Benefit of 18F-fluorocholine PET imaging in parathyroid surgery.

OBJECTIVES: To assess the additional diagnostic value of 18F-fluorocholine PET imaging in preoperative localization of pathologic parathyroid glands in clinically manifest hyperparathyroidism in case of negative or conflicting ultrasound and scintigraphy results. METHODS: A retrospective, single-institution study of 26 patients diagnosed with hyperparathyroidism. In cases where ultrasound and scintigraphy failed to detect the location of an adenoma in order to allow a focused surgical approach, an additional 18F-fluorocholine PET scan was performed and its results were compared with the intraoperative findings. RESULTS: A total of 26 patients underwent 18F-fluorocholine PET/CT (n = 11) or PET/MRI (n = 15). Adenomas were detected in 25 patients (96.2%). All patients underwent surgery, and the location predicted by PET hybrid imaging was confirmed intraoperatively by frozen section and adequate parathyroid hormone drop after removal. None of the patients needed revision surgery during follow-up. CONCLUSIONS: These results demonstrate that 18F-fluorocholine PET imaging is a highly accurate method to detect parathyroid adenomas even in case of previous localization failure by other imaging examinations. KEY POINTS: • With 18 F-fluorocholine PET imaging, parathyroid adenomas could be detected in 96.2%. • 18 F-fluorocholine imaging is a highly accurate method to detect parathyroid adenomas. • We encourage its use, where ultrasound fails to detect an adenoma.

Discrimination and anatomical mapping of PET-positive lesions: comparison of CT attenuation-corrected PET images with coregistered MR and CT images in the abdomen.

PURPOSE: PET/MR has the potential to become a powerful tool in clinical oncological imaging. The purpose of this prospective study was to evaluate the performance of a single T1-weighted (T1w) fat-suppressed unenhanced MR pulse sequence of the abdomen in comparison with unenhanced low-dose CT images to characterize PET-positive lesions. METHODS: A total of 100 oncological patients underwent sequential whole-body (18)F-FDG PET with CT-based attenuation correction (AC), 40 mAs low-dose CT and two-point Dixon-based T1w 3D MRI of the abdomen in a trimodality PET/CT-MR system. PET-positive lesions were assessed by CT and MRI with regard to their anatomical location, conspicuity and additional relevant information for characterization. RESULTS: From among 66 patients with at least one PET-positive lesion, 147 lesions were evaluated. No significant difference between MRI and CT was found regarding anatomical lesion localization. The MR pulse sequence used performed significantly better than CT regarding conspicuity of liver lesions (p < 0.001, Wilcoxon signed ranks test), whereas no difference was noted for extrahepatic lesions. For overall lesion characterization, MRI was considered superior to CT in 40 % of lesions, equal to CT in 49 %, and inferior to CT in 11 %. CONCLUSION: Fast Dixon-based T1w MRI outperformed low-dose CT in terms of conspicuity and characterization of PET-positive liver lesions and performed similarly in extrahepatic tumour manifestations. Hence, under the assumption that the technical issue of MR AC for whole-body PET examinations is solved, in abdominal PET/MR imaging the replacement of low-dose CT by a single Dixon-based MR pulse sequence for anatomical lesion correlation appears to be valid and robust.

Assessment of successful incorporation of cages after cervical or lumbar intercorporal fusion with [(18)F]fluoride positron-emission tomography/computed tomography.

