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Table of contentsA1 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 Koljević Marković, Milica Janković, V Miler Jerković, M Paskaš, G Pupić, R Džodić, D PopovićA34 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.

Current shunt treatments of hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid (CSF) and intracranial pressure (ICP) fluctuations, suffer malfunctions caused by changes in patient’s posture. Research toward a quantitative model describing posture dependent dynamics of CSF related pressures such as ICP and blood pressure (BP) shall provide relevant information that can lead to a better understanding of CSF dynamics and thus, improved treatment outcomes. In this pilot study, ICP and femoral blood pressure (FBP) were measured concurrently in anaesthetized as well as awake and freely moving rats using radio telemetry. It was shown that despite the inherent challenges of limited space for sensor implants and rapid movements leading to strong artefacts, influences on CSF related pressure fluctuations due to posture changes can be observed in individual rats

Introduction: In radiotherapy, tumors may move due to the patient’s respiration, which decreases treatment accuracy. Some motion mitigation methods require measuring the tumor position during treatment. Current available sensors often suffer from time delays, which degrade the motion mitigation performance. However, the tumor motion is often periodic and continuous, which allows predicting the motion ahead. Method and Materials: A couch tracking system was simulated in MATLAB and five prediction filters selected from literature were implemented and tested on 51 respiration signals (median length: 103 s). The five filters were the linear filter (LF), the local regression (LOESS), the neural network (NN), the support vector regression (SVR), and the wavelet least mean squares (wLMS). The time delay to compensate was 320 ms. The normalized root mean square error (nRMSE) was calculated for all prediction filters and respiration signals. The correlation coefficients between the nRMSE of the prediction filters were computed. Results: The prediction filters were grouped into a low and a high nRMSE group. The low nRMSE group consisted of the LF, the NN, and the wLMS with a median nRMSE of 0.14, 0.15, and 0.14, respectively. The high nRMSE group consisted of the LOESS and the SVR with both a median nRMSE of 0.34. The correlations between the low nRMSE filters were above 0.87 and between the high nRMSE filters it was 0.64. Conclusion: The low nRMSE prediction filters not only have similar median nRMSEs but also similar nRMSEs for the same respiration signals as the high correlation shows. Therefore, good prediction filters perform similarly for identical respiration patterns, which might indicate a minimally achievable nRMSE for a given respiration pattern.

Abstract: [Carbonyl-11C]WAY-100635 is a potent and effective antagonist for the 5-HT1A receptor subtype. We aimed to assess the status of [carbonyl-11C]WAY-100635 and its main radio-metabolites, [carbonyl-11C]desmethyl-WAY-100635 and [carbonyl- 11C]cyclohexanecarboxylic acid, on the basis of an improved radio-HPLC method. Common methods were characterized by preparative HPLC columns with long runtimes and/or high flow rates. Considering the short half-life of C-11, we developed a more rapid and solvent saving HPLC assay, allowing a fast, efficient and reliable quantification of these major metabolites. [Copyright &y& Elsevier]

Objectives: This study sought to elucidate the diagnostic performance of 0.55 T magnetic resonance imaging (MRI) for pediatric dental imaging, specifically in terms of the image quality (IQ) for detecting ectopic and/or supernumerary teeth, compared with routine ultra-low-dose computed tomography (ULD-CT) of the jaw., Materials and Methods: A total of 16 pediatric patients (mean age: 12.4 ± 2.6 years, range: 9-17 years) with ectopic and/or supernumerary teeth screened from January 2023 to January 2024 were enrolled in this prospective, single-center study. All patients underwent ULD-CT as the clinical reference standard and 0.55 T MRI as the study scan on the same day. A 0.6-mm isotropic 3-dimensional T1w FLASH sequence was developed with a dedicated field of view of the upper and lower jaws. ULD-CT was performed using a new single-source computed tomography (CT) scanner equipped with a tin filter (Sn100, slice thickness: 1 mm, quality reference mAs: 24). The IQ for the tooth axis, the tooth length, the tooth root, root resorptions, cysts, the periodontal ligament space, and the mandibular canal was evaluated twice by 3 senior readers using a 5-point Likert scale (LS) (LS score of 1: insufficient, 3: reduced IQ but sufficient for clinical use, and 5: perfect) and compared between both methods. Subsequently, the results were dichotomized into nonvalid (LS score of ≤2) and valid (LS score of ≥3) for clinical use., Results: A total of 49 ectopic and/or supernumerary teeth in 16 pediatric patients were investigated using ULD-CT (CTDI: 0.43 ± 0.09 mGy) and 0.55 T MRI. The mean MRI acquisition time was 9:45 minutes. Motion artifacts were nonsignificantly different between 0.55 T MRI and ULD-CT (P = 0.126). The IQ for the tooth axis, the tooth root, root resorptions, and cysts was similar between the methods. The IQ for the periodontal ligament space and tooth length favored ULD-CT by 14% (confidence interval [CI]: 4.3%-24%) and 7.5% (CI: 1.8%-13%), respectively, whereas that for the mandibular canal favored 0.55 T MRI by -35% (CI: -54%-16%). Sufficient IQ was found especially for cystic lesions (CT: 100% sufficient, MRI: 95% sufficient), the tooth root (CT: 100%, MRI: 98%), root resorptions (CT: 94%; MRI: 85%), the tooth axis (CT: 100%; MRI: 98%), and the tooth length (CT: 99%; MRI: 91%)., Conclusions: The findings indicate that 0.55 T MRI is a feasible, radiation-free technique for delineating ectopic and/or supernumerary teeth in pediatric patients. Nevertheless, to date, 0.55 T MRI has not yet been able to provide an optimal IQ for all anatomical tooth and jaw structures. In cases of advanced clinical indications that require optimal spatial resolution, high-resolution CT or cone-beam CT may still be necessary., Competing Interests: Conflicts of interest and sources of funding: M.U., M.S.M. and M.K. are members of the speaker's bureau of Siemens Healthcare GmbH. H.-P.F. and P.A. are employees of Siemens Healthineers (Imaging Science Institute, University Hospital Erlangen, Germany). All other authors have no affiliation with any organization that has a direct or indirect financial interest in the subject discussed in the study., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

