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Osama Mawlawi

Publications and source records attributed to Osama Mawlawi.

At least 19 recordsLinked to original sources
PubMed2007

Detection of interval distant metastases: clinical utility of integrated CT-PET imaging in patients with esophageal carcinoma after neoadjuvant therapy.

BACKGROUND: The objective of the study was to determine the utility of integrated computed tomography / positron emission tomography (CT-PET) imaging for detecting interval distant metastases and assessing therapeutic response in patients with locally advanced, potentially resectable esophageal carcinoma after neoadjuvant therapy. METHODS: A retrospective study was performed of 88 patients with potentially resectable esophageal carcinoma who received neoadjuvant therapy before planned surgical resection. CT-PET before and after completion of neoadjuvant was used for evaluating therapeutic response; response criteria were based on qualitative and semiquantitative analyses. RESULTS: Neoadjuvant therapy comprised chemoradiotherapy in 85 patients, with prior induction chemotherapy in 39 patients. Fifty-five patients proceeded to esophagectomy. Repeat CT-PET was performed after induction chemotherapy (n = 23) and after completing chemoradiotherapy (n = 85). CT-PET identified the interval appearance of metastatic disease in 7 (8%) patients. For assessment of locoregional therapeutic response, CT-PET was unable to predict pathological response to neoadjuvant therapy in the primary tumor or locoregional lymph nodes. CT-PET had sensitivity, specificity, and positive and negative predictive values of 57%, 46%, 39%, and 64%, respectively, for detection of residual macroscopic malignancy within the primary tumor; and sensitivity, specificity, and positive and negative predictive values of 0%, 90%, 0%, and 69% for detection of residual malignancy within resected lymph nodes. CONCLUSIONS: CT-PET performed after neoadjuvant therapy in patients with potentially resectable esophageal carcinoma is important for detecting interval metastases that preclude surgical resection, but is of limited utility for assessing locoregional therapeutic response.

Adenocarcinoma↗
PubMed2006

Early detection of chemoradioresponse in esophageal carcinoma by 3'-deoxy-3'-3H-fluorothymidine using preclinical tumor models.

PURPOSE: Early identification of esophageal cancer patients who are responding or resistant to combined chemoradiotherapy may lead to individualized therapeutic approaches and improved clinical outcomes. We assessed the ability of 3'-deoxy-3'-(18)F-fluorothymidine positron emission tomography (FLT-PET) to detect early changes in tumor proliferation after chemoradiotherapy in experimental models of esophageal carcinoma. EXPERIMENTAL DESIGN: The in vitro and ex vivo tumor uptake of [(3)H]FLT in SEG-1 human esophageal adenocarcinoma cells were studied at various early time points after docetaxel plus irradiation and validated with conventional assessments of cellular proliferation [thymidine (Thd) and Ki-67] and [(18)F]FLT micro-PET imaging. Imaging-histologic correlation was determined by comparing spatial Ki-67 and [(18)F]FLT distribution in autoradiographs. Comparison with fluorodeoxyglucose (FDG) was done in all experiments. RESULTS: In vitro [(3)H]FLT and [(3)H]Thd uptake rapidly decreased in SEG-1 cells 24 hours after docetaxel with a maximal reduction of over 5-fold (P = 0.005). The [(3)H]FLT tumor-to-muscle uptake ratio in xenografts declined by 75% compared with baseline (P < 0.005) by 2 days after chemoradiotherapy, despite the lack of change in tumor size. In contrast, the decline of [(3)H]FDG uptake was gradual and less pronounced. Tumor uptake of [(3)H]FLT was more closely correlated with Ki-67 expression (r = 0.89, P < 0.001) than was [(3)H]FDG (r = 0.39, P = 0.08). Micro-PET images depicted similar trends in reduction of [(18)F]FLT and [(18)F]FDG tumor uptake. Autoradiographs displayed spatial correlations between [(18)F]FLT uptake and histologic Ki-67 distribution in preliminary studies. CONCLUSIONS: FLT-PET is suitable and more specific than FDG-PET for depicting early reductions in tumor proliferation that precede tumor size changes after chemoradiotherapy.

