Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel-Lindau disease-related tumours.

AIMS: Although inactivation of the von Hippel-Lindau gene (VHL) on chromosome 3p25 is considered to be the major cause of hereditary endolymphatic sac tumours (ELSTs), the genetic background of sporadic ELST is largely unknown. The aim of this study was to determine the prevalence of VHL mutations in sporadic ELSTs and compare their characteristics to VHL-disease-related tumours. METHODS: Genetic and epigenetic alterations were compared between 11 sporadic and 11 VHL-disease-related ELSTs by targeted sequencing and DNA methylation analysis. RESULTS: VHL mutations and small deletions detected by targeted deep sequencing were identified in 9/11 sporadic ELSTs (82%). No other cancer-related genetic pathway was altered except for TERT promoter mutations in two sporadic ELST and one VHL-disease-related ELST (15%). Loss of heterozygosity of chromosome 3 was found in 6/10 (60%) VHL-disease-related and 10/11 (91%) sporadic ELSTs resulting in biallelic VHL inactivation in 8/10 (73%) sporadic ELSTs. DNA methylation profiling did not reveal differences between sporadic and VHL-disease-related ELSTs but reliably distinguished ELST from morphological mimics of the cerebellopontine angle. VHL patients were significantly younger at disease onset compared to sporadic ELSTs (29 vs. 52 years, p < 0.0001, Fisher's exact test). VHL-disease status was not associated with an increased risk of recurrence, but the presence of clear cells was found to be associated with shorter progression-free survival (p = 0.0002, log-rank test). CONCLUSION: Biallelic inactivation of VHL is the main mechanism underlying ELSTs, but unknown mechanisms beyond VHL may rarely be involved in the pathogenesis of sporadic ELSTs.

Task-based assessment of neck CT protocols using patient-mimicking phantoms-effects of protocol parameters on dose and diagnostic performance.

OBJECTIVES: To assess how modifying multiple protocol parameters affects the dose and diagnostic performance of a neck CT protocol using patient-mimicking phantoms and task-based methods. METHODS: Six patient-mimicking neck phantoms containing hypodense lesions of 1 cm diameter and 30 HU contrast and one non-lesion phantom were examined with 36 CT protocols. All possible combinations of the following parameters were investigated: 100- and 120-kVp tube voltage; tube current modulation (TCM) noise levels of SD 7.5, 10, and 14; pitches of 0.637, 0.813, and 1.388; filtered back projection (FBP); and iterative reconstruction (AIDR 3D). Dose-length products (DLPs) and lesion detectability (assessed by 14 radiologists) were compared with the clinical standard protocol (120 kVp, TCM SD 7.5, 0.813 pitch, AIDR 3D). RESULTS: The DLP of the standard protocol was 25 mGy•cm; the area under the curve (AUC) was 0.839 (95%CI: 0.790-0.888). Combined effects of tube voltage reduction to 100 kVp and TCM noise level increase to SD 10 optimized protocol performance by improving dose (7.3 mGy•cm) and detectability (AUC 0.884, 95%CI: 0.844-0.924). Diagnostic performance was significantly affected by the TCM noise level at 120 kVp (AUC 0.821 at TCM SD 7.5 vs. 0.776 at TCM SD 14, p = 0.003), but not at 100-kVp tube voltage (AUC 0.839 at TCM SD 7.5 vs. 0.819 at TCM SD 14, p = 0.354), the reconstruction method at 100 kVp (AUC 0.854 for AIDR 3D vs. 0.806 for FBP, p < 0.001), but not at 120-kVp tube voltage (AUC 0.795 for AIDR 3D vs. 0.793 for FBP, p = 0.822), and the tube voltage for AIDR 3D reconstruction (p < 0.001), but not for FBP (p = 0.226). CONCLUSIONS: Combined effects of 100-kVp tube voltage, TCM noise level of SD 10, a pitch of 0.813, and AIDR 3D resulted in an optimal neck protocol in terms of dose and diagnostic performance. Protocol parameters were subject to complex interactions, which created opportunities for protocol improvement. KEY POINTS: • A task-based approach using patient-mimicking phantoms was employed to optimize a CT system for neck imaging through systematic testing of protocol parameters. • Combined effects of 100-kVp tube voltage, TCM noise level of SD 10, a pitch of 0.813, and AIDR 3D reconstruction resulted in an optimal protocol in terms of dose and diagnostic performance. • Interactions of protocol parameters affect diagnostic performance and should be considered when optimizing CT techniques.

Scout-guided needle placement-a technical approach for dose reduction in CT-guided periradicular infiltration.

PURPOSE: To develop and evaluate a technical approach for CT-guided periradicular infiltration using quantitative needle access and guidance parameters extracted from CT scout images. METHODS: Five 3D-printed phantoms of the abdomen mimicking different patients were used to develop a technical approach for scout-guided periradicular infiltration. The needle access point, puncture depth, and needle angulation were calculated using measurements extracted from anterior-posterior and lateral CT scout images. Fifty needle placements were performed with the technique thus developed. Dose exposure and number of image acquisitions were compared with ten procedures performed using a conventional free-hand technique. Data were analyzed with the Mann-Whitney U test. RESULTS: Parameters derived solely from scout images provided adequate guidance for successful and reliable needle placement. Needle guidance was performed with the same equipment as the standard periradicular infiltration. Two scout images and 3.5 ± 2.3 (mean ± SD) single-shot images for needle positioning were acquired. Mean DLP ± SD was 3.8 ± 2.5 mGy cm. The number of single-shot acquisitions was reduced by 68% and the overall dose was reduced by 84% in comparison with the conventional free-hand technique (p < 0.0001). CONCLUSION: Scout-guided needle placement for periradicular infiltration is feasible and reduces radiation exposure significantly.