As a concept, drainage of excess fluid volume in the cranium has been around for more than 1000 years. Starting with the original decompression-trepanation of Abulcasis to modern programmable shunt systems, to other nonshunt-based treatments such as endoscopic third ventriculostomy and choroid plexus cauterization, we have come far as a field. However, there are still fundamental limitations that shunts have yet to overcome: namely posture-induced over- and underdrainage, the continual need for valve opening pressure especially in pediatric cases, and the failure to reinstall physiologic intracranial pressure dynamics. However, there are groups worldwide, in the clinic, in industry, and in academia, that are trying to ameliorate the current state of the technology within hydrocephalus treatment. This chapter aims to provide a historical overview of hydrocephalus, current challenges in shunt design, what members of the community have done and continue to do to address these challenges, and finally, a definition of the "perfect" shunt is provided and how the authors are working toward it., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objectives: This study evaluates the impact of a scanner-integrated, customized clinical decision support system (CDSS) on the acquisition technique, scan range, and reconstruction in thoracoabdominal CT., Materials and Methods: We applied CDSS in contrast-enhanced examinations of the trunk with various clinical indications on a recent scanner with the capability of dual-energy CT (DECT), anatomic landmark detection (ALD), and iterative metal-artifact reduction (MAR). Simple and comprehensive questions about the patient's breath hold capability, the anatomical region of interest, and metal implants can be answered after the localizer. The acquisition technique (single energy, SECT, or dual energy), scan range (chest-abdomen-pelvis or chest-abdomen), and reconstruction technique (with or without MAR) were then automatically adapted in the examination protocols in coherence with these selections. Retrospectively, we compared the usage rates for these techniques in 624 examinations on the study scanner with 740 examinations on a comparable scanner without CDSS. Subgroup analysis of effective dose (ED), scan duration, and image quality (IQ) was performed in the study group., Results: CDSS leads to an increased usage rate of DECT (64.4% vs. 2.8%) and MAR (75.4% vs. 44.0%). All scan range adaptations by ALD were successful. The resulting subjective IQ between single energy and DECT acquisitions was comparable (all p > 0.05). Scan duration was significantly longer in DECT than in SECT (16.9 s vs. 6.5 s; p < 0.001). However, the objective IQ was significantly higher in DECT (CNRD 2.1 vs. 1.8; p < 0.01), and the ED significantly lower (6.7 mSv vs. 7.6 mSv; p = 0.004)., Conclusion: CDSS for thoracoabdominal CT leads to a substantially increased usage rate of innovative techniques during acquisition and reconstruction. Patients with adapted protocols benefit from improved image quality and increased post-processing options at lower radiation doses., Competing Interests: Declaration of Competing Interest SD, MK, MU and MM are part of the speakers bureau of Siemens Healthcare GmbH., (Copyright © 2023. Published by Elsevier B.V.)

