radiolabeled metabolites bound specifically to the 5-HT2A receptor and did not interfere with the interpretation of regional [18F]altanserin-specific binding parameters obtained using either a conventional 4C model or the Logan graphical analysis method. In summary, these results demonstrate that the test-retest variability of [18F]altanserin-specific binding is comparable to that of other PET radiotracers and that the regional specific binding of [18F]altanserin in human brain was correlated with the known regional distribution of 5-HT2A receptors. These findings support the usefulness of [18F]altanserin as a radioligand for PET studies of 5-HT2A receptors.     

A simple method for the study of cytosolic content of oligonucleotides in cells

BACKGROUND: Nonuniform attenuation in the thorax can generate artifacts in single-photon emission computed tomographic myocardial perfusion studies that mimic coronary artery disease. In this article we present both phantom and simulation data, as well as clinical data, in support of an emission-based method that provides reliable correction for attenuation effects without the need for a transmission measurement. METHODS AND RESULTS: The attenuation map is derived from the measured distribution of 99mTc-labeled macroaggregated albumin in the lungs and a radioactive binder wrapped about the thorax. This information is acquired as part of a dual-isotope acquisition during the rest 201Tl study. Segmentation is used to define the interiors of lung and body compartments, which are assigned a single attenuation coefficient for each of the two tissue types. The appropriateness of this approach was investigated by examining the measured attenuation coefficients in a group of 80 individuals (40 male, 40 female) from positron emission tomographic transmission studies. The correction technique was evaluated with computer simulations, a physical phantom, and clinical data acquired from 20 patients. Analysis of the positron emission tomographic data found a small SD in the mean attenuation coefficients for the body (<5%) and lungs (<15%). The application of emission-based attenuation-correction technique produced a substantial reduction in the magnitude of the attenuation artifact in images obtained from both the phantom and the simulation studies. The emission-based attenuation-correction technique was easily applied to myocardial perfusion studies, where it had a significant effect, resulting in changes in interpretation for nine of 20 patients. CONCLUSIONS: The results of this study provide strong support for the concept that an attenuation map can be generated with fixed attenuation values in place of those that are directly measured. Thus the emission-based attenuation-correction technique can be considered an inexpensive alternative to transmission-based correction methods. Because the emission-based correction technique does not require any additional hardware, it has the major advantage of being applicable to all single-photon emission computed tomographic systems.     

FDG PET and dual-head gamma camera positron coincidence detection imaging of suspected malignancies and brain disorders

The purpose of the study was to compare the diagnostic accuracy of fluorodeoxyglucose (FDG) images obtained with a dual-head coincidence gamma camera (DHC) with those obtained with a dedicated PET in a series of 26 patients. METHODS: Nineteen patients with known or suspected malignancies and 7 patients with neurological disorders underwent PET imaging after injection of approximately 10 mCi of FDG. Whole-body imaging was performed on 19 patients and brain imaging on 7 patients. DHC images were then acquired for 30 min over the region of interest using a dual-head gamma camera equipped with 3/8-in.-thick NaI(TI) crystals and parallel slit-hole collimators. The images were reconstructed in the normal mode, using photopeak/photopeak, photopeak/Compton and Compton/photopeak coincidence events. RESULTS: Although the spatial resolutions of PET with a dedicated PET scanner and of DHC are in the same range, the lesion detectability remains superior with PET (4 mm for PET versus 13.5 mm for DHC in phantom experiments) with a contrast ratio of 5:1. This is most probably attributable to the higher sensitivity of PET (2238 coincidences/min/microCi for PET versus 89 coincidences/min/microCi for DHC). The pattern of uptake and interpretation for brain imaging was similar on both PET and DHC images in all patients. In the 19 oncology patients, 38 lesions ranging from 0.7 to 5 cm were detected by PET. DHC imaging detected 28 (73%) of these lesions. Among the 10 lesions not seen with DHC, 5 were less than 1.2 cm, 2 were located centrally within the liver and suffered from marked attenuation effects and 3 were adjacent to regions with high physiological activity. The nondetectability of some lesions with DHC compared with PET can be explained by several factors: (a) start of imaging time (mean+/-SD: 73+/-16 min for PET versus 115+/-68 min for DHC, leading to FDG decay to 6.75 mCi for PET and 5.2 mCi for DHC); (b) limited efficiency of a 3/8-inch-thick Nal(TI) crystal to detect 18F photons; (c) suboptimal two-dimensional reconstruction algorithm; and (d) absence of soft-tissue attenuation correction for centrally located lesions. CONCLUSION: FDG DHC imaging is a promising technique for oncological and brain imaging.     

