Faculty Bibliography

AIM/OBJECTIVE:To describe the (18)F-fluorodihydro-xyphenylalanine ((18)F-DOPA), positron emission tomography (PET) and magnetic resonance imaging (MRI) appearance of pheochromocytomas, with a focus on the presence or absence of typical MRI features. MATERIALS AND METHODS/METHODS:Eleven patients with histologically-verified pheochromocytoma [sporadic (n=9), multiple endocrine neoplasia (MEN) 2A syndrome (n=2)] were enrolled retrospectively. All patients underwent an MRI examination of the upper abdomen. Nine out of 11 patients underwent (18)F-DOPA PET/CT, and the remaining two patients underwent independent PET and computed tomography (CT) examinations. (18)F-DOPA-PET/CT examinations were considered positive when an increased tracer accumulation in the adrenal region, as shown on CT images, was observed. When an adrenal mass was detected on MRI, the T1 and T2 signal intensity and contrast enhancement pattern were recorded. Based on MR characteristics, the lesions were divided into typical and atypical. RESULTS:Ten out of 11 patients had one lesion, while one patient had two lesions. All pheochromocytomas were detected by both PET/CT and MRI. On (18)F-DOPA scans, all lesions showed an increased tracer accumulation, with a mean maximum standardized uptake value (SUVmax) of 13.7±5.75. Eight out of 12 pheochromocytomas exhibited typical MRI features, with intermediate signal intensity on T1-weighted images in-phase, absence of signal drop on T1-weighted images out-of-phase, high signal intensity on T2-weighted images, and clear contrast enhancement in the arterial phase. The remaining four lesions exhibited atypical MRI features, namely absence of one of the listed criteria. CONCLUSION/CONCLUSIONS:In the assessment of pheochromocytoma, the combination of (18)F-DOPA PET with MRI is superior to MRI-alone. (18)F-DOPA PET/MRI may yield a higher diagnostic confidence for the detection of pheochromocytoma than (18)F-DOPA PET/CT.

UNLABELLED:Because of its higher soft-tissue contrast, whole-body integrated PET/MR offers potential advantages over PET/CT for evaluation of bone lesions. However, unlike PET/CT, PET/MR ignores the contribution of cortical bone in the attenuation map. Thus, the aims of this study were to evaluate the diagnostic performance of whole-body integrated (18)F-FDG PET/MR specifically for bone lesions and to analyze differences in standardized uptake value (SUV) quantification between PET/MR and PET/CT. METHODS:One hundred nineteen patients with (18)F-FDG-avid primary malignancies underwent a single-injection, dual-imaging protocol using (18)F-FDG on a PET/CT scanner and a subsequent PET/MR scan with a T1-weighted volumetric interpolated breath-hold examination (VIBE) Dixon sequence for attenuation correction and an unenhanced coronal T1-weighted turbo spin-echo (TSE) sequence for bone analysis. Three sets of images (CT with PET [from PET/CT; set A], T1-weighted VIBE Dixon with PET [set B], and T1-weighted TSE with PET [both from PET/MR; set C]) were analyzed. Two readers rated every lesion using a 4-point scale for lesion conspicuity on PET, a 4-point scale for anatomic allocation of PET-positive lesions, and a 5-point scale for the nature of every lesion based on its appearance on morphologic imaging and uptake on PET. For all lesions and for representative regions of normal bone, SUV analysis was performed for PET/MR and PET/CT. RESULTS:In total, 98 bone lesions were identified in 33 of 119 patients, and 630 regions of normal bone were analyzed. Visual lesion conspicuity on PET was comparable for PET/CT (mean rating, 2.82 ± 0.45) and PET/MR (2.75 ± 0.51; P = 0.3095). Anatomic delineation and allocation of suggestive lesions was significantly superior with T1-weighted TSE MRI (mean rating, 2.84 ± 0.42) compared with CT (2.57 ± 0.54, P = 0.0001) or T1-weighted VIBE Dixon MRI (2.57 ± 0.54, P = 0.0002). No significant difference in correct classification of malignant bone lesions was found among sets A (85/90), B (84/90), and C (86/90). For bone lesions and regions of normal bone, a highly significant correlation existed between the mean SUVs for PET/MR and PET/CT (R = 0.950 and 0.917, respectively, each P < 0.001). However, substantially lower mean SUVs were found for PET/MR than for PET/CT both for bone lesions (12.4% ± 15.5%) and for regions of normal bone (30.1% ± 27.5%). CONCLUSION/CONCLUSIONS:Compared with PET/CT, fully integrated whole-body (18)F-FDG PET/MR is technically and clinically robust for evaluation of bone lesions despite differences in attenuation correction. PET/MR, including diagnostic T1-weighted TSE sequences, was superior to PET/CT for anatomic delineation and allocation of bone lesions. This finding might be of clinical relevance in selected cases--for example, primary bone tumors, early bone marrow infiltration, and tumors with low uptake on PET. Thus, a diagnostic T1-weighted TSE sequence is recommended as a routine protocol for oncologic PET/MR.