Animals↗
PubMed2006

PET and planar imaging of tumor hypoxia with labeled metronidazole.

RATIONALE AND OBJECTIVES: This study was aimed to develop 99mTc- and 68Ga-labeled metronidazole (MN) using ethylenedicysteine (EC) as a chelator and evaluate their potential use to assess tumor hypoxia. MATERIALS AND METHODS: EC-MN was labeled with 99mTc in the presence of tin (II) chloride. Labeling EC-MN with 68Ga was achieved by adding 68GaCl3 (2 mCi with 3.4 microg cold GaCl3). In vitro cellular uptakes of 99mTc- and 68Ga-EC-MN were obtained in various types of tumor cells at 0.5-4 hours. Tissue distribution and PET imaging of 99mTc and 68Ga-EC-MN were evaluated in breast tumor-bearing rats at 0.5-4 hours. Tumor oxygen tension was measured using an oxygen probe. RESULTS: There were similar cellular uptakes (2-10%) between 99mTc- and 68Ga-EC-MN at 0.5-4 hours. In vivo biodistribution of 99mTc- and 68Ga-EC-MN in breast tumor-bearing rats showed increased tumor-to-blood and tumor-to-muscle count density ratios as a function of time. Positron emission tomography images confirmed that the tumors could be visualized clearly with 68Ga-EC-MN. Oxygen tension in tumor tissue was determined to be 6-10 mm Hg compared with 40-50 mm Hg in normal muscle tissue. CONCLUSIONS: The results indicated that it is feasible to use 99mTc- and 68Ga-EC-MN for assessment of tumor hypoxia. These agents may be useful in selecting and evaluating cancer therapy.

Animals↗
PubMed2006

PET/CT imaging techniques, considerations, and artifacts.

In the past few years, positron emission tomography/computed tomography (PET/CT) imaging has increasingly been used for the diagnosis, staging, and restaging of malignant diseases. The success of this emerging modality has primarily been due to its ability to combine the advantages of both PET and CT imaging while minimizing their separate weaknesses. The aim of this paper is to provide an overview of the basis behind PET/CT imaging, its advantages, and discuss its imaging artifacts with special emphasis on proposed correction techniques. A brief discussion regarding the use of PET/CT imaging for radiation treatment planning is also presented.

Artifacts↗
PubMed2006

Interobserver and intraobserver variability of standardized uptake value measurements in non-small-cell lung cancer.

OBJECTIVES: To assess interobserver and intraobserver variabilities in measuring the maximal standardized uptake value (SUV) of non-small-cell lung cancer. METHODS: Positron emission tomography-computed tomography examinations of 20 consecutive patients referred for initial evaluation of newly diagnosed non-small-cell lung cancer were retrospectively reviewed by 5 experienced positron emission tomography-computed tomography readers, who independently measured the maximal SUV/body weight of the primary tumors. Interobserver and intraobserver variabilities were assessed by using 4 statistical methods: correlation, regression analysis, Bland-Altman analysis, and analysis of variance. The SUV measurements derived in the study were compared with the SUV measurements documented in the original reports using correlation and regression analysis. The percentages of tumors whose retrospective SUV measurements were more than 20% different and more than 25% different from those in the original report were assessed. RESULTS: Both interobserver and intraobserver SUV measurements were highly reproducible. Pearson correlation coefficients were greater than 0.95 and 0.94, respectively. Good interobserver and intraobserver agreement was shown with regression analysis (F test P value >0.05), the Bland-Altman analysis, and analysis of variance (F test P value >0.95). The mean original SUV was much less than the mean study SUV (P<0.05). The study SUV differed from the SUV of the original report by more than 20% in 50% of the tumors, and by more than 25% in 45% of the tumors. CONCLUSIONS: There was excellent interobserver and intraobserver agreement in SUVs measured in the study environment but poor agreement between study SUVs and those documented in original reports, which can affect treatment decisions substantially.

