Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling.

A head coil system with an integrated orbiting transmission point source mechanism for attenuation correction in PET/MRI.

The combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) provides a benefit for diagnostic imaging. Still, attenuation correction (AC) is a challenge in PET/MRI compared to stand-alone PET and PET-computed tomography (PET/CT). In the absence of photonic transmission sources, AC in PET/MRI is usually based on retrospective segmentation of MR images or complex additional MR-sequences. However, most methods available today are still challenged by either the incorporation of cortical bone or substantial anatomical variations of subjects. This leads to a bias in quantification of tracer concentration in PET. Therefore, we have developed a fully integrated transmission source system for PET/MRI of the head to enable direct measurement of attenuation coefficients using external positron emitters, which is the reference standard in AC. Based on a setup called the 'liquid drive' presented by Jones et al (1995) two decades ago, we built a head coil system consisting of an MR-compatible hydraulic system driving a point source on a helical path around a 24-channel MR-receiver coil to perform a transmission scan. Sinogram windowing of the moving source allows for post-injection measurements. The prototype was tested in the Siemens Biograph mMR using a homogeneous water phantom and a phantom with air cavities and a Teflon (PTFE) cylinder. The second phantom was measured both with and without emission activity. For both measurements air, water and Teflon were clearly distinguishable and homogeneous regions of the phantom were successfully reproduced in the AC map. For water the linear attenuation coefficient was measured as (0.096 ± 0.005) cm-1 in accordance with the true physical value. This combined MR head coil and transmission source system is, to our knowledge, the first working example to use an orbiting point source in PET/MRI and may be helpful in providing fully-quantitative PET data in neuro-PET/MRI.

An international survey on hybrid imaging: do technology advances preempt our training and education efforts?

BACKGROUND: Hybrid PET/CT and PET/MRI are increasingly important technologies in the evaluation of malignancy and require cooperation between radiologists and specialists in molecular imaging. The aim of our study was to probe the mindsets of radiological and nuclear medicine professionals in regard to current hybrid imaging practice and to assess relevant training aspirations and perceived shortfalls, particularly amongst young professionals. In this context, we initiated an international survey on "Hybrid Imaging Training". METHODS: An online survey was prepared on-line and launched on October-2, 2016. It was composed of 17 multiple-choice and open questions regarding the professional background, a perspective on hybrid imaging training efforts and lessons to be learned from disparate craft groups. The survey ran for 2 weeks. We report total responses per category and individual free-text responses. RESULTS: In total, 248 responses were collected with a mean age of all responders of (41 ± 11) y. Overall, 36% were within the target age range of (20-35) y. Across all responders, the majority (72%) commented on there being too few hybrid imaging experts in their country, whereas only 1% said that there were too many. Three quarters of the responders were in favour of a curriculum allowing sub-specialisation in hybrid imaging. With respect to reporting of hybrid imaging, confidence increased with age. The average rating across all responders on the level of cooperation among the two specialties suggested a low overall level of satisfaction. However, the survey feedback indicated the local (on-site) cooperation being somewhat better than the perceived cooperation between the relevant associations on a European level. CONCLUSION: We consider these results to represent an appropriate cross-section of professional opinions of imaging experts across different demographic and hierarchical levels. Collectively they provide evidence supporting a need to address current shortfalls in developing hybrid imaging expertise through national educational plans, and, thus, contribute to helping improve patient care.

Impact of motion compensation and partial volume correction for 18F-NaF PET/CT imaging of coronary plaque.

