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Background and Aims Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. Methods Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). Results Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (−0.098, 0.138), and of the carotids 0.014 (−0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. Conclusions In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings. [ABSTRACT FROM AUTHOR]

Rationale: There is upper airway inflammation in patients with obstructive sleep apnea (OSA), which reduces with continuous positive airway pressure (CPAP) therapy. Objectives: Validate the use of positron emission tomography (PET)/magnetic resonance imaging (MRI) to quantify metabolic activity within the pharyngeal mucosa of patients with OSA against nasal lavage proteomics and assess the impact of CPAP therapy. Methods: Adults with OSA underwent [18F]-Fluoro-2-deoxy-Dglucose PET/MRI of the neck before and 3 months after initiating CPAP. Nasal lavage samples were collected. Inflammatory protein expression from samples was analyzed using the Olink platform. Upper airway imaging segmentation was performed. Target-tobackground ratio (TBRmax) was calculated from target pharyngeal maximum standard uptake values (SUV) and personalized background mean SUV. Most-diseased segment TBRmax was identified per participant at locations with the highest PET avidity. Correlation analysis was performed between baseline TBRmax and nasal lavage proteomics. TBRmax was compared before and after CPAP using linear mixed-effect models. Results: Among 38 participants, the baseline mean age was 46.3 years (standard deviation [SD], 12.5), 21% were female, the mean body mass index was 30.9 kg/m² (SD, 4.6), and the mean respiratory disturbance index measured by peripheral arterial tonometry was 31 events/h (SD, 16.4). There was a significant positive correlation between pharyngeal mucosa most-diseased segment TBRmax and nasal lavage proteomic inflammation (r = 0.41 [P,0.001, false discovery rate = 0.002]). Primary analysis revealed a reduction in the most-diseased segment TBRmax after a median of 2.91 months of CPAP therapy (20.86 [standard error (SE)60.30; P = 0.007]). Stratified analysis by smoking status revealed a significantly decreased most-diseased segment TBRmax after CPAP therapy among never-smokers but not among ever-smokers (21.01 [SE60.39; P = 0.015] vs. 20.64 [SE60.49; P = 0.201]). Conclusions: CPAP therapy reduces metabolic activity measured by PET/MRI within the upper airway of adults with OSA. Furthermore, PET/MRI measures of upper airway metabolic activity correlate with a noninvasive marker of inflammation (i.e., nasal lavage inflammatory protein expression). [ABSTRACT FROM AUTHOR]

The current standard for measuring coronary artery calcification to determine the extent of atherosclerosis is by calculating the Agatston score from computed tomography (CT). However, the Agatston score disregards pixel values less than 130 Hounsfield Units (HU) and calcium regions less than 1 mm 2 . Due to this thresholding, the score is not sensitive to small, weakly attenuating regions of calcium deposition and may not detect nascent micro-calcification. A recently proposed metric called the spatially weighted calcium score (SWCS) also utilizes CT but does not include a threshold for HU and does not require elevated signals in contiguous pixels. Thus, the SWCS is sensitive to weakly attenuating, smaller calcium deposits and may improve the measurement of coronary heart disease risk. Currently, the SWCS is underutilized owing to the added computational complexity. To promote translation of the SWCS into clinical research and reliable, repeatable computation of the score, the aim of this study was to develop a semi-automatic graphical tool that calculates both the SWCS and the Agatston score. The program requires gated cardiac CT scans with a calcium hydroxyapatite phantom in the field of view. The phantom allows for deriving a weighting function, from which each pixel's weight is adjusted, allowing for the mitigation of signal variations and variability between scans. With all three anatomical views visible simultaneously, the user traces the course of the four main coronary arteries by placing points or regions of interest. Features such as scroll-to-zoom, double-click to delete, and brightness/contrast adjustment, along with written guidance at every step, make the program user-friendly and easy to use. Once tracing the arteries is complete, the program generates reports, which include the scores and snapshots of any visible calcium. The SWCS may reveal the presence of subclinical disease, which may be used for early intervention and lifestyle changes.