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

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