Aged↗
PubMed2006

Attenuation correction of PET cardiac data with low-dose average CT in PET/CT.

We proposed a low-dose average computer tomography (ACT) for attenuation correction (AC) of the PET cardiac data in PET/CT. The ACT was obtained from a cine CT scan of over one breath cycle per couch position while the patient was free breathing. We applied this technique on four patients who underwent tumor imaging with 18F-FDG in PET/CT, whose PET data showed high uptake of 18F-FDG in the heart and whose CT and PET data had misregistration. All four patients did not have known myocardiac infarction or ischemia. The patients were injected with 555-740 MBq of 18F-FDG and scanned 1 h after injection. The helical CT (HCT) data were acquired in 16 s for the coverage of 100 cm. The PET acquisition was 3 min per bed of 15 cm. The duration of cine CT acquisition per 2 cm was 5.9 s. We used a fast gantry rotation cycle time of 0.5 s to minimize motion induced reconstruction artifacts in the cine CT images, which were averaged to become the ACT images for AC of the PET data. The radiation dose was about 5 mGy for 5.9 s cine duration. The selection of 5.9 s was based on our analysis of the respiratory signals of 600 patients; 87% of the patients had average breath cycles of less than 6 s and 90% had standard deviations of less than 1 s in the period of breath cycle. In all four patient studies, registrations between the CT and the PET data were improved. An increase of average uptake in the anterior and the lateral walls up to 48% and a decrease of average uptake in the septal and the inferior walls up to 16% with ACT were observed. We also compared ACT and conventional slow scan CT (SSCT) of 4 s duration in one patient study and found ACT was better than SSCT in depicting average respiratory motion and the SSCT images showed motion-induced reconstruction artifacts. In conclusion, low-dose ACT improved registration of the CT and the PET data in the heart region in our study of four patients. ACT was superior than SSCT for depicting average respiration motion in a patient study.

Artifacts↗
PubMed2006

Quantifying the effect of IV contrast media on integrated PET/CT: clinical evaluation.

OBJECTIVES: The use of IV contrast media in PET/CT can result in an overestimation of PET attenuation factors that potentially can affect interpretation. The objective of this study was to quantify the effect of IV contrast media in PET/CT and assess its impact on patients with intrathoracic malignancies. MATERIALS AND METHODS: Nine patients had CTs performed with and without IV contrast media followed by (18)F-FDG PET. PET images were reconstructed using contrast-enhanced and unenhanced CT. To quantify the effect of contrast media on standardized uptake values (SUV), similar regions of interest (ROIs) were drawn on the subclavian vein, heart, liver, spleen, and site of malignancy on both CT and corresponding reconstructed PET images, and the mean and maximum values were compared. In addition, two physicians blinded to the imaging parameters that were used evaluated the reconstructed PET images to assess whether IV contrast media had an effect on clinical interpretation. RESULTS: For all patient studies, the subclavian vein region on the ipsilateral side of contrast media administration had the highest increase in CT numbers with a corresponding average SUV(max) increase of 27.1%. Similarly, ROIs of the heart and at the site of malignancy showed an increase in the maximum attenuation value with a corresponding average SUV(max) increase of 16.7% and 8.4%, respectively. Other locations had relatively small attenuation value differences with a correspondingly negligible SUV variation. CONCLUSION: Although there is a significant increase in SUV in regions of high-contrast concentration when contrast-enhanced CT is used for attenuation correction, this increase is clinically insignificant. Accordingly, in PET/CT, IV contrast-enhanced CT can be used in combination with the PET to evaluate patients with cancer.

Contrast Media↗
PubMed2006

Truncation artifact on PET/CT: impact on measurements of activity concentration and assessment of a correction algorithm.