Recent studies have suggested that 18F-NaF-PET enables visualization and quantification of plaque micro-calcification in the coronary tree. However, PET imaging of plaque calcification in the coronary arteries is challenging because of the respiratory and cardiac motion as well as partial volume effects. The objective of this work is to implement an image reconstruction framework, which incorporates compensation for respiratory as well as cardiac motion (MoCo) and partial volume correction (PVC), for cardiac 18F-NaF PET imaging in PET/CT. We evaluated the effect of MoCo and PVC on the quantification of vulnerable plaques in the coronary arteries. Realistic simulations (Biograph TPTV, Biograph mCT) and phantom acquisitions (Biograph mCT) were used for these evaluations. Different uptake values in the calcified plaques were evaluated in the simulations, while three 'plaque-type' lesions of 36, 31 and 18 mm3 were included in the phantom experiments. After validation, the MoCo and PVC methods were applied in four pilot NaF-PET patient studies. In all cases, the MoCo-based image reconstruction was performed using the STIR software. The PVC was obtained from a local projection (LP) method, previously evaluated in preclinical and clinical PET. The results obtained show a significant increase of the measured lesion-to-background ratios (LBR) in the MoCo + PVC images. These ratios were further enhanced when using directly the tissue-activities from the LP method, making this approach more suitable for the quantitative evaluation of coronary plaques. When using the LP method on the MoCo images, LBR increased between 200% and 1119% in the simulated data, between 212% and 614% in the phantom experiments and between 46% and 373% in the plaques with positive uptake observed in the pilot patients. In conclusion, we have built and validated a STIR framework incorporating MoCo and PVC for 18F-NaF PET imaging of coronary plaques. First results indicate an improved quantification of plaque-type lesions.

Combined PET/MRI: from Status Quo to Status Go. Summary Report of the Fifth International Workshop on PET/MR Imaging; February 15-19, 2016; Tübingen, Germany.

This article provides a collaborative perspective of the discussions and conclusions from the fifth international workshop of combined positron emission tomorgraphy (PET)/magnetic resonance imaging (MRI) that was held in Tübingen, Germany, from February 15 to 19, 2016. Specifically, we summarise the second part of the workshop made up of invited presentations from active researchers in the field of PET/MRI and associated fields augmented by round table discussions and dialogue boards with specific topics. This year, this included practical advice as to possible approaches to moving PET/MRI into clinical routine, the use of PET/MRI in brain receptor imaging, in assessing cardiovascular diseases, cancer, infection, and inflammatory diseases. To address perceived challenges still remaining to innovatively integrate PET and MRI system technologies, a dedicated round table session brought together key representatives from industry and academia who were engaged with either the conceptualisation or early adoption of hybrid PET/MRI systems. Discussions during the workshop highlighted that emerging unique applications of PET/MRI such as the ability to provide multi-parametric quantitative and visual information which will enable not only overall disease detection but also disease characterisation would eventually be regarded as compelling arguments for the adoption of PET/MR. However, as indicated by previous workshops, evidence in favour of this observation is only growing slowly, mainly due to the ongoing inability to pool data cohorts from independent trials as well as different systems and sites. The participants emphasised that moving from status quo to status go entails the need to adopt standardised imaging procedures and the readiness to act together prospectively across multiple PET/MRI sites and vendors.

32nd International Austrian Winter Symposium : Zell am See, the Netherlands. 20-23 January 2016.

