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.

PET/CT versus body coil PET/MRI: how low can you go?

OBJECTIVES: The purpose of this study was to evaluate if positron emission tomography (PET)/magnetic resonance imaging (MRI) with just one gradient echo sequence using the body coil is diagnostically sufficient compared with a standard, low-dose non-contrast-enhanced PET/computed tomography (CT) concerning overall diagnostic accuracy, lesion detectability, size and conspicuity evaluation. METHODS AND MATERIALS: Sixty-three patients (mean age 58 years, range 19-86 years; 23 women, 40 men) referred for either staging or restaging/follow-up of various malignant tumours (malignant melanoma, lung cancer, breast cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, CUP, gynaecology tumours, pleural mesothelioma, oesophageal cancer, colorectal cancer, stomach cancer) were prospectively included. Imaging was conducted using a tri-modality PET/CT-MR set-up (full ring, time-of-flight Discovery PET/CT 690, 3 T Discovery MR 750, both GE Healthcare, Waukesha, WI). All patients were positioned on a dedicated PET/CT- and MR-compatible examination table, allowing for patient transport from the MR system to the PET/CT without patient movement. In accordance with RECIST 1.1 criteria, measurements of the maximum lesion diameters on CT and MR images were obtained. In lymph nodes, the short axis was measured. A four-point scale was used for assessment of lesion conspicuity: 1 (>25 % of lesion borders definable), 2 (25-50 %), 3 (50-75 %) and 4 (>75 %). For each lesion the corresponding anatomical structure was noted based on anatomical information of the spatially co-registered PET/CT and PET/MRI image sections. Additionally, lesions were divided into three categories: "tumour mass", "lymph nodes" and "lesions". Differences in overall lesion detectability and conspicuity in PET/CT and PET/MRI, as well as differences in detectability based on the localisation and lesion type, were analysed by Wilcoxon signed rank test. RESULTS: A total of 126 PET-positive lesions were evaluated. Overall, no statistically significant superiority of PET/CT over PET/MRI or vice versa in terms of lesion conspicuity was found (p = 0.095; mean score CT 2.93, mean score MRI 2.75). A statistically significant superiority concerning conspicuity of PET/CT over PET/MRI was found in pulmonary lesions (p = 0.016). Additionally, a statistically significant superiority of PET/CT over PET/MRI in "lymph nodes" regarding lesion conspicuity was also found (p = 0.033). A higher mean score concerning bone lesions were found for PET/CT compared with PET/MRI; however, these differences did not achieve statistical significance. CONCLUSION: Overall, PET/MRI with body coil acquisition does not match entirely the diagnostic accuracy of standard low-dose PET/CT. Thus, it might only serve as a back-up solution in very few patients. Overall, more time needs to be invested on the MR imaging part (higher matrix, more breath-holds, additional surface coil acquired sequences) to match up with the standard low-dose PET/CT. MAIN MESSAGES: • Evaluation of whether PET/MRI with one sequence using body coil is diagnostically sufficient compared with PET/CT • PET/MRI with body coil does not match entirely the diagnostic accuracy of standard low-dose PET/CT • PET/MRI might only serve as a backup solution in patients.

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.

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.

Anderson-Fabry disease: long-term echocardiographic follow-up under enzyme replacement therapy.

AIMS: Anderson-Fabry disease affects various organ systems due to glycosphingolipid accumulation. Enzyme replacement therapy (ERT) has been reported to decrease left ventricular wall thickening (LVWT) and to improve diastolic dysfunction. METHODS AND RESULTS: This prospective study included 29 patients (patients; mean age 37 +/- 13 years) with genetically, enzymatically and/or biopsy-proven Anderson-Fabry disease and long-time ERT. Data on symptoms, cardiac medications and history of hypertension were collected and all patients had comprehensive echocardiographic examination prior to ERT and at follow-up. Disease was at an early stage with a total mean Mainz severity score index of only 18.6 +/- 13.0. Prior to ERT, 79% of patients reported acroparesthesia. The median creatinine level was 121 +/- 108 mcmol/L and LVWT was present in nine patients (31%). Binary appearance of the interventricular septum was found in 20% and posterobasal fibrosis in 83%. At median follow-up of 37 months, acroparesthesia decreased to 55% (P = 0.016). There was no change in creatinine levels. The incidence of LVWT was unchanged, only an increase in interventricular septal wall thickness from 11.7 +/- 0.4 to 12.5 +/- 0.5 was observed (P = 0.009). Left atrial size and the percentage of patients with binary appearance and posterobasal fibrosis were unchanged. There was a small improvement in diastolic function (29% decrease of E/Ea; P < 0.002). CONCLUSION: Our Anderson-Fabry cohort had successful long-time ERT with impressive amelioration of subjective symptoms. Although there was not much improvement in cardiac changes apart from a slight improvement of diastolic function, at least, there was no progression of cardiac disease. For complete reversibility of cardiac changes in Anderson-Fabry disease, ERT might have to be started earlier in life and/or prescribed for a longer time.

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.

TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin.