Recently, the combination of rituximab and bendamustine (R-Benda) has been defined as highly active in patients with follicular lymphomas, but little is known about the efficacy of R-Benda in mucosa-associated lymphoid tissue (MALT) lymphoma. In a retrospective analysis, we have defined 14 patients with MALT lymphoma undergoing therapy with R-Benda. Seven patients were female and seven male (aged 44-88 years), and all had relapsed extragastric MALT lymphoma. R-Benda was given at first relapse in ten patients, while four patients had more than two prior forms of therapy. Bendamustine was given at a dose of 90 mg/m(2) on days 2 and 3 in ten patients and at 70 mg/m(2) in three patients, while all received 375 mg/m(2) rituximab on day 1. Ten patients received six courses of therapy, while two patients discontinued therapy after three, and one after four courses for personal reasons, while one patient had progressive disease after four courses. Tolerance of therapy was excellent, and all except one patient responded. Ten patients achieved a complete remission (CR) (71 %), three a partial remission (21 %), while one patient progressed. Toxicities were mild and mainly hematological but did not result in relevant delays or the necessity for dose reductions. After a median follow-up of 23 months (range, 4-42+), 13 patients are alive and one patient has relapsed 23 months after initial CR. Our data suggest high activity and good tolerance of R-Benda in patients with relapsed MALT lymphoma despite intensive pretreatment in some patients. In view of this, prospective studies are warranted.

BACKGROUND:Orbital marginal zone B-cell lymphoma (OAML) constitutes for the most frequent diagnosis in orbital lymphoma. Relatively little data, however, have been reported in larger cohorts of patients staged in a uniform way and no therapy standard exists to date. MATERIAL AND METHODS/METHODS:We have retrospectively analyzed 60 patients diagnosed and treated at our institution 1999-2012. Median age at diagnosis was 64 years (IQR 51-75) and follow-up time 43 months (IQR 16-92). All patients had undergone uniform extensive staging and histological diagnosis was made by a reference pathologist according to the WHO classification. RESULTS:The majority of patients presented with stage IE (n = 40/60, 67%), three had IIE/IIIE and the remaining 17 stage IVE. Seven patients with IVE had bilateral orbital disease whereas the others showed involvement of further organs. Treatment data were available in 58 patients. Local treatment with radiotherapy (14/58, 24%) or surgery (3/58, 5%) resulted in response in 82% of patients. A total of 26 patients (45%) received systemic treatment with a response rate of 85%. Nine patients received antibiotics as initial therapy; response rate was 38%. Watchful-waiting was the initial approach in 6/58 patients. In total 28/58 patients (48%) progressed and were given further therapy. Median time-to-progression in this cohort was 20 months (IQR 9-39). There was no difference in time-to-progression after first-line therapy between the different therapy arms (p = 0.14). Elevated beta-2-microglobulin, plasmacytic differentiation, autoimmune disorder and site of lymphoma were not associated with a higher risk for progress. CONCLUSION/CONCLUSIONS:Our data underscore the excellent prognosis of OAML irrespective of initial therapy, as there was no significant difference in time-to-progression and response between local or systemic therapy. In the absence of randomized trials, the least toxic individual approach should be chosen for OAML.

The purpose of this study was to evaluate whether texture-based analysis of standard MRI sequences and diffusion-weighted imaging can help in the discrimination of parotid gland masses. The MR images of 38 patients with a biopsy- or surgery-proven parotid gland mass were retrospectively analyzed. All patients were examined on the same 3.0 Tesla MR unit, with one standard protocol. The ADC (apparent diffusion coefficient) values of the tumors were measured with three regions of interest (ROIs) covering the entire tumor. Texture-based analysis was performed with the texture analysis software MaZda (version 4.7), with ROI measurements covering the entire tumor in three slices. COC (co-occurrence matrix), RUN (run-length matrix), GRA (gradient), ARM (auto-regressive model), and WAV (wavelet transform) features were calculated for all ROIs. Three subsets of 10 texture features each were used for a linear discriminant analysis (LDA) in combination with k nearest neighbor classification (k-NN). Using histology as a standard of reference, benign tumors, including subtypes, and malignant tumors were compared with regard to ADC and texture-based values, with a one-way analysis of variance with post-hoc t-tests. Significant differences were found in the mean ADC values between Warthin tumors and pleomorphic adenomas, as well as between Warthin tumors and benign lesions. Contrast-enhanced T1-weighted images contained the most relevant textural information for the discrimination between benign and malignant parotid masses, and also for the discrimination between pleomorphic adenomas and Warthin tumors. STIR images contained the least relevant texture features, particularly for the discrimination between pleomorphic adenomas and Warthin tumors. Texture analysis proved to differentiate benign from malignant lesions, as well as pleomorphic adenomas from Warthin tumors, based on standard T(1w) sequences (without and with contrast). Of all benign parotid masses, Warthin tumors had significantly lower ADC values than the other entities.