TABLE OF CONTENTS: A1 68Ga-PSMA PET/CT in staging and restaging of Prostate Cancer Patients: comparative study with 18F-Choline PET/CTW Langsteger, A Rezaee, W Loidl, HS Geinitz, F Fitz, M Steinmair, G Broinger, L Pallwien-Prettner, M BeheshtiA2 F18 Choline PET - CT: an accurate diagnostic tool for the detection of parathyroid adenoma?L Imamovic, M Beheshti, G Rendl, D Hackl, O Tsybrovsky, M Steinmair, K Emmanuel, F Moinfar, C Pirich, W LangstegerA3 [18F]Fluoro-DOPA-PET/CT in the primary diagnosis of medullary thyroid carcinomaA Bytyqi, G Karanikas, M Mayerhöfer, O Koperek, B Niederle, M HartenbachA4 Variations of clinical PET/MR operations: An international survey on the clinical utilization of PET/MRIT Beyer, K Herrmann, J CzerninA5 Standard Dixon-based attenuation correction in combined PET/MRI: Reproducibility and the possibility of Lean body mass estimationI Rausch, P Rust, MD DiFranco, M Lassen, A Stadlbauer, ME Mayerhöfer, M Hartenbach, M Hacker, T BeyerA6 High resolution digital FDG PET/MRI imaging for assessment of ACL graft viabilityK Binzel, R Magnussen, W Wei, MU Knopp, DC Flanigan, C Kaeding, MV KnoppA7 Using pre-existing hematotoxicity as predictor for severe side effects and number of treatment cycles of Xofigo therapyA Leisser, M Nejabat, M Hartenbach, G Kramer, M Krainer, M Hacker, A HaugA8 QDOSE - comprehensive software solution for internal dose assessmentWencke Lehnert, Karl Schmidt, Sharok Kimiaei, Marcus Bronzel, Andreas KlugeA9 Clinical impact of Time-of-Flight on next-generation digital PET imaging of Yttrium-90 radioactivity following liver radioembolizationCL Wright, K Binzel, J Zhang, Evan Wuthrick, Piotr Maniawski, MV KnoppA10 Snakes in patients! Lessons learned from programming active contours for automated organ segmentationM Blaickner, E Rados, A Huber, M Dulovits, H Kulkarni, S Wiessalla, C Schuchardt, RP Baum, B Knäusl, D GeorgA11 Influence of a genetic polymorphism on brain uptake of the dual ABCB1/ABCG2 substrate [11C]tariquidarM Bauer, B Wulkersdorfer, W Wadsak, C Philippe, H Haslacher, M Zeitlinger, O LangerA12 Outcome prediction of temporal lobe epilepsy surgery from P-glycoprotein activity. Pooled analysis of (R)-[11C]-verapamil PET data from two European centresM Bauer, M Feldmann, R Karch, W Wadsak, M Zeitlinger, MJ Koepp, M-C Asselin, E Pataraia, O LangerA13 In-vitro and in-vivo characterization of [18F]FE@SNAP and derivatives for the visualization of the melanin concentrating hormone receptor 1M Zeilinger, C Philippe, M Dumanic, F Pichler, J Pilz, M Hacker, W Wadsak, M MitterhauserA14 Reducing time in quality control leads to higher specific radioactivity of short-lived radiotracersL Nics, B Steiner, M Hacker, M Mitterhauser, W WadsakA15 In vitro 11C-erlotinib binding experiments in cancer cell lines with epidermal growth factor receptor mutationsA Traxl, Thomas Wanek, Kushtrim Kryeziu, Severin Mairinger, Johann Stanek, Walter Berger, Claudia Kuntner, Oliver LangerA16 7-[11C]methyl-6-bromopurine, a PET tracer to measure brain Mrp1 function: radiosynthesis and first PET evaluation in miceS Mairinger, T Wanek, A Traxl, M Krohn, J Stanek, T Filip, M Sauberer, C Kuntner, J Pahnke, O LangerA17 18F labeled azidoglucose derivatives as "click" agents for pretargeted PET imagingD Svatunek, C Denk, M Wilkovitsch, T Wanek, T Filip, C Kuntner-Hannes, J Fröhlich, H MikulaA18 Bioorthogonal tools for PET imaging: development of radiolabeled 1,2,4,5-TetrazinesC Denk, D Svatunek, T Wanek, S Mairinger, J Stanek, T Filip, J Fröhlich, H Mikula, C Kuntner-HannesA19 Preclinical evaluation of [18F]FE@SUPPY- a new PET-tracer for oncologyT Balber, J Singer, J Fazekas, C Rami-Mark, N Berroterán-Infante, E Jensen-Jarolim, W Wadsak, M Hacker, H