The QIBA Profile for FDG PET/CT as an Imaging Biomarker Measuring Response to Cancer Therapy.

The Quantitative Imaging Biomarkers Alliance (QIBA) Profile for fluorodeoxyglucose (FDG) PET/CT imaging was created by QIBA to both characterize and reduce the variability of standardized uptake values (SUVs). The Profile provides two complementary claims on the precision of SUV measurements. First, tumor glycolytic activity as reflected by the maximum SUV (SUVmax) is measurable from FDG PET/CT with a within-subject coefficient of variation of 10%-12%. Second, a measured increase in SUVmax of 39% or more, or a decrease of 28% or more, indicates that a true change has occurred with 95% confidence. Two applicable use cases are clinical trials and following individual patients in clinical practice. Other components of the Profile address the protocols and conformance standards considered necessary to achieve the performance claim. The Profile is intended for use by a broad audience; applications can range from discovery science through clinical trials to clinical practice. The goal of this report is to provide a rationale and overview of the FDG PET/CT Profile claims as well as its context, and to outline future needs and potential developments.

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 smoker's brain during actual cigarette smoking using PET with 3-s temporal resolution and (11)C-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.

Target localization using scanner-acquired SPECT data.

Target localization using single photon emission computed tomography (SPECT) and planar imaging is being investigated for guiding radiation therapy delivery. Previous studies on SPECT-based localization have used computer-simulated or hybrid images with simulated tumors embedded in disease-free patient images where the tumor position is known and localization can be calculated directly. In the current study, localization was studied using scanner-acquired images. Five fillable spheres were placed in a whole body phantom. Sphere-to-background 99mTc radioactivity was 6:1. Ten independent SPECT scans were acquired with a Trionix Triad scanner using three detector trajectories: left lateral 180°, 360°, and right lateral 180°. Scan time was equivalent to 4.5 min. Images were reconstructed with and without attenuation correction. True target locations were estimated from 12 hr SPECT and CT images. From the 12 hr SPECT scan, 45 sets of orthogonal planar images were used to assess target localization; total acquisition time per set was equivalent to 4.5min. A numerical observer localized the center of the targets in the 4.5 min SPECT and planar images. SPECT-based localization errors were compared for the different detector trajectories. Across the four peripheral spheres, and using optimal iteration numbers and postreconstruction smoothing, means and standard deviations in localization errors were 0.90 ± 0.25 mm for proximal 180° trajectories, 1.31 ± 0.51 mm for 360° orbits, and 3.93 ± 1.48 mm for distal 180° trajectories. This rank order in localization performance is predicted by target attenuation and distance from the target to the collimator. For the targets with mean localization errors < 2 mm, attenuation correction reduced localization errors by 0.15 mm on average. The improvement from attenuation correction was 1.0 mm on average for the more poorly localized targets. Attenuation correction typically reduced localization errors, but for well-localized targets, the detector trajectory generally had a larger effect. Localization performance was found to be robust to iteration number and smoothing. Localization was generally worse using planar images as compared with proximal 180° and 360° SPECT scans. Using a proximal detector trajectory and attenuation correction, localization errors were within 2 mm for the three superficial targets, thus supporting the current role in biopsy and surgery, and demonstrating the potential for SPECT imaging inside radiation therapy treatment rooms.

Performance comparison of a dedicated total breast PET system with a clinical whole-body PET system: a simulation study.

