Use of perfusion PET/CT imaging to assess cardiac function and repair in murine diabetic cardiac models and subsequent refinement and validation of predictive in silico cardiac models

• Main Author: Alenezi, Aishah
• Format: Dissertation
• Language: English
• Published: Cardiff University 2022

Micro-positron emission tomography (micro-PET) imaging is a powerful imaging modality in cardiovascular studies for the assessment of mice cardiac function in-vivo. This modality offers an insight into biochemical changes on a molecular level through quantifying myocardial blood flow (MBF), and glucose metabolism (MGM) as prognostic biomarkers in cardiovascular diseases (CVDs). In the past decade, the amount of cardiovascular research using micro-PET/CT has increased widely to understand human diseases, standardize imaging protocols, or to evaluate treatment interventions. Until recently, there has been a lack of a standard quantitative PET/CT protocols to quantify MBF and MGM due to the challenges associated with small animal imaging such as resolution, animal handling and the complexity of image analysis with the compartmental modelling method. The combination of a well performing micro-PET/CT scanner and accurate and repeatable imaging protocols could provide invaluable qualitative and quantitative data that might resolve questions about a potential gene therapy. Accordingly, we have gathered interesting data about the bactericidal/permeability-increasing fold-containing- family-B-member-4 longevity associated variant (LAV-BPIFB4) gene that has been identified by our collaborators and that has shown therapeutic effects in protecting against CVDs and age-related pathologies. This gene variant has been demonstrated to enhance revascularization and reduce endothelial dysfunction in mice. Therefore, this research aimed to first demonstrate the feasibility of our micro-PET/CT scanner to assess cardiac function in murine models through developing accurate and repeatable imaging protocol sets. Next, investigating the beneficial effects of the LAV-BPIFB4 gene in maintaining cardiac function using diabetic and elderly mice models. Our standardized imaging protocols produced accurate and repeatable quantitative PET data of both MBF and MGM using a compartmental modelling quantification method. Importantly, our results from both murine models demonstrated the therapeutic role of the gene in preserving cardiac function by enhancing its contractile function, improved blood flow and reduced capillary rarefaction. PET data were consistent with echocardiography and histological results. Our findings confirmed that our micro-PET/CT scanner allows the quantitative evaluation of cardiac perfusion and metabolism in mice models, as well as demonstrating the beneficial influence of the LAV-BPIFB4 gene treatment. This research has the potential to be extended for further refinement of the imaging methods or to investigate the duration of the effect of the gene and the metabolic mechanisms that have caused its therapeutical action.