Combined PET/MRI: Multi-modality Multi-parametric Imaging Is Here: Summary Report of the 4th International Workshop on PET/MR Imaging; February 23-27, 2015, Tübingen, Germany.

This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both technical versatility and acceptance by clinical and research-driven users from the status quo of last year. Still, with only minimal evidence of progress made in exploiting the true complementary nature of the PET and MRI-based information, PET/MRI is still yet to achieve its potential. In that regard, the conclusion of last year's meeting "the real work has just started" still holds true.

Combined PET/MR: The Real Work Has Just Started. Summary Report of the Third International Workshop on PET/MR Imaging; February 17-21, 2014, Tübingen, Germany.

This paper summarises the proceedings and discussions at the third annual workshop held in Tübingen, Germany, dedicated to the advancement of the technical, scientific and clinical applications of combined PET/MRI systems in humans. Two days of basic scientific and technical instructions with "hands-on" tutorials were followed by 3 days of invited presentations from active researchers in this and associated fields augmented by round-table discussions and dialogue boards with specific themes. These included the use of PET/MRI in paediatric oncology and in adult neurology, oncology and cardiology, the development of multi-parametric analyses, and efforts to standardise PET/MRI examinations to allow pooling of data for evaluating the technology. A poll taken on the final day demonstrated that over 50 % of those present felt that while PET/MRI technology underwent an inevitable slump after its much-anticipated initial launch, it was now entering a period of slow, progressive development, with new key applications emerging. In particular, researchers are focusing on exploiting the complementary nature of the physiological (PET) and biochemical (MRI/MRS) data within the morphological framework (MRI) that these devices can provide. Much of the discussion was summed up on the final day when one speaker commented on the state of PET/MRI: "the real work has just started".

[Fine-needle aspiration cytology of thyroid nodules: molecular diagnostics in a routine diagnostic setting]. / Feinnadelzytologie von Schilddrüsenknoten: Molekulare Diagnostik in der klinischen Routine.

BACKGROUND AND OBJECTIVE: Results for the detection of point mutations and rearrangements have thus far been obtained by fresh material of fine needle aspiration cytology (FNAC). After a first retrospective study we report on the diagnostic detection in routinely obtained, consecutive air-dried FNAC smears. METHODS: RNA and DNA was extracted from 154 consecutive routine air-dried FNAC smears: 80 with microfollicular proliferation (MFP), 45 with follicular neoplasia (FN), 26 with the cytological diagnosis of papillary carcinomas (PTC) and 3 which were suspicious for malignancy. PAX8/PPARG and RET/PTC3 rearrangements were detected by qPCR, while BRAF and RAS point mutations were detected by pyrosequencing. RESULTS: Only 0.7 % and 5.3 % of the routine air-dried FNAC samples did not allow analysis of a point mutation or rearrangements, respectively. NRAS mutations could be detected in 7 MFP smears, and in one of FN and PTC samples, respectively. HRAS mutations were detected in one MPF and one FN sample. A KRAS mutation was only detected in one FN sample, whereas BRAF mutations were detected in 20 samples with PTC (but in no other sample). PAX8/PPARG was detected in 2 MFP samples, while RET/PTC was detected in only one MFP sample. In total, 13.8 % MFP-FNAC, 6.7 % FN-FNAC, and 80.8 % PTC-FNAC samples harbored a mutation. CONCLUSION: These results demonstrate that rearrangements and point mutations can be detected in routinely obtained air-dried FNAC samples.

[Nuclear medicine in Europe: education]. / Nuklearmedizin in Europa. Die Ausbildungssituation.

The technical developments that have taken place in the preceding years (PET, hybrid imaging) have changed nuclear medicine. The future cooperation with radiologists will be challenging as well as positioning nuclear medicine in an European context. It can also be expected that education in nuclear medicine will undergo a harmonization process in the states of the European Union. In this paper, we describe how nuclear medicine education is organized in several European countries. We aim to stimulate constructive discussions on the future development of the specialization in nuclear medicine in Germany.