This paper presents a novel PET geometry for breast cancer imaging. The scanner consists of a 'stadium' (a rectangle with two semi-circles on opposite sides) shaped ring, along with anterior and posterior panels to provide high sensitivity and high spatial resolution for an imaging field-of-view (FOV) that include both breasts, mediastinum and axilla. We simulated this total-breast PET system using GATE and reconstructed the coincidence events using a GPU-based list-mode image reconstruction implementing maximum likelihood expectation-maximization (ML-EM) algorithm. The rear-panel is made up of a single layer of LSO crystals (3.2 × 3.2 × 20 mm3each), while the 'stadium'-shaped elongated ring and the anterior panel are made with dual-layered LSO crystals (1.6 × 1.6 × 6 mm3each). The energy resolution and coincidence resolving time of all detectors are assumed to be 12% and 250 ps full-width-at-half-maximum, respectively. Various sized simulated lesions (4, 5, 6 mm) having 4:1, 5:1, and 6:1 lesion-to-background radioactivity concentration ratios, mimicking different biological uptakes, were strategically located throughout a volumetric torso phantom. We compared system sensitivity and lesion detectability of the dedicated total-breast PET system to a state-of-the-art clinical whole-body PET scanner. The mean sensitivity of the total-breast PET system is 3.21 times greater than that of a whole-body PET scanner in the breast regions. The total-breast PET system also provides better contrast-recovery coefficients for lesions of all sizes and lesion-to-background ratios in the breast when compared to a reference clinical whole-body PET scanner. Receiver operating characteristics (ROC) study shows the area under the ROC curve is 0.948 and 0.924 for the total-breast system and the whole-body PET scanner, respectively, in the detection of 4 mm diameter lesions with 4:1 lesion-to-background ratio. This study demonstrates our novel geometry can provide an imaging FOV larger than conventional PEM systems to simultaneously image both breasts, chest wall and axillae with significantly improved lesion detectability in the breasts when compared to a whole-body PET scanner.

A systematic review of the factors affecting accuracy of SUV measurements.

OBJECTIVE: There is growing interest in using PET/CT for evaluating early response to therapy in cancer treatment. Although widely available and convenient to use, standardized uptake value (SUV) measurements can be influenced by a variety of biologic and technologic factors. Many of these factors can be addressed with close attention to detail and appropriate quality control. This article will review factors potentially affecting SUV measurements and provide recommendations on ways to minimize when using serial PET to assess early response to therapy. CONCLUSION: Scanner and reconstruction parameters can significantly affect SUV measurements. When using serial SUV measurements to assess early response to therapy, imaging should be performed on the same scanner using the same image acquisition and reconstruction protocols. In addition, attention to detail is required for accurate determination of the administered radiopharmaceutical dose.

Increasing uptake time in FDG-PET: standardized uptake values in normal tissues at 1 versus 3 h.

OBJECTIVE: Positron emission tomography (PET) imaging at more than 1 h after 2-deoxy-2-[(18)F]fluoro-D: -glucose (FDG) administration may result in less blood pool activity and possibly decreased normal FDG uptake in tissues such as liver. Lower normal background activity could be an important component of improved image contrast on delayed imaging. Increasing FDG uptake in normal organs, however, may mitigate the beneficial effects of blood pool clearance. The purpose of this study is to determine the normal tissue and blood pool FDG uptake at 1 and 3 h after injection. SUBJECTS AND METHODS: Ninety-nine patients with known or suspected malignancy referred for FDG-PET-computed tomography (CT) were retrospectively evaluated. PET imaging was performed at either 1 h (60 +/- 15 min; n = 50) or at 3 h (180 +/- 15 min; n = 49) after FDG administration. Normal tissue FDG uptake without involvement by malignancy or influenced by artifact (misregistration, "brown fat," focal muscle uptake, focal atherosclerotic disease) was confirmed by inspection of both the PET and CT scans. Aortic blood pool, adipose tissue, bone marrow, cerebellum, liver, lungs, muscle, and spleen were quantitatively evaluated by CT-guided region of interest analysis in three contiguous slices. Mean standardized uptake values (SUVs) were analyzed using one-way analysis of variance. RESULTS: Mean SUVs on the 3- versus 1-h images were significantly lower for aortic blood pool 13% (p < 0.0001) and adipose tissue 20% (p < 0.008). FDG uptake showed significant increases at 3 h compared to 1-h imaging in the cerebellum 40% (p < 0.0001), bone marrow 25% (p = 0.003), muscle 21% (p = 0.0004), and spleen 13% (p = 0.01). The liver and lung showed no significant differences (1%, p = 0.85; -2%, p = 0.62, respectively). CONCLUSIONS: On FDG imaging at 3 h compared to 1 h, significant changes were apparent, but the magnitude of changes was modest overall. Three-hour delayed imaging demonstrated significantly lower aortic blood pool and adipose tissue activity and significantly higher cerebellum, muscle, spleen, and bone marrow activity. Hepatic and lung activities were not significantly different. These results suggest that previously reported improvements in tumor image contrast with delayed imaging may be primarily due to cumulative FDG uptake within the tumor rather than reduction in normal background activity.

