High-pitch CT pulmonary angiography (CTPA) with ultra-low contrast medium volume for the detection of pulmonary embolism: a comparison with standard CTPA.

OBJECTIVE: To investigate the feasibility and image quality of high-pitch CT pulmonary angiography (CTPA) with reduced iodine volume in normal weight patients. METHODS: In total, 81 normal weight patients undergoing CTPA for suspected pulmonary arterial embolism were retrospectively included: 41 in high-pitch mode with 20 mL of contrast medium (CM); and 40 with normal pitch and 50 mL of CM. Subjective image quality was assessed and rated on a 3-point scale. For objective image quality, attenuation and noise values were measured in all pulmonary arteries from the trunk to segmental level. Contrast-to-noise ratio (CNR) was calculated. Radiation dose estimations were recorded. RESULTS: There were no statistically significant differences in patient and scan demographics between high-pitch and standard CTPA. Subjective image quality was rated good to excellent in over 90% of all exams with no significant group differences (p = 0.32). Median contrast opacification was lower in high-pitch CTPA (283.18 [216.06-368.67] HU, 386.81 [320.57-526.12] HU; p = 0.0001). CNR reached a minimum of eight in all segmented arteries, but was lower in high-pitch CTPA (8.79 [5.82-12.42], 11.01 [9.19-17.90]; p = 0.005). Median effective dose of high-pitch CTPA was lower (1.04 [0.72-1.27] mSv/mGy·cm; 1.49 [1.07-2.05] mSv/mGy·cm; p < 0.0001). CONCLUSION: High-pitch CTPA using ultra-low contrast volume (20 mL) rendered diagnostic images for the detection of pulmonary arterial embolism in most instances. Compared to standard CTPA, the high-pitch CTPA exams with drastically reduced contrast medium volume had also concomitantly reduced radiation exposure. However, objective image quality of high-pitch CTPA was worse, though likely still within acceptable limits for confident diagnosis. CLINICAL RELEVANCE: This study provides valuable insights on the performance of a high-pitch dual-source CTPA protocol, offering potential benefits in reducing contrast medium and radiation dose while maintaining sufficient image quality for accurate diagnosis in patients suspected of pulmonary embolism. KEY POINTS: • High-pitch CT pulmonary angiography (CTPA) with ultra-low volume of contrast medium and reduced radiation dose renders diagnostic examinations with comparable subjective image quality to standard CTPA in most patients. • Objective image quality of high-pitch CTPA is reduced compared to standard CTPA, but contrast opacification and contrast-to-noise ratio remain above diagnostic thresholds. • Challenges of high-pitch CTPA may potentially be encountered in patients with severe heart failure or when performing a Valsalva maneuver during the examination.

KS0365, a novel activator of the transient receptor potential vanilloid 3 (TRPV3) channel, accelerates keratinocyte migration.

BACKGROUND AND PURPOSE: Ca2+ signalling mediated by the thermosensitive, non-selective, Ca2+ -permeable transient receptor potential channel TRPV3 is assumed to play a critical role in regulating several aspects of skin functions, such as keratinocyte proliferation, differentiation, skin barrier formation and wound healing. Studying the function of TRPV3 in skin homeostasis, however, is still constrained by a lack of potent and selective pharmacological modulators of TRPV3. EXPERIMENTAL APPROACH: By screening an in-house compound library using fluorometric intracellular Ca2+ assays, we identified two chemically related hits. The more potent and efficient TRPV3 activator 2-(2-chloro-3-isopropylcyclopent-2-en-1-yl)-4-methylphenol (KS0365) was further evaluated in fluo-4-assisted Ca2+ assays, different Ca2+ imaging approaches, electrophysiological studies, cytotoxicity and migration assays. KEY RESULTS: KS0365 activated recombinant and native mouse TRPV3 more potently and with a higher efficacy compared with 2-APB and did not activate TRPV2 or TRPV4 channels. The activation of TRPV3 by KS0365 super-additively accelerated the EGF-induced keratinocyte migration, which was inhibited by the TRP channel blocker ruthenium red or by siRNA-mediated TRPV3 knockdown. Moreover, KS0365 induced strong Ca2+ responses in migrating front cells and in leading edges of keratinocytes. CONCLUSIONS AND IMPLICATIONS: The selective TRPV3 activator KS0365 triggers increases in [Ca2+ ]i with most prominent signals in the leading edge and accelerates migration of keratinocytes. TRPV3 activators may promote re-epithelialization upon skin wounding.

TRPV3 endogenously expressed in murine colonic epithelial cells is inhibited by the novel TRPV3 blocker 26E01.

TRPV3 is a Ca2+-permeable cation channel, prominently expressed by keratinocytes where it contributes to maintaining the skin barrier, skin regeneration, and keratinocyte differentiation. However, much less is known about its physiological function in other tissues and there is still a need for identifying novel and efficient TRPV3 channel blockers. By screening a compound library, we identified 26E01 as a novel TRPV3 blocker. 26E01 blocks heterologously expressed TRPV3 channels overexpressed in HEK293 cells as assessed by fluorometric intracellular free Ca2+ assays (IC50 = 8.6 µM) but does not affect TRPV1, TRPV2 or TRPV4 channels. Electrophysiological whole-cell recordings confirmed the reversible block of TRPV3 currents by 26E01, which was also effective in excised inside-out patches, hinting to a rather direct mode of action. 26E01 suppresses endogenous TRPV3 currents in the mouse 308 keratinocyte cell line and in the human DLD-1 colon carcinoma cell line (IC50 = 12 µM). In sections of the gastrointestinal epithelium of mice, the expression of TRPV3 mRNA follows a gradient along the gastrointestinal tract, with the highest expression in the distal colon. 26E01 efficiently attenuates 2-aminoethoxydiphenyl borate-induced calcium influx in primary colonic epithelial cells isolated from the distal colon. As 26E01 neither shows toxic effects on DLD-1 cells at concentrations of up to 100 µM in MTT assays nor on mouse primary colonic crypts as assessed by calcein-AM/propidium iodide co-staining, it may serve as a useful tool to further study the physiological function of TRPV3 in various tissues.