The association between the renin-angiotensin system and the hypothalamic-pituitary-adrenal axis in anxiety disorders: A systematic review of animal studies.

Anxiety is characterized as the emotional response in anticipation of a future threat. This hypervigilant state comprehends a cascade of neuroendocrine and physiological processes, involving the renin-angiotensin system (RAS) and hypothalamic-pituitary-adrenal axis (HPA). Excessive and chronic anxiety may ultimately lead to the development of anxiety disorders. This systematic review aimed to investigate experimental studies using animal models that explored the relationship between RAS and the HPA axis in anxiety disorders. A systematic search was conducted in MEDLINE/PubMed, Embase and Web of Science, and was performed according to PRISMA guidelines. The inclusion criteria was mainly the mention of RAS, HPA axis, and an anxiety disorder in the same study. Quality of studies was evaluated according to the table of risk of bias from SYRCLE. From 12 eligible studies, 7 were included. Research in rats and mice shows that the overactivation of the RAS and HPA axis triggers several neuroendocrine reactions, mainly mediated by AT1 receptors, which promote anxiety-like behaviors and positive feedback for its hyperactivation. On the contrary, the administration of antihypertensive drugs, such as angiotensin AT1 receptor blocker, propitiated the regulation of the RAS and HPA axis, maintaining homeostasis even amid aversive situations. Assessment of risk of bias revealed a pronounced unclear to high risk in several categories, which thus jeopardize the comparability and reproducibility of the results. Nonetheless, the preclinical evidence indicates that the hyperactivation of both RAS and HPA axis during stress exerts deleterious consequences, inducing anxiogenic responses. Moreover, the compiled results show that the modulation of both systems by the administration of AT1 receptor blockers produce anxiolytic effects in animal models and may constitute a new venue for the treatment of anxiety-like disorders.

ECG-gated quiescent-interval single-shot MR angiography of the lower extremities: initial experience at 3 T.

AIM: To evaluate the feasibility of unenhanced electrocardiography (ECG)-gated quiescent-interval single-shot magnetic resonance angiography (QISS-MRA) of the lower extremities at 3 T. MATERIALS AND METHODS: Twenty-five patients with known or suspected peripheral arterial disease underwent ECG-gated QISS-MRA and contrast-enhanced MRA (CE-MRA) at 3 T. Two independent readers performed a per-segment evaluation of the MRA datasets. Image quality was rated on a four-point scale (1 = excellent to 4 = non-diagnostic; presented as medians with interquartile range). Diagnostic performance of QISS-MRA was evaluated using CE-MRA as the reference standard. RESULTS: QISS-MRA and CE-MRA of all patients were considered for analysis, resulting in 807 evaluated vessel segments for each MRA technique. Readers 1 and 2 rated image quality of QISS-MRA as diagnostic in 97.3% and 97% of the vessel segments, respectively. CE-MRA was rated diagnostic in all vessel segments. Image quality of the proximal vessel segments, including the infrarenal aorta, iliac arteries, and common femoral artery, was significantly lower on QISS-MRA compared to CE-MRA [image quality score across readers: 2 (1,3) versus 1 (1,1) p < 0.001]. In the more distal vessel segments, image quality of QISS-MRA was excellent and showed no significant difference compared to CE-MRA [image quality score across readers: 1 (1,1) versus 1 (1,1) p = 0.036]. Diagnostic performance of QISS-MRA was as follows (across readers): sensitivity: 87.5% (95% CI: 80.2-92.4%); specificity: 96.1% (95% CI: 93.6-97.6%); diagnostic accuracy: 94.9% (95% CI: 92.6-96.5%). CONCLUSIONS: QISS-MRA of the lower extremities is feasible at 3 T and provides high image quality, especially in the distal vessel segments.

Computer-aided pulmonary nodule detection - performance of two CAD systems at different CT dose levels.