Monte Carlo (MC) simulations of X-ray image devices require splitting the simulation into two parts (i.e. the generation of x-rays and the actual imaging). The X-ray production remains unchanged for repeated imaging and can thus be stored in phase space (PhS) files and used for subsequent MC simulations. Especially for medical images these dedicated PhS files require a large amount of data storage, which is partly why Generative Adversarial Networks (GANs) were recently introduced. We enhanced the approach by a conditional GAN to model multiple energies using one network. This study compares the use of PhSs, GANs, and conditional GANs as photon source with measurements. An X-ray -based imaging system (i.e. ImagingRing) was modelled in this study. half-value layers (HVLs), focal spot, and Heel effect were measured for subsequent comparison. MC simulations were performed with GATE-RTion v1.0 considering the geometry and materials of the imaging system with vendor specific schematics. A traditional GAN model as well as the favourable conditional GAN was implemented for PhS generation. Results of the MC simulation were in agreement with the measurements regarding HVL, focal spot, and Heel effect. The conditional GAN performed best with a non-saturated loss function with R1 regularisation and gave similarly results as the traditional GAN approach. GANs proved to be superior to the PhS approach in terms of data storage and calculation overhead. Moreover, a conditional GAN enabled an energy interpolation to separate the network training process from the final required X-ray energies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier GmbH.)

Although extensive research on brown adipose tissue (BAT) has stimulated optimism in the battle against obesity and diabetes, BAT physiology and organ crosstalk are not fully understood. Besides BAT, melanin-concentrating hormone (MCH) and its receptor (MCHR1) play an important role in energy homeostasis. Because of the link between hypothalamic MCH neurons and sympathetic BAT activation via β-adrenoceptors, we investigated the expression and physiological role of the MCHR1 in BAT. MCHR1 was detected in rodent and human BAT with RT-qPCR and western blot analyses. In vivo imaging in rats used the glucose analog [ 18 F]FDG and the MCHR1-tracer [ 11 C]SNAP-7941. We found that the β3-adrenoceptor (ADRB3) agonist CL316,243 increased [ 11 C]SNAP-7941 uptake in BAT. Additionally, a pharmacological concentration of SNAP-7941-a low-affinity ADRB3 ligand-stimulated [ 18 F]FDG uptake, reflecting BAT activation. In cultured human adipocytes, CL316,243 induced MCHR1 expression, further supporting a direct interaction between MCHR1 and ADRB3. These findings characterized MCHR1 expression in rodent and human BAT for the first time, including in vitro and in vivo data demonstrating a link between MCHR1 and the β3-adrenergic system. The presence of MCHR1 in BAT emphasizes the role of BAT in energy homeostasis and may help uncover treatment approaches for obesity., (© 2021 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals LLC on behalf of New York Academy of Sciences.)

Background: Radiation dose at CT should be as low as possible without compromising diagnostic quality., Objective: To assess the potential for maximum dose reduction of pediatric lung dual-source CT with spectral shaping and advanced iterative reconstruction (ADMIRE)., Materials and Methods: We retrospectively analyzed dual-source CT acquisitions in a full-dose group (FD: 100 kV, 64 reference mAs) and in three groups with spectral shaping and differing reference mAs values (Sn: 100 kV, 96/64/32 reference mAs), each group consisting of 16 patients (age mean 11.5 years, standard deviation 4.8 years, median 12.8 years, range 1.3-18 years). Advanced iterative reconstruction of images was performed with different strengths (FD: ADMIRE Level 2; Sn: ADMIRE Levels 2, 3 and 4). We analyzed dose parameters and measured noise. Diagnostic confidence and detectability of lung lesions as well as anatomical structures were assessed using a Likert scale (from 1 [unacceptable] to 4 [fully acceptable])., Results: Compared to full dose, effective dose was reduced to 16.7% in the Sn 96 group, 11.1% in Sn64, and 5.5% in Sn32 (P<0.001). Noise values of Sn64 ADM4 did not statistically differ from those in FD ADM2 (45.7 vs. 38.9 Hounsfield units [HU]; P=0.132), whereas noise was significantly higher in Sn32 ADM4 compared to Sn64 ADM4 (61.5 HU; P<0.001). A Likert score >3 was reached in Sn64 ADM4 regarding diagnostic confidence (3.2) and detectability of lung lesions (3.3). For detectability of most anatomical structures, no significant differences were found between FD AM2 and Sn64 ADM4 (P≥0.05)., Conclusion: In pediatric lung dual-source CT, spectral shaping together with ADMIRE 4 enable radiation dose reduction to about 10% of a full-dose protocol while maintaining an acceptable diagnostic quality.

