[Positron emission tomography 2013 in Germany. Results of the query and current status]. / Positronenemissionstomographie 2013 in Deutschland. Ergebnisse der Erhebung und Standortbestimmung.

AIM: Five years after the first survey the positron emission tomography (PET) council of the German Society of Nuclear Medicine (DGN) repeated a survey to re-evaluate the status of PET diagnostics in Germany based on the data of the year 2013. METHODS: A web-based questionnaire was used for gathering information retrospectively. Details regarding the physicians involved in PET operations, PET systems, and radiopharmaceuticals were also part of the survey as well as indications and number of studies. Furthermore, the role of PET and PET/CT within the diagnostic process was evaluated. In addition, official statistical hospital reports were analysed. RESULTS: Responses from 52 sites were analysed. They reported a total of 38,350 PET studies in 2013. In the majority of cases PET was used in oncologic indications (87%). Further main applications were: neurology 6%, cardiology 1%, and inflammation 5%. University or other hospitals performed 85% of the studies. The portion of in-patients was 26%. Hybrid systems (56 PET/CT, 5 PET/MRT, and 2 stand-alone PET) were most frequently used for imaging. The radiotracers were labelled with F-18 in 90% of the studies, whereas Ga-68 was used in 9% and C-11 in 1%. Lung tumours were the most investigated tumour entity (40%), followed by malignant lymphoma (8%), tumours of the gastrointestinal tract (5%), and NET (5%). 20% of the 333 physicians hold a PET certificate awarded by the DGN. More than 50% of the facilities were certified according ISO9001, KTQ or QEP standard. The findings of nearly 60% of the oncological studies were discussed interdisciplinary in a tumour board. In federal statistical reports a 56% increase of in-patient PET operations during 5 years was found. CONCLUSION: In Germany, a moderate increase (9% per year) of PET studies is observed, but compared with other industrialised countries PET is still less established.

[Ga-68-PSMA PET/CT for prostate cancer]. / Ga-68-PSMA-PET/CT bei Prostatakarzinom.

Prostate-specific membrane antigen (PSMA) is expressed as a cell surface protein physiologically in the prostate and can be found in all stages of prostate cancer. Even in castration-resistant prostate cancers, this overexpression of PSMA occurs. Due to the enzymatic activity of PSMA it was possible develop specific inhibitors from which "small molecule" radiopharmaceuticals were derived. By coupling the specific binding motif glutamate-urea-lysine with the chelator HBED-CC, which complexes Ga-68 very effectively, a new radiopharmaceutical is available for Ga-68-PSMA-PET/CT. According to the first results in patients with prostate carcinoma, this new diagnostic tool exhibited advantages in image quality compared to choline-PET/CT. An initial study demonstrated the higher contrast of the PET signal and an improved diagnostic accuracy. The properties of even further new PSMA PET radiopharmaceuticals can be of increasing importance for the diagnostic work-up of prostate cancer in all stages. In conjunction with therapeutic PSMA radiopharmaceuticals, a new field of theragnostics is opened.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

Multi-centre calibration of an adaptive thresholding method for PET-based delineation of tumour volumes in radiotherapy planning of lung cancer.

PURPOSE: To evaluate the calibration of an adaptive thresholding algorithm (contrast-oriented algorithm) for FDG PET-based delineation of tumour volumes in eleven centres with respect to scanner types and image data processing by phantom measurements. METHODS: A cylindrical phantom with spheres of different diameters was filled with FDG realizing different signal-to-background ratios and scanned using 5 Siemens Biograph PET/CT scanners, 5 Philips Gemini PET/CT scanners, and one Siemens ECAT-ART PET scanner. All scans were analysed by the contrast-oriented algorithm implemented in two different software packages. For each site, the threshold SUVs of all spheres best matching the known sphere volumes were determined. Calibration parameters a and b were calculated for each combination of scanner and image-analysis software package. In addition, "scanner-type-specific" calibration curves were determined from all values obtained for each combination of scanner type and software package. Both kinds of calibration curves were used for volume delineation of the spheres. RESULTS: Only minor differences in calibration parameters were observed for scanners of the same type (Δa ≤4%, Δb ≤14%) provided that identical imaging protocols were used whereas significant differences were found comparing calibration parameters of the ART scanner with those of scanners of different type (Δa ≤60%, Δb ≤54%). After calibration, for all scanners investigated the calculated SUV thresholds for auto-contouring did not differ significantly (all p>0.58). The resulting sphere volumes deviated by less than -7% to +8% from the true values. CONCLUSION: After multi-centre calibration the use of the contrast-oriented algorithm for FDG PET-based delineation of tumour volumes in the different centres using different scanner types and specific imaging protocols is feasible.