The purpose of this study is to assess the successful incorporation of cages in patients after cervical or lumbar intercorporal fusion with positron-emission tomography/computed tomography (PET/CT). Twenty patients (14 female and 6 male; mean age 58 years, age range 38-73 years) with 30 cervical (n = 13) or lumbar (n = 17) intercorporal fusions were prospectively enrolled in this study. Time interval between last intercorporal intervention and PET/CT ranged from 2 to 116 months (mean 63; median 77 months). IRB approval was obtained for all patients, and written informed consent was obtained from all patients. About 30 min prior to PET/CT scanning, 97-217 MBq (mean 161 MBq) 18F-fluoride were administered intravenously. Patients were imaged in supine position on a combined PET/CT system (Discovery RX/STE, 16/64 slice CT, GE Healthcare). 3D-PET emission data were acquired for 1.5 and 2 min/bed position, respectively, and reconstructed by a fully 3D iterative algorithm (VUE Point HD) using low-dose CT data for attenuation correction. A dedicated diagnostic thin-slice CT was optionally acquired covering the fused region. Areas of increased 18F-fluoride uptake around cages were determined by one double-board certified radiologist/nuclear physician and one board certified radiologist in consensus. In 12/20 (60%) patients, increased 18F-fluoride uptake around cages was observed. Of the 30 intercorporal fusions, 15 (50%) showed increased 18F-fluoride uptake. Median time between intervention and PET/CT examination in cages with increased uptake was 37 months (2-116 months), median time between intervention and PET/CT examination in those cages without increased uptake was 91 months (19-112 months), p (Wilcoxon) = 0.01 (one-sided). 14/29 (48%) cages with a time interval > 1 year between intervention and PET/CT scan showed an increased uptake. In conclusion, PET/CT frequently shows increased 18F-fluoride uptake in cervical and lumbar cages older than 1 year (up to almost 8 years in cervical cages and 10 years in lumbar cages) possibly indicating unsuccessful fusion due to increased stress/microinstability.

18F-FDG-PET and MRI in patients with malignancies of the liver and pancreas. Accuracy of retrospective multimodality image registration by using the CT-component of PET/CT.

PURPOSE: To evaluate the accuracy of retrospective rigid image registration and fusion between F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) of the upper abdomen. PATIENTS, MATERIAL, METHODS: Image fusion of PET and MRI was performed in 30 patients with suspected malignancy of the liver or pancreas. Using a commercially available image fusion tool capable of rigid manual point-based registration, PET-Images were retrospectively registered and fused by matching eight homologous points in the 3D spoiled gradient echo (GRE) MRI sequences acquired in portal venous phase and in the CT-component of PET/CT. Two separate observers (R1, R2) assessed accuracy of image registration by determining the distances in the x-, y- and z-axis as well as the absolute distance between anatomical landmarks which differed from the landmarks chosen for registration. Quality of fusion was graded using a three point grading scale (1 poorly fused; 2 satisfactory fused; 3 correctly fused) and compared to hybrid PET/CT fusion. RESULTS: Mean time of registration per patient was less than 2 minutes. Objective registration assessment showed errors between 2.4-6.3 mm in x-axis: mean 3.6 mm (R1); 4.6 mm (R2), 2.3-9.3 mm in y-axis (mean 5.1 mm; 5.5 mm) and 3.3-12.0 mm in z-axis (mean 5.9 mm; 5.9 mm.) The mean error in absolute distance between points was 6.0-16.8 mm (mean 9.9 mm; 10.6 mm). In visual assessment, most fusions were graded to be satisfactory or correctly fused: R1, R2: grade 3, 11/30 (36.7%), 22/30 (73.3%); grade 2, 13/30 (43.3%), 8/30 (26.7%); grade 1, 6/30 (20%), 0/30 (0%). Fusions were mostly comparable to hybrid PET/CT fusions. All of the fusions were defined as diagnostically relevant by both observers. CONCLUSION: Retrospective rigid image fusion of FDG-PET and MRI of the upper abdomen using the CT-component of PET/CT for registration is feasible without adaptation in image acquisition protocols and shows sub-centimeter registration errors in most cases.

Limited value of 18F-FDG PET/CT and S-100B tumour marker in the detection of liver metastases from uveal melanoma compared to liver metastases from cutaneous melanoma.