Background: Conventional 2D inversion recovery (IR) and phase sensitive inversion recovery (PSIR) late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) have been widely incorporated into routine CMR for the assessment of myocardial viability. However, reliable suppression of fat signal, and increased isotropic spatial resolution and volumetric coverage within a clinically feasible scan time remain a challenge. In order to address these challenges, this work proposes a highly efficient respiratory motion-corrected 3D whole-heart water/fat LGE imaging framework., Methods: An accelerated IR-prepared 3D dual-echo acquisition and motion-corrected reconstruction framework for whole-heart water/fat LGE imaging was developed. The acquisition sequence includes 2D image navigators (iNAV), which are used to track the respiratory motion of the heart and enable 100% scan efficiency. Non-rigid motion information estimated from the 2D iNAVs and from the data itself is integrated into a high-dimensional patch-based undersampled reconstruction technique (HD-PROST), to produce high-resolution water/fat 3D LGE images. A cohort of 20 patients with known or suspected cardiovascular disease was scanned with the proposed 3D water/fat LGE approach. 3D water LGE images were compared to conventional breath-held 2D LGE images (2-chamber, 4-chamber and stack of short-axis views) in terms of image quality (1: full diagnostic to 4: non-diagnostic) and presence of LGE findings., Results: Image quality was considered diagnostic in 18/20 datasets for both 2D and 3D LGE magnitude images, with comparable image quality scores (2D: 2.05 ± 0.72, 3D: 1.88 ± 0.90, p-value = 0.62) and overall agreement in LGE findings. Acquisition time for isotropic high-resolution (1.3mm 3 ) water/fat LGE images was 8.0 ± 1.4 min (3-fold acceleration, 60-88 slices covering the whole heart), while 2D LGE images were acquired in 5.6 ± 2.2 min (12-18 slices, including pauses between breath-holds) albeit with a lower spatial resolution (1.40-1.75 mm in-plane × 8 mm slice thickness)., Conclusion: A novel framework for motion-corrected whole-heart 3D water/fat LGE imaging has been introduced. The method was validated in patients with known or suspected cardiovascular disease, showing good agreement with conventional breath-held 2D LGE imaging, but offering higher spatial resolution, improved volumetric coverage and good image quality from a free-breathing acquisition with 100% scan efficiency and predictable scan time.

Purpose: In precision radiotherapy, the intrafractional motion causes substantial uncertainty. Traditionally, the target volume is expanded to cover the tumor in all positions. Alternative approaches are gating and adaptive tracking, which require a time delay as small as possible between the actual tumor motion and the reaction to effectively compensate the motion. Current treatment machines often exhibit large time delays. Prediction filters offer a promising means to mitigate these time delays by predicting the future respiratory motion., Methods: A total of 18 prediction filters were implemented and their hyperparameters optimized for various time delays and noise levels. A set of 93 traces were standardized to a sampling frequency of 25 Hz and smoothed using the Fourier transform with a 3 Hz cutoff frequency. The hyperparameter optimization was carried out with ten traces, and the optimal hyperparameters were evaluated on the remaining 83 traces., Results: For smooth traces, the wavelet least mean squares prediction filter and the linear filter reached normalized root mean square errors of below 0.05 for time delays of 160 and 480 ms, respectively. For noisy signals, the performance of the prediction filters deteriorated and led to similar results., Conclusions: Linear methods for prediction filters are sufficient for respiratory motion signals. Reducing the measurement noise generally improves the performance of the prediction filters investigated in this study, even during breathing irregularities., (© 2019 American Association of Physicists in Medicine.)

Introduction: Intrafractional motion can cause substantial uncertainty in precision radiotherapy. Traditionally, the target volume is defined to be sufficiently large to cover the tumor in every position. With the robotic treatment couch, a real-time motion compensation can improve tumor coverage and organ at risk sparing. However, this approach poses additional requirements, which are systematically developed and which allow the ideal robotic couch to be specified., Methods and Materials: Data of intrafractional tumor motion were collected and analyzed regarding motion range, frequency, speed, and acceleration. Using this data, ideal couch requirements were formulated. The four robotic couches Protura, Perfect Pitch, RoboCouch, and RPSbase were tested with respect to these requirements., Results: The data collected resulted in maximum speed requirements of 60 mm/s in all directions and maximum accelerations of 80 mm/s 2 in the longitudinal, 60 mm/s 2 in the lateral, and 30 mm/s 2 in the vertical direction. While the two robotic couches RoboCouch and RPSbase completely met the requirements, even these two showed a substantial residual motion (40% of input amplitude), arguably due to their time delays., Conclusion: The requirements for the motion compensation by an ideal couch are formulated and found to be feasible for currently available robotic couches. However, the performance these couches can be improved further regarding the position control if the demanded speed and acceleration are taken into account as well., (© 2019 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([ 18 F]FDG) and [ 18 F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti-TNF antibody, for 4 weeks. Before and after treatment period, mice received either [ 18 F]FDG, for detecting inflammatory processes, or [ 18 F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUV mean ) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [ 18 F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [ 18 F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti-TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [ 18 F]FDG µPET/CT imaging allows to quantify and monitor inflammation-mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc., (© 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.)