[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.

[Nuclear Medicine in Germany. Key data from official statistics]. / Nuklearmedizin in Deutschland. Kennzahlen aus offiziellen Statistiken.

AIM: To explain the spectrum and number of in-vivo nuclear medicine examinations and therapies based on official statistics about out-patient and in-patient care. Trends in time of the frequency and spectrum of procedures as well as data on the health care structure for nuclear medicine in Germany should be collected. METHODS: Data from the Gesundheitsberichterstattung des Bundes, from the frequency statistics of the statutory health insurance for out-patients and from the Bundesärztekammer were used. Customized queries were performed to analyse temporal changes. RESULTS: Nuclear medicine physicians are more frequently consulted by out-patients over the last years (2008: 2024498; 2009: 2164664) and the number of colleagues in private practice increased. For in-patients, the frequency of conventional nuclear medicine procedures (mainly for brain, lymphatic system, lung and heart) increased since 2008 after a decline in previous years (2009: 323515; +4.6%) and the number of PET(/CT) examinations continued to rise (2009: 25123; +18%), even if changes in OPS keys may hamper comparisons. Nearly 600 gamma cameras and 76 PET(/CT) scanners were installed in hospitals in 2008. Nuclear medicine procedures are increasingly performed as cross sectional imaging like SPECT(/CT) and PET(/CT). With the supply shortfall with 99Mo, the frequency of thyroid scans with 123I iodine increased as well as the use of 18F PET as a substitute for conventional bone scans. The number of radionuclide therapies, in particular non-thyroid treatments, increased since the mid-nineties and stabilized at nearly 50000 cases per year with shorter lengths of stay. CONCLUSION: The details of the present analysis may help to understand the positive evolution of key numbers for nuclear medicine.

Retrospective web-based multicenter evaluation of ¹8F-FDG-PET and CT derived predictive factors. Radioimmunotherapy with yttrium-90-ibritumomab tiuxetan in follicular non Hodgkin's lymphoma.

AIM: Although predictive factors (PF) for conventional lymphoma therapy are established and frequently used in clinical practice and medical research, the PF for radioimmunotherapy (RIT) have not been fully defined until now. The aim of this multicenter evaluation is to prove the feasibility of the multicenter web-based data collection and to preliminary explore imaging findings and prediction of therapy response in patients with follicular lymphoma (FL) following radioimmunotherapy (RIT) with 90Y-ibritumomab tiuxetan. PATIENTS, METHODS: We retrospectively analyzed and correlated clinical and imaging data (CT and FDG-PET) before and after RIT as documented by the RIT-Network. Evaluation of treatment response was done on both patient and lesion basis. Every measurable lesion was analyzed in terms of standardized uptake value (SUV), volume (CT and PET) and response. PF were identified using a uni- and multivariate model. A web-based system was used for the documentation and evaluation of clinical and imaging data. RESULTS: 16 patients with at least one PET before and after RIT were eligible for analysis. Concerning response three months postRIT, 5 patients achieved a CR, 6 patients a PR and 4 patients remained with NC. A total of 159 lesions were measured (mean 10±8). In the multivariate model the log lesion volume (p < 0.0001), the total (p = 0.03) and maximum lesion volume (p = 0.05) were predictors for response (CR + PR). Concerning the lesional CR initial small lesion volume (p = 0.009) and its high metabolic activity (p = 0.01) were identified as predictors. The web-based system showed no major disturbances allowing secure data transfer and central image interpretation in a reasonable time. CONCLUSION: The use of a web-based multicenter archiving system for clinical and imaging data is technically feasible in a multicenter setting and allows a central analysis. This preliminary analysis suggests that FDG-PET may predict the likelihood of response to RIT.

[Bone scanning with sodium 18F-fluoride PET and PET/CT. German guideline Version 1.0.]. / Skelettdiagnostik mittels 18F-Natriumfluorid-PET und -PET/CT. DGN-Leitlinie Version 1.0.

In nuclear medicine, bone scanning is based on the principle of scintigraphy using bone-seeking radiopharmaceuticals which accumulate in sites of increased bone formation. From a historical point of view, (18)F-fluoride was one of the first osteotropic tracers which was replaced by (99m)Tc-labelled polyphosphonates. With the development of modern PET equipment the superior diagnostic performance of (18)F-fluoride PET for the detection and characterization of osseous lesions was proven in comparison to conventional bone scanning. Recently, its importance as a substitute of conventional skeletal scintigraphy increased in a time with limited availability of (99)Mo/(99m)Tc. To ensure health care during this period, (18)F-fluoride PET currently became part of common outpatient care. This guideline comprehends recommendations on indications, protocols, interpretation and reporting of (18)F-fluoride PET and PET/CT.