Quantitative effects of contrast enhanced CT attenuation correction on PET SUV measurements.

PURPOSE: The presence of contrast materials on computed tomography (CT) images can cause problems in the attenuation correction of positron emission tomography (PET) images. These are because of errors converting the CT attenuation of contrast to 511-keV attenuation and by the change in tissue enhancement over the duration of the PET emission scan. Newer CT-based attenuation correction (CTAC) algorithms have been developed to reduce these errors. METHODS: To evaluate the effectiveness of the modified CTAC technique, we performed a retrospective analysis on 20 patients, comparing PET images using unenhanced and contrast-enhanced CT scans for attenuation correction. A phantom study was performed to simulate the effects of contrast on radiotracer concentration measurements. RESULTS: There was a maximum difference in calculated radiotracer concentrations of 5.9% within the retrospective data and 7% within the phantom data. CONCLUSION: Using a CTAC algorithm that de-emphasizes high-density areas, contrast-enhanced CT can be used for attenuation mapping without significant errors in quantitation.

Evaluation of combined cardiac positron emission tomography and coronary computed tomography angiography for the detection of coronary artery disease.

BACKGROUND: Coronary artery disease is a leading cause of morbidity and mortality. Multiple imaging modalities are used to screen for significant coronary artery disease. We report the concordance between coronary computed tomography angiography (CTA) and stress cardiac positron emission tomography (CPET) to detect significant coronary artery disease, the feasibility of combining CTA and CPET in one diagnostic test, and the ability of CTA and CPET to detect significant coronary artery disease by comparison with cardiac catheterization. METHODS: Forty patients were prospectively enrolled and imaged with a hybrid PET/CT scanner. Eighteen patients had cardiac catheterization data for comparison. Concordance of findings between diagnostic tests was assessed by examining overall percentage in agreement, area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values. RESULTS: The overall agreement between CTA and CPET for detecting significant coronary artery disease was 76.3% with a sensitivity and specificity of 91.7 and 69.2%, respectively. The overall agreement between CTA and cardiac catheterization for detecting significant coronary artery disease was 81.3% with a sensitivity and specificity of 81.8 and 80.0%, respectively. The overall agreement between CPET and cardiac catheterization for detecting significant coronary artery disease was 77.8% with a sensitivity and specificity of 76.9 and 80.0%, respectively. CONCLUSION: CTA and CPET can be performed in a single diagnostic test interval to simultaneously assess the extent of coronary artery disease and its hemodynamic significance. The sensitivity and specificity of CTA and CPET are similar to existing noninvasive screening tests.

SPECT/CT physical principles and attenuation correction.

Using nuclear medicine techniques, physiologic activity and processes can be identified in a way that is unique from other modalities. Oftentimes it is helpful to know the exact location of the physiologic uptake that is visualized on a scan. Knowing the exact location can sometimes help to distinguish normal from abnormal physiologic uptake. When an abnormality has been identified, knowing the exact location can then be helpful in treatment planning. The ability to provide precise localization of physiologic data from nuclear medicine studies is now possible with hybrid SPECT/CT systems. Additionally, these systems provide an accurate attenuation correction of the nuclear medicine image data. After reading this article, the technologist will be able to list and describe the inherent problems associated with SPECT image acquisition and reconstruction, briefly explain how data acquired from the CT scanner are used to provide attenuation correction data for SPECT and anatomic information for diagnostic purposes, list and briefly describe the different types of clinical SPECT/CT systems, and discuss the importance of accurate CT and SPECT image registration.