Viernstein, M MitterhauserA20 Investigation of Small [18F]-Fluoroalkylazides for Rapid Radiolabeling and In Vivo Click ChemistryC Denk, D Svatunek, B Sohr, H Mikula, J Fröhlich, T Wanek, C Kuntner-Hannes, T FilipA21 Microfluidic 68Ga-radiolabeling of PSMA-HBED-CC using a flow-through reactorS Pfaff, C Philippe, M Mitterhauser, M Hartenbach, M Hacker, W WadsakA22 Influence of 24-nor-ursodeoxycholic acid on hepatic disposition of [18F]ciprofloxacin measured with positron emission tomographyT Wanek, E Halilbasic, M Visentin, S Mairinger, B Stieger, C Kuntner, M Trauner, O LangerA23 Automated 18F-flumazenil production using chemically resistant disposable cassettesP Lam, M Aistleitner, R Eichinger, C ArtnerA24 Similarities and differences in the synthesis and quality control of 177Lu-DOTA-TATE, 177Lu -HA-DOTA-TATE and 177Lu-DOTA-PSMA (PSMA-617)H Eidherr, C Vraka, A Haug, M Mitterhauser, L Nics, M Hartenbach, M Hacker, W WadsakA25 68Ga- and 177Lu-labelling of PSMA-617H Kvaternik, R Müller, D Hausberger, C Zink, RM AignerA26 Radiolabelling of liposomes with 67Ga and biodistribution studies after administration by an aerosol inhalation systemU Cossío, M Asensio, A Montes, S Akhtar, Y te Welscher, R van Nostrum, V Gómez-Vallejo, J LlopA27 Fully automated quantification of DaTscan SPECT: Integration of age and gender differencesF VandeVyver, T Barclay, N Lippens, M TrochA28 Lesion-to-background ratio in co-registered 18F-FET PET/MR imaging - is it a valuable tool to differentiate between low grade and high grade brain tumor?L Hehenwarter, B Egger, J Holzmannhofer, M Rodrigues-Radischat, C PirichA29 [11C]-methionine PET in gliomas - a retrospective data analysis of 166 patientsN Pötsch, I Rausch, D Wilhelm, M Weber, J Furtner, G Karanikas, A Wöhrer, M Mitterhauser, M Hacker, T Traub-WeidingerA30 18F-Fluorocholine versus 18F-Fluorodeoxyglucose for PET/CT imaging in patients with relapsed or progressive multiple myeloma: a pilot studyT Cassou-Mounat, S Balogova, V Nataf, M Calzada, V Huchet, K Kerrou, J-Y Devaux, M Mohty, L Garderet, J-N TalbotA31 Prognostic benefit of additional SPECT/CT in sentinel lymph node mapping of breast cancer patientsS Stanzel, G Pregartner, T Schwarz, V Bjelic-Radisic, B Liegl-Atzwanger, R AignerA32 Evaluation of diagnostic value of TOF-18F-FDG PET/CT in patients with suspected pancreatic cancerS Stanzel, F Quehenberger, RM AignerA33 New quantification method for diagnosis of primary hyperpatahyroidism lesions and differential diagnosis vs thyropid nodular disease in dynamic scintigraphyA Koljevic Markovic, Milica Jankovic, V Miler Jerkovic, M Paskas, G Pupic, R Dzodic, D PopovicA34 A rare case of diffuse pancreatic involvement in patient with merkel cell carcinoma detected by 18F-FDGMC Fornito, D FamiliariA35 TSH-stimulated 18F-FDG PET/CT in the diagnosis of recurrent/metastatic radioiodine-negative differentiated thyroid carcinomas in patients with various thyroglobuline levelsP Koranda, H Polzerová, I Metelková, L Henzlová, R Formánek, E Buriánková, M KamínekA36 Breast Dose from lactation following I131 treatmentWH Thomson, C LewisA37 A new concept for performing SeHCAT studies with the gamma cameraWH Thomson, J O'Brien, G James, A NotghiA38 Whole body F-18-FDG-PET and tuberculosis: sensitivity compared to x-ray-CTH Huber, I Stelzmüller, R Wunn, M Mandl, F Fellner, B Lamprecht, M GabrielA39 Emerging role 18F-FDG PET-CT in the diagnosis and follow-up of the infection in heartware ventricular assist system (HVAD)MC Fornito, G LeonardiA40 Validation of Poisson resampling softwareWH Thomson, J O'Brien, G JamesA41 Protection of PET nuclear medicine personnel: problems in satisfying dose limit requirementsJ Hudzietzová, J Sabol, M Fülöp.