PURPOSE/OBJECTIVE:To determine the feasibility of texture analysis for the classification of gastric adenocarcinoma, lymphoma, and gastrointestinal stromal tumors on contrast-enhanced hydrodynamic-MDCT images. MATERIALS AND METHODS/METHODS:The arterial phase scans of 47 patients with adenocarcinoma (AC) and a histologic tumor grade of [AC-G1, n=4, G1, n=4; AC-G2, n=7; AC-G3, n=16]; GIST, n=15; and lymphoma, n=5, and the venous phase scans of 48 patients with AC-G1, n=3; AC-G2, n=6; AC-G3, n=14; GIST, n=17; lymphoma, n=8, were retrospectively reviewed. Based on regions of interest, texture analysis was performed, and features derived from the gray-level histogram, run-length and co-occurrence matrix, absolute gradient, autoregressive model, and wavelet transform were calculated. Fisher coefficients, probability of classification error, average correlation coefficients, and mutual information coefficients were used to create combinations of texture features that were optimized for tumor differentiation. Linear discriminant analysis in combination with a k-nearest neighbor classifier was used for tumor classification. RESULTS:On arterial-phase scans, texture-based lesion classification was highly successful in differentiating between AC and lymphoma, and GIST and lymphoma, with misclassification rates of 3.1% and 0%, respectively. On venous-phase scans, texture-based classification was slightly less successful for AC vs. lymphoma (9.7% misclassification) and GIST vs. lymphoma (8% misclassification), but enabled the differentiation between AC and GIST (10% misclassification), and between the different grades of AC (4.4% misclassification). No texture feature combination was able to adequately distinguish between all three tumor types. CONCLUSION/CONCLUSIONS:Classification of different gastric tumors based on textural information may aid radiologists in establishing the correct diagnosis, at least in cases where the differential diagnosis can be narrowed down to two histological subtypes.

OBJECTIVES/OBJECTIVE:To compare fused gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI (diffusion-weighted imaging) for the assessment of abdominal neuroendocrine tumours (NETs). METHODS:Eighteen patients with suspected or histologically proven NETs of the abdomen were enrolled in this retrospective study. All patients underwent Ga-68-DOTANOC PET/CT for a primary search, staging, or restaging, and received an additional MRI, including dynamic gadoxetate-enhanced T1-weighted sequences and DWI (b-values 50, 300 and 600). Co-registered gadoxetate-enhanced PET/MRI and PET/DWI were separately analysed for NET lesions by a nuclear medicine physician and a radiologist in consensus. Sensitivity and specificity were calculated on a per-region, per-organ and per-patient basis. RESULTS:Eighty-seven out of 684 anatomical regions, and 23 out of 270 organs, were NET-positive in 14 out of 18 patients. Region-based sensitivities and specificities were 97.7 % and 99.7 % for gadoxetate-enhanced PET/MRI and 98.9 % and 99.7 % for PET/DWI. Organ-based sensitivities and specificities were 91.3 % and 99.6 % for gadoxetate-enhanced PET/MRI and 95.7 % and 99.6 % for PET/DWI. Finally, patient-based sensitivities and specificities were 100 % and 100 % for gadoxetate-enhanced PET/MRI and 100 % and 75 % for PET/DWI. Sensitivities and specificities of the two methods did not differ significantly. CONCLUSIONS:Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI are equally useful for the assessment of abdominal NETs. KEY POINTS/CONCLUSIONS:• Positron emission tomography and magnetic resonance imaging can both assess neuroendocrine tumours. • Fusion of PET/MR imaging provides helpful information. • Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI assess neuroendocrine tumours equally well. • PET/DWI is inherently simpler than gadoxetate-enhanced PET/MRI. • Only benign hepatic lesions pose a potential diagnostic dilemma for PET/DWI.

