Introduction: Atherosclerosis, the major source of cardiovascular diseases, is one of the leading causes of death. During atherosclerosis the arterial wall is affected by a complex process of lipid driven inflammation that leads to thickening of the arterial wall resulting in a so called plaque. Because of plaque growth, the lumen of the artery gradually narrows. As the lumen area is decreasing, reduction and even restriction of blood flow can occur, which can lead to a heart attack or stroke depending on the affected artery. Biomechanical stresses are known to influence the development of the disease. Those stress are the plaque structural stress (PSS) and wall shear stress (WSS) induced by the blood flow at the vessel wall. The aim of this project was to study the contribution of these biomechanical stresses and their combination to plaque progression in human coronary arteries. In order to investigate this effect a new methodology for the calculation of the stresses was introduced that utilizes the image modalities optical coherence tomography (OCT) and intravascular ultrasound (IVUS). The combination of those two image modalities can provide more accurate information regarding the plaque composition than the approaches that have been applied so far. In particular the cap thickness, which is the region shielding the lipid rich necrotic core from the blood flow, is crucial for structural stress calculations. Methods: The new methodology consisted of three steps. During the first step image data from the image modalities optical coherence tomography (OCT) and intravascular ultrasound (IVUS) were fused. The resulted images were cross-sections of the human coronary arteries that consisted of the lumen and the outer wall obtained from IVUS and the fibrous cap obtained from OCT. However, they did not contain information about the size of the necrotic core; thus, the second step was to reconstruct the necrotic core. For that purpose an algorithm from the literature was implemented that can reconstruct the necrotic core. The produced geometry resulting from the second step consisted of the same features as those from step one but they also included the contours of the necrotic core. The third step was the calculation of the PSS using those 2D geometries. The WSS data were obtained from another study. For the statistical analysis the data of both stress calculations were ranked as low, medium and high. Two different approaches for the definition of the thresholds of those ranks were used, vessel specific and absolute thresholds. In the vessel specific approach the thresholds of the aforementioned ranks were specific for each vessel, while in the second approach the threshold values were based on the whole sample size. Those two approaches were studied in order to explore if the response of the vessels depends to the absolute values of biomechanical stresses or it is relative to their respective biomechanical stresses. Change in wall thickness was used as metric to quantify the plaque progression. In order to study the contribution of the biomechanical stresses to the plaque progression in the human coronary arteries, statistical analysis was carried out using ANOVA with plaque progression as dependent variable and PSS and WSS as independent variables. Results: Plaque development was significantly related to WSS using both approaches to rank the WSS values into low, mid and high. In general, regions exposed to low WSS showed the most plaque progression. The individual effect of PSS was not statistically significant using both approaches, however there was a trend demonstrating that high PSS could promote plaque development. When PSS and WSS were combined using the vessel specific approach to rank the data, there was plaque progression for the cases of low WSS combined with any level of plaque structural stress. However, only WSS had a statistically significant effect in this case revealing that the resulted effect was entirely estimated by WSS. If absolute thresholds were used for both WSS and PSS, there was no statistical effect. Despite that, there was a trend showing that high PSS combined with high WSS could promote plaque development. Conclusions: During this project a new methodology was utilized in order to study the contribution of WSS, PSS and their combination to the plaque development in human coronary arteries. It was also the first study that utilized the combination of the image modalities OCT and IVUS in that topic. It was demonstrated that WSS could promote plaque development. PSS also enhanced plaque progression but with no statistically significant effect. Regarding the combination, it was demonstrated that the effect was explained completely by wall shear stress for the vessel specific approach. For the absolute thresholds approach, there was no statistically significant effect. However, more data are required to validate these results.