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".

Variation of system performance, quality control standards and adherence to international FDG-PET/CT imaging guidelines. A national survey of PET/CT operations in Austria.

AIM: To gather information on clinical operations, quality control (QC) standards and adoption of guidelines for FDG-PET/CT imaging in Austrian PET/CT centres. METHODS: A written survey composed of 68 questions related to A) PET/CT centre and installation, B) standard protocol parameters for FDG-PET/CT imaging of oncology patients, and C) standard QC procedures was conducted between November and December 2013 among all Austrian PET/CT centres. In addition, a NEMA-NU2 2012 image quality phantom test was performed using standard whole-body imaging settings on all PET/CT systems with a lesion-to-background ratio of 4. Recovery coefficients (RC) were calculated for each lesion and PET/CT system. RESULTS: A) 13 PET/CT systems were installed in 12 nuclear medicine departments at public hospitals. B) Average fasting prior to FDG-PET/CT was 7.6 (4-12) h. All sites measured blood glucose levels while using different cut-off levels (64%: 150 mg/dl). Weight-based activity injection was performed at 83% sites with a mean FDG activity of 4.1 MBq/kg. Average FDG uptake time was 55 (45-75) min. All sites employed CT contrast agents (variation from 1%-95% of the patients). All sites reported SUV-max. C) Frequency of QC tests varied significantly and QC phantom measurements revealed significant differences in RCs. CONCLUSION: Significant variations in FDG-PET/CT protocol parameters among all Austrian PET/CT users were observed. Subsequently, efforts need to be put in place to further standardize imaging protocols. At a minimum clinical PET/CT operations should ensure compliance with existing guidelines. Further, standardized QC procedures must be followed to improve quantitative accuracy across PET/CT centres.

Whole-body PET/MRI: the effect of bone attenuation during MR-based attenuation correction in oncology imaging.

PURPOSE: In combined PET/MRI standard PET attenuation correction (AC) is based on tissue segmentation following dedicated MR sequencing and, typically, bone tissue is not represented. We evaluate PET quantification in whole-body (WB)-PET/MRI following MR-AC without considering bone attenuation and then investigate different strategies to account for bone tissue in clinical PET/MR imaging. To this purpose, bone tissue representation was extracted from separate CT images, and different bone representations were simulated from hypothetically derived MR-based bone classifications. METHODS: Twenty oncology patients referred for a PET/CT were injected with either [18F]-FDG or [18F]-NaF and imaged on PET/CT (Biograph TruePoint/mCT, Siemens) and PET/MRI (mMR, Siemens) following a standard single-injection, dual-imaging clinical WB-protocol. Routine MR-AC was based on in-/opposed-phase MR imaging (orgMR-AC). PET(/MRI) images were reconstructed (AW-OSEM, 3 iterations, 21 subsets, 4mm Gaussian) following routine MR-AC and MR-AC based on four modified attenuation maps. These modified attenuation maps were created for each patient by non-linear co-registration of the CT images to the orgMR-AC images, and adding CT bone mask values representing cortical bone: 1200HU (cortCT), spongiosa bone: 350HU (spongCT), average CT value (meanCT) and original CT values (orgCT). Relative difference images of the PET following AC using the modified attenuation maps were compared. SUVmean was calculated in anatomical reference regions and for PET-positive lesions. RESULTS: The relative differences in SUVmean across patients following orgMR-AC and orgCT in soft tissue lesions and in bone lesions were similar (range: 0.0% to -22.5%), with an average underestimation of SUVmean of 7.2% and 10.0%, respectively when using orgMR-AC. In bone lesions, spongCT values were closest to orgCT (median bias of 1.3%, range: -9.0% to 13.5%) while the overestimation of SUVmean with respect to orgCT was highest for cortCT (40.8%, range: 1.5% to 110.8%). For soft tissue lesions the bias was highest using cortCT (13.4%, range: -2.3% to 17.3%) and lowest for spongCT (-2.2%, range: 0.0% to -13.7%). CONCLUSIONS: In PET/MR imaging using standard MR-AC PET uptake values in soft lesions and bone lesions are underestimated by about 10%. In individual patients this bias can be as high as 22%, which is significant during clinical follow-up exams. If bone segmentation is available, then assigning a fixed attenuation value of spongious bone to all bone structures appears reasonable and results in only a minor bias of 5%, or less in uptake values of soft tissue and bone lesions.