A radiopaque 3D printed, anthropomorphic phantom for simulation of CT-guided procedures.

OBJECTIVES: To develop an anthropomorphic phantom closely mimicking patient anatomy and to evaluate the phantom for the simulation of computed tomography (CT)-guided procedures. METHODS: Patient CT images were printed with aqueous potassium iodide solution (1 g/mL) on paper. The printed paper sheets were stacked in alternation with 1-mm thick polyethylene foam layers, cut to the patient shape and glued together to create an anthropomorphic abdomen phantom. Ten interventional radiologists performed periradicular infiltration on the phantom and rated the phantom procedure regarding different aspects of suitability for simulating CT-guided procedures. RESULTS: Radiopaque printing in combination with polyethylene foam layers achieved a phantom with detailed patient anatomy that allowed needle placement. CT-guided periradicular infiltration on the phantom was rated highly realistic for simulation of anatomy, needle navigation and overall course of the procedure. Haptics were rated as intermediately realistic. Participants strongly agreed that the phantom was suitable for training and learning purposes. CONCLUSIONS: A radiopaque 3D printed, anthropomorphic phantom provides a realistic platform for the simulation of CT-guided procedures. Future work will focus on application for training and procedure optimisation. KEY POINTS: • Radiopaque 3D printing combined with polyethylene foam achieves patient phantoms for CT-guided procedures. • Radiopaque 3D printed, anthropomorphic phantoms allow realistic simulation of CT-guided procedures. • Realistic visual guidance is a key aspect in simulation of CT-guided procedures. • Three-dimensional printed phantoms provide a platform for training and optimisation of CT-guided procedures.

Training of CT-guided Periradicular Therapy in a Realistic Simulation Environment - Evaluation and Recommendations for a Training Curriculum.

RATIONALE AND OBJECTIVES: To evaluate the training of computed tomography (CT)-guided periradicular therapy in a realistic simulation environment and to derive recommendations for a training curriculum. MATERIALS AND METHODS: A novel simulation environment including the use of a 3D printed, patient-mimicking phantom was used to train medical students to perform CT-guided periradicular therapy of the lumbar spine. Seventeen participants underwent three training sessions (day 0, day 7, and after day 28) with six procedures per session. Procedure duration and the number of fluoroscopy image acquisitions were recorded. Participants' performance was assessed by an independent investigator using a six-point checklist scale (0 = lowest, 6 = highest). In addition, participants self-evaluated their skills and the simulation training in questionnaires. RESULTS: Procedure durations and image acquisitions decreased after one training session (p < 0.001) without further improvement thereafter (p > 0.6). They also decreased within training sessions and were lowest after five procedures in all sessions. Performance scores improved after the first session to nearly perfect scores in the second session (mean 5.7; 95%CI: 5.5-6.0; p < 0.001) and decreased again in the third session (mean 4.9; 95%CI: 4.6-5.3; p = 0.008). Participants were satisfied with their training progress and felt adequately prepared to perform CT-guided periradicular therapies on patients after the training. CONCLUSION: Simulation-based training of CT-guided periradicular therapy in a realistic environment is effective and should ideally be performed with one training session consisting of five procedures shortly before treating the first patient.

Multimodality cardiac computed tomography angiography and magnetic resonance with clinical-grade scanners provide robust assessment of cardiac morphology and function in rabbits.

BACKGROUND: Non-invasive computer tomography (CT)- and magnetic resonance (MR)-based cardiac imaging still remains challenging in rodents. To investigate the robustness of non-invasive multimodality cardiac imaging in rabbits using clinical-grade CT and MR scanners. METHODS: A total of 16 rabbits (2.7-4.0 kg) serially underwent cardiac-gated imaging using a clinical-grade 256-row CT and a 1.5 Tesla MR-scanner at baseline and at 4-month follow-up (16±1 weeks). Image analysis included image quality (5-grade scale), left ventricular (LV) volumes, LV stroke volume, LV diameters, LV wall thickness and ejection fraction (LVEF). RESULTS: Cardiac MR (CMR) and CT angiography (CTA) provide images with an overall good image quality (excellent or good quality: CMR 82% vs. CTA 78%, P=0.68). Linear regression analysis demonstrated a good correlation of all diameters (diam.) and volumes (vol.) as assessed by CTA and CMR (diam.: r=0.9, 95% CI: 0.8-0.9; vol.: r=0.8, 95% CI: 0.6-0.9; P<0.0001 for both). CTA-based volumetric analysis revealed slightly higher LVEF values as compared to CMR (CTA: 64%±1%, CMR: 59%±1%, P=0.002). Analysis of inter-/intra-observer agreement demonstrated excellent agreements for diameters (CMR: 98.5%/98.7%; CTA: 98.2%/97.4%) and volumes (CMR: 99.9%/98.8%; CTA 98.7%/98.7%). Finally, serial CMR- and CTA-based assessment of cardiac diameters and volumes delivered excellent intersession agreements of baseline versus follow-up data (diam.: CMR: r=0.89; CTA: r=0.92; vol.: CMR: r=0.87; CTA: r=0.96, P<0.0001 for all). CONCLUSIONS: Multimodality non-invasive assessment of cardiac function and aortic hemodynamics is feasible and robust in rabbits using clinical-grade and MR and CT scanners. These imaging modalities could improve serial cardiac assessment for disease monitoring in preclinical settings.