OBJECTIVE: Discrepancy between fields of view (FOVs) in a PET/CT scanner causes a truncation artifact when imaging extends beyond the CT FOV. The purposes of this study were to evaluate the impact of this artifact on measurements of 18F-FDG activity concentrations and to assess a truncation correction algorithm. MATERIALS AND METHODS: Two phantoms and five patients were used in this study. In the first phantom, three inserts (water, air, bone equivalent) were placed in a water-filled cylinder containing 18F-FDG. In the second phantom study, a chest phantom and a 2-L bottle fitted with a bone insert were used to simulate a patient's torso and arm. Both phantoms were imaged while positioned centrally (baseline) and at the edge of the CT FOV to induce truncation. PET images were reconstructed using attenuation maps from truncated and truncation-corrected CT images. Regions of interest (ROIs) drawn on the inserts, simulated arm, and background water of the baseline truncated and truncation-corrected PET images were compared. In addition, extremity malignancies of five patients truncated on CT images were reconstructed with and without correction and the maximum standard uptake values (SUVs) of the malignancies were compared. RESULTS: Truncation artifact manifests as a rim of high activity concentration at the edge of the truncated CT image with an adjacent low-concentration region peripherally. The correction algorithm minimizes these effects. Phantom studies showed a maximum variation of -5.4% in the truncation-corrected background water image compared with the baseline image. Activity concentration in the water insert was 6.3% higher while that of air and bone inserts was similar to baseline. Extremity malignancies showed a consistent increase in the maximum SUV after truncation correction. CONCLUSION: Truncation affects measurements of 18F-FDG activity concentrations in PET/CT. A truncation-correction algorithm corrects truncation artifacts with small residual error.

Adult↗
PubMed2006

Incidental findings on integrated PET/CT that do not accumulate 18F-FDG.

OBJECTIVE: The purpose of this study was to report the prevalence of abnormalities that do not show increased 18F-FDG uptake on the CT component of integrated PET/CT in patients with non-small cell lung cancer. MATERIALS AND METHODS: Images from all PET/CT studies performed consecutively between April and October 2003 on patients with non-small cell lung cancer were retrospectively reviewed. All abnormalities present on the CT component of the PET/CT scans that did not show abnormally increased 18F-FDG uptake were documented. RESULTS: Three hundred twenty-one patients with non-small cell lung cancer (179 men, 142 women; mean age, 67 years; age range, 38-91 years) underwent initial staging (198/321 [62%]) or restaging (123/321 [38%]) PET/CT imaging during the study period. In 263 (82%) of the patients, CT showed 1,231 abnormalities that were not 18F-FDG avid. The abnormalities were located in the thorax (n = 650), abdomen and pelvis (n = 444), head and neck (n = 69), and bony skeleton (n = 68). In total, 298 (24%) of the abnormalities that were not 18F-FDG avid were located outside the range of a standard thoracic CT scan. The clinical importance of these abnormalities was classified as major (n = 48 [4%]), moderate (n = 465 [38%]), or minor (n = 718 [58%]). Four (1%) of the patients had findings of major clinical importance that did not show increased 18F-FDG uptake and were previously unsuspected. CONCLUSION: Among patients with non-small cell lung cancer undergoing PET/CT, there is a high prevalence of CT abnormalities that do not show correlative 18F-FDG avidity but that may be clinically important.

Adult↗
PubMed2005

Respiration artifacts in whole-body (18)F-FDG PET/CT studies with combined PET/CT tomographs employing spiral CT technology with 1 to 16 detector rows.

