Heart function assessment during aging in apolipoprotein E knock-out mice

Liehn, Elisa A.; Lupan, Ana-Mihaela; Diaconu, Rodica; Ioana, Mihai; Streaţă, Ioana; Manole, Catalin G.; Burlacu, Alexandrina

doi:10.15190/d.2021.15

Cited by 7 publications

(8 citation statements)

References 15 publications

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“…Four weeks after myocardial infarction, the left ventricular ejection fraction was determined by acquiring two-dimensional (long and short axis) and M-mode (long and short axis) echocardiographic imaging using a small-animal ultrasound imager (Vevo 770, FUJIFILM VisualSonics, Toronto, ON, Canada). Finally, the hearts were excised and prepared for further analysis, as previously described [ 71 ].…”

Section: Methodsmentioning

confidence: 99%

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Schumacher

Curaj

Staudt

et al. 2022

IJMS

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Myocardial infarction is remains the leading cause of death in developed countries. Recent data show that the composition of the extracellular matrix might differ despite similar heart function and infarction sizes. Because collagen is the main component of the extracellular matrix, we hypothesized that changes in inflammatory cell recruitment influence the synthesis of different collagen subtypes in myofibroblasts, thus changing the composition of the scar. We found that neutrophils sustain the proliferation of fibroblasts, remodeling, differentiation, migration and inflammation, predominantly by IL-1 and PPARγ pathways (n = 3). They also significantly inhibit the mRNA expression of fibrillar collagen, maintaining a reduced stiffness in isolated myofibroblasts (n = 4–5). Reducing the neutrophil infiltration in CCR1−/− resulted in increased mRNA expression of collagen 11, moderate expression of collagen 19 and low expression of collagen 13 and 26 in the scar 4 weeks post infarction compared with other groups (n = 3). Mononuclear cells increased the synthesis of all collagen subtypes and upregulated the NF-kB, angiotensin II and PPARδ pathways (n = 3). They increased the synthesis of collagen subtypes 1, 3, 5, 16 and 23 but reduced the expression of collagens 5 and 16 (n = 3). CCR2−/− scar tissue showed higher levels of collagen 13 (n = 3), in association with a significant reduction in stiffness (n = 4–5). Upregulation of the inflammation-related genes in myofibroblasts mostly modulated the fibrillar collagen subtypes, with less effect on the FACIT, network-forming and globular subtypes (n = 3). The upregulation of proliferation and differentiation genes in myofibroblasts seemed to be associated only with the fibrillar collagen subtype, whereas angiogenesis-related genes are associated with fibrillar, network-forming and multiplexin subtypes. In conclusion, although we intend for our findings to deepen the understanding of the mechanism of healing after myocardial infarction and scar formation, the process of collagen synthesis is highly complex, and further intensive investigation is needed to put together all the missing puzzle pieces in this still incipient knowledge process.

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Section: Methodsmentioning

confidence: 99%

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Schumacher

Curaj

Staudt

et al. 2022

IJMS

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“…Cardiac segmentation plays a crucial role in understanding and analyzing cardiac anatomy and function. For example, 3D left ventricle segmentations can be used to calculate key functional metrics such as stroke volume, ejection fraction, and cardiac output [2,3]. In this study, we focus on the use of photon-counting computed tomography (PCCT) to segment the whole heart including the four cardiac chambers, the aorta, pulmonary artery, inferior and superior vena cava, myocardium, and the pulmonary tree in APOE mouse genotypes.…”

Section: Introductionmentioning

confidence: 99%

Whole heart CNN-based segmentation for phenotypical analysis of APOE mouse models using photon counting cine cardiac micro-CT data

Allphin,

Nadkarni,

Han

et al. 2024

Medical Imaging 2024: Clinical and Biomedical Imaging

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This paper presents a deep learning approach to automated segmentation of cardiac structures in 5D (3D + Time + Energy) photon-counting micro-CT (PCCT) imaging sets . We have acquired, reconstructed, and fully segmented a preclinical dataset of cardiac micro-PCCT scans in APOE mouse models. These APOE genotypes serve as models of varying degrees of risk of Alzheimer's disease and cardiovascular disease. The dataset of user-guided segmentations served as the training data for a deep learning 3D UNet model capable of segmenting the four primary cardiac chambers, the aorta, pulmonary artery, inferior and superior vena cava, myocardium, and the pulmonary tree. Experimental results demonstrate the effectiveness of the proposed methodology in achieving reliable and efficient cardiac segmentation. We demonstrate the difference in performance when using single-energy PCCT images versus decomposed iodine maps as input. We achieved an average Dice score of 0.799 for the network trained on single-energy images and 0.756 for the network trained using iodine maps. User-guided segmentations took approximately 45 minutes/mouse while CNN segmentation took less than 1 second on a system with a single RTX 5000 GPU. This novel deep learning-based cardiac segmentation approach holds significant promise for advancing phenotypical analysis in mouse models of cardiovascular disease, offering a reliable and time-efficient solution for researchers working with photon-counting micro-CT imaging data.

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“…Alternative imaging methods have been used in mice for cardiac studies. For example, both echocardiography [ 15 , 16 ] and MRI [ 17 ] have been used to examine the cardiac and vascular characteristics of APOE KO mice. In the absence of APOE, mice develop severe atherosclerosis due to the accumulation of remnant lipoproteins, thereby underlining the crucial role of APOE in lipoprotein metabolism and CVD [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Advanced photon counting CT imaging pipeline for cardiac phenotyping of apolipoprotein E mouse models

Allphin,

Mahzarnia,

Clark

et al. 2023

PLoS ONE

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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.

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Heart function assessment during aging in apolipoprotein E knock-out mice

Cited by 7 publications

References 15 publications

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Endogenous Modulation of Extracellular Matrix Collagen during Scar Formation after Myocardial Infarction

Whole heart CNN-based segmentation for phenotypical analysis of APOE mouse models using photon counting cine cardiac micro-CT data

Advanced photon counting CT imaging pipeline for cardiac phenotyping of apolipoprotein E mouse models

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