bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/807420

Inter-reader agreement of 18F-FDG PET/CT for the quantification of carotid artery plaque inflammation

Johnsrud, K.·Seierstad, T.·Russell, D.·Revheim, M.-E.
View original source ↗Export metadata ↓

Abstract

BackgroundA significant proportion of ischemic strokes are caused by emboli from unstable atherosclerotic carotid artery plaques with inflammation being a key feature of plaque instability and stroke risk. Positron emission tomography (PET) depicting the uptake of 2-deoxy-2-(18F)-fluoro-D-glucose (18F-FDG) in carotid artery plaques is a promising technique to quantify plaque inflammation. A consensus on the methodology for plaque localization and quantification of inflammation by 18F-FDG PET/computed tomography (CT) in atherosclerosis has not been established. High inter-reader agreement is essential if 18F-FDG PET/CT is to be used as a clinical tool for the assessment of unstable plaques and stroke risk. The aim of our study was to assess the inter-reader variability of different methods for quantification of 18F-FDG uptake in carotid atherosclerotic plaques with a separate CT angiography (CTA) providing anatomical guidance. Methods and resultsForty-three patients with carotid artery stenosis [≥]70% underwent 18F-FDG PET/CT. Two independent readers separately delineated the plaque in all axial PET slices containing the atherosclerotic plaque and the maximum standardized uptake value (SUVmax) from each slice was measured. Uptake values with and without background correction were calculated. Intraclass correlation coefficients were highest for uncorrected uptake values (0.97-0.98) followed by those background corrected by subtraction (0.89-0.94) and lowest for those background corrected by division (0.74-0.79). There was a significant difference between the two readers definition of plaque extension, but this did not affect the inter-reader agreement of the uptake parameters. ConclusionsQuantification methods without background correction have the highest inter-reader agreement for 18F-FDG PET of carotid artery plaque inflammation. The use of the single highest uptake value (max SUVmax) from the plaque will facilitate the methods clinical utility in stroke prevention.

Source connections

Explore related subjects

pathologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Johnsrud, K., Seierstad, T., Russell, D., Revheim, M.-E.. 2019-10-16. Inter-reader agreement of 18F-FDG PET/CT for the quantification of carotid artery plaque inflammation. https://doi.org/10.1101/807420

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

NAE1-Dependent Protein Neddylation Preserves Endothelial Identity and Vascular Integrity

Background: Endothelial dysfunction is a central driver of cardiovascular and inflammatory diseases, yet the post-translational mechanisms that preserve endothelial homeostasis remain incompletely understood. Protein neddylation, the covalent conjugation of a ubiquitin-like modifier, regulates diverse cellular processes, yet its physiological role in the vascular endothelium remains unknown. This study investigated whether protein neddylation is required to preserve endothelial identity and vascular homeostasis. Methods: We generated tamoxifen-inducible endothelial-specific Nae1 knockout mice to inhibit neddylation and combined bulk RNA sequencing, single-cell and single-nucleus transcriptomics, quantitative proteomics, biochemical analyses, and gain- and loss-of-function approaches to define the role of endothelial neddylation in vascular homeostasis and inflammatory injury. Results: Endothelial-specific Nae1 deletion caused rapid mortality associated with vascular leakage, platelet accumulation, inflammation, and multi-organ injury. Multi-omics analyses demonstrated profound loss of endothelial identity, characterized by suppression of core endothelial programs and activation of inflammatory, procoagulant, and pyroptotic pathways. Single-cell analyses revealed progressive endothelial dysfunction culminating in depletion of the endothelial population and remodeling of the vascular niche. Mechanistically, endothelial neddylation deficiency activated gasdermin D (GSDMD)- and gasdermin E (GSDME)-dependent pyroptosis, whereas dual inhibition of GSDMD and GSDME markedly attenuated inflammatory transcriptomic remodeling, vascular injury, hepatocyte death, immune cell infiltration, and platelet accumulation. Translational analyses demonstrated reduced endothelial neddylation in experimental endotoxemia and decreased expression of neddylation pathway components in human atherosclerosis and COVID-19 datasets. Conversely, restoration of endothelial neddylation partially reversed inflammatory endothelial transcriptomic reprogramming in vivo. Conclusions: NAE1-dependent protein neddylation is an essential regulator of endothelial identity and vascular integrity. Loss of endothelial neddylation promotes gasdermin-dependent pyroptosis and thrombo-inflammatory vascular injury, whereas restoration of the neddylation pathway mitigates inflammatory endothelial dysfunction. These findings identify endothelial neddylation as a fundamental mechanism maintaining vascular homeostasis and a potential therapeutic target for cardiovascular and inflammatory diseases.

pathology↗
bioRxiv2019

Big data reveals deep associations in physical examination indicators and can help predict overall underlying health status

Because of lacking of the systematic investigation of correlations between the physical examination indicators (PEIs), currently most of them are independently used for disease warning. This results in very limited diagnostic values of general physical examination. Here, we first systematically analyzed the correlations between 221 PEIs in healthy and in 34 unhealthy states in 803,614 peoples in China. We revealed rich relevant between PEIs in healthy physical status (7,662 significant correlations, 31.5% of all). However, in disease conditions, the PEI correlations changed. We further focused on the difference of these PEIs between healthy and 35 unhealthy physical status, 1,239 significant PEI difference were discovered suggesting as candidate disease markers. Finally, we established machine learning algorithms to predict the health status by using 15%-16% PEIs by feature extraction, which reached 66%-99% precision predictions depending on the physical state. This new encyclopedia of PEI correlation provides rich information to chronic disease diagnosis. Our developed machine learning algorithms will have fundamental impact in practice of general physical examination.

pathology↗
bioRxiv2019

Cell therapy as a new approach on hepatic fibrosis of murine model of Schistosoma mansoni infection

Schistosomiasis is an acute and chronic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Schistosomiasis is disease that are prevalent in or unique to tropical and subtropical regions. Previous studies have shown that the role of bone marrow mesenchymal stem cells (BMSCs) therapy in improvement of hepatic fibrosis. Therefore, the current study was designed to assess the therapeutic role of BMSCs in murine schistosomiasis mansoni. BMSCs derived male mice were intraperitoneal injected into female mice that received S. mansoni cercariae through subcutaneous route. Mice were divided into four groups: negative control group (noninfected non treated); positive control group (infected non treated); BMSCs treated group; and untreated group. Liver histopathology and immunohistochemically were evaluated. BMSC intraperitoneal injection resulted in a significant reduction in liver collagen, granuloma size, and significant increase in OV-6 expression in the Schistosomiasis treated mice group. There was overall improvement of the pathological changes of the liver. The findings support that BMSCs has a regenerative potential in the histopathology and function of the liver tissue by decreasing liver fibrosis.

pathology↗