PURPOSE: Co-registration accuracy in combined whole-body (WB) PET/CT imaging is impaired by respiration-induced mismatches between the CT and the PET. Furthermore, PET/CT misregistration may bias the PET tracer distribution following CT-based attenuation correction (CT-AC). With the introduction of multi-row CT technology of up to 16 detector rows into PET/CT designs, we investigated the incidence of respiration artifacts in WB PET/CT examinations of patients who were unable to follow any breath-hold instructions. METHODS: A total of 80 WB studies from six international sites operating PET/CT tomographs with 1-, 2-, 4-, 6-, 8-, and 16-row spiral CT were included. PET/CT examinations were acquired with the patients breathing normally during both the CT and the PET scan, and CT-AC was performed routinely. All studies were anonymized and reviewed independently by three radiologists and three nuclear medicine specialists. We report the frequency and severity of artifacts on CT and PET for the thorax and the abdomen. RESULTS: In WB PET/CT imaging of normally breathing patients, significant gains in diagnostic image quality can be expected from employing CT technology with six or more detector rows. In our study, fewer PET images appear distorted than corresponding CT images, which is due to the limited propagation of only mild CT image artifacts after the resampling of the CT-based attenuation map during CT-AC. CONCLUSION: In whole-body PET/CT imaging of normally breathing patients, respiration-induced artifacts are reduced in both magnitude and prominence for PET/CT systems employing CT components of six or more detector rows.

Adolescent↗
PubMed2005

Prediction of panic response to a respiratory stimulant by reduced orbitofrontal cerebral blood flow in panic disorder.

OBJECTIVE: Lack of appropriate top-down governance by frontal cortical regions over a hypersensitive amygdala-centered fear neurocircuitry has been hypothesized to be central in the pathophysiology of panic disorder. The aim of this study was to examine regional cerebral blood flow changes in response to anxiety/panic provocation in subjects with panic disorder and healthy comparison subjects. METHOD: Quantitative water method positron emission tomography was used to obtain brain images of five untreated subjects with panic disorder and five healthy comparison subjects before and during anxiogenic challenge with intravenous doxapram, an acute respiratory stimulant. RESULTS: Baseline perfusion of the orbitofrontal cortex predicted panic attacks: lower perfusion was associated with heightened anxiety in response to doxapram challenge. CONCLUSIONS: The orbitofrontal cortex may be important in the regulation of responding to fear and is a potential area of aberrant functioning in panic disorder.

Adult↗
PubMed2005

PET/CT imaging artifacts.

The purpose of this paper is to introduce the principles of PET/CT imaging and describe the artifacts associated with it. PET/CT is a new imaging modality that integrates functional (PET) and structural (CT) information into a single scanning session, allowing excellent fusion of the PET and CT images and thus improving lesion localization and interpretation accuracy. Moreover, the CT data can also be used for attenuation correction, ultimately leading to high patient throughput. These combined advantages have rendered PET/CT a preferred imaging modality over dedicated PET. Although PET/CT imaging offers many advantages, this dual-modality imaging also poses some challenges. CT-based attenuation correction can induce artifacts and quantitative errors that can affect the PET emission images. For instance, the use of contrast medium and the presence of metallic implants can be associated with focal radiotracer uptake. Furthermore, the patient's breathing can introduce mismatches between the CT attenuation map and the PET emission data, and the discrepancy between the CT and PET fields of view can lead to truncation artifacts. After reading this article, the technologist should be able to describe the principles of PET/CT imaging, identify at least 3 types of image artifacts, and describe the differences between PET/CT artifacts of different causes: metallic implants, respiratory motion, contrast medium, and truncation.

Artifacts↗
PubMed2005

Attenuation correction of PET images with respiration-averaged CT images in PET/CT.