BACKGROUND: Tumor necrosis factor (TNF)-alpha has pleiotropic effects in cytokine-mediated inflammation underlying atherogenesis. Activation of this inflammatory process is assumed to be different in diabetic and non-diabetic individuals. Previous studies in non-diabetic subjects showed no association between TNF-alpha -308G>A polymorphism and coronary artery disease. METHODS: Vascular complications and cytokine serum concentrations were assessed as a function of the TNF-alpha -308G>A polymorphism in 76 diabetic patients on low-dose aspirin. RESULTS: Of 76 adult diabetic patients, 18 (24%) carried the TNF-alpha -308A allele (17 AG, 1 AA) and 58 (76%) carried wild-type alleles (GG). Prevalence of macrovascular complications was 33% in TNF-alpha -308A allele carriers (AG+AA) and 78% in wild-type allele carriers (GG) (p<0.001). In contrast, prevalence of microvascular complications was 78% and 84%, respectively, and did not significantly differ between the study groups. TNF-alpha -308A allele carriers (AG+AA) compared to wild-type allele carriers (GG) had significantly lower median serum concentrations of hs-C-reactive protein (1.5 vs 2.9 mg/L, p=0.030), interleukin 1-beta (0.9 vs 1.2 ng/L, p=0.046), and interleukin-6 (3.6 vs 4.9 ng/L, p=0.023). In multiple regression analysis, the prevalence of macrovascular diabetic complications was significantly associated with TNF-alpha -308G>A polymorphism (p<0.001) and serum concentrations of HDL-cholesterol (p=0.007) while confounding effects of further variables were excluded. CONCLUSION: TNF-alpha -308G>A polymorphism modulates cytokine serum concentrations and macrovascular complications in diabetic patients on aspirin. Diabetic carriers of the TNF-alpha -308A allele might benefit more from a prophylaxis with low dose aspirin than non-carriers.

F-18-fluorodeoxyglucose (FDG) positron-emission tomography of Echinococcus multilocularis liver lesions: prospective evaluation of its value for diagnosis and follow-up during benzimidazole therapy.

BACKGROUND: Long-term benzimidazole therapy benefits patients with non-resectable alveolar echinococcosis (AE). Methods to assess early therapeutic efficacy are lacking. Recently, AE liver lesions were reported to exhibit increased F-18-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET). To assess the value of FDG-PET for diagnosis and follow-up of AE patients. PATIENTS/METHODS: Twenty-six consecutive patients with newly diagnosed AE were enrolled. Baseline evaluation included CT and FDG-PET. Thirteen patients (11 women; median age 50 years, range 40-76) were resected, the remaining 13 (8 women; median age 60 years, range 39-72) had non-resectable disease, were started on benzimidazoles, and CT and FDG-PET were repeated at 6, 12 and 24 months of therapy. Twelve consecutive patients with newly diagnosed cystic echinococcosis (CE) of the liver were also subjected to baseline FDG-PET. RESULTS: In 21/26 AE patients, baseline PET scans showed multifocally increased FDG uptake in the hepatic lesions' periphery, while liver lesions were FDG negative in 11/12 CE patients. Thus, sensitivity and specificity of FDG-PET for AE vs. CE were 81% and 92%, respectively. In 5 of 10 non-resectable patients with increased baseline FDG uptake, the intensity of uptake decreased (or disappeared) during benzimidazole therapy, in 3 by >or=2 grades within the initial 6 months. CONCLUSIONS: FDG-PET is a sensitive and specific adjunct in the diagnosis of suspected AE and can help in differentiating AE from CE. The rapid improvement of positive PET scans with benzimidazole therapy in some patients indicates that absent FDG uptake does not necessarily reflect parasite viability.

Diagnostic and clinical perspectives of fusion imaging in cardiology: is the total greater than the sum of its parts?

Positron emission tomography, cardiovascular magnetic resonance and multislice computed tomography have contributed to changing our pathophysiological understanding of many conditions. Clinically, they have provided new tools for the identification of preclinical disease and a better understanding of how disease progresses. The application of these imaging modalities to preclinical disease and the use of these techniques in patients with overt cardiovascular disease are reviewed.

[Painful shoulder in the elderly--not always of degenerative nature]. / Schulterschmerz im Alter--nicht immer degenerativer Natur.

A 81-year-old man suffered, without any preceding trauma, from progressive pain of his left shoulder since 3 weeks. The left upper arm was warm and swollen with a palpable solid mass. Mild normocytic anemia and an increased erythrocyte sedimentation reaction were determined. X-ray showed an osteolytic lesion of left humerus with pathological fracture and involvement of soft tissue. Multiple myeloma was diagnosed from the biopsy of this lesion, detection of paraprotein IgA Kappa in the serum, and a 15-20% plasma cell infiltration of the bone marrow. The patient responded well to radio-therapy and intravenous application of biphosphonates--the fracture healed by conservative therapy. The treating physician--on the basis of clinical experience and by intuition--has to decide considering medical history and clinical findings whether musculoskeletal pain must be investigated further. Diagnosis of multiple myeloma requires monoclonal protein (paraprotein) in the serum or urine, plasma cell infiltration of the bone marrow, and evidence of end-organ damage (anemia, renal insufficiency, bone lesions or hypercalcemia).