Food standards and quality control are important means to ensure public health. In the last decade, melamine has become a rather notorious example of food adulteration: Spiking products with low-cost melamine in order to feign high amino acid content exploits the lack in specificity of the established Kjeldahl method for determining organic nitrogen. This work discusses the responses of a sensor based on quartz crystal microbalances (QCM) coated with molecularly imprinted polymers (MIP) to detect melamine in real life matrices both in a selective and a sensitive manner. Experiments in pure milk revealed no significant sensor responses. However, sensor response increased to a frequency change of -30Hz after diluting the matrix ten times. Systematic evaluation of this effect by experiments in melamine solutions containing bovine serum albumin (BSA) and casein revealed that proteins noticeably influence sensor results. The signal of melamine in water (1600 mg/L) decreases to half of its initial value, if either 1% BSA or casein are present. Higher protein concentrations decrease sensor responses even further. This suggests significant interaction between the analyte and proteins in general. Follow-up experiments revealed that centrifugation of tagged serum samples results in a significant loss of sensor response, thereby further confirming the suspected interaction between protein and melamine.

Purpose: The melanin-concentrating hormone receptor 1 (MCHR1) has become an important pharmacological target, since it may be involved in various diseases, such as diabetes, insulin resistance, and obesity. Hence, a suitable positron emission tomography radiotracer for the in vivo assessment of the MCHR1 pharmacology is imperative. The current paper contrasts the extensive in vitro, in vivo, and ex vivo assessments of the radiotracers [ 18 F]FE@SNAP and [ 11 C]SNAP-7941 and provides comprehensive information about their biological and physicochemical properties. Furthermore, it examines their suitability for first-in-man imaging studies., Procedures: Kinetic real-time cell-binding studies with [ 18 F]FE@SNAP and [ 11 C]SNAP-7941 were conducted on adherent Chines hamster ovary (CHO-K1) cells stably expressing the human MCHR1 and MCHR2. Small animal imaging studies on mice and rats were performed under displacement and baseline conditions, as well as after pretreatment with the P-glycoprotein/breast cancer resistant protein inhibitor tariquidar. After the imaging studies, detailed analyses of the ex vivo biodistribution were performed. Ex vivo metabolism was determined in rat blood and brain and analyzed at various time points using a quantitative radio-HPLC assay., Results: [ 11 C]SNAP-7941 demonstrates high uptake on CHO-K1-hMCHR1 cells, whereas no uptake was detected for the CHO-K1-hMCHR2 cells. In contrast, [ 18 F]FE@SNAP evinced binding to CHO-K1-hMCHR1 and CHO-K1-hMCHR2 cells. Imaging studies with [ 18 F]FE@SNAP and [ 11 C]SNAP-7941 showed an increased brain uptake after tariquidar pretreatment in mice, as well as in rats, and exhibited a significant difference between the time-activity curves of the baseline and blocking groups. Biodistribution of both tracers demonstrated a decreased uptake after displacement. [ 11 C]SNAP-7941 revealed a high metabolic stability in rats, whereas [ 18 F]FE@SNAP was rapidly metabolized., Conclusions: Both radiotracers demonstrate appropriate imaging properties for the MCHR1. However, the pronounced metabolic stability as well as superior selectivity and affinity of [ 11 C]SNAP-7941 underlines the decisive superiority over [ 18 F]FE@SNAP.

Background: Peripherally inserted central catheters (PICCs) provide secure intravenous access for the delivery of life-sustaining medications and nutrition. They are commonly used in pediatrics. Confirmation of correct central catheter tip position is crucial. Verification is usually done by a radiograph. The aim of this study is to evaluate the ability of Fractional Multiscale image Processing (FMP) to detect PICC tips on the digital chest radiographs of neonates., Methods: A total of 94 radiographs of 47 patients were included in the study. 29 patients were male, 18 were female. The mean age of all examined children was 9.2 days (range 0-99 days). In total, six readers (two radiologists, two residents in radiology, one last year medical student, one neonatologist) evaluated 94 unprocessed and catheter-enhanced radiographs using a 5-point Likert scale (1 = poor catheter tip visualization, 5 = excellent catheter tip visualization). Additionally, the two radiologists evaluated the diagnostic confidence for chest pathologies using a 5-point Likert scale (1 = poor diagnostic confidence, 5 = excellent diagnostic confidence). Radiographs were evaluated on a dedicated workstation., Results: In all cases, the catheter-enhanced radiograph rated higher than (n = 471), or equal (n = 93) to, the unprocessed radiograph when visualizing catheter tips. 87% of the catheter-enhanced radiographs obtained a rating of 4 or higher, while only 42% of unprocessed radiographs received 4 or more points. Regarding diagnostic confidence for chest pathologies one radiologist rated two catheter-enhanced radiographs higher than the unprocessed radiographs, while all other 186 evaluations rated the catheter-enhanced radiographs equal to (n = 78) or lower than (n = 108) the unprocessed radiographs. Only 60% of the catheter-enhanced radiographs yielded a diagnostic confidence of 4 or higher, while 90% of the unprocessed images received 4 or more points., Conclusion: Catheter-enhanced digital chest radiographs demonstrate improved visualization of low contrast PICC tips in neonates compared to unprocessed radiographs. Furthermore, they enable detection of accompanying chest pathologies. However, definitive diagnosis of chest pathologies should be made on unprocessed radiographs.