FDG-PET/CT in pediatric solid tumors.

Positron emission tomography/computed tomography (PET/CT) has become an important imaging modality in the non-invasive evaluation and monitoring of children with known or suspected malignant diseases. In sarcoma patients, [18F]FDG (FDG) PET and FDG PET/CT is useful in staging, therapy monitoring, and detection of relapse. However, FDG PET has been proven to be less sensitive than chest CT in the detection of pulmonary metastases derived from sarcoma. This disadvantage has been overcome using a PET/CT scanner. In neuroblastoma patients, PET using FDG is indicated in MIBG-negative cases. Furthermore, there are specific PET tracers for tumors of the sympathetic nervous system, such as [11C]Hydroxyephedrine (HED) and [18F]-labeled dihydrophenylalanine (F-DOPA), which can be used for PET/CT imaging for detection of disease, staging and monitoring therapy. However, there are only few studies using specific PET tracers in neuroblastoma patients. In other pediatric malignancies including germ cell tumors and hepatoblastoma PET and PET/CT may be helpful in individual cases, but the literature in these entities is limited so far. Although publications on the additional value of the combined PET/CT compared to both stand-alone modalities are still limited in pediatrics, it can already be anticipated that the combination of morphological and functional information obtained by integrated PET/CT will improve the accuracy of staging and will change patient management in a significant number of pediatric patients.

PET surveillance of patients with Ewing sarcomas of the trunk: Must the lower legs be included?

AIM: FDG-PET(/CT) is frequently used in surveillance of Ewing sarcoma (ES) patients. Since ES and PNET (primitive neuroectodermal tumours) may cause peripheral metastases some centers routinely recommend whole body PET acquisition from head to toe what may necessitate repositioning of the patient and thus extending examination time. It is not clear yet whether inclusion of lower leg adds to the diagnostic accuracy of PET scanning, especially in primary tumors of the trunk. PATIENTS, METHOD: 40 patients with ES and PNET of the trunk who were referred for surveillance after primary therapy with complete remission, were evaluated retrospectively: 27 men, 13 women; mean age at diagnosis 16.3 (3-35) years. At the time of diagnosis 28 patients had localized and 12 metastatic disease. Almost all of the patients had undergone a combined chemotherapy with surgery or/and radiotherapy. 156 follow-up PET scans of the legs of these patients were evaluated retrospectively. RESULTS: only in three (1.9%) of 156 scans a pathologic FDG accumulation was attributed to metastatic disease of the lower extremities. In these cases the observation of metastatic disease in the legs did not alter therapy, since in all three cases a multifocal disease progression was observed. CONCLUSION: scanning of the lower legs may be omitted during follow-up in patients in whom the primary tumor was located in the trunk and in whom no clinical signs pointing to metastases in the lower legs are present. This provides a sufficient diagnostic power and a shorter examination time, thus increasing patient comfort and scanner availability.

[Procedure guidelines for whole-body 18F-FDG PET and PET/CT in children with malignant diseases]. / Empfehlungen zur Durchführung der Ganzkörper-18F-FDG-PET und -PET/CT bei Kindern mit onkologischen Erkrankungen. Anpassung der EANM-Guideline an aktuelle Gegebenheiten in Deutschland.

The purpose of these guidelines is to offer the nuclear medicine and the appropriate interdisciplinary team a framework for performing and reporting positron emission tomography (PET) and the combination with computed tomography (PET/CT) in children with malignant diseases mainly using the radiopharmaceutical 18F-fluorodeoxy-glucose (FDG). These guidelines are based on the recent guidelines of the Paediatric Committee of the European Association of Nuclear Medicine (EANM) (57) and have been translated and adapted to the current conditions in Germany. The adaptation of CT-parameters using PET/CT in children is covered in a more detailed way than in the EANM guideline taking into account that in Germany already a good portion of PET examinations is performed using an integrated PET/CT-scanner. Furthermore, a CT-scan without adoption of the CT acquisition parameters would result in a not tolerably high radiation exposition of the child. There are excellent guidelines for FDG PET and PET/CT in oncology published by the German Society of Nuclear Medicine (Deutsche Gesellschaft für Nuklearmedizin, DGN) (42) and EANM (4). These guidelines aim at providing additional information on issues particularly relevant to PET and PET/CT imaging in children. These guidelines should be taken in the context of local and national current standards of quality and rules.