PURPOSE: The objective of this study was to evaluate the value of (18)F-FDG PET/CT and S-100B tumour marker for the detection of liver metastases from uveal melanoma in comparison to liver metastases from cutaneous melanoma. METHODS: A retrospective evaluation was conducted of 27 liver metastases in 13 patients with uveal melanoma (UM) (mean age: 56.8, range: 30-77) and 43 liver metastases in 14 patients (mean age: 57.9, range: 40-82) with cutaneous melanoma (CM) regarding size and FDG uptake by measuring the maximum standardized uptake value (SUV(max)). S-100B serum tumour markers were available in 20 patients. Cytology, histology, additional morphological imaging and follow-up served as reference standard. In nine patients liver metastases were further evaluated histologically regarding GLUT-1 and S-100 receptor expression and regarding epithelial or spindle cell growth pattern. RESULTS: Of 27 liver metastases in 6 of 13 patients (46%) with UM, 16 (59%) were FDG negative, whereas all liver metastases from CM were positive. Liver metastases from UM showed significantly (p < 0.001) lower SUV(max) (mean: 3.5, range: 1.5-13.4) compared with liver metastases from CM (mean: 6.6, range: 2.3-15.3). In four of six (66.7%) patients with UM and liver metastases S-100B was normal and in two (33.3%) increased. All PET-negative liver metastases were detectable by morphological imaging (CT or MRI). S-100B was abnormal in 13 of 14 patients with liver metastases from CM. S-100B values were significantly higher (p = 0.007) in the CM patient group (mean S-100B: 10.9 microg/l, range: 0.1-115 microg/l) compared with the UM patients (mean: 0.2 microg/l, range: 0.0-0.5 microg/l). Histological work-up of the liver metastases showed no obvious difference in GLUT-1 or S-100 expression between UM and CM liver metastases. The minority (36%) of patients with UM had extrahepatic metastases and the majority (86%) of patients with CM had extrahepatic metastases, respectively. There was a close to significant trend to better survival of UM patients compared with CM patients (p = 0.06). CONCLUSION: FDG PET/CT and serum S-100B are not sensitive enough for the detection of liver metastases from UM, whereas liver metastases from cutaneous melanoma are reliably FDG positive and lead regularly to increased S-100B tumour markers. The reason for the lower FDG uptake in UM liver metastases remains unclear. We recommend to perform combined contrast-enhanced PET/CT in order to detect FDG-negative liver metastases from UM.

Unsuspected osteomyelitis is frequent in persistent diabetic foot ulcer and better diagnosed by MRI than by 18F-FDG PET or 99mTc-MOAB.

AIM: Prevalence, optimal diagnostic approach and consequences of clinically unsuspected osteomyelitis in diabetic foot ulcers are unclear. Early diagnosis of this infection may be crucial to ensure correct management. METHODS: We conducted a prospective study in 20 diabetic patients with a chronic foot ulcer (>8 weeks) without antibiotic pretreatment and without clinical signs for osteomyelitis to assess the prevalence of clinically unsuspected osteomyelitis and to compare the value of magnetic resonance imaging (MRI), 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and 99mTc-labelled monoclonal antigranulocyte antibody scintigraphy (99mTc-MOAB). Those with suggestive scans underwent bone biopsy for histology (n = 7). RESULTS: Osteomyelitis was confirmed by biopsy in seven of the 20 clinically unsuspected foot ulcers. Presence of osteomyelitis was not related to age, ulcer size, ulcer duration, duration of diabetes or HbA1c. C-reactive protein was slightly elevated in patients with osteomyelitis (35.1 +/- 16.0 mg L(-1) vs. 12.2 +/- 2.6 mg L(-1) in patients with and without osteomyelitis respectively; P = 0.07). MRI was positive in six of the seven patients with proven osteomyelitis, whereas 18F-FDG PET and 99mTc-MOAB were positive only in (the same) two patients. Of the seven patients with osteomyelitis, five had lower limb amputation and in one patient the ulcer was persisting after 24 months of follow-up. In contrast, of the 13 patients without detectable signs of osteomyelitis on imaging modalities only two had lower limb amputation and two persisting ulcers. CONCLUSIONS: Clinically unsuspected osteomyelitis is frequent in persisting foot ulcers and is a high risk factor for adverse outcome. MRI appears superior to 18F-FDG PET and 99mTc-MOAB in detecting foot ulcer-associated osteomyelitis and might be the preferred imaging modality in patients with nonhealing diabetic foot ulcers.

The additional value of CT images interpretation in the differential diagnosis of benign vs. malignant primary bone lesions with 18F-FDG-PET/CT.