OBJECTIVES/OBJECTIVE:To determine, in patients with melanoma, the dependence of PET sensitivity on pulmonary metastasis size, and to determine patients who require further evaluation for definite staging. METHODS:Of 183 melanoma patients who underwent (18)F-fluorodeoxyglucose PET/computed tomography (CT) for staging or follow-up between January 2008 and June 2011, 38 patients (18 women and 20 men; mean age 62.0 ± 14.7 years) with one or more pulmonary metastases visible on CT were included in the retrospective study. Each pulmonary metastasis was rated as positive or negative on PET, and lesion size (maximum transverse diameter) was assessed on CT. PET sensitivity was calculated according to the lesions' size, in 2-mm steps. RESULTS:A total of 181 pulmonary metastases were analysed. PET sensitivity was 7.9 % for lesions of 4-5 mm; 33.3 % for lesions of 6-7 mm; 56.8 % for lesions of 8-9 mm; 63.6 % for lesions of 10-11 mm; 100 % for lesions of 12-14 mm; and 100 % for lesions of at least 15 mm. The differences in sensitivity between the size groups were significant (P < 0.001) CONCLUSIONS: With current state-of-the-art PET/CT technology, additional tests are necessary for definitive staging of melanoma patients who have one or more PET-negative lung nodules less than 12 mm in diameter on expiratory CT. KEY POINTS/CONCLUSIONS:• PET cannot rule out malignancy in pulmonary nodules less than 12 mm on expiratory CT. • Melanoma patients with PET-negative pulmonary nodules less than 12 mm require additional tests. • Knowledge of these factors can help interpretation of PET and PET/CT findings.

T(2) relaxation time mapping provides information about the biochemical status of intervertebral discs. The present study aimed to determine whether texture features extracted from T(2) maps or geometric parameters are sensitive to the presence of abnormalities at the posterior aspect of lumbar intervertebral discs, i.e. bulging and herniation. Thirty-one patients (21 women and 10 men; age range 18-51 years) with low back pain were enrolled. MRI of the lumbar spine at 3.0 Tesla included morphological T(1) - and T(2) -weighted fast spin-echo sequences, and multi-echo spin-echo sequences that were used to construct T(2) maps. On morphological MRI, discs were visually graded into 'normal', 'bulging' or 'herniation'. On T(2) maps, texture analysis (based on the co-occurrence matrix and wavelet transform) and geometry analysis of the discs were performed. The three T(2) texture features and geometric parameters best-suited for distinguishing between normal discs and discs with bulging or herniation were determined using Fisher coefficients. Statistical analysis comprised ANCOVA and post hoc t-tests. Eighty-two discs were classified as 'normal', 49 as 'bulging' and 20 showed 'herniation.' The T(2) texture features Entropy and Difference Variance, and all three pre-selected geometric parameters differed significantly between normal and bulging, normal and herniated, and bulging and herniated discs (p < 0.05). These findings suggest that T(2) texture features and geometric parameters are sensitive to the presence of abnormalities at the posterior aspect of lumbar intervertebral discs, and may thus be useful as quantitative biomarkers that predict disease.

OBJECTIVES/OBJECTIVE:To determine the value of intravenous contrast medium in (68)Ga-DOTA-Phe(1)-Tyr(3)-octreotide - (68)Ga-DOTATOC - PET/CT for the detection of abdominal neuroendocrine tumours (NET). METHODS:In fifty-five patients with known or suspected NETs of the abdomen PET/CT was performed on a 64-row multi-detector hybrid system. For PET, 150 MBq of (68)Ga-DOTATOC were injected intravenously. Full-dose unenhanced, and arterial- and venous-phase contrast-enhanced CT images were obtained. Unenhanced and contrast-enhanced PET/CT images were evaluated separately for the presence of NETs on a per-region basis, by two separate teams with different experience levels. RESULTS:On unenhanced PET/CT, sensitivity and specificity ranged from 89.3% (junior team) to 92% (senior team), and 99.1% (junior team) to 99.2% (senior team), respectively. On contrast-enhanced PET/CT, sensitivity and specificity ranged from 92.3% (junior team) to 98.5% (senior team), and 99.4% (junior team) to 99.5% (senior team), respectively. These increases in sensitivity and specificity, due to the use of contrast-enhanced images, were statistically significant (P < 0.05). CONCLUSIONS:Intravenous contrast medium only moderately, aleit significantly, improves the sensitivity of (68)Ga-DOTATOC PET/CT for the detection of abdominal NETs, and hardly affects specificity. Thus, while contrast enhancement is justified to achieve maximum sensitivity, unenhanced images may be sufficient for routine PET/CT in NET patients. KEY POINTS/CONCLUSIONS:Contrast media moderately improve the sensitivity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. Contrast media hardly affect the specificity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. Unenhanced PET/CT is sufficient for routine imaging of patients with neuroendocrine tumours.