Guidelines for 18F-FDG PET and PET-CT imaging in paediatric oncology.

OBJECTIVE: The purpose of these guidelines is to offer to the nuclear medicine team a framework that could prove helpful in daily practice. These guidelines contain information related to the indications, acquisition, processing and interpretation of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) in paediatric oncology. The Oncology Committee of the European Association of Nuclear Medicine (EANM) has published excellent procedure guidelines on tumour imaging with (18)F-FDG PET (Bombardieri et al., Eur J Nucl Med Mol Imaging 30:BP115-24, 2003). These guidelines, published by the EANM Paediatric Committee, do not intend to compete with the existing guidelines, but rather aim at providing additional information on issues particularly relevant to PET imaging of children with cancer. CONCLUSION: The guidelines summarize the views of the Paediatric Committee of the European Association of Nuclear Medicine. They should be taken in the context of "good practice" of nuclear medicine and of any national rules, which may apply to nuclear medicine examinations. The recommendations of these guidelines cannot be applied to all patients in all practice settings. The guidelines should not be deemed inclusive of all proper procedures or exclusive of other procedures reasonably directed to obtaining the same results.

The new EANM paediatric dosage card: additional notes with respect to F-18.

INTRODUCTION: The previously published European Association of Nuclear Medicine (EANM) paediatric dosage card recommends 70 MBq F-18 or F-18 Fluoro-2-Deoxyglucose (F-18-FDG) as the "minimum recommended activity". DISCUSSION: Two recent publications demonstrate that when utilising F-18-labelled radiopharmaceuticals the administration of lower activities for small children is possible without losing image quality. CONCLUSION: In the light of these findings the EANM dosimetry and paediatrics committee have decided to reduce the value for the "minimum recommended activity" for both F-18 and F-18-FDG to 26 MBq for 2D- and 14 MBq for 3D-acquisitions.

[18F]-FDG-PET in clinical stage I/II non-seminomatous germ cell tumours: results of the German multicentre trial.

PURPOSE: The aim of this study was to determine the predictive values of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in primary staging in patients with newly diagnosed non-seminomatous germ cell tumour (NSGCT) clinical stage I/II. PATIENTS AND METHODS: The hypothesis was that FDG-PET would improve the negative predictive value (NPV) from 70% to 90%, thus requiring a total of 169 patients. All scans underwent visual analysis by a reference team of nuclear medicine physicians. Results were validated by histology following retroperitoneal lymph node dissection. RESULTS: Only 72 of the planned 169 patients were included, due to poor accrual. The prevalence of nodal involvement was 26%. Correct nodal staging by FDG-PET was achieved in 83% compared with correct computed tomography (CT) staging in 71%. CT had a sensitivity and specificity of 41% and 95%, respectively. Positive predictive value (PPV) and NPV were 87% and 67%, respectively. FDG-PET had a sensitivity and specificity of 66% and 98%, respectively. PPV was 95%. The primary end point was not reached, with an NPV of 78%. CONCLUSION: FDG-PET as a primary staging tool for NSGCT yielded only slightly better results than CT. Both methods had a high specificity while false-negative findings were more frequent with CT. FDG-PET is mostly useful as a diagnostic tool in case of questionable CT scan.

[Procedure guidelines for MIBG-scintigraphy in children].

The German translation of the EANM guideline for MIBG scintigraphy in children (Olivier P et al. EJNM MI 2003; 30: B45-B50; Hahn K. Der Nuklearmediziner 2002; 25: 101-105) was reviewed and actualized according to current publications, legal requirements and conditions in Germany. For the first time this guideline was generated in consensus with the neuroblastoma study group of the Association of Paediatric Haematologie and Oncology (GPOH) with the result of an interdisciplinary recommendation. Further main alterations are related to the recommended (123)I activities with respect to the new EANM Paediatric Dosage Card and the explicit recommendation of SPECT.