OBJECTIVE: To evaluate the value of a dedicated interpretation of the CT images in the differential diagnosis of benign vs. malignant primary bone lesions with 18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). MATERIALS AND METHODS: In 50 consecutive patients (21 women, 29 men, mean age 36.9, age range 11-72) with suspected primary bone neoplasm conventional radiographs and 18F-FDG-PET/CT were performed. Differentiation of benign and malignant lesions was separately performed on conventional radiographs, PET alone (PET), and PET/CT with specific evaluation of the CT part. Histology served as the standard of reference in 46 cases, clinical, and imaging follow-up in four cases. RESULTS: According to the standard of reference, conventional 17 lesions were benign and 33 malignant. Sensitivity, specificity, and accuracy in assessment of malignancy was 85%, 65% and 78% for conventional radiographs, 85%, 35% and 68% for PET alone and 91%, 77% and 86% for combined PET/CT. Median SUV(max) was 3.5 for benign lesions (range 1.6-8.0) and 5.7 (range 0.8-41.7) for malignant lesions. In eight patients with bone lesions with high FDG-uptake (SUV(max) >or= 2.5) dedicated CT interpretation led to the correct diagnosis of a benign lesion (three fibrous dysplasias, two osteomyelitis, one aneurysmatic bone cyst, one fibrous cortical defect, 1 phosphaturic mesenchymal tumor). In four patients with lesions with low FDG-uptake (SUV(max) < 2.5) dedicated CT interpretation led to the correct diagnosis of a malignant lesion (three chondrosarcomas and one leiomyosarcoma). Combined PET/CT was significantly more accurate in the differentiation of benign and malignant lesions than PET alone (p = .039). There was no significant difference between PET/CT and conventional radiographs (p = .625). CONCLUSION: Dedicated interpretation of the CT part significantly improved the performance of FDG-PET/CT in differentiation of benign and malignant primary bone lesions compared to PET alone. PET/CT more commonly differentiated benign from malignant primary bone lesions compared with conventional radiographs, but this difference was not significant.

Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography.

BACKGROUND: Monitoring contrast medium wash-in kinetics in hyperemic myocardium by magnetic resonance (MR) allows for the detection of stenosed coronary arteries. In this prospective study, the quality of a multislice MR approach with respect to the detection and sizing of compromised myocardium was determined and compared with positron emission tomography (PET) and quantitative coronary angiography. METHODS AND RESULTS: A total of 48 patients and healthy subjects were studied by MR using a multislice hybrid echo-planar pulse sequence for monitoring the myocardial first pass kinetics of gadolinium-diethylenetriamine pentaacetic acid bismethylamide (Omniscan; 0.1 mmol/kg injected at 3 mL/s IV) during hyperemia (dipyridamole 0.56 mg/kg). Signal intensity upslope as a measure of myocardial perfusion was calculated in 32 sectors per heart from pixelwise parametric maps in the subendocardial layer and for full wall thickness. Before coronary angiography, coronary flow reserve (hyperemia induced by dipyridamole 0.56 mg/kg) was determined in corresponding sectors by (13)N-ammonia PET. Receiver-operator characteristic analysis of subendocardial upslope data revealed a sensitivity and specificity of 91% and 94%, respectively, for the detection of coronary artery disease as defined by PET (mean coronary flow reserve minus 2SD of controls) and a sensitivity and specificity of 87% and 85%, respectively, in comparison with quantitative coronary angiography (diameter stenosis >/=50%). The number of pathological sectors per patient on PET and MR studies correlated linearly (slope, 0.94; r=0.76; P<0.0001). CONCLUSIONS: The presented MR approach reliably identifies patients with coronary artery stenoses and provides information on the amount of compromised myocardium, even when perfusion abnormalities are confined to the subendocardial layer. This modality may qualify for its clinical application in the management of coronary artery disease.

High-resolution intravascular magnetic resonance imaging: monitoring of plaque formation in heritable hyperlipidemic rabbits.

