Current research projects
Many of our research projects cut across each of our research themes and also span engineering, medicine and science. We have many projects underway and only some are presented here. Our research is well supported by the NHMRC and UWA, and our work has featured on the cover of both leading clinical science and biomedical engineering journals.
Abdominal aortic aneurysm (AAA) rupture risk assessment
The current method used to determine if an AAA is at risk of rupture is to measure the maximum diameter using medical imaging. AAAs bigger than 5 - 5.5cm in diameter are considered at risk, and the patient will usually be offered surgery. However, smaller AAAs can rupture and larger ones often remain stable and may never rupture. Therefore, can we predict which patients would benefit from surgery? We believe so.
As part of this long-running project, and through generous funding from the NHMRC, we have recently developed a new method to predict the risk of rupture. This method has been refined into a freely available software pipeline called BioPARR – Biomechanics based Prediction of Aneurysm Rupture Risk.
Our approach overcomes some of the key obstacles that were hindering clinical implementation, namely the uncertainty in aneurysmal wall thickness and lack of knowledge of patient-specific material properties. We begin by registering CT and MRI together to create our 3D reconstructions and then apply a novel solid mechanics approach to determine the stresses in the vessel. We are now testing our approach on a large number of patients to demonstrate that 3D biomechanics-based methods outperforms the current 2D diameter approach, and provides a real benefit to patient care.
This figure shows how we predicted the exact location of rupture 4 months before the rupture actually happened. In this case, the patient refused surgery and was then repaired after his AAA ruptured.
We are very interested in the nature of blood flow in both healthy and diseased arteries. We use computational fluid dynamics (CFD) to simulate the haemodynamics in a wide range of anatomical regions at all sizes scales. Understanding the nature of the blood flow and the data than can be derived from the flow, such as wall shears stress, can significantly help towards developing new treatments, design new medical devices and further our knowledge as to why and how haemodynamics impacts the development of healthy and diseased arteries.
The figure shows the dispersion of platelets and monocytes over the cardiac cycle within an isolated iliac artery aneurysm. As the particles changes colour, they are staying in the system longer.
Haemodynamics in the placental vasculature
This project investigates the placental vasculature of mice. We simulate the haemodynamics using physiological inputs to our models and compute the wall shear stresses. The figure shows the shear stress in the upper branches of the network which form the start of a much larger, dense network of intraplacental vessels. This information can be used to determine nitric oxide (NO) production and also the transport of oxygen and nutrients. The red arrows indicate the direction of flow.
Where and why do aneurysms develop?
Aneurysms are prone to develop in certain anatomical regions, such as the abdominal aorta. But why are they so common here? We try answer this, and other questions, by simulating the blood flow in the region and by designing studies that investigate a range of potential geometric variations and the impact of blood flow. The iliac arteries are a somewhat unique anatomical region to help our understanding and we are currently determining why the internal iliac artery is prone to aneurysmal disease, yet the external iliac artery is not.
This video shows the velocity-coloured flow over the cardiac cycle entering the sac of an iliac artery aneurysm and clearly demonstrates the cyclic impingement of blood onto the far side of the sac. This impingement is where the aneurysm later ruptured.
Type B aortic dissection
There is little evidence indicating which cases of Type B aortic dissection (AD) should be repaired and which should be conservatively managed via medication. This is primarily because it is difficult for clinicians to predict which cases will develop complications and thus require surgery. Recent evidence indicates that CFD-derived data, such as wall shear stress, can predict complications. We have shown in single case studies that our methods highlight the areas of rapid aortic expansion (an established complication and marker of repair). In this project we are expanding our knowledge in this area and combining new imaging methods to help identify patients at risk.
The first figure shows a reconstruction of a case of type B AD and the second one shows the evolution of intramural haematoma, a condition often associated with aortic dissection. The models are 3D reconstructions from CT at several time points in the early care of the patient.
Coronary artery disease
Disease of the small arteries in and around the heart is a major contributor to the growing problem of CVD. The role between wall shear stress and plaque progression and rupture is well studied, however, recent advancements in medical imaging allow us to gain new insights into the problem. In this project we combine intravascular optical coherence tomography (OCT) with other imaging modalities such as CT and PET/CT with the radiotracer 18f-sodium fluoride (18f-NaF) to understanding the role of wall shear stress and the microcalcification process in this arteries.
Video showing typical intravascular OCT images that we use to create high-quality reconstructions of the vessel lumen.
We then compute the haemodynamics and wall shear stress and return it to the clinician in an easy to interpret format with full 3D manipulation.
CVD often manifests in the microcirculation long before it show signs in the larger arteries. The retina is one of the few places that the microvasculature can be observed non-invasively. In this project, we take standard fundus photographs of the retina and convert them into computational models.
The image shows the process from fundus image (left) to velocity simulation (right).
Soft tissue biomechanics
How vessels and other cardiac tissue behave when subjected to mechanical stimulus is central to many aspects of CVD. We know that arteries stiffen as we age, but by how much? And how much does my artery differ in mechanical behaviour than yours? What about plaques and thrombus that build up within our arteries as we get older? How do they behave? And how does inflammation, calcification and other biological processes impact mechanical behaviour?
These questions can be answered by biomechanically testing tissue from either patients undergoing surgery or from animal models. We use various forms of biomechanical experimentation to measure mechanical properties such as stiffness and strength. At VascLab we have apparatus capable of uniaxial and biaxial tensile testing, as well as pressure-diameter testing.
The figure shows intraluminal thrombus which is present in most clinically-relevant aortic aneurysms. We can separate the tissue into its layers and biomechanically tensile test each layer. This allows us to measure the stiffness and strength. One application of this data is to better inform our computational models.
The combination of 3D printing with existing tissue engineering strategies has opened the door for many new applications. We are currently exploring the use of 3D bioprinting for several different applications with the hope of one day being able to print patient-specific body parts for implantation.