Near-Field High-Energy Spectroscopic Gamma Imaging Using a Rotation Modulation Collimator.

Certain trace elements are vital to the body and elemental imbalances can be indicators of certain diseases including cancer and liver diseases. Neutron Stimulated Emission Computed Tomography (NSECT) is being developed as spectroscopic imaging technique to non-invasively and non-destructively measure and image elemental concentrations within the body. A region of interest is illuminated via a high-energy beam of neutrons that scatter inelastically with elemental nuclei within the body. The excited nuclei then relax by emitting characteristic gamma rays. Acquiring the gamma spectrum in a tomographic manner allows not only the identification of elements, but also the formation of images representing spatial distributions of specific elements. We are developing a high-energy position-sensitive gamma camera that allows full illumination of the entire region of interest. Because current scintillation crystal based position-sensitive gamma cameras operate in too low of an energy range, we are adapting high-energy gamma imaging techniques used in space-based imaging. A High Purity Germanium (HPGe) detector provides high-resolution energy spectra while a rotating modulation collimator (RMC) placed in front of the detector modulates the incoming signal to provide spatial information. The purpose of this manuscript is to describe the near-field RMC geometry, which varies greatly from the infinite-focus space-based applications, and how it modulates the incident gamma flux. A simple geometric model is presented and then used to reconstruct two-dimensional planar images of both simulated point sources and extended sources.

Regional brain activity correlates of nicotine dependence.

Fifteen smokers participated in a study investigating brain correlates of nicotine dependence. Dependence was reduced by having subjects switch to denicotinized cigarettes for 2 weeks while wearing nicotine skin patches. Positron emission tomography (PET) scans assessed regional cerebral metabolic rate for glucose (rCMRglc) after overnight nicotine abstinence on three occasions: (1) at baseline; (2) after 2 weeks of exposure to denicotinized cigarettes+nicotine patches; and (3) 2 weeks after returning to smoking the usual brands of cigarettes. Craving for cigarettes and scores on the Fagerström Test of Nicotine Dependence (FTND) questionnaire decreased at the second session relative to the first and last sessions. Regional brain metabolic activity (normalized to whole brain values) at session 2 also showed a significant decrease in the right hemisphere anterior cingulate cortex. Exploratory post hoc analyses showed that the change in craving across sessions was negatively correlated with the change in rCMRglc in several structures within the brain reward system, including the ventral striatum, orbitofrontal cortex and pons. The between-session difference in thalamus activity (right hemisphere) was positively correlated with the difference in FTND scores. Correlational analyses also revealed that reported smoking for calming effects was associated with a decrease (at session 2) in thalamus activity (bilaterally) and with an increase in amygdala activity (left hemisphere). Reported smoking to enhance pleasurable relaxation was associated with an increase in metabolic activity of the dorsal striatum (caudate, putamen) at session 2. These findings suggest that reversible changes in regional brain metabolic activity occur in conjunction with alterations in nicotine dependence. The results also highlight the likely role of thalamic gating processes as well as striatal reward and corticolimbic regulatory pathways in the maintenance of cigarette addiction.

Comparison of Bayesian penalized likelihood reconstruction versus OS-EM for characterization of small pulmonary nodules in oncologic PET/CT.