In precision radiotherapy, the intrafractional motion can cause a considerable uncertainty of the location of the tumor to be treated. An established approach is the expansion of the target volume to account for the motion. An alternative approach is couch-tracking, in which the patient is continually moved to compensate the intrafractional motion. However, couch-tracking itself might induce uncertainty of the patient's body position, because the body is non-rigid. One hundred healthy volunteers were positioned supine on a robotic couch. Optical markers were placed on the torso of the volunteers as well as on the couch, and their positions were tracked with an optical surface measurement system. Using these markers, the uncertainty of the body position relative to the couch position was estimated while the couch was static or moving. Over the included 83 healthy volunteers, the median of the uncertainty increased by 0.8 mm (SI), 0.4 mm (LR) and 0.4 mm (AP) when the couch moved. Couch motion was found to increase the uncertainty of the body position relative to the couch. However, this uncertainty is one order of magnitude smaller than the intrafractional tumor motion amplitudes to be compensated. Therefore, even with body motion present, the couch-tracking approach is a viable option. The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal (SNCTP000001878).

Introduction: Due to the high candidate exclusion rate during a drug development process, an early prediction of the pharmacokinetic behavior would be needed. Accordingly, high performance bioaffinity chromatography (HPBAC) approaches are growing in popularity, however, there is a lack of knowledge and no consensus about the relation between HPBAC measurements, in vivo distribution and blood brain barrier (BBB) penetration behavior. With respect to radiotracers, there is almost no reference data available for plasma protein binding (PPB), permeability (Pm) and the membrane coefficient (K IAM ). Thus, this study was aimed at exploring the relevance of measuring PPB, Pm and K IAM for the prediction of BBB penetration., Methods: Measurements of %PPB, Pm and K IAM were performed using HPBAC. In total, 113 compounds were tested, 43 with brain uptake, 30 not showing brain uptake and 40 with known interactions with efflux transporters. Additionally, ClogP and HPLC logP ow pH7.4 data were collected., Results: %PPB, K IAM , Pm and ClogP values were in the same range for each of the three groups. A significant difference was observed for the HPLC logP ow pH7.4 between CNS penetrating drug group (CNS pos ) and the non-penetrating drug group (CNS neg ), as well as for the CNS neg towards the drug group interacting with efflux transporters (DRUG efflux ). However, as the other experimental data, also the HPLC logP ow pH7.4 showed a broad overlapping of the single values between the groupings., Conclusion: Experimental reference values (logP, Pm, K IAM & PPB) of commonly used PET tracers and drugs showing different BBB penetration behavior are provided. The influence of the logP on brain uptake depends strongly on the selected method. However, using a single parameter (experimental or calculated) to predict BBB penetration or for the classification of drug groups is inexpedient., (Copyright © 2017. Published by Elsevier Inc.)

Background: Resolving the kinetic mechanisms of biomolecular interactions have become increasingly important in early-phase drug development. Since traditional in vitro methods belong to dose-dependent assessments, binding kinetics is usually overlooked. The present study aimed at the establishment of two novel experimental approaches for the assessment of binding affinity of both, radiolabelled and non-labelled compounds targeting the A 3 R, based on high-resolution real-time data acquisition of radioligand-receptor binding kinetics. A novel time-resolved competition assay was developed and applied to determine the K i of eight different A 3 R antagonists, using CHO-K1 cells stably expressing the hA 3 R. In addition, a new kinetic real-time cell-binding approach was established to quantify the rate constants k on and k off , as well as the dedicated K d of the A 3 R agonist [ 125 I]-AB-MECA. Furthermore, lipophilicity measurements were conducted to control influences due to physicochemical properties of the used compounds., Results: Two novel real-time cell-binding approaches were successfully developed and established. Both experimental procedures were found to visualize the kinetic binding characteristics with high spatial and temporal resolution, resulting in reliable affinity values, which are in good agreement with values previously reported with traditional methods. Taking into account the lipophilicity of the A 3 R antagonists, no influences on the experimental performance and the resulting affinity were investigated., Conclusions: Both kinetic binding approaches comprise tracer administration and subsequent binding to living cells, expressing the dedicated target protein. Therefore, the experiments resemble better the true in vivo physiological conditions and provide important markers of cellular feedback and biological response.