Three-dimensional positron emission tomography imaging system and its application for medical use

Current positron emission tomography is capable for three dimensional data acquisition and reconstruction (3D PET). The main advantage of 3D PET is its detectability for lower tracer concentrations. The images by a 3D PET have better signal to noise ratios compared to those by conventional 2D PET. This point is especially important for the studies of distributions of ligands for neuroreceptors such as F-18 FDOPA and C-11 YM-01951, since these ligands show low accumulation in brain. Reduction of scanning time is useful as well for patients are permitting extended scanning periods     

Psychiatric disorder onset and first treatment contact in the United States and Ontario

The aim of the study was to evaluate the quality of routine brain perfusion single-photon emission tomography (SPET) images in Finnish nuclear medicine laboratories. Twelve laboratories participated in the study. A three-dimensional high resolution brain phantom (Data Spectrum's 3D Hoffman Brain Phantom) was filled with a well-mixed solution of technetium-99m (110 MBq), water and detergent. Acquisition, reconstruction and printing were performed according to the clinical routine in each centre. Three nuclear medicine specialists blindly evaluated all image sets. The results were ranked from 1 to 5 (poor quality-high quality). Also a SPET performance phantom (Nuclear Associates' PET/SPECT Performance Phantom PS 101) was filled with the same radioactivity concentration as the brain phantom. The parameters for the acquisition, the reconstruction and the printing were exactly the same as with the brain phantom. The number of detected "hot" (from 0 to 8) and "cold" lesions (from 0 to 7) was visually evaluated from hard copies. Resolution and contrast were quantified from digital images. Average score for brain phantom images was 2.7 +/- 0.8 (range 1.5-4.5). The average diameter of the "hot" cylinders detected was 16 mm (range 9.2-20.0 mm) and that of the "cold" cylinders detected, 11 mm (5.9-14.3 mm) according to visual evaluation. Quantification of digital images showed that the hard copy was one reason for low-quality images. The quality of the hard copies was good only in four laboratories and was amazingly low in the others when comparing it with the actual structure of the brain phantom. The described quantification method is suitable for optimizing resolution and contrast detectability of hard copies. This study revealed the urgent need for external quality assurance of clinical brain perfusion SPET images.     

Clinical impact of pharmacokinetically-guided dose adaptation of 5-fluorouracil: results from a multicentric randomized trial in patients with locally advanced head and neck carcinomas

A significant link between 5-fluorouracil (5FU) plasma concentration and its therapeutic activity has been demonstrated in colon and head and neck cancer patients for 5FU used as a continuous infusion. Dose adjustment based on pharmacokinetic follow-up has been proposed to decrease hematological and digestive toxicities, but the clinical impact of this approach has not yet been demonstrated. A randomized multicentric study was conducted to evaluate the clinical interest of 5FU dose adaptation guided by pharmacokinetics. One hundred twenty-two head and neck cancer patients were randomly assigned to receive induction chemotherapy with cisplatin (100 mg/m2, day 1) and 5FU (96-h continuous infusion), either at standard dose (St-arm; 4 g/m2) or at a dose adjusted according to the 5FU area under the curve (AUC0-48h; PK-arm). In total, 106 patients were evaluable for toxicity and response. In the PK-arm (n = 49), 5FU doses and area under the curve were significantly reduced during cycle 2 and cycle 3 (P < 0.001) as compared with the St-arm (n = 57). Grade 3-4 neutropenia and thrombopenia were significantly more frequent in the St-arm as compared with the PK-arm (17.5% versus 7.6%, respectively; P = 0.013). No grade 3-4 mucositis occurred in the PK-arm, whereas 5.1% was observed in the St-arm (P < 0.01). The objective response rate was comparable in the two treatment arms: 77.2% in the St-arm versus 81.7% in the PK-arm. The present study is the first to demonstrate, in a randomized design, the clinical interest of an individual 5FU dose adaptation based on pharmacokinetic survey, in terms of therapeutic index improvement.     

Intermodality, retrospective image registration in the thorax

The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.     

