Ambient particulate matter (PM) exposure is associated with atherosclerosis and inflammatory bowel disease. Ultrafine particles (UFP, dp < 0.1–0.2 μm) are redox active components of PM. We hypothesized that orally ingested UFP promoted atherogenic lipid metabolites in both the intestine and plasma via altered gut microbiota composition. Low density lipoprotein receptor-null (Ldlr−/−) mice on a high-fat diet were orally administered with vehicle control or UFP (40 μg/mouse/day) for 3 days a week. After 10 weeks, UFP ingested mice developed macrophage and neutrophil infiltration in the intestinal villi, accompanied by elevated cholesterol but reduced coprostanol levels in the cecum, as well as elevated atherogenic lysophosphatidylcholine (LPC 18:1) and lysophosphatidic acids (LPAs) in the intestine and plasma. At the phylum level, Principle Component Analysis revealed significant segregation of microbiota compositions which was validated by Beta diversity analysis. UFP-exposed mice developed increased abundance in Verrocomicrobia but decreased Actinobacteria, Cyanobacteria, and Firmicutes as well as a reduced diversity in microbiome. Spearman’s analysis negatively correlated Actinobacteria with cecal cholesterol, intestinal and plasma LPC18:1, and Firmicutes and Cyanobacteria with plasma LPC 18:1. Thus, ultrafine particles ingestion alters gut microbiota composition, accompanied by increased atherogenic lipid metabolites. These findings implicate the gut-vascular axis in a atherosclerosis model.
In this study, we demonstrate that CEST fingerprinting is more efficient (5 times faster) compared with pulsed quantitative CEST. It is also shown that the results of the proposed CEST fingerprinting technique are much closer to the literature values than pulsed quantitative CEST at 3 T.
Purpose To develop a dynamic contrast‐enhanced (DCE) MRI method capable of high spatiotemporal resolution, 3D carotid coverage, and T1‐based quantification of contrast agent concentration for the assessment of carotid atherosclerosis using a newly developed Multitasking technique. Methods 5D imaging with 3 spatial dimensions, 1 T1 recovery dimension, and 1 DCE time dimension was performed using MR Multitasking based on low‐rank tensor modeling, which allows direct T1 quantification with high spatiotemporal resolution (0.7 mm isotropic and 595 ms, respectively). Saturation recovery preparations followed by 3D segmented fast low angle shot readouts were implemented with Gaussian‐density random 3D Cartesian sampling. A bulk motion removal scheme was developed to improve image quality. The proposed protocol was tested in phantom and human studies. In vivo scans were performed on 14 healthy subjects and 7 patients with carotid atherosclerosis. Kinetic parameters including area under the concentration versus time curve (AUC), vp, Ktrans, and ve were evaluated for each case. Results Phantom experiments showed that T1 measurements using the proposed protocol were in good agreement with reference value (R2=0.96). In vivo studies demonstrated that AUC, vp, and Ktrans in the patient group were significantly higher than in the control group (0.63 ± 0.13 versus 0.42 ± 0.12, P < 0.001; 0.14 ± 0.05 versus 0.11 ± 0.03, P = 0.034; and 0.13 ± 0.04 versus 0.08 ± 0.02, P < 0.001, respectively). Results from repeated subjects showed good interscan reproducibility (intraclass correlation coefficient: vp, 0.83; Ktrans, 0.87; ve, 0.92; AUC, 0.94). Conclusion Multitasking DCE is a promising approach for quantitatively assessing the vascularity properties of the carotid vessel wall.
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