BACKGROUND: The individual makeup of atherosclerotic plaque has been identified as a dominant prognostic factor. With the use of an intravascular magnetic resonance (MR) catheter coil, we evaluated the effectiveness of high-resolution MR in the study of the development of atherosclerotic lesions in heritable hyperlipidemic rabbits. METHODS AND RESULTS: Sixteen hyperlipidemic rabbits were investigated at the ages of 6, 12, 24, and 36 months. The aorta was studied with digital subtraction angiography and high-resolution MR with the use of a surface coil and an intravascular coil that consisted of a single-loop copper wire integrated in a 5F balloon catheter. Images were correlated with histological sections regarding wall thickness, plaque area, and plaque components. Digital subtraction angiography revealed no abnormalities in the 6- and 12-month-old rabbits and only mild stenoses in the 24- and 36-month-old rabbits. High-resolution imaging with surface coils resulted in an in-plane resolution of 234x468 microm. Delineation of the vessel wall was not possible in younger rabbits and correlated only poorly with microscopic measurements in the 36-month-old rabbits. Intravascular images achieved an in-plane resolution of 117x156 microm. Increasing thickness of the aortic wall and plaque area was observed with increasing age. In the 24- and 36-month-old animals, calcification could be differentiated from fibrous and fatty tissue on the basis of the T2-fast spin echo images, as confirmed by histological correlation. CONCLUSIONS: Atherosclerotic evolution of hyperlipidemic rabbits can be monitored with high-resolution intravascular MR imaging. Image quality is sufficient to determine wall thickness and plaque area and to differentiate plaque components.

Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography.

BACKGROUND: Measurement of coronary sinus blood flow (CSF) by phase-contrast magnetic resonance (PC-MR) imaging at rest and during hyperemia may allow noninvasive assessment of global coronary hemodynamics. METHODS AND RESULTS: Sixteen healthy volunteers (age, 22 to 32 years) were examined with MR and PET in random order within 1 to 2 days. At rest and during hyperemia (dipyridamole 0.56 mg/kg), CSF was measured by a cine PC-MR technique (temporal resolution, 40 ms; spatial resolution, 1.25x0.8 mm(2)), and myocardial blood flow (MBF) was measured by [(13)N]NH(3) PET. PET and MR agreed closely for coronary flow reserve (CFR; mean difference, 2.2+/-14.7%; Bland-Altman method). CSF divided by either total left ventricular mass or an estimate of drained myocardium (LVM(drain)) correlated highly with PET flow data (r=0.93 and 0.95, respectively) and with measures of oxygen demand, ie, heart rate, afterload-corrected fiber shortening, and peak systolic stress determined by MR (overall correlation coefficients, 0.81 and 0.87, respectively, multivariate analysis). CSF/LVM(drain) did not differ significantly from PET-derived MBF (difference, 3.6+/-16.6%). In orthotopic heart transplant recipients (n=9), CFR was reduced and blood supply-demand relationships at rest were shifted toward higher flows (P<0.0001). CONCLUSIONS: This integrated MR approach allows comprehensive assessment of autoregulated and hyperemic coronary flow and is suitable for serial measurements in patients. In transplanted hearts, elevated resting flow is the major cause of reduced CFR.

Changes of cerebral blood flow during short-term exposure to normobaric hypoxia.

Decreased arterial partial oxygen pressure (PaO2) below a certain level presents a strong stimulus for increasing cerebral blood flow. Although several field studies examined the time course of global cerebral blood flow (gCBF) changes during hypoxia at high altitude, little was known about the regional differences in the flow pattern. Positron emission tomography (PET) with [(15)O]H2O was used on eight healthy volunteers to assess regional cerebral blood flow (rCBF) during short-term exposure to hypoxia corresponding to simulated altitudes of 3,000 and 4,500 m. Scans at the simulated altitudes were preceded and followed by baseline scans at the altitude of Zurich (450 m, baseline-1 and baseline-2). Each altitude stage lasted 20 minutes. From baseline to 4,500 m, gCBF increased from 34.4 +/- 5.9 to 41.6 +/- 9.0 mL x minute(-1) x 100 g(-1) (mean +/- SD), whereas no significant change was noted at 3,000 m. During baseline-2 the flow values returned to those of baseline-1. Statistical parametric mapping identified the hypothalamus as the only region with excessively increased blood flow at 4,500 m (+32.8% +/- 21.9% relative to baseline-1). The corresponding value for the thalamus, the structure with the second largest increase, was 19.2% +/- 16.3%. Compared with the rest of the brain, an excessive increase of blood flow during acute exposure to hypoxia is found in the hypothalamus. The functional implications are at present unclear. Further studies of this finding should elucidate its meaning and especially focus on a potential association with the symptoms of acute mountain sickness.

PET with 18fluorodeoxyglucose and hexamethylpropylene amine oxime SPECT in late whiplash syndrome.

