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Platelets have been shown to be a main contributor to thrombus formation in stenotic arteries leading to acute coronary syndromes. It is thought that increased activation and adhesion of platelets under variable shear and complex flow conditions contribute to thrombosis. The objective of this work was to evaluate the relationship between asymmetric stenosis hemodynamics and platelet adhesion using in-vitro models developed to properly simulate physiological conditions. In this study, platelet rich plasma was circulated through stenotic and straight coronary artery models. Adhesion results were obtained by post-perfusion fluorescent labelling and imaging of adhered platelets. Analysis of platelet area coverage has shown maximum adhesion occurs in the distal region of the stenosis. Most likely this is due to increased exposure time of platelets to the wall of the recirculation zone following the stenosis and that exposure being directly after a period of high shear stress. This result gives us a better understanding of the importance of both shear and flow conditions in coronary artery thrombosis.

Atherothrombosis can induce acute myocardial infarction and stroke by progressive stenosis of a blood vessel lumen to full occlusion. The goal of this research is to determine what shear rates are pertinent to an occluding blood vessel, the rate of thrombus growth relative to wall shear rates, and to develop a predictive model for estimating length of time to thrombus occlusion for a given atherosclerotic lesion. Computational studies of severely stenotic idealized vessels were performed to investigate the wall shear rates that may exist. The study shows that maximum shear rates in severe short stenoses were found to exceed 250,000 1/s (9,500 dynes/cm2). We utilize an in vitro experiment consisting of blood flow through a collagen coated stenosis to study the rate of thrombus growth. Growth is monitored through light microscopy and a camera. Computational fluid dynamics are used to determine shear rates along the thrombus surface as it grows. We found a strong positive correlation between thrombus growth rates and shear rates up to 6,000 1/s after a log-log transformation (r=0.85, p<0.0001). Growth rates at pathologic shear rates were typically 2-4 times greater than for physiologic shear rates below 400 s-1. To determine whether transport or kinetic binding limits the rate of thrombus growth, a computational model of platelet transport was developed. The model allows for thrombus growth by occluding computational cells. We show that thrombus is transport rate-limited for shear rates below 6,000 1/s, while it is more likely to be kinetic rate-limited for higher shear rates. Predictions of occlusion times based on the model demonstrate that increases in stenosis severity results in decreased time to occlusion.

To aid diagnosis, treatment planning, and patient education, clinicians require tools to anal- yse and explore the increasingly large three-dimensional (3-D) datasets generated by modern medical scanners. Direct volume rendering is one such tool finding favour with radiologists and surgeons for its photorealistic representation. More recently, volume illustration — or non-photorealistic rendering (NPR) — has begun to move beyond the mere depiction of data, borrowing concepts from illustrators to visually enhance desired information and suppress un- wanted clutter. Direct volume rendering generates images by accumulating pixel values along rays cast into a 3-D image. Transfer functions allow users to interactively assign material properties such as colour and opacity (a process known as classification). To achieve real-time framerates, the rendering must be accelerated using a technique such as 3-D texture mapping on commod- ity graphics processing units (GPUs). Unfortunately, current methods do not allow users to intuitively enhance regions of interest or suppress occluding structures. Furthermore, addi- tional scalar images describing clinically relevant measures have not been integrated into the direct rendering method. These tasks are essential for the effective exploration, analysis, and presentation of 3-D images. This body of work seeks to address the aforementioned limitations. First, to facilitate the research program, a flexible architecture for prototyping volume illustration methods is pro- posed. This program unifies a number of existing techniques into a single framework based on 3-D texture mapping, while also providing for the rapid experimentation of novel methods. Next, the prototyping environment is employed to improve an existing method—called tagged volume rendering — which restricts transfer functions to given spatial regions using a number of binary segmentations (tags). An efficient method for implementing binary tagged volume rendering is presented, along with various technical considerations for improving the classifi- cation. Finally, the concept of greyscale tags is proposed, leading to a number of novel volume visualisation techniques including position modulated classification and dynamic exploration. The novel methods proposed in this work are generic and can be employed to solve a wide range of problems. However, to demonstrate their usefulness, they are applied to a specific case study. Ischaemic heart disease, caused by narrowed coronary arteries, is a leading healthconcern in many countries including Australia. Computed tomography angiography (CTA) is an imaging modality which has the potential to allow clinicians to visualise diseased coronary arteries in their natural 3-D environment. To apply tagged volume rendering for this case study, an active contour method and minimal path extraction technique are proposed to segment the heart and arteries respectively. The resultant images provide new insight and possibilities for diagnosing and treating ischaemic heart disease.