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Multiscale Determinants of Myocardial Mechanics

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

About This PhD Project

Project Description

First Supervisor: Dr David Nordsletten
Second Supervisor: Professor Reza Razavi

Understanding the health and function of heart muscle is critical to the assessment of a range of cardiac pathologies. Diseases of the heart often lead to fundamental alterations in structures of the heart – extending from the cell-level to the whole organ. A spectrum of imaging modalities have been introduced that provide some insight into the structural characteristics of the heart. However, the capacity to quantify the impact of these structural changes on the biomechanics of the heart muscle remains an unmet need. The aim of this PhD is to characterize the complex multiscale structure of the myocardium and establish biomechanical models