BACKGROUND: Many patients have cognitive abnormalities and psychological problems after whiplash injury to the cervical spine. To our knowledge, neuroradiologic imaging has not depicted brain damage that explains the symptoms. Parietotemporo-occipital perfusion deficits on hexamethylpropylene amine oxime (HMPAO) SPECT studies have been described among patients who have sustained whiplash injury. METHODS: We examined 13 patients with typical late whiplash syndrome (study group) using HMPAO SPECT, 18fluorodeoxyglucose (FDG) PET, and MRI of the brain and compared the findings with those for 16 control subjects who underwent FDG PET. RESULTS: In the study group, statistical parametric mapping revealed significantly decreased FDG uptake in the frontopolar and lateral temporal cortex and in the putamen. The frontopolar hypometabolism correlated significantly with scores of the Beck Depression Inventory. However, in individual cases, reliability in the depiction of hypometabolic areas was relatively low. No alterations were found in the parietotemporo-occipital area. In these areas, decreased uptake of HMPAO and FDG correlated with cortical mass. CONCLUSION: FDG PET did not allow reliable diagnosis of metabolic disturbances for individual patients. Therefore, we do not recommend FDG PET or HMPAO SPECT as a diagnostic tool in routine examinations of patients with late whiplash syndrome.

Regional quantitative noninvasive assessment of cerebral perfusion and function with N-isopropyl-[123I]p-iodoamphetamine.

Although several reports on the clinical usefulness of N-isopropyl-[123]p-iodoamphetamine (IMP) in the diagnosis of cerebral disease have appeared in the literature, quantitative, noninvasive measurements of regional cerebral blood flow with this method pose difficulties because cerebral IMP uptake not only depends on cerebral perfusion but also on cerebral function. Rather than trying to develop a method to measure cerebral perfusion with IMP, we have chosen to test a method to quantitatively evaluate planar and emission computed tomographic (ECT) studies by comparing the data obtained in patients with established pathology (n = 51, number of scans = 54) with the data obtained in a group of normal individuals (n = 10, number of scans = 11). Using this method, absolute cerebral IMP uptake (counts/pixel/mCi/min) and planar anterior right-left ratios were obtained. Also measured were right-left ratios obtained from 12 paired regions in three ECT slices. In the control group, we found an IMP uptake of 35.6 +/- 4.3 cts/pixel/mCi/min and right-left ratios around 1.00 (s.d. less than 2%). The evaluation of the patients cerebral IMP uptake asymmetries relative to the normal standard values is a useful adjunct to qualitative image analysis in assessing the presence and severity of disease, as qualitative analysis is prone to false-positive and negative results. Cerebral IMP uptake as measured in cts/pixel/mCi/min is abnormal only in severe cerebral disease and therefore generally a less helpful parameter.

Bronchogenic carcinoma mimicking metastatic thyroid carcinoma.

We present a case of a false-positive 131I scan in the follow-up of a patient with papillary thyroid carcinoma, which developed 24 yr after radiation therapy for Hodgkin's disease. In the primary evaluation of a neck mass, histology was typical for a papillary thyroid carcinoma and thyroglobulin staining was positive. After total thyroidectomy, 131I uptake was seen in the hilum and right lung. The initial interpretation of these foci as metastatic disease was not supported by the progressive clinical course despite radioiodine treatment. Hence, repeated bronchial brushings and cytology of the pleural effusion were obtained. These specimens were negative in thyroglobulin staining and positive for synoptophysin, a marker for small-cell bronchial carcinoma. Thereby a small to medium cell undifferentiated bronchial carcinoma was demonstrated, which apparently was actively taking up iodine. In conclusion, an atypical clinical course of a suspected metastatic thyroid carcinoma should lead to a reevaluation of the initial diagnosis to prevent an inappropriate therapeutic regimen.

Whole-body PET: physiological and artifactual fluorodeoxyglucose accumulations.

