Contrast-enhanced computed tomography as a 3D histopathology tool to improve the knowledge of microstructural changes caused by cardiac pathologies

Details

Supervisors

Kerckhofs, Greet

Faculty

Ecole polytechnique de Louvain

Degree label

Master [120] : ingénieur civil biomédical, à finalité spécialisée

Abstract

CVDs are the leading cause of mortality worldwide and the main contributor of disability. Even though the current advances in CVD prevention and treatments have reduced the number of premature deaths and disabilities due to CVDs, cardiac disorders continue to be a serious public health concern. Morever, little is known on the microstructural changes occurring at different stages of cardiac diseases. Obtaining such information would be highly valuable to understand the onset of cardiac disorders. However, in most cardiac research, classical 2D histology remains the gold standard for observing individual tissue constituents, but cannot reveal the 3D architecture. Histopathology is an important tool to identify pathology-induced microstructural changes, hence there is a need for 3D high resolution imaging techniques to better understand cardiac microstructural changes. The aim of this thesis is to assess the relevance of CECT as 3D histopathology tool to improve the knowledge of microstructural changes caused by cardiac pathologies. Heart samples from two animal models were provided to be analyzed. The first ones were affected by pressure overload-induced hypertrophy, commonly responsible of HF, and the second ones corresponded to a model of mitral valve regurgitation. As the microstructural changes occurring are not the same for both diseases, different objectives divided into two categories were evaluated. The first category concerns technical objectives, to evaluate if there is a better imaging protocol, depending on the temperature and resolution to image the microstructures. The second category focuses on the biological side, to evaluate if there is a difference between control and diseased samples in terms of microstructure. In this work, we have confirmed the valuable potential of CECT as a 3D histopathology tool, via two models. The first one allowed to demonstrate the presence of hypertrophy and fibrosis, while the second one allowed the segmentation of the mitral valve, as well as the distinction of the two leaflets and the chordae. While hypertrophy and fibrosis have been well studied through classical 2D histology, the 2D character of the technique and single sectioning do not allow to reveal 3D cardiac microstructure. The mitral valve apparatus has not been studied as much with new imaging techniques, and its microstructure remains to be discovered on certain points (e.g. length of the chordae, branching). The impact of the different imaging protocols could also be assessed. In conclusion, there is not one imaging protocol better than the others, as it strongly depends on the initial research question and what one is trying to visualize. In general, a low resolution is sufficient to visualize the main components of the heart, but in order to visualize the microstructures, a high resolution will be necessary. Room temperature is preferred to observe fibrosis and fast freezing is preferred to observe muscle fibers. The advantage of this imaging technique is that different protocols can be combined because no destruction of the tissue is required. Regarding the biological aspects studied, whether for pressure overload-induced hypertrophy or mitral valve regurgitation, more samples are needed to draw any conclusion. Nevertheless, the results obtained already give other promising leads for microstructural analysis, which will further improve the knowledge of microstructural changes occurring during cardiac diseases.