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Objective: The purpose of our study was to evaluate a visual PET/CT scoring system for the differentiation of benign and early malignant esophageal uptake., Materials and Methods: Thirty-six consecutive patients with precancerous or early malignant esophageal lesions including Barrett's esophagus, Tis, T1, and T2 adenocarcinomas were eligible. Findings of these patients were compared with 66 patients who had reported increased esophageal (18)F-FDG uptake due to benign esophageal disorders. Lesions were evaluated with scores using the following characteristics in PET/CT: FDG uptake intensity (low = 0, moderate = 1, high = 2), FDG uptake eccentricity (concentric = 0, eccentric = 1), FDG uptake focality (diffuse = 0, segmental = 1, focal = 2), esophageal thickness on the CT component (normal = 0, thickening = 1, mass = 2), and location (distal third of the esophagus = 0, middle third of the esophagus = 1, proximal third of the esophagus = 2)., Results: Early malignant lesions had higher scores in FDG uptake intensity (p = 0.003; chi-square), eccentricity (p < 0.001), and focality (p < 0.001) compared with benign lesions. No significant difference was seen in esophageal thickness on CT (p = 0.168) and in location of the lesion (p = 0.291). Binary logistic regression analysis with a stepwise forward inclusion of all score components including the maximum standardized uptake value (SUV) of the lesions revealed that a total score combining eccentricity and focality scores has the highest accuracy of predicting early malignant disease. Using a threshold of equal or higher than 2 in the combined total focality-eccentricity score, the sensitivity was 83.3% and specificity was 68.2% for predicting early malignant disease., Conclusion: Focality and eccentricity of FDG uptake prove to be valuable PET/CT characteristics for the differentiation of nonspecific FDG uptake in the esophagus.

Objective: The objective of our study was to investigate the use of PET in the detection of malignant peripheral nerve sheath tumors (MPNSTs) in patients with neurofibromatosis type 1 (NF1)., Materials and Methods: Forty-five patients with NF1 who underwent whole-body PET for suspected MPNST based on clinical symptoms or radiologic examinations were retrospectively evaluated. Ten patients underwent additional carbon-11 (11C) methionine PET because of equivocal 18F-FDG PET findings or because of a discrepancy between the FDG PET and clinical findings. PET images were evaluated for the distribution and uptake pattern, and the standardized uptake values (SUVs) were obtained. Twenty-seven patients underwent biopsy or surgery of the detected lesions and 18 patients were followed up clinically and with repeat imaging studies., Results: Fifty lesions were identified on FDG PET. There were eight false-positive results and one false-negative on FDG PET. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET in detecting MPNSTs in patients with NF1 were 95%, 72%, 71%, 95%, and 82%, respectively. Using 11C methionine PET in combination with FDG PET reduced the number of false-positive results from eight to two, which increased the specificity from 72% to 91%. In five patients, 11C methionine FDG PET contributed additional information about nontarget lesions that influenced treatment planning., Conclusion: FDG PET is a sensitive technique in the detection of MPNSTs in patients with NF1. The addition of 11C methionine PET increases specificity in equivocal cases. PET may improve preoperative tumor staging by detecting metastases or second primary tumors, which often are present in patients with NF1.

Objective: The objective of this study was to determine the optimal breathing protocol for combined PET/CT scans of the thorax., Subjects and Methods: Eighty combined PET/CT scans were obtained in 64 patients (30 women, 34 men; mean age, 57 years; range, 19-86 years). The 80 PET/CT scans consisted of five group of patients (16 PET/CT scans per group) who underwent whole-body combined 18F-FDG PET/CT with different CT breathing protocols: expiration, mid suspended breath-hold, quiet breathing, small breath in, and regular breath in. The quality of alignment was analyzed at the diaphragm, aortic arch, heart, thoracic spine, and lung apices using a scale of ratings from 1 (very poor) to 5 (excellent). The Kruskal-Wallis test was used to compare alignment between breathing protocols for each anatomic reference point., Results: Alignment of the PET and CT data sets was excellent with three breathing protocols: expiration, mid suspended breath-hold, and quiet breathing, with no statistical differences. Significant misalignment occurred at the diaphragm (p < 0.0001) and heart (p < 0.0001) with the small breath-in and regular breath-in techniques., Conclusion: Excellent image fusion of combined PET/CT data sets in the thorax, especially at the diaphragm and heart, can be achieved with expiration, mid suspended breath-hold, or quiet breathing. Quiet breathing is recommended for optimal patient comfort during acquisition of attenuation-correction CT data sets.