UNLABELLED: The purpose of this study was to semiquantitatively identify artifactual and physiological soft-tissue accumulations in whole-body FDG-PET scans with the aim of defining their frequency and anatomic distribution. METHODS: Fifty whole-body FDG-PET scans performed for the staging of malignant melanoma were obtained from transaxial scans and reconstructed without absorption correction by filtered backprojection in the form of coronal and sagittal sections. The patients were asked to stay n.p.o. for at least 4 hr and interrogated about their physical activity prior to injection and until scanning. Classification of FDG organ accumulations was done using grades 0-6. Means and standard deviations on this scale were then calculated for multiple organs and muscle groups and tabulated. RESULTS: On this grading scale, viscera showed uptake grades between 1.7 +/- 0.5 and 2.05 +/- 1.0. Except for the intestines, the activity in these organs was homogeneously distributed. Relatively high average uptake values of 2.0-4.2 (s.d. > or = 2.3) were found in various muscle groups, especially the orbital musculature. Myocardial uptake was visible in 90% of the scans. Reconstruction artifacts were seen around the renal collecting system and the bladder. CONCLUSION: Most of the "normal" accumulations of FDG in nonattenuation corrected whole-body PET are readily recognized and distinct from the usually focal FDG accumulation associated with metastatic disease, but the diagnostician must be familiar with them. Muscular FDG uptake is related to physical activity prior and immediately following injection and can be minimized by proper patient instructions and positioning.

Planar coincidence scintigraphy and PET in staging malignant melanoma.

UNLABELLED: This study describes a comparison of simulated planar positron coincidence scintigraphy (PCS) with PET in the whole-body staging of patients with malignant melanoma using 2-18F-fluoro-2-deoxy-D-glucose (FDG). METHODS: In 55 patients with either known metastatic or newly diagnosed malignant melanoma, whole-body PET scanning was performed on a conventional full-ring dedicated PET tomograph, and multiaxial sections were obtained. Furthermore, anteroposterior projection images simulating images of a dual-head Anger camera operating in coincidence mode were obtained from the PET raw data. Each study was evaluated separately and blindly. Imaging findings were confirmed by biopsy or by at least one imaging modality in addition to PET. RESULTS: A total of 108 lesions were evaluated, of which 76 proved to be melanoma metastases. Whole-body PET correctly demonstrated 68 metastases, 6 lesions were classified as questionable metastases and 2 were missed. Whole-body PCS correctly demonstrated 14 metastases, 22 lesions were classified as questionable metastases and 40 metastases were missed. The sensitivities of whole-body PET and whole-body PCS were 89% and 18%, respectively. In PCS lesions in regions of high background activity, such as in the abdomen, were missed more often than in PET (p < 0.05). The tumor-to-background contrast was generally lower in PCS than in PET. A further decrease in PCS detection was found in lesions of < 22 mm in diameter. CONCLUSION: The lack of sensitivity precludes the clinical use of whole-body PCS in staging malignant melanoma.

A pharmacokinetic and MRI study of unilamellar gadolinium-, manganese-, and iron-DTPA-stearate liposomes as organ-specific contrast agents.

Small unilamellar liposomes that contain the lipophilic chelate DTPA-stearate (DTPASA) were used as carriers for the paramagnetic metal ions gadolinium, manganese, and iron. The iron liposomes were unstable in vitro and thus not studied further. The natural targeting properties of these liposomes to the reticuloendothelial system was used in rats and dogs for the imaging of liver and spleen. In vitro incubations with human plasma, followed by high-pressure liquid chromatography (HPLC) separation of the Gd-DTPASA and Mn-DTPASA liposomes showed that after an incubation period of 24 hours, only 4% of the gadolinium was bound to the plasma proteins, whereas, with the Mn-DTPASA liposomes, a transfer of 40% manganese was seen. These results indicate that the Mn-DTPASA complex is not stable. On T1-weighted images, both liposome preparations gave a strong signal enhancement of the organs of the mononuclear phagocyte system (MPS). Gadolinium liposomes accumulated in the liver of rats at a peak concentration 4 hours after application and at a higher concentration compared with the manganese liposomes. Gd-DTPASA liposomes had an elimination half-time from the liver of 61 hours. Manganese liposomes produced stronger contrast at lower concentrations and had faster elimination kinetics from the liver, with a major elimination half-time of 10 hours. Both chelate complexes were eliminated predominantly by the hepatobiliary route. Thus, liposomal Gd-DTPASA appears to be a stable, efficient, and specific magnetic resonance imaging (MRI) contrast agent for the upper abdomen.

Nonionic polyethylene glycol-ferrioxamine as a renal magnetic resonance contrast agent.