OBJECTIVE: To determine whether the recently introduced Bayesian penalized likelihood PET reconstruction (Q.Clear) increases the visual conspicuity and SUVmax of small pulmonary nodules near the PET resolution limit, relative to ordered subset expectation maximization (OS-EM). METHODS: In this institutional review board-approved and HIPAA-compliant study, 29 FDG PET/CT scans performed on a five-ring GE Discovery IQ were retrospectively selected for pulmonary nodules described in the radiologist's report as "too small to characterize", or small lung nodules in patients at high risk for lung cancer. Thirty-two pulmonary nodules were assessed, with mean CT diameter of 8 mm (range 2-18). PET images were reconstructed with OS-EM and Q.Clear with noise penalty strength ß values of 150, 250, and 350. Lesion visual conspicuity was scored by three readers on a 3-point scale, and lesion SUVmax and background liver and blood pool SUVmean and SUVstdev were recorded. Comparison was made by linear mixed model with modified Bonferroni post hoc testing; significance cutoff was p < 0.05. RESULTS: Q.Clear improved lesion visual conspicuity compared to OS-EM at ß = 150 (p < 0.01), but not 250 or 350. Lesion SUVmax was increased compared to OS-EM at ß = 150 and 250 (p < 0.01), but not 350. CONCLUSION: In a cohort of small pulmonary nodules with size near an 8 mm PET full-width half maximum, Q.Clear significantly increased lesion visual conspicuity and SUVmax compared to our standard non- time-of-flight OS-EM reconstruction, but only with low noise penalization. Q.Clear with ß = 150 may be advantageous when evaluation of small pulmonary nodules is of primary concern.

Characterization of 3-Dimensional PET Systems for Accurate Quantification of Myocardial Blood Flow.

Three-dimensional (3D) mode imaging is the current standard for PET/CT systems. Dynamic imaging for quantification of myocardial blood flow with short-lived tracers, such as 82Rb-chloride, requires accuracy to be maintained over a wide range of isotope activities and scanner counting rates. We proposed new performance standard measurements to characterize the dynamic range of PET systems for accurate quantitative imaging. METHODS: 82Rb or 13N-ammonia (1,100-3,000 MBq) was injected into the heart wall insert of an anthropomorphic torso phantom. A decaying isotope scan was obtained over 5 half-lives on 9 different 3D PET/CT systems and 1 3D/2-dimensional PET-only system. Dynamic images (28 × 15 s) were reconstructed using iterative algorithms with all corrections enabled. Dynamic range was defined as the maximum activity in the myocardial wall with less than 10% bias, from which corresponding dead-time, counting rates, and/or injected activity limits were established for each scanner. Scatter correction residual bias was estimated as the maximum cavity blood-to-myocardium activity ratio. Image quality was assessed via the coefficient of variation measuring nonuniformity of the left ventricular myocardium activity distribution. RESULTS: Maximum recommended injected activity/body weight, peak dead-time correction factor, counting rates, and residual scatter bias for accurate cardiac myocardial blood flow imaging were 3-14 MBq/kg, 1.5-4.0, 22-64 Mcps singles and 4-14 Mcps prompt coincidence counting rates, and 2%-10% on the investigated scanners. Nonuniformity of the myocardial activity distribution varied from 3% to 16%. CONCLUSION: Accurate dynamic imaging is possible on the 10 3D PET systems if the maximum injected MBq/kg values are respected to limit peak dead-time losses during the bolus first-pass transit.

3'-Deoxy-3'-[F-18]fluorothymidine positron emission tomography in patients with recurrent glioblastoma multiforme: comparison with Gd-DTPA enhanced magnetic resonance imaging.

INTRODUCTION: The accumulation of 3'-deoxy-3'-[F-18]fluorothymidine (FLT) on positron emission tomography (PET) images in patients with glioblastoma multiforme was evaluated and correlated with gadopentetate dimeglumine (Gd-DTPA) enhancement in magnetic resonance images (MRIs). METHODS: FLT studies in 10 patients with recurrent glioblastoma multiforme were retrospectively investigated. Dynamic emission data were acquired for 60 minutes immediately after injection of FLT. The standardized uptake value (SUV) for tumor and reference tissue (contralateral hemisphere and ipsilateral cerebellum) was calculated. The volumes of the metabolically active part of the tumor (V (PET)) and that of the Gd-DTPA enhancing part of the tumor (V (MR)) were calculated. RESULTS: FLT uptake in tumors peaked before 5 minutes and sometimes as early as 0.5 minutes, and reached a constant level at approximately 10 minutes after injection. The reference tissue time-activity curves had an early peak and reached a constant low background level. All tumors had increased FLT uptake and showed Gd-DTPA enhancement. The SUV in tumor was significantly higher than that in the reference tissue (P<0.0001). A significant correlation between V (PET) and V (MR) was found (P<0.0001) although there was a difference in the areas of Gd-DTPA enhancement and FLT uptake. CONCLUSION: These preliminary results indicate that FLT-PET may be useful for the detection of recurrent glioblastoma multiforme. Our data in a relatively small patient population do not support a clear-cut relationship between FLT accumulation and Gd-DTPA enhancement. Further pathologic correlation will determine if it can be used for detecting recurrent tumoral disease.