[Positron emission tomography 2008 in Germany - results of the query and current status]. / Positronenemissionstomographie 2008 in Deutschland - Ergebnisse der Erhebung und Standortbestimmung.

AIM: The working group on positron emission tomography (PET) of the DGN (German Society of Nuclear Medicine) initiated this first survey to collect and analyse information on the practise of PET in Germany in the year 2008. METHODS: A questionnaire was sent to PET performing facilities (medical practices, hospitals, university hospitals and others) for retrospective data acquisition. Details regarding the equipment and examination procedures were examined as well as indications and number of studies. In addition, the role of PET within the diagnostic process was evaluated. RESULTS: Responses from 65 sites were analysed. Their technical equipment consisted of 77 PET scanners (40 of them were combined PET/CT devices). About 63500 PET studies had been performed with 86% in the field of oncology, 8% in neurology and 3% in cardiology. The radiotracers were labelled with 18F in 91% of the studies, whereas 68Ga was used in 4% and 11C in 3%. The analyses revealed lung tumours as the most investigated tumour entity, followed by malignant lymphoma, tumours of the gastro-intestinal tract and prostate cancer (about 14000, 6000, 5000 and 2000). Corresponding to the new scanners and software procedures, the number of studies with attenuation correction by CT was high (68%) and nearly all studies were reconstructed iteratively (99%). The PET images were analysed quantitatively in the majority of cases (91%). The clinical reports, which included image documentation for the greater part, were posted regularly within 3 days. However, in 70% of the sites electronic transfer possibilities were used additionally to speed up the diagnostic process. The high standard of quality was demonstrated by the fact, that 40 facilities were engaged in a tumour board. Further on, one third of the physicians had gained a PET certification awarded by the DGN. CONCLUSION: Relative to the high general standard of diagnostic instrumentation in Germany, PET is less established, in particular when compared with other industrialised countries such as USA and Switzerland.

Acceptor-photobleaching FRET analysis of core kinetochore and NAC proteins in living human cells.

Faithful chromatin segregation is mediated and controlled by the kinetochore protein network which assembles at centromeres. In this study, the neighbourhood relations of inner kinetochore and nucleosome-associated complex (NAC) proteins were analysed in living human interphase cells by acceptor photobleaching FRET. The data indicate that CENP-U is in close vicinity to CENP-I as well as to CENP-B and that CENP-M is close to CENP-T.

Low-frequency rTMS of the premotor cortex reduces complex movement patterns in a patient with pantothenate kinase-associated neurodegenerative disease (PKAN).

INTRODUCTION: Pantothenate kinase-associated neurodegenerative disease (PKAN) is a secondary generalized dystonia associated with an accumulation of iron in the basal ganglia and increased motor cortex excitability. A pilot study in three patients with secondary generalized dystonia had reported a reduced frequency of painful axial spasms following inhibitory 1-Hz repetitive transcranial magnetic stimulation (rTMS) applied over the premotor cortex. PATIENT AND METHODS: We compared the effects of real versus sham rTMS on the frequency of the complex movement pattern and the need for additional benzodiazepine medication in a 6-year-old male patient with PKAN. A 20-minute session of left premotor 1-Hz rTMS was performed daily on 5 consecutive days. RESULTS: The occurrence of the complex movement pattern was gradually reduced from three to two attacks daily to one attack daily by real rTMS while sham rTMS had no effect. This reduction was obtained concomitantly with a similar reduction of additional benzodiazepines for both real and sham rTMS sessions. CONCLUSION: Inhibitory rTMS of the premotor cortex may be used to temporarily control motor symptoms in PKAN.

Para-[(123)I]iodo-L-phenylalanine in patients with pancreatic adenocarcinoma: tumour uptake, whole-body kinetics, dosimetry.

