Language

English

Publication Date

1-1-2023

Journal

PLoS One

DOI

10.1371/journal.pone.0291733

PMID

37796905

PMCID

PMC10553338

PubMedCentral® Posted Date

10-5-2023

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Cardiovascular disease (CVD) is associated with the apolipoprotein E (APOE) gene and lipid metabolism. This study aimed to develop an imaging-based pipeline to comprehensively assess cardiac structure and function in mouse models expressing different APOE genotypes using photon-counting computed tomography (PCCT).

Methods: 123 mice grouped based on APOE genotype (APOE2, APOE3, APOE4, APOE knockout (KO)), gender, human NOS2 factor, and diet (control or high fat) were used in this study. The pipeline included PCCT imaging on a custom-built system with contrast-enhanced in vivo imaging and intrinsic cardiac gating, spectral and temporal iterative reconstruction, spectral decomposition, and deep learning cardiac segmentation. Statistical analysis evaluated genotype, diet, sex, and body weight effects on cardiac measurements.

Results: Our results showed that PCCT offered high quality imaging with reduced noise. Material decomposition enabled separation of calcified plaques from iodine enhanced blood in APOE KO mice. Deep learning-based segmentation showed good performance with Dice scores of 0.91 for CT-based segmentation and 0.89 for iodine map-based segmentation. Genotype-specific differences were observed in left ventricular volumes, heart rate, stroke volume, ejection fraction, and cardiac index. Statistically significant differences were found between control and high fat diets for APOE2 and APOE4 genotypes in heart rate and stroke volume. Sex and weight were also significant predictors of cardiac measurements. The inclusion of the human NOS2 gene modulated these effects.

Conclusions: This study demonstrates the potential of PCCT in assessing cardiac structure and function in mouse models of CVD which can help in understanding the interplay between genetic factors, diet, and cardiovascular health.

Keywords

Mice, Humans, Animals, Apolipoprotein E2, Apolipoprotein E4, Apolipoproteins E, Apolipoprotein E3, Tomography, X-Ray Computed, Mice, Knockout, Cardiovascular Diseases, Iodine

Published Open-Access

yes

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.