Characterization of septal penetration in 511 keV SPECT.

BACKGROUND: Single photon emission computed tomography (SPECT) with 511 keV photons is a challenging modality and collimators for this purpose require trade-offs among resolution, sensitivity and septal penetration. While PET is the modality of choice for imaging at 511 keV, there are some procedures, e.g., dual-isotope imaging, in which 511 keV SPECT has a role. AIM: To measure the imaging properties of a VPC-93 SPECT collimator designed for imaging at 511 keV and to isolate the effects of septal penetration. METHODS: NaI gamma camera projection images of (18)F (511 keV) and (99m)Tc (140 keV) point sources were measured and the corresponding modulation transfer functions calculated. The projection images were reconstructed via filtered back-projection to obtain the tomographic three-dimensional (3-D) point spread function. Differences between the 511 and 140 keV results were attributed mainly to septal penetration. Contrast measurements were made separately using (18)F and (99m)Tc of a 20 cm phantom containing hot spheres and a warm background. Both isotopes were also used in imaging studies of a 3-D Hoffman brain phantom. RESULTS: Reconstructed 511 keV point source images were spatially extended with more than half of the total reconstructed counts appearing away from the point source region. The number of false counts contained in the image as a function of distance from the true source location remains approximately constant for large distances out to at least 14 cm. Septal penetration results in a rapid roll-off with spatial frequency of collimator response. The response of the collimator to 511 keV photons falls to half of its 0-frequency response at 0.03 cm(-1). For 140 keV photons this value is 0.20 cm(-1). A result is reduced image contrast as measured in the phantom sphere studies. Septal penetration causes image degradation through large-scale blurring. Image noise characteristics are modified and correlations are extended into many transaxial planes. CONCLUSIONS: Both 2-D and 3-D point spread functions for 511 and 140 keV photons using the VPC-93 collimator have been measured. Septal penetration unfavourably affects image resolution and changes image noise characteristics. Without compensation, the effects of septal penetration are readily apparent in images of real objects.

Quantitative differences in [(18)F] NaF PET/CT: TOF versus non-TOF measurements.

[(18)F] sodium fluoride (NaF) PET/CT is a current, clinically relevant method to assess bone metastases. Time-of-flight (TOF) PET provides better statistical data quality, which can improve either lower image noise or improve resolution, or both, depending on the image reconstruction. Improved resolution can improve quantitative measurements of standardized uptake value (SUV) in small structures. These quantitative differences may be important in both clinical interpretation and multicenter clinical trials where quantification is integral to assessing response to therapy. The purpose of this study is to determine if and by how much SUV quantitatively differs between TOF and conventional non-TOF reconstructions in [(18)F] NaF PET/CT. SUV measurements (mean and maximum) were compared in TOF and non-TOF [(18)F] NaF PET-CT reconstructions for 47 prostate cancer patients in normal regions including: soft tissue (n=282 total regions; liver, aorta, posterior abdominal fat, bladder, brain, and paraspinal muscles), and osseous structures (n=188; T12 vertebral body, femoral diaphyseal cortex, femoral head, and lateral rib). Comparisons were also made for benign degenerative changes (n=281) and metastases (n=159). TOF and non-TOF SUVs were assessed with paired t-test and linear correlations. Normal soft tissue showed lower SUVmean for TOF compared to non-TOF in liver, brain, and adipose. All osseous structures showed higher SUVmean for TOF compared to non-TOF including normal regions, degenerative joint disease, and metastases. For all metastatic lesions, the average SUVmean increased by 2.5%, and in degenerative joint disease it increased by 3.5% on TOF reconstructions. Smaller lesion size was a significant factor influencing this increase in SUVmean. TOF SUVmean values are higher in osseous structures and lower in background soft tissue structures. While these differences are statistically significant, the magnitudes of these changes are relatively modest. Smaller osseous lesions may have higher contrast and higher SUVmean values with TOF reconstruction compared to non-TOF reconstructions. The differences in TOF vs. non-TOF images should be considered when evaluating response to therapy and in the design of multi-center clinical trials.