Integration of FDG-PET/CT into external beam radiation therapy planning: technical aspects and recommendations on methodological approaches.

UNLABELLED: This work addresses the clinical adoption of FDG-PET/CT for image-guided radiation therapy planning (RTP). As such, important technical and methodological aspects of PET/CT-based RTP are reviewed and practical recommendations are given for routine patient management and clinical studies. First, recent developments in PET/CT hardware that are relevant to RTP are reviewed in the context of quality control and system calibration procedures that are mandatory for a reproducible adoption of PET/CT in RTP. Second, recommendations are provided on image acquisition and reconstruction to support the standardization of imaging protocols. A major prerequisite for routine RTP is a complete and secure data transfer to the actual planning system. Third, state-of-the-art tools for image fusion and co-registration are discussed briefly in the context of PET/CT imaging pre- and post-RTP. This includes a brief review of state-of-the-art image contouring algorithms relevant to PET/CT-guided RTP. Finally, practical aspects of clinical workflow and patient management, such as patient setup and requirements for staff training are emphasized. PET/CT-guided RTP mandates attention to logistical aspects, patient set-up and acquisition parameters as well as an in-depth appreciation of quality control and protocol standardization. CONCLUSION: Upon fulfilling the requirements to perform PET/CT for RTP, a new dimension of molecular imaging can be added to traditional morphological imaging. As a consequence, PET/CT imaging will support improved RTP and better patient care. This document serves as a guidance on practical and clinically validated instructions that are deemed useful to the staff involved in PET/CT-guided RTP.

Variations of clinical SPECT/CT operations: an international survey.

AIM: This survey gathers information about clinical SPECT/CT operations worldwide to help guide standardization of clinical SPECT/CT imaging. METHODS: An international, web-based survey of SPECT/CT users was initiated in 12/2010 through an e-mail distribution. Users were asked 71 questions related to (A) demographics, (B) SPECT/CT operations/utilization and (C) variations in imaging protocols. RESULTS: Collected responses originated from 117 imaging centers in the Americas (66%), Europe (20%), Asia-Pacific (11%) and the Middle-East (3%), with the majority of responding sites representing public health care institutions (69%). Most sites operate 1-2 SPECT/CT-systems (74%), typically installed in Nuclear Medicine departments (84%) with extensive prior SPECT-only experience (82%). Only 14% of SPECT/CTs are installed in Radiology departments. Clinical SPECT/CT imaging is performed either as routine (51%) or ad-hoc "add-on" procedure (49%) with a high inter-site and inter-examination variability. The main application of the integrated CT is to provide anatomical localization of the tracer uptake rather than to produce contrast-enhanced or other high-quality CT images. Consequently, in only 22% of the sites a CT contrast injector is installed. Only 6% of centers use SPECT/CT devices for stand-alone CT procedures. CONCLUSION: An international survey among clinical SPECT/CT users revealed that SPECT/CT is a not a routine component of nuclear medicine procedures. The majority of the centers responding do not fully utilize the diagnostic potential of the CT components. Significant variations in standard imaging protocols were observed. These findings illustrate the need for training and standardization and underscore the need for revisiting the role of SPECT/CT in diagnostic imaging.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

The effect of MR surface coils on PET quantification in whole-body PET/MR: results from a pseudo-PET/MR phantom study.