UNLABELLED: Recently, p-[(123)I]iodo-L-phenylalanine (IPA) was clinically validated for brain tumour imaging. Preclinical studies demonstrated uptake of IPA into pancreatic adenocarcinoma suggesting its diagnostic application in patients with pancreatic tumours. The aim was to study the tumour uptake of IPA in patients with pancreatic adenocarcinoma and to analyse its biodistribution and dosimetry to assess the radiation dose resulting from its diagnostic use. PATIENTS, METHODS: Seven patients with pancreatic adenocarcinoma underwent whole-body scintigraphies and SPECT up to 24 h after administration of 250 MBq of IPA. Tumour uptake of IPA was assessed visually. Time activity curves and the corresponding residence times were determined for whole-body, kidneys, liver, spleen, lung, heart content, brain, and testes. Mean absorbed doses for various organs and the effective dose were assessed based on the MIRD formalism using OLINDA/EXM. RESULTS: IPA exhibited no accumulation in proven manifestations of pancreatic adenocarcinomas. IPA was exclusively eliminated by the urine and showed a delayed clearance from blood. Residence times were 0.26 +/- 0.09 h for kidneys, 0.38 +/- 0.19 h for liver, 0.15 +/- 0.07 h for spleen, 0.51 +/- 0.20 h for lungs, 0.22 +/- 0.07 h for heart content, 0.11 +/- 0.05 h for brain, 0.014 +/- 0.005 h for testes and 6.4 +/- 2.2 h for the remainder. The highest absorbed doses were determined in the urinary bladder wall and in the kidneys. According to the ICRP 60 the effective dose resulting from 250 MBq IPA was 3.6 +/- 0.7 mSv. CONCLUSION: Para-[(123)I]iodo-L-phenylalanine can be used in diagnostic nuclear medicine with acceptable radiation doses. Besides its proven validity for brain tumour imaging, IPA does not appear to be suitable as tracer for pancreatic cancer.

[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.

Localization of precentral gyrus in image-guided surgery for motor cortex stimulation.

According to recent clinical data, motor cortex stimulation (MCS) is an alternative treatment for central pain syndromes. We present our minimal invasive technique of image guidance for the placement of motor cortex stimulating electrode and assess the clinical usefulness of both neuronavigation and vacuum headrest. Neuronavigation was used for identification of precentral gyrus and accurate planning of the single burr-hole. The exact location was reconfirmed by intraoperative phase reversal of somatosensory evoked potential (SSEP) and clinical response after electrical stimulation test. Implementation of navigation technique facilitated localization of the precentral gyrus with a high degree of accuracy. Determination of stimulating electrode placement was possible in every case. Postoperative clinical and neuroradiological evaluations were performed in each patient. All patients experienced postoperative relief from pain. Our preliminary series may confirm image guidance as a useful tool for surgery of MCS. Additionally, minimal and safe exposure can be performed using a single burr-hole and vacuum head rest.

Comparison of minimally invasive surgical skills of neurosurgeons versus general surgeons: is there a difference in the first exposure to a virtual reality simulator?

OBJECTIVE: The increasing use of minimally invasive surgery, which has a longer learning curve compared to open surgery lets the necessity to develop training programs to improve endoscopic skills of trainees become ever clearer. The aim of this study was to compare the endoscopic skills of neurosurgeons versus general surgeons at first exposure to a virtual reality simulator. METHODS: 72 general surgeons who visited the 122nd Conference of the German Surgeons Society (DGCH in Munich 2005) and 35 neuroendoscopic surgeons, who visited the Third World Conference of the International Study Group of Neuroendoscopy (ISGNE in Marburg 2005) participated in this study. Each participant performed the basic module "clip application" on the virtual reality simulator (LapSim). All participants were given the same pretest instructions. Time to complete the task, error score and economy of motion were recorded. RESULTS: The general surgeons performed the clip application faster, but with more errors than neuroendoscopic surgeons. However, the difference of both parameters was not significant. Both surgeon groups have a similar score for economy of motion. CONCLUSION: Although neuroendoscopic surgeons were exposed to a foreign procedure and unfamiliar equipment, they were able to perform virtual endoscopy with similar accuracy as general surgeons, who are adapted to these endoscopic instruments and procedures and do these daily.

Spatial perception predicts laparoscopic skills on virtual reality laparoscopy simulator.

OBJECTS: This study evaluates the influence of visual-spatial perception on laparoscopic performance of novices with a virtual reality simulator (LapSim(R)). MATERIALS AND METHODS: Twenty-four novices completed standardized tests of visual-spatial perception (Lameris Toegepaste Natuurwetenschappelijk Onderzoek [TNO] Test(R) and Stumpf-Fay Cube Perspectives Test(R)) and laparoscopic skills were assessed objectively, while performing 1-h practice sessions on the LapSim(R), comprising of coordination, cutting, and clip application tasks. Outcome variables included time to complete the tasks, economy of motion as well as total error scores, respectively. RESULTS: The degree of visual-spatial perception correlated significantly with laparoscopic performance on the LapSim(R) scores. Participants with a high degree of spatial perception (Group A) performed the tasks faster than those (Group B) who had a low degree of spatial perception (p = 0.001). Individuals with a high degree of spatial perception also scored better for economy of motion (p = 0.021), tissue damage (p = 0.009), and total error (p = 0.007). CONCLUSION: Among novices, visual-spatial perception is associated with manual skills performed on a virtual reality simulator. This result may be important for educators to develop adequate training programs that can be individually adapted.