PET studies of the influences of nicotine on neural systems in cigarette smokers.

OBJECTIVE: The effects of acute nicotine administration and smoking on brain function were investigated in two studies, with the primary goal of identifying neural systems that mediate these effects. METHOD: In study 1, 18 healthy volunteer cigarette smokers were exposed to three conditions in a single session: 1) smoking a nicotine-containing cigarette, 2) smoking a denicotinized cigarette, or 3) receiving intravenous nicotine injections in conjunction with smoking a denicotinized cigarette. In study 2, 16 subjects smoked a nicotine-containing and denicotinized cigarette in each of two sessions 2 hours after receiving the nicotinic antagonist mecamylamine (10 mg) or placebo orally. Regional cerebral blood flow (rCBF) was assessed by using the bolus (15)O-labeled water method and positron emission tomography. Subjective measures of smoking withdrawal symptoms were also collected. RESULTS: A principal-components analysis of rCBF data pooled from the two studies identified three factors consisting of frontal, striatal, and reticular systems. The amygdala was considered as a separate region of interest. Nicotine increased normalized rCBF in the left frontal region and decreased rCBF in the left amygdala. The rCBF in the right hemisphere reticular system was related to nicotine dose in an inverted-U-shaped pattern and was strongly related to self-reported craving for cigarettes and to the addiction scale of a smoking motivation questionnaire. The effects of mecamylamine on rCBF were generally opposite to those of nicotine. CONCLUSIONS: The results indicate that nicotine influences brain regions involved in arousal and reward and suggest specific functional systems that may be linked to motivationally significant aspects of tobacco dependence.

Aging and attentional guidance during visual search: functional neuroanatomy by positron emission tomography.

Positron emission tomography (PET) was used to examine adult age differences in neural activation during visual search. Target detection was less accurate for older adults than for younger adults, but both age groups were successful in using color to guide attention to a subset of display items. Increasing perceptual difficulty led to greater activation of occipitotemporal cortex for younger adults than for older adults, apparently as the result of older adults maintaining higher levels of activation within the easier task conditions. The results suggest that compensation for age-related decline in the efficiency of occipitotemporal cortical functioning was implemented by changes in the relative level of activation within this visual processing pathway, rather than by the recruitment of other cortical regions.

Time course of tetrahydrocannabinol-induced changes in regional cerebral blood flow measured with positron emission tomography.

While several studies are available on the immediate effects of marijuana and its active ingredient tetrahydrocannabinol (THC) on regional cerebral blood flow (rCBF), we examined the effects of intravenous infusion of THC on rCBF and behavior over a 120-min. period using positron emission tomography. Indices of rCBF, intoxication and physiology were measured at baseline and 30, 60, 90 and 120 min. after a 20-min. intravenous infusion of 0.15 or 0.25 mg/min. of THC, or placebo given to 47 subjects. The rCBF remained increased up to 120 min. after the high-dose THC infusion. Significant increases were seen in global perfusion and in the frontal, insular and anterior cingulate regions. Changes were greater in the right hemisphere. After the high dose, cerebellar flow was increased at both 30 and 60 min. The anterioposterior ratio of cortical rCBF increased in both hemispheres, and remained significantly greater than in the placebo condition until 120 min. in the right hemisphere. Intoxication peaked at 30 min. and remained elevated at 120 min. THC had significant effects on global CBF and rCBF, and feeling intoxicated accounted for changes in rCBF better than plasma level of THC.