Background: Intrafractional motion can be a substantial uncertainty in precision radiotherapy. Conventionally, the target volume is expanded to account for the motion. Couch-tracking is an alternative, where the patient is moved to compensate for the tumor motion. However, the couch motion may influence the patient's stress and respiration behavior decreasing the couch-tracking effectiveness., Methods: In total, 100 volunteers were positioned supine on a robotic couch, which moved dynamically and respiration synchronized. During the measurement, the skin conductivity, the heartrate, and the gaze location were measured indicating the volunteer's stress. Volunteers rated the subjective motion sickness using a questionnaire. The measurement alternated between static and tracking segments (three cycles), each 1 min long., Results: The respiration amplitude showed no significant difference between tracking and static segments, but decreased significantly from the first to the last tracking segment (p < 0.0001). The respiration frequency differed significantly between tracking and static segments (p < 0.0001), but not between the first and the last tracking segment. The physiological parameters and the questionnaire showed mild signals of stress and motion sickness., Conclusion: Generally, people tolerated the couch motions. The interaction between couch motion and the patient's breathing pattern should be considered for a clinical implementation., Trial Registration: The study was registered at ClinicalTrials.gov (NCT02820532) and the Swiss national clinical trials portal ( SNCTP000001878 ) on June 20, 2016.

The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

Background: The melanin-concentrating hormone receptor 1 (MCHR1), which is highly expressed in the lateral hypothalamus, plays a key role in energy homeostasis, obesity and other endocrine diseases. Hence, there is a major interest in in vivo imaging of this receptor. A PET tracer would allow non-invasive in vivo visualization and quantification of the MCHR1. The aim of the study was the ex vivo evaluation of the MCHR1 ligand [(18)F]FE@SNAP as a potential PET tracer for the MCHR1., Methods: [(18)F]FE@SNAP was injected directly into the jugular vein of awake naïve rats for ex vivo brain autoradiography, biodistribution and additional blood metabolite analysis. Blocking experiments were conducted using the unlabeled MCHR1 ligand SNAP-7941., Results: A high uptake of [(18)F]FE@SNAP was observed in the lateral hypothalamus and the ventricular system. Both regions were significantly blocked by SNAP-7941. Biodistribution evinced the highest uptake in the kidneys, adrenals, lung and duodenum. Specific blocking with SNAP-7941 led to a significant tracer reduction in the heart and adrenals. In plasma samples, 47.73 ± 6.1 % of a hydrophilic radioactive metabolite was found 45 min after tracer injection., Conclusions: Since [(18)F]FE@SNAP uptake was significantly blocked in the lateral hypothalamus, there is strong evidence that [(18)F]FE@SNAP is a highly suitable agent for specific MCHR1 imaging in the central nervous system. Additionally, this finding is supported by the specific blocking in the ventricular system, where the MCHR1 is expressed in the ependymal cells. These findings suggest that [(18)F]FE@SNAP could serve as a useful imaging and therapy monitoring tool for MCHR1-related pathologies.

Diagnostic imaging of head and neck cancer has made enormous progress during recent years. Next to morphological imaging modalities (computed tomography [CT] and magnetic resonance imaging [MRI]), there are also hybrid imaging systems that combine functional and morphological information (positron emission tomography [PET]/CT and PET/MRI). The aim of this study was to compare the diagnostic accuracy of PET/MRI in the diagnosis of head and neck cancer with other imaging modalities (MRI, CT, PET/CT). Ten patients (nine male and one female) with histologically proven oral squamous cell carcinoma participated in an 18 F-FDG-PET/CT scan and an additional 18 F-FDG PET/MRI scan prior to surgery. The morphological and functional results were compared with the histological results. Inclusion criteria were histologically proven oral squamous cell carcinoma and no prior surgical intervention, medical therapy, or local external radiation. There was no significant correlation between tumor differentiation and maximum standard uptake values. Functional imaging showed a slightly better correlation with the measurement of the maximal tumor diameter, whereas pure morphological imaging showed a better correlation with the measurement of infiltration depth. Only with PET/MRI could correct lymph node staging be reached; the other imaging tools showed false-negative or false-positive results. In conclusion, we showed in our limited patient cohort that PET/MRI is superior to the morphological imaging modalities, especially for lymph node staging., (Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Purpose: The adenosine A3 receptor (A3R) is involved in cardiovascular, neurological and tumour-related pathologies and serves as an exceptional pharmaceutical target in the clinical setting. A3R antagonists are considered antiinflammatory, antiallergic and anticancer agents, and to have potential for the treatment of asthma, COPD, glaucoma and stroke. Hence, an appropriate A3R PET tracer would be highly beneficial for the diagnosis and therapy monitoring of these diseases. Therefore, in this preclinical in vivo study we evaluated the potential as a PET tracer of the A3R antagonist [(18)F]FE@SUPPY., Methods: Rats were injected with [(18)F]FE@SUPPY for baseline scans and blocking scans (A3R with MRS1523 or FE@SUPPY, P-gp with tariquidar; three animals each). Additionally, metabolism was studied in plasma and brain. In a preliminary experiment in a mouse xenograft model (mice injected with cells expressing the human A3R; three animals), the animals received [(18)F]FE@SUPPY and [(18)F]FDG. Dynamic PET imaging was performed (60 min in rats, 90 min in xenografted mice). In vitro stability of [(18)F]FE@SUPPY in human and rat plasma was also evaluated., Results: [(18)F]FE@SUPPY showed high uptake in fat-rich regions and low uptake in the brain. Pretreatment with MRS1523 led to a decrease in [(18)F]FE@SUPPY uptake (p = 0.03), and pretreatment with the P-gp inhibitor tariquidar led to a 1.24-fold increase in [(18)F]FE@SUPPY uptake (p = 0.09) in rat brain. There was no significant difference in metabolites in plasma and brain in the treatment groups. However, plasma concentrations of [(18)F]FE@SUPPY were reduced to levels similar to those in rat brain after blocking. In contrast to [(18)F]FDG uptake (p = 0.12), the xenograft model showed significantly increased uptake of [(18)F]FE@SUPPY in the tissue masses from CHO cells expressing the human A3R (p = 0.03). [(18)F]FE@SUPPY was stable in human plasma., Conclusion: Selective and significant tracer uptake of [(18)F]FE@SUPPY was found in xenografted mice injected with cells expressing human A3R. This finding supports the strategy of evaluating [(18)F]FE@SUPPY in "humanized animal models". In conclusion, preclinical evaluation points to the suitability of [(18)F]FE@SUPPY as an A3R PET tracer in humans.