Objective: The objective of our study was to assess the relative performance of mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET for the detection of liver metastases from adenocarcinoma of the colon and pancreas., Materials and Methods: Imaging data of 34 patients (23 men, 11 women; age range, 44-78 years) with adenocarcinoma of the colon (n = 27) or adenocarcinoma of the pancreas (n = 7) who had undergone mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET were retrospectively reviewed for the presence and number of liver metastases. Histopathology (n = 25) or follow-up imaging (n = 9) served as the standard of reference. Breath-hold T1-weighted gradient-recalled echo, respiratory-triggered T2-weighted fast spin-echo, and mangafodipir trisodium-enhanced axial fat-saturated high-spatial-resolution (256 x 512) T1-weighted gradient-recalled echo images were obtained on a 1.5-T scanner. FDG PET was performed after the injection of 15-20 mCi (555-740 MBq) of FDG. The sensitivity, positive predictive value, and accuracy were calculated for each technique. The performances of the two techniques were compared using the Fisher's exact test., Results: Thirty patients had hepatic metastases and four had no hepatic metastases according to the standard of reference. The total number of metastases was 79, including 33 that measured less than 1 cm. Based on a per-patient analysis, MRI and FDG PET showed sensitivities of 96.6% and 93.3%, positive predictive values of 100% and 90.3%, and accuracies of 97.1% and 85.3%, respectively. According to a per-lesion analysis, MRI and FDG PET showed sensitivities of 81.4% and 67.0%, positive predictive values of 89.8% and 81.3%, and accuracies of 75.5% and 64.1%, respectively. MRI detected more hepatic metastases than FDG PET (p = 0.016). Of the 33 subcentimeter lesions confirmed on the standard of reference, all were identified on MRI, whereas only 12 were detected on FDG PET (p = 0.0001)., Conclusion: In patients with colon and pancreatic adenocarcinoma, high-spatial-resolution mangafodipir trisodium-enhanced liver MRI and whole-body FDG PET were comparable in the detection of patients with liver metastases. FDG PET provided additional information about extrahepatic disease and was useful in initial staging. However, significantly more and smaller liver metastases were detected on MRI than on FDG PET.

Objective: The objective of our study was to evaluate FDG uptake in patients with cardiac lipomatous hypertrophy of the interatrial septum (LHIS)., Conclusion: Increased FDG uptake occurs in LHIS, a benign fatty infiltration of the interatrial septum. Increased uptake in the right heart on FDG PET warrants correlation with additional imaging to assess for LHIS and avoid false interpretation of malignancy.

Objective: Our purpose was to describe three adult patients in whom we found increased thymic uptake of FDG on positron emission tomography and thymic enlargement with convex lateral margins on CT. Subsequent biopsy or resection showed normal thymic tissue., Conclusion: In three adults, we found a physiologic uptake of FDG by the thymus with standardized uptake values in the range of thymic neoplasia.

Objective: The purpose of this study was to determine if nonlinear registration of clinically acquired thoracic CT and FDG positron emission tomography (PET) data sets supports more detailed interpretation of metastatic thoracic disease when compared with interpretations from nonregistered PET studies., Conclusion: In 11 of 16 data sets of patients imaged for detection of metastatic disease, interpretations from PET studies were correctly altered with registration information. All changes were either improvements in tumor localization or correct interpretation of less metastatic involvement.