Whole-body imaging of oncologic patients using 16-channel PET-CT. Evaluation of an i.v. contrast enhanced MDCT protocol.

AIM: This study evaluated a MDCT protocol for contrast-enhanced 16-channel PET-CT with regard to scan range and duration of a whole-body (18)F-FDG PET-CT examination, the occurrence of contrast-material induced artefacts and quantitative assessment of CT attenuation. PATIENTS, METHODS: 205 patients (51.9+/-12.4 years) with different malignant tumours underwent whole-body PET-CT; the study protocol had been approved by the institutional review board. Contrast-enhanced MDCT (16 x 1.5 mm; 120 ml Iomeprol 3 ml/s, 50 ml saline chaser bolus, scan delay 70 s; oral contrast) was also used for attenuation correction. From MDCT data mean scan range and duration, occurrence of contrast media-induced artefacts, and mean CT densities of jugular (jv) and subclavian (scv), superior (vcs) and inferior (vci) caval, portal (pv), and bilateral external iliac veins, pulmonary (ap) and iliac arteries, descending thoracic and abdominal aorta, all cardiac chambers, as well as both liver lobes, spleen, adrenal glands and kidneys were determined. RESULTS: Attenuation corrected PET images were free of contrast media-related image artefacts. Homogeneous contrast enhancement was found in the mediastinal veins (right/left jv 171+/-34/171+/-35, scv 127+/-50/127+/-40, vcs 153+/-36 HU) and arteries (e.g. ap 145+/-26/151+/-26). Cardiac chambers, abdominal vessels (e.g. vci 138+/-24, pv 159+/-25 HU), and parenchymal organs revealed sufficient and homogenous contrast-enhancement in all cases. No beam-hardening artefacts occurred in the neighbourhood of the subclavian veins. CONCLUSION: The chosen whole-body (18)F-FDG 16-slice PET-CT protocol allowed for craniocaudal CT scanning with high vessel and parenchymal contrast revealing no IV contrast-media induced artefacts in attenuation-corrected PET data sets.

[Procedure guideline for radioiodine therapy and 131iodine whole-body scintigraphy in paediatric patients with differentiated thyroid cancer]. / Verfahrensanweisung zur Radioiodtherapie und 131I-Ganzkörperszintigraphie bei differenzierten Schilddrüsenkarzinomen im Kindes- und Jugendalter.

The procedure guideline for radioiodine ((131)I) therapy and (131)I whole-body scintigraphy of differentiated thyroid cancer in paediatric patients is the counterpart to the procedure guidelines (version 3) for adult patients and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Characteristics of thyroid cancer in children are the higher aggressiveness of papillary thyroid cancer, the higher frequency of extrathyroidal extension and of disseminated pulmonary metastases as well as the high risk of local recurrences. Radioiodine therapy is generally recommended in children, the (131)I activity depends on the children's body weight. Radioiodine ablation in children with small papillary cancer (< or =1 cm) should be considered. TSH stimulation is reached two weeks (children) or three weeks (adolescents) after withdrawal of thyroid hormones. Anti-emetic drugs are highly recommended. CT of the chest and examination of pulmonary function are clearly indicated if there is any suspicion on metastases. 3-6 months after (131)I ablation, the (131)I whole-body scintigraphy is highly recommended as lymph node metastases are frequently detected in paediatric patients. Follow-up care should be arranged in shorter intervals than in adults to test the compliance and to adapt dosage of thyroid hormones to the children's body weight. Reference values of fT3 are higher in children than in adults. Evidence is insufficient to describe in which constellation the TSH may be kept within the low normal level. Therefore, TSH suppression is generally recommended.

The new EANM paediatric dosage card.