UNLABELLED: Attenuation correction (AC) of PET images with helical CT (HCT) in PET/CT matches only the spatial resolution of CT and PET, not the temporal resolution. We therefore proposed the use of respiration-averaged CT (ACT) to match the temporal resolution of CT and PET and evaluated the improvement of tumor quantification in PET images of the thorax with ACT. METHODS: First, we examined 100 consecutive clinical PET/CT studies for the frequency and magnitude of misalignment at the diaphragm position between the HCT and the PET data. Patients were injected with 555-740 MBq of (18)F-FDG and scanned 1 h after injection. The HCT data were acquired at the following settings: 120 kV, 300 mA, pitch of 1.35:1, collimation of 8 x 1.25 mm, and rotation cycle of 0.5 s. Patients were instructed to hold their breath at midexpiration during HCT of the thorax. The PET acquisition was 3 min per bed. Second, we retrospectively analyzed studies of 8 patients (1 with esophageal cancer and 7 with lung cancer). Each study included regular PET/CT followed by 4-dimensional (4D) CT for radiation treatment planning. We compared the results of AC of the PET data with HCT and ACT. There were 13 tumors in these 8 patients. The 4D CT data were acquired at the following settings: 120 kV, 50-150 mA, cine duration of 1 breathing cycle plus 1 s, collimation of 8 x 1.25 mm, and rotation cycle of 0.5 s. The acquisition was taken when the patient was in the free-breathing state. We averaged the 10 phases of the 4D CT data to obtain ACT for AC of the PET data. Both the ACT and the HCT data were used for AC of the same PET data. RESULTS: There was a misalignment between the HCT and the PET data in 50 of 100 patient studies. In 34 studies, the misalignment was greater than 2 cm. In a comparison of HCT and ACT, 5 tumors had differences in standardized uptake values (SUV) between HCT-and ACT-attenuation-corrected PET of less than 20%, and 4 tumors had differences in SUV of more than 50%. The latter 4 tumors were found in the patient with esophageal cancer and in 2 of the patients with lung cancer. The PET data from these 3 patients had a misalignment of 2-4.5 cm relative to the HCT data. Breathing artifacts were significantly reduced by ACT. Seven of the 8 patients had a lower diaphragm position on HCT than on ACT, suggesting that the patients tended to hold a deeper breath during HCT than during ACT. CONCLUSION: The high rate of misalignment suggested a potential mismatch between the HCT and the PET data with the limited-breath-hold CT protocol. In the comparison of HCT and ACT, significant differences (>50%) in SUV were attributable to different breathing states between HCT and PET. The PET data corrected by ACT did not show breathing artifacts, suggesting that ACT may be more accurate than HCT for AC of the PET data.

Aged↗
PubMed2004

Striatal amphetamine-induced dopamine release in patients with schizotypal personality disorder studied with single photon emission computed tomography and [123I]iodobenzamide.

BACKGROUND: Previous imaging studies demonstrated that schizophrenia is associated with increased amphetamine-induced dopamine (DA) release in the striatum, most pronounced during episodes of illness exacerbation. Schizotypal personality disorder (SPD) is a schizophrenia spectrum disorder, genetically related to schizophrenia. The goal of this study was to investigate striatal DA function in patients with SPD. METHODS: In our study, 13 SPD patients and 13 matched healthy control subjects underwent single photon emission computed tomography (SPECT) scan during bolus plus constant infusion of the D2/3 radiotracer [123I]iodobenzamide (IBZM). Striatal specific to nonspecific equilibrium partition coefficient (V(3)") was measured at baseline and following amphetamine administration (.3 mg/kg). RESULTS: No significant differences were observed in baseline V(3)" between groups. Amphetamine induced a larger decrease in [123I]IBZM V(3)" in SPD patients (-12 +/- 5%) compared with control subjects (-7 +/- 5%, p =.03). CONCLUSIONS: The reduction in [123I]IBZM V(3)" induced by amphetamine in SPD was similar to that observed in remitted schizophrenia patients (-10 +/- 9%, n = 17), but significantly lower than that observed during illness exacerbation (-24 +/- 13%, n = 17). This suggests that DA dysregulation in schizophrenia spectrum disorders might have a trait component, present in remitted patients with schizophrenia and in SPD, and a state component, associated with psychotic exacerbations but not SPD.

Adult↗
PubMed2004

Performance characteristics of a newly developed PET/CT scanner using NEMA standards in 2D and 3D modes.