PURPOSE: To evaluate the impact of dose reduction on the performance of computer-aided lung nodule detection systems (CAD) of two manufacturers by comparing respective CAD results on ultra-low-dose computed tomography (ULD-CT) and standard dose CT (SD-CT). MATERIALS AND METHODS: Multi-slice computed tomography (MSCT) data sets of 26 patients (13 male and 13 female, patients 31 - 74 years old) were retrospectively selected for CAD analysis. Indication for CT examination was staging of a known primary malignancy or suspected pulmonary malignancy. CT images were consecutively acquired at 5 mAs (ULD-CT) and 75 mAs (SD-CT) with 120 kV tube voltage (1 mm slice thickness). The standard of reference was determined by three experienced readers in consensus. CAD reading algorithms (pre-commercial CAD system, Philips, Netherlands: CAD-1; LungCARE, Siemens, Germany: CAD-2) were applied to the CT data sets. RESULTS: Consensus reading identified 253 nodules on SD-CT and ULD-CT. Nodules ranged in diameter between 2 and 41 mm (mean diameter 4.8 mm). Detection rates were recorded with 72 % and 62 % (CAD-1 vs. CAD-2) for SD-CT and with 73 % and 56 % for ULD-CT. Median false positive rates per patient were calculated with 6 and 5 (CAD-1 vs. CAD-2) for SD-CT and with 8 and 3 for ULD-CT. After separate statistical analysis of nodules with diameters of 5 mm and greater, the detection rates increased to 83 % and 61 % for SD-CT and to 89 % and 67 % for ULD-CT (CAD-1 vs. CAD-2). For both CAD systems there were no significant differences between the detection rates for standard and ultra-low-dose data sets (p > 0.05). CONCLUSION: Dose reduction of the underlying CT scan did not significantly influence nodule detection performance of the tested CAD systems.

Linear and volume measurements of pulmonary nodules at different CT dose levels - intrascan and interscan analysis.

PURPOSE: To compare the interobserver variability of the unidimensional diameter and volume measurements of pulmonary nodules in an intrascan and interscan analysis using semi-automated segmentation software on ultra-low-dose computed tomography (ULD-CT) and standard dose CT (SD-CT) data. MATERIALS AND METHODS: In 33 patients with pulmonary nodules, two chest multi-slice CT (MSCT) datasets (1 mm slice thickness; 20 % reconstruction overlap) had been consecutively acquired with an ultra-low dose (120 kV, 5 mAs) and standard dose technique (120 kV, 75 mAs). MSCT data was retrospectively analyzed using the segmentation software OncoTREAT (MeVis, Bremen, Germany, version 1.3). The volume of 229 solid pulmonary nodules included in the analysis as well as the largest diameter according to RECIST (Response Evaluation Criteria for Solid Tumors) were measured by two radiologists. Interobserver variability was calculated and SD-CT and ULD-CT data compared in an intrascan and interscan analysis. RESULTS: The median nodule diameter (n = 229 nodules) was registered with 8.2 mm (range: 2.8 to 43.6 mm, mean: 10.8 mm). The nodule volume ranged between 0.01 and 49.1 ml (median 0.1 ml, mean 1.5 ml). With respect to interobserver variability, the intrascan analysis did not reveal statistically significant differences (p > 0.05) between ULD-CT and SD-CT with broader limits of agreement for relative differences of RECIST measurements (-31.0 % + 27.0 % mean -2.0 % for SD-CT; -27.0 % + 38.6 %, mean 5.8 % for ULD-CT) than for volume measurements (-9.4 %, 8.0 %, mean 0.7 % for SD-CT; -13 %, 13 %, mean 0.0 % for ULD-CT). The interscan analysis showed broadened 95 % confidence intervals for volume measurements (-26.5 % 29.1 % mean 1.3 %, and -25.2 %, 29.6 %, mean 2.2 %) but yielded comparable limits of agreement for RECIST measurements. CONCLUSION: The variability of nodule volumetry assessed by semi-automated segmentation software as well as nodule size determination by RECIST appears to be independent of the acquisition dose in the CT source dataset. This is particularly important regarding size determination of pulmonary nodules in screening trials using low-dose CT data for follow-up imaging.