PURPOSE: The use of magnetic resonance (MR) radiofrequency (RF) surface coils is a prerequisite for high-quality positron emission tomography (PET)/MR imaging. In lack of in-gantry transmission (TX) sources, the exact position of the RF coils is unknown in PET/MR, and may, therefore, lead to false attenuation correction (AC) of the emission (EM) data. The authors assess lesion and background quantification in AC-PET by mimicking different PET/MR imaging situations using a whole-body (WB) PET-only tomograph. METHODS: Phantom experiments were performed on a PET tomograph with 68 Ge-rod TX sources. First, a 15-cm plastic cylinder was filled uniformly with [18F]-FDG to simulate a head study. Second, a NEMA NU-2001 image quality phantom (35 x 25 x 25 cm3) was filled uniformly with [18F]-FDG to simulate torso imaging. The phantom contained six lesions (10-38 mm diameter, lesion-to-background ratio 6:1) centred around a 5 cm diameter lung insert. EM and TX measurements were acquired with and without MR head (cylinder) and surface (NU-2001 phantom) RF coils in place. The following imaging situations were mimicked in both head and torso phantom studies: (1) PET scan without MR coils in EM and TX for reference, (2) PET scan with coils in both EM and TX, and (3) PET scan with coils in EM but without coils in TX. Two more set-ups were performed for the torso phantom: (4) PET scan with coils in EM only and phantom shifted slightly compared to (3), and (5) PET scan with coils in EM and TX following local displacement of the surface coils. PET EM data (1)-(4) were corrected for attenuation and scatter using cold TX data. Imaging situations (1)-(3) were repeated with the cylinder phantom and head coil in a combined PET/MR prototype system employing template-based AC. RESULTS: Head phantom: In case the MR head coils were not accounted for during AC (3), central and peripheral background activity concentration was underestimated by 13%-19% when compared to the reference setup (1). The effects of MR coil omission during AC was replicated in the repeat study with the combined PET/MR prototype. Torso phantom: All lesions were equally visible on all AC-PET images. The effects of disregarding MR surface RF coils during AC [(3) vs (1)] were 4%, or less. A slightly higher bias was observed when accounting for the RF surface coils that were shifted between EM and TX (5). The effect of coil misalignment and neglect during AC on the quantification of the simulated lungs was insignificant compared to the noise levels in AC-PET. CONCLUSIONS: Unaccounted attenuation from MR surface coils causes a regional bias of AC-PET data in body regions near the MR coils. Bias of central regions was more noticeable in smaller-size objects. In torso studies with body surface coils, the visibility of central lesions on PET was unaffected by MR coils following incomplete AC. Coil misalignment of several cm between emission and attenuation images causes an error that was comparable to that arising from unaccounted MR coil attenuation but small compared to the average standard deviation of the activity concentration levels.

[E-learning in nuclear medicine - a nationwide survey in Germany]. / E-Learning in der Nuklearmedizin: Eine Erhebung an deutschen Universitäten.

AIM: To assess available e-learning concepts and programmes for nuclear medicine at university hospitals in Germany. METHODS: All (34) departments of nuclear medicine at German university hospitals were asked to participate in an anonymized online survey. Questions were categorized into four topics: 1.) clinic and education; 2.) on-site strategies for e-learning; 3.) available e-learning offers and 4.) free text comments on experiences and expectations. All input was reviewed descriptively; free text was analyzed analytically. RESULTS: The response rate was 56% (19/34). 13/19 responses indicated well-defined e-learning strategies, mainly to support frontal teaching courses. Future e-learning perspectives focus on clinical case studies with sufficient imaging materials. Only 7/19 university hospitals operate a centralized e-learning platform (e. g. Moodle). The acceptance of the available e-learning options by the students is considered relatively poor. CONCLUSIONS: Today e-learning concepts for nuclear medicine are available at selected university hospitals only. All responders wish to expand on e-learning but many report the lack of administrative support to do so. These data could be regarded as a basis for discussions of inter-university teaching scenarios.