INTRODUCTION: In a recent publication, Jacobs et al. proposed the use of three tracer-dependent dosage cards for paediatric nuclear medicine. MATERIALS AND METHODS: Based upon this work, the EANM dosimetry and paediatrics committees introduce a condensed and revised version of this dosage card for major nuclear medicine paediatric diagnostic procedures, replacing the previous card by Piepsz et al. and including a set of minimum activities. RESULTS: The activities to be administered result in weight-independent effective doses to the children. In addition, the introduction of minimum activities guarantees a minimum standard of image quality throughout Europe and avoids a variety of administered activities in children of the same weight in different countries, which was the case when using the previous EANM dosage card.

High diagnostic value of 18F-FDG-PET in pediatric patients with chronic inflammatory bowel disease.

Diagnosis of chronic inflammatory bowel disease (IBD) in children requires noninvasive, atraumatic diagnostic tools that depict localization and acuity of inflammation and yield only a low radiation dose. This retrospective analysis evaluates the diagnostic potential of FDG-PET. Twenty-six consecutive FDG-PET scans of 23 patients (age: 2-16, years, 14 M, 9 F) with suspected IBD were analyzed in this retrospective study. Results were compared to endoscopic, histologic, and abdominal ultrasound (US) finding. In these examinations, presence of inflammation was evaluated in each patient in 8 bowel segments (score 1-4). Standardized uptake values (SUVs) for FDG-PET were measured for all segments. Sensitivity, specificity, and accuracy were calculated using histology as the standard of reference on a segment-based analysis (pathologic if inflammation score > or = 3 or SUV(max)/SUV(liver)>1.2). With histology as the standard of reference, FDG-PET showed a sensitivity/specificity/accuracy of 98%/68%/8%/3 as compared to endoscopy (90%/75%/82%) and US (56%/92%/75%). For the small bowel, FDG-PET was even more reliable (100%/86%/90%). Because of its high sensitivity and accuracy,FDG-PET is an excellent, noninvasive diagnostic tool for IBD. Depicting inflammation in the whole bowel, while being not traumatic, it is attractive for use especially in children. FDG-PET is especially reliable for the small bowel and can inform application of topical therapy.

Mucinous cystadenocarcinoma--an extremely rare tumor in a young patient.

We report on an extremely rare case of pulmonary mucinous cystadenocarcinoma. A 29-year-old male patient was admitted because of progressive enlargement of a right lower lobe mass over a period of 10 years. Right lower lobectomy was performed after a malignant mucinous cystadenocarcinoma was diagnosed by intraoperative frozen section. PET and CT scans did not detect metastatic disease. This case is the youngest patient reported so far with a malignant pulmonary mucinous cystadenocarcinoma and highlights the importance of close follow-up of indeterminate pulmonary nodules in patients with unremarkable history.

Tumor staging using whole-body high-resolution 16-channel PET-CT: does additional low-dose chest CT in inspiration improve the detection of solitary pulmonary nodules?

For optimal image fusion between CT and F-18-FDG-PET, the acquisition of CT images is performed in mild expiratory suspension, which might compromise the detection of lung metastases. This study aimed at evaluating the influence of expiration on the detection of solitary pulmonary nodules (SPN) and at assessing if additional inspiratory low-dose CT (I-LDCT) of the chest can improve the detection of potential lung metastases performing whole-body 16-channel PET-CT. Sixty-six patients with malignant tumors underwent PET-CT: contrast-enhanced CT was acquired during mild expiration and was used for fusion with PET images; additionally, chest I-LDCT was performed at deep inspiration. Two radiologists reported all SPN detected at I-LDCT and the expiratory CT scan independently. Overall, 53% of 128 SPN (mean: 3.8+/-0.2 mm) were detected at both respiratory states: 51 SPN only at I-LDCT, and 9 nodules only at expiratory CT. Of the SPN, 117/128 were classified as certain; 45 of those were additionally detected at I-LDCT, and 6 nodules at expiratory CT. A 100% detection rate was reached in SPN >4 mm at I-LDCT versus >8 mm at expiratory CT (all P<0.001). Additional I-LDCT of the chest significantly improves the detection of SPN at whole-body F-18-FDG-PET-CT and thus is recommended as part of the standard protocol for oncological patients.