Objective: This study evaluated and optimized the performance of an automated artificial neural network image interpreter in the diagnosis of pulmonary embolism on ventilation-perfusion lung scans. The computer interpretations were compared with the interpretations of three experienced observers., Materials and Methods: Digital data were obtained from 100 patients with normal findings on chest radiographs who were undergoing both radionuclide ventilation-perfusion scanning and pulmonary angiography. Interpretations of differently trained neural networks were compared with those of three experienced nuclear medicine practitioners unaware of the clinical diagnosis., Results: Machines running neural networks performed similarly to experienced scan interpreters in the detection of pulmonary embolism. Both the human observers and the networks performed best in cases with large emboli. Neural network performance was best in the right lung, when the networks were trained using only cases with large emboli and when networks were trained independently in the right and left lungs. The best predictions resulted from a collaborative interpretation incorporating both the human and computer predictions., Conclusion: Computers running artificial neural networks using scan data obtained directly from the anterior and posterior ventilation and perfusion images, without human involvement, perform comparably with experienced observers in patients with normal findings on chest radiographs. Human observers can improve their interpretations by incorporating computer output to formulate diagnostic prediction. The method of training the networks is critical to optimizing performance.

Objective: In pharmaceutical clinical trials, quantitative measurements on medical images are often conducted to confirm drug efficacy. This study aims to compare the quantitative image analysis performance of an off-site core laboratory with the performance of investigators from multiple clinical sites., Materials and Methods: In a phase I clinical trial, 25 healthy subjects underwent dynamic brain single-photon emission computed tomography (SPECT) scintigraphy with 123I-Altropane, a cocaine analogue with high affinity and selectivity for dopamine transporter sites in the striatum. In 20 patients examined on-site and off-site, a total of 80 measurements were made to calculate the drug's binding potential. A trained technologist off-site at a central core laboratory and on-site investigators at different clinical sites performed the image analysis. These results were compared with measurements made by a subspecialty radiologist whose assessments were the reference standard. Statistical analysis was performed using multiple regression analysis., Results: Measurements from the central core laboratory (off-site) highly correlated (r = 0.95) with measurements of the reference standard. Measurements from the clinical sites (on-site) grouped together had lower correlation (r = 0.84) with the reference standard. This difference was statistically significant (p < 0.05)., Conclusion: Training and experience in the specific type of image analysis are critical in obtaining consistent data. Quantitative analysis by dedicated personnel at a core laboratory provides highly reproducible results. The findings support off-site assessment of medical images in pharmaceutical clinical trials.

Objective: To obtain initial data on the safety and efficacy of a novel polymeric, synthetic blood pool contrast agent [O-monomethoxypoly(ethylene glycol)-O'succinyl]poly(N-epsilon-L-lysyl [99mTc]diethylenetriamine pentaacetate monoamide, we performed a preclinical evaluation and phase 1 clinical trial under an investigator-sponsored investigational new drug application., Materials and Methods: Methoxypoly(ethylene glycol)ethylenetriaminopentaacetic acid was formulated into a kit containing the polymer, stannous chloride, and a buffer. Kits were stored in frozen form for subsequent labeling with technetium-99m. Acute and subacute toxicity studies were carried out in rats and rabbits. Healthy human volunteers (n = 6) were then enrolled in a prospective, open-label phase 1 clinical study., Results: Animal studies showed no signs of acute or subacute toxicity at doses 280 times the proposed dose for humans. In the clinical trial with humans, no significant abnormalities of laboratory values, ECG findings, or hemodynamic parameters were seen. One volunteer experienced facial flushing and palpitations. Four volunteers showed typical blood pool biodistribution, with a blood half-life of 20.6 +/- 2.3 hr. At 24 hr after administration, 22.1% +/- 2.5% of the injected dose had been excreted through the kidneys. Two other volunteers showed a different biodistribution (primarily to liver and spleen), presumably associated with labeling instability., Conclusion: Synthetic methoxypoly(ethylene glycol)-grafted polymers can have long circulation times in humans. Pharmaceuticals based on such polymers are expected to have clinical applications in cardiovascular imaging, gastrointestinal bleeding studies, and capillary leak imaging.