A reinvestigation of the lithium-rich section of the Li-Ge phase diagram reveals the existence of two new phases, Li17Ge4 and Li4.10Ge (Li16.38Ge4). Their structures are determined by X-ray diffraction experiments of large single crystals obtained from equilibrated melts with compositions Li95Ge5 and Li85Ge15. Excess melt is subsequently removed through isothermal centrifugation at 400 °C and 530 °C, respectively. Li17Ge4 crystallizes in the space group F4[combining macron]3m (a = 18.8521(3) Å, V = 6700.1(2) Å(3), Z = 20, T = 298 K) and Li4.10Ge (Li16.38Ge4) in Cmcm (a = 4.5511(2) Å, b = 22.0862(7) Å, c = 13.2751(4) Å, V = 1334.37(8) Å(3), Z = 16, T = 123 K). Both phases are isotypic with their Si counterparts and are further representative of the Li17Pb4 and Li4.11Si structure types. Additionally, the solid solutions Li17Si4-xGex follows Vegard's law. A comparison of the GeLin coordination polyhedra shows that isolated Ge atoms are 13- and 14-coordinated in Li17Ge4, whereas in Li16.38Ge4 the Ge atoms possess coordination numbers 12 and 13. Regarding the thermodynamic stability, Li16.38Ge4 is assigned a high-temperature phase existing between ∼400 °C and 627 °C, whereas Li17Ge4 decomposes peritectically at 520-522 °C. Additionally, the decomposition of Li16.38Ge4 below ∼400 °C was found to be very sluggish. These findings are manifested by differential scanning calorimetry, long-term annealing experiments and the results from melt equilibration experiments. Interestingly, the thermodynamic properties of the lithium-rich tetrelides Li17Tt4 and Li4.1Tt (Li16.4Tt4) are very similar (Tt = Si, Ge). Besides Li15Tt4, Li14Tt6, Li12Tt7, and LiTt, the title compounds are further examples of isotypic tetrelides in the systems Li-Tt.

The novel ternary Zintl phase Li18Na2Ge17 was synthesized from a stoichiometric melt and characterized crystallographically. It crystallizes in the trigonal space group P31m (No. 157) with a = 17.0905(4) Å, c = 8.0783(2) Å, and V = 2043.43(8) Å(3) (final R indices R1 = 0.0212 and wR2 = 0.0420 for all data). The structure contains three different Zintl anions in a 1:1:1 ratio: isolated anions Ge(4-), tetrahedra [Ge4](4-), and truncated, Li-centered tetrahedra [Li@Ge12](11-), whose hexagonal faces are capped by four Li cations, resulting in the Friauf polyhedra [Li@Li4Ge12](7-). According to the Zintl-Klemm concept, Li18Na2Ge17 is an electronically balanced Zintl phase, as experimentally verified by its diamagnetism. The compound is structurally related to Li7RbGe8, which also contains [Ge4](4-) and [Li@Li4Ge12](7-) in its anionic substructure. However, exchanging the heavier alkali metal cation Rb for Na in the mixed-cation germanides leads to drastic changes in stoichiometry and crystal packing, demonstrating the great effects that cations exert on such Zintl phases through optimized cluster sheathing and space filling.