Serum-free production and purification of chimeric IgA antibodies.

Natural IgA antibodies are abundantly produced in vivo to protect serosal surfaces from invading infectious organisms. However, the immunotherapeutic potential of IgA has hardly been explored, although there is evidence that recombinant IgA antibodies may broaden the armentarium to combat certain infectious or malignant diseases. One of the limitations for exploring IgA's therapeutic activity has been the difficulty to obtain enough recombinant material with desired specificity for in vivo studies. Here, we describe the production and purification of monomeric recombinant IgA1 and IgA2 antibodies under serum-free conditions. For antibody production, suspension adapted CHO-K1 cells and a glutamine synthetase selection vector were used, which resulted in specific production rates of up to 2.2 pg/cell/day. Purities of >95% of monomeric antibodies were obtained by a combination of affinity chromatography-using an anti-kappa-light chain matrix-and size exclusion chromatography. Purified antibodies displayed the expected biochemical characteristics and were functionally fully active. Importantly, all required reagents and methods are commercially available and not dependent on the specificity of the desired antibody. In addition, all employed technologies and methodologies are similar to those used for the production of therapeutic IgG antibodies - thus allowing further up-scaling and streamlining according to existing antibody production technologies. In conclusion, the described methodology may assist in the development of recombinant IgA antibodies for therapeutic applications.

Prediction of the oversulphated chondroitin sulphate contamination of unfractionated heparin by ATR-IR spectrophotometry.

The detection of a contamination of heparin with oversulphated chondroitin sulphate (OSCS) was first analysed in an unfractionated heparin batch supplied to the US API-market in April 2006. OSCS is a semi-synthetic derivative of the natural occuring glycosaminoglycan chondroitin sulphate. Moreover some spectroscopic characteristics of the substance overlap with those of heparin, so that the infrared (IR) spectra are visually difficult to distinguish whereas (1)H-NMR (Nuclear Magnetic Resonance) spectroscopy or capillary electrophoresis (CE) provides identification by a simple visual inspection of either the spectrum or the electropherogram respectively. However, applying special tools of Multivariate Data Analysis (MVA) to the IR spectra an identification of the contaminated samples is possible. In detail a rapid Attenuation Total Reflectance-Infrared (ATR-IR) measurement was selected, which does not require any sample preparation. The result (contaminated or not contaminated) is predicted within a few minutes. A method transfer to mobile ATR-IR spectrometers seems to be possible. The analysis is based on the fact that the fingerprint of the OSCS IR spectrum (1st derivative) complies with a theoretically calculated principal component in the MVA.

Quality assessment of unfractionated heparin using 1H nuclear magnetic resonance spectroscopy.

Due to problems, especially anaphylactoid reactions, raised by impure unfractionated heparin the quality assessment of heparin has to be reconsidered. Neither the USP nor the European Pharmacopoeia are able to guarantee the purity of heparin, i.e., the limitation of oversulfated chondroitin sulfate (OSCS) which was found to be the reason for the allergic adverse effects. In the first run the regulatory authorities ask for 1H NMR spectroscopic and capillary electrophoretic measurements in order to characterize the impurity profile of heparin. Using an optimized 1H NMR method the limit of detection for OSCS was found to be 0.1%. In addition, it is possible to reliably quantify both OSCS and dermatan sulfate (DS), the latter being an indicator of poor purification of the unfractionated heparin. Screening of more than 100 heparin samples collected from international markets revealed a high number of samples containing substantial amounts of DS and a number of samples containing OSCS in an amount higher than 0.1%.