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Background: The adoption of four‐dimensional cone beam computed tomography (4DCBCT) for image‐guided lung cancer radiotherapy is increasing, especially for hypofractionated treatments. However, the drawbacks of 4DCBCT include long scan times (∼240 s), inconsistent image quality, higher imaging dose than necessary, and streaking artifacts. With the emergence of linear accelerators that can acquire 4DCBCT scans in a short period of time (9.2 s) there is a need to examine the impact that these very fast gantry rotations have on 4DCBCT image quality. Purpose: This study investigates the impact of gantry velocity and angular separation between x‐ray projections on image quality and its implication for fast low‐dose 4DCBCT with emerging systems, such as the Varian Halcyon that provide fast gantry rotation and imaging. Large and uneven angular separation between x‐ray projections is known to reduce 4DCBCT image quality through increased streaking artifacts. However, it is not known when angular separation starts degrading image quality. The study assesses the impact of constant and adaptive gantry velocity and determines the level when angular gaps impair image quality using state‐of‐the‐art reconstruction methods. Methods: This study considers fast low‐dose 4DCBCT acquisitions (60–80 s, 200‐projection scans). To assess the impact of adaptive gantry rotations, the angular position of x‐ray projections from adaptive 4DCBCT acquisitions from a 30‐patient clinical trial were analyzed (referred to as patient angular gaps). To assess the impact of angular gaps, variable and static angular gaps (20°, 30°, 40°) were introduced into evenly separated 200 projections (ideal angular separation). To simulate fast gantry rotations, which are on emerging linacs, constant gantry velocity acquisitions (9.2 s, 60 s, 120 s, 240 s) were simulated by sampling x‐ray projections at constant intervals using the patient breathing traces from the ADAPT clinical trial (ACTRN12618001440213). The 4D Extended Cardiac‐Torso (XCAT) digital phantom was used to simulate projections to remove patient‐specific image quality variables. Image reconstruction was performed using Feldkamp‐Davis‐Kress (FDK), McKinnon‐Bates (MKB), and Motion‐Compensated‐MKB (MCMKB) algorithms. Image quality was assessed using Structural Similarity‐Index‐Measure (SSIM), Contrast‐to‐Noise‐Ratio (CNR), Signal‐to‐Noise‐Ratio (SNR), Tissue‐Interface‐Width‐Diaphragm (TIW‐D), and Tissue‐Interface‐Width‐Tumor (TIW‐T). Results: Patient angular gaps and variable angular gap reconstructions produced similar results to ideal angular separation reconstructions, while static angular gap reconstructions produced lower image quality metrics. For MCMKB‐reconstructions, average patient angular gaps produced SSIM‐0.98, CNR‐13.6, SNR‐34.8, TIW‐D‐1.5 mm, and TIW‐T‐2.0 mm, static angular gap 40° produced SSIM‐0.92, CNR‐6.8, SNR‐6.7, TIW‐D‐5.7 mm, and TIW‐T‐5.9 mm and ideal produced SSIM‐1.00, CNR‐13.6, SNR‐34.8, TIW‐D‐1.5 mm, and TIW‐T‐2.0 mm. All constant gantry velocity reconstructions produced lower image quality metrics than ideal angular separation reconstructions regardless of the acquisition time. Motion compensated reconstruction (MCMKB) produced the highest contrast images with low streaking artifacts. Conclusion: Very fast 4DCBCT scans can be acquired provided that the entire scan range is adaptively sampled, and motion‐compensated reconstruction is performed. Importantly, the angular separation between x‐ray projections within each individual respiratory bin had minimal effect on the image quality of fast low‐dose 4DCBCT imaging. The results will assist the development of future 4DCBCT acquisition protocols that can now be achieved in very short time frames with emerging linear accelerators. [ABSTRACT FROM AUTHOR]

Background and Purpose Menthol, a naturally occurring compound in the essential oil of mint leaves, is used for its medicinal, sensory and fragrant properties. Menthol acts via transient receptor potential ( TRPM8 and TRPA1) channels and as a positive allosteric modulator of recombinant GABAA receptors. Here, we examined the actions of menthol on GABAA receptor-mediated currents in intact midbrain slices. Experimental Approach Whole-cell voltage-clamp recordings were made from periaqueductal grey ( PAG) neurons in midbrain slices from rats to determine the effects of menthol on GABAA receptor-mediated phasic IPSCs and tonic currents. Key Results Menthol (150-750 μM) produced a concentration-dependent prolongation of spontaneous GABAA receptor-mediated IPSCs, but not non- NMDA receptor-mediated EPSCs throughout the PAG. Menthol actions were unaffected by TRPM8 and TRPA1 antagonists, tetrodotoxin and the benzodiazepine antagonist, flumazenil. Menthol also enhanced a tonic current, which was sensitive to the GABAA receptor antagonists, picrotoxin (100 μM), bicuculline (30 μM) and Zn2+ (100 μM), but unaffected by gabazine (10 μM) and a GABAC receptor antagonist, 1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA; 50 μM). In addition, menthol potentiated currents induced by the extrasynaptic GABAA receptor agonist THIP/gaboxadol (10 μM). Conclusions and Implications These results suggest that menthol positively modulates both synaptic and extrasynaptic populations of GABAA receptors in native PAG neurons. The development of agents that potentiate GABAA-mediated tonic currents and phasic IPSCs in a manner similar to menthol could provide a basis for novel GABAA-related pharmacotherapies. [ABSTRACT FROM AUTHOR]