The MR relaxation properties of ferrioxamine-B, a chelate of iron, were investigated in vitro and in vivo to establish the potential use of the compound as a paramagnetic contrast agent. Whereas the paramagnetic relaxivity of ferrioxamine-B is such that, compared to gadolinium-DTPA (Gd-DTPA), two to three times higher concentrations are necessary to produce the same relaxation effects, the toxicity of the iron ion should be much lower because of the availability of physiological metabolic pathways. Preliminary experiments in three dogs under invasive cardiovascular monitoring demonstrated that high-dose bolus application (0.1-0.3 mmol/kg body weight) of ferrioxamine-B leads to a precipitous blood pressure drop to almost zero, lasting for several minutes. This reaction seems most likely the result of a negative inotropic effect of ferrioxamine-B. In order to reduce these side effects ferrioxamine was modified to a nonionic derivative, PEG-ferrioxamine-B. In vivo experiments with this compound did not demonstrate any substantial change in blood pressure. Dynamic MR imaging of the kidneys and the liver was performed after bolus injection of the compound in six dogs. The results indicate that PEG-ferrioxamine-B produces effects very similar to Gd-DTPA, resulting in T1-mediated signal intensity increases in the liver and in the early stages of passage through the kidneys. During the phase of medullary concentration, T2 effects seem to dominate visualization of the renal medulla. The nonionic PEG-ferrioxamine-B derivative appears to offer an alternative to gadolinium-containing chelates as an MR contrast agent.

Cardiac volumetry. Comparison of echoplanar and conventional cine-magnetic resonance data-acquisition strategies.

RATIONALE AND OBJECTIVES: Ejection fraction (EF) measurements obtained using conventional cine-magnetic resonance imaging (MRI) are accurate but time-consuming. With echoplanar imaging (EPI), these data can be acquired much faster. In this study, EF and cardiac output (CO) measurements based on EPI data are compared with those measurements based on cine-MRI images. METHODS: Twelve subjects were examined on a 1.5-T imager equipped with a special EPI gradient system. The entire heart was imaged with contiguous axial 10-mm sections using cine-MRI and EPI techniques. With cine-MRI, 20 frames were acquired over 256 cardiac cycles; with EPI, 24 frames were obtained over four RR intervals using an electrocardiogram-triggered four-shot acquisition strategy. Ejection fraction and CO were calculated based on the summation of the individual end-systolic and end-diastolic volumes. Ejection fraction and CO measurements based on the two different data sets were compared. RESULTS: Multishot EPI was 50 times faster than cine-MRI. The short acquisition time permitted breath-hold imaging. The high temporal (16 to 24 frames/RR interval) and spatial resolution (1.56 x 1.56 mm in plane) of the multishot EPI images enabled delineation of the ventricular lumen at end-systole and end-diastole in a fashion similar to cine-MRI. Echoplanar imaging EF and CO measurements correlated well with cine-MRI EF measurements, with correlation coefficients of 0.96 and 0.94, respectively. The 95% confidence interval of the EF measurement differences between the two techniques was narrow, ranging from -5.2 to 5.7 EF percentage points. CONCLUSIONS: Accurate volumetric EF and CO measurements are possible based on ultrafast multishot EPI data sets as part of an integrated MRI-based cardiac evaluation.

Detection of extrathoracic metastases by positron emission tomography in lung cancer.

BACKGROUND: Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated in a prospective study the role of whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in mediastinal nodal staging with a positive predictive value of 96%. The study was continued to further evaluate the value of whole-body FDG PET in detecting unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical treatment by conventional staging. METHODS: One hundred patients underwent clinical evaluation, chest and upper abdominal computed tomography scan, mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and routine laboratory tests. In 94 patients with stage IIIa or less and 6 with suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were present additional diagnostic methods were applied. All findings in the FDG PET were confirmed histologically or radiologically. RESULTS: Unexpected ETMs were detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition 6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There was no false positive finding of ETM. Weight loss was correlated with the occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of 6 patients (67%). Pathologic laboratory findings were not predictive for ETM. CONCLUSIONS: Whole-body FDG PET improves detection of ETMs in patients with non-small cell lung cancer otherwise elegible for operation. In 14% of patients (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were understaged.