UNLABELLED: This study evaluates the 2-dimensional (2D) and 3-dimensional (3D) performance characteristics of a newly developed PET/CT scanner using the National Electrical Manufacturers Association (NEMA) NU 2-1994 (NU94) and NEMA NU 2-2001 (NU01) standards. The PET detector array consists of 10,080 individual bismuth germanate crystals arranged in 24 rings of 420 crystals each. The size of each crystal is 6.3 x 6.3 x 30 mm in the axial, transaxial, and radial dimensions, respectively. The PET detector ring diameter is 88.6 cm with axial and transaxial fields of view (FOVs) of 15.7 and 70 cm, respectively. The scanner has a uniform patient port of 70 cm throughout the PET and CT FOV, and the PET scanner is equipped with retractable septa to allow 2D and 3D imaging. METHODS: Spatial resolution, scatter fraction, sensitivity, counting rate, image quality, and accuracy as defined by the NEMA protocols of NU94 and NU01 for 2D and 3D modes are evaluated. The 2D mode data were acquired with a maximum ring difference of 5, whereas the 3D mode acquisition used ring differences of 23. Both 2D and 3D mode data were acquired with an energy window of 375-650 keV. Random estimation from singles counting rate was applied to all relevant analysis. In addition, images from 2 clinical whole-body oncology studies acquired in 2D and 3D modes are shown to demonstrate the image quality obtained from this scanner. RESULTS: The 2D NU94 transaxial resolution is 6.1-mm full width at half maximum (FWHM) 1 cm off center and increases to 6.9 mm tangential and 8.1 mm radial at a radius (R) of 20 cm. NU01 2D average transaxial (axial) FWHM resolution measured 6.1 (5.2) mm at R = 1 cm and 6.7 (6.1) mm at R = 10 cm. The NU94 scatter fraction for 2D (3D) was 13% (29%), whereas the NU01 scatter fraction gave 19% (45%). NU01 peak 2D (3D) noise equivalent counting rate (T(2)/[T + R + S]) was 90.2 (67.8) kilocount per second (kcps) at 52.5 (12) kBq/mL. Total 2D (3D) system sensitivity for true events is 8 (32.9) kcps/kBq/mL for NU94 and 1.95 (9.2) kcps/Bq for NU01. CONCLUSION: The results show excellent system sensitivity with relatively uniform resolution throughout the FOV, making this scanner highly suitable for whole-body studies.

Adult↗
PubMed2003

Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum.

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3") was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (DeltaV3") in limbic (ventral striatum, -15.3 +/- 11.8%) and sensorimotor (postcommissural putamen, -16.1 +/- 9.6%) regions compared with associative regions (caudate and precommissural putamen, -8.1 +/- 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in DeltaV3" between limbic (-17.8 +/- 13.8%), sensorimotor (-16.6 +/- 9.9%), and associative regions (-7.5 +/- 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger DeltaV3" in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.

Affect↗
PubMed2002

Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with 11C McN 5652.

RATIONALE: Although selective serotonin reuptake inhibitors (SSRIs) are widely used in the treatment of anxiety and depressive disorders, the occupancy of the serotonin reuptake transporter (SERT) achieved in humans at typical clinical doses by these agents remains poorly characterized. OBJECTIVE: The purpose of this study was to determine the occupancy of the SERT achieved in vivo by the SSRI paroxetine in social phobia patients at typical antianxiety doses. METHODS: Measures of SERT availability were obtained with positron emission tomography and the SERT radiotracer [(11)C](+)-McN 5652 in five patients with social phobia before and during treatment with paroxetine at usual therapeutic doses (20-40 mg per day). RESULTS: Occupancy of the SERT by paroxetine was high in all subjects and in all regions measured after 3-6 months of continuous treatment. CONCLUSIONS: The results of this study in an anxiety disorder sample are consistent with previously reported results in a depressed sample and suggest that paroxetine at therapeutic doses achieves very high occupancy levels of the SERT.

Adult↗