Population pharmacokinetics of gentamicin in horses

OBJECTIVE: To develop and validate a population pharmacokinetic model for gentamicin in horses, using retrospective clinical data. ANIMALS: 62 horses that had been treated IV with multiple doses of gentamicin at our veterinary teaching hospital between 1987 and 1996. Procedure-46 horses were assigned to the study group, and 16 to the validation group. Detailed history of dosage, sample collection times, and selected pathophysiologic variables were recorded for each patient. Samples were analyzed by use of a fluorescence polarization immunoassay method. Pharmacostatistical analysis was conducted, using computer software. The predictive model correlates pharmacokinetic parameters to concomitant pathophysiologic variables and estimates the inter- and intraindividual variability in disposition. RESULTS: A two-compartment model best described the data. Clearance (CI) was linearly correlated to body weight and serum creatinine concentration. Volume of the central compartment (Vd(c)) was linearly related to body weight. Interindividual coefficients of variability for CI and Vd(c) were 24 and 16%, respectively. The residual variability (intraindividual) was 13%; mean prediction error percent (bias) was 2%; and mean absolute prediction error percent (precision) was 29%. CONCLUSIONS: Population pharmacokinetic analysis allows study of the basic features of gentamicin disposition in horses with sparse data per individual. A considerable proportion of the pharmacokinetic variability of gentamicin in our study population was explained by differences in body weight and serum creatinine concentration. CLINICAL RELEVANCE: Population pharmacokinetics can be used to design first-dosage regimens according to the clinical characteristics of individual animals. Population pharmacokinetic models could also be included in Bayesian forecasting strategies to improve plasma concentration predictions in individual patients.     

Real-time homogeneous assay of rapid cycle polymerase chain reaction product for identification of Leptonema illini

The validation study is described of a new modelling method that has been developed, using tracer kinetic modelling with positron emission tomography (PET) to achieve non-invasive measurement of myocardial metabolic rate of glucose (MMRGlc). Eight data sets obtained from dynamic cardiac PET 2-[18F]fluoro-2-deoxy-D-glucose (FDG) studies on human subjects are employed, and the estimation of MMRGlc using both the new and traditional methods is compared. The results from all eight human FDG studies are consistent with those from previous computer simulations. With the new method, the estimated mean of K (a parameter directly proportional to MMRGlc) increases by about 8%, and that of k 4 (the rate constant of FDG dephosphorylation) decreases by about 48%. The approach should be more suitable for use in dynamic cardiac PET studies when non-invasive means are used to obtain the plasma time-activity curve from left-ventricle PET images.     

Genetic and developmental influences on infant mouse ultrasonic calling. II. Developmental patterns in the calls of mice 2-12 days of age

Both 360 degrees and 180 degrees rotation acquisition methods have been used in myocardial single photon emission tomography (SPET) studies. We compared both methods using 201Tl, 99Tcm and 123I radiopharmaceuticals with phantoms and clinical models. Myocardial phantom studies with anterior and inferior defects were performed using 201Tl, 99Tcm and 123I. Clinical models of 14 typical situations, including normal subjects, patients with anterior or inferior defects and a high right hemi-diaphragm, were studied. The radiopharmaceuticals were 201Tl, 99Tcm-sestamibi, 123I-BMIPP and 123I-MIBG. Four sets of 180 degrees anterior rotation data with starting angles of (A) posterior, (B) LPO 30 degrees, (C) LPO 60 degrees and (D) left lateral direction were generated and compared with 360 degrees rotation SPET. A polar map display was used for quantification. In phantom studies, the defect contrast on the map was higher in the anterior defect with 180 degrees rotation than with 360 degrees rotation. However, it was decreased in the inferior defect, particularly with 201Tl, because of decreased wall activity around the defect. In the patient model with anterior or inferior defects, the defect contrast was improved with 180 degrees SPET by up to 10%. A slight decrease in the normal region was also noted in the 180 degrees reconstruction. The effect of diffuse liver activity on the inferior region depended on the rotation range. A patient with a high right hemi-diaphragm showed a lower inferior count with 360 degrees SPET. In conclusion, the 360 degrees acquisition was superior to the 180 degrees acquisition in the phantom with defects. Clinically, the quantitative differences in radionuclide types (99Tcm, 123I or 201Tl) were not significant for quantifying a moderate degree (50-60% of peak count) of defect. However, we note quantitative variation depending on the rotation range in the 180 degrees method.     

Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions

We analyzed the noise characteristics of two-dimensional (2-D) and three-dimensional (3-D) images obtained from the GE Advance positron emission tomography (PET) scanner. Three phantoms were used: a uniform 20-cm phantom, a 3-D Hoffman brain phantom, and a chest phantom with heart and lung inserts. Using gated acquisition, we acquired 20 statistically equivalent scans of each phantom in 2-D and 3-D modes at several activity levels. From these data, we calculated pixel normalized standard deviations (NSD's), scaled to phantom mean, across the replicate scans, which allowed us to characterize the radial and axial distributions of pixel noise. We also performed sequential measurements of the phantoms in 2-D and 3-D modes to measure noise (from interpixel standard deviations) as a function of activity. To compensate for the difference in axial slice width between 2-D and 3-D images (due to the septa and reconstruction effects), we developed a smoothing kernel to apply to the 2-D data. After matching the resolution, the ratio of image-derived NSD values (NSD2D/NSD3D)2 averaged throughout the uniform phantom was in good agreement with the noise equivalent count (NEC) ratio (NEC3D/NEC2D). By comparing different phantoms, we showed that the attenuation and emission distributions influence the spatial noise distribution. The estimates of pixel noise for 2-D and 3-D images produced here can be applied in the weighting of PET kinetic data and may be useful in the design of optimal dose and scanning requirements for PET studies. The accuracy of these phantom-based noise formulas should be validated for any given imaging situation, particularly in 3-D, if there is significant activity outside the scanner field of view.     

Measurement of Bed Load Velocity using an Acoustic Doppler Current Profiler

A new technique has been developed to measure the apparent velocity of bed load (va) using an acoustic Doppler current profiler. The technique involves estimating the bias in bottom tracking due to a moving bottom. Mean va measured at sampling stations in the gravel-bed Fraser River correlated well (r2 = 0.93,?n = 9) with mean bed load transport rates measured using conventional samplers. Mean va was also correlated (r2 = 0.44,?n = 19) with boundary shear stress estimated by a log-law fit to the mean velocity profile. Estimates of va from individual 5 s ensemble averages were extremely variable: the coefficient of variation for a sampling station ranged from 1.0 to 6.4, and 25 min of sampling were required to achieve stable estimates of the mean and coefficient of variation (within 5% error). Variance was due to both real temporal variability of transport and measurement error. The mechanisms that produce this variability are discussed and preliminarily quantified.     

Attenuation corrected myocardial PET after application of 18FDG: effect on the determination of regional myocardial uptake values

AIM: Post injection transmission measurement (PIT) can be performed using rotating 68Ge/68Ga linesources. This study estimates attenuation coefficients, count densities and relative regional uptake values of PIT corrected cardiac PET (E-PIT) compared to routinely pre-injection transmission measurement (RT). METHODS: A thorax-phantom with homogeneously filled myocardium or with simulated defects and six patients with advanced coronary artery disease were studied using ECAT Exact tomograph (Siemens CTI) equipped with three rotating linesources. Transmission was performed twice (PIT, RT), attenuation coefficients and emission data were analysed, the latter without attenuation correction (E-UK), corrected with PIT (E-PIT) and with RT (E-RT) (count density, standard and relative uptake values). RESULTS: Both in phantom and patient studies attenuation coefficients differed significantly between PIT and RT. Comparing E-PIT and E-RT, regional uptake values were different only in phantom simulation with myocardial radioactivity concentrations higher than 10 kBq x ml-1. The image contrast between defects and remaining myocardium in the phantom studies or the standard and relative uptake values in patient studies did not vary significantly. CONCLUSION: Under clinical conditions a post injection transmission measurement does not influence the accuracy of regional myocardial uptake values relevantly.     

Evaluation of exercise tolerance of patients with heart failure and its clinical significance

A new method of PET attenuation using post-injection transmission scan is presented, which is especially useful in 18F-FDG static studies. The transmission scan is acquired right before the emission scan, which is used to subtract the emission component from the transmission data. When the effect of measurement condition upon the image noise was evaluated with a 20 cm diameter cylindrical phantom, an increase in the injection dose inflated the noise and caused artifacts. There was an optimum dose that minimized the image noise. As the external source activity increased, the image noise decreased, and the optimum dose increased linearly, which enabled estimation of the optimum injection dose under a given external source. When the total (emission plus transmission) scan time was fixed, longer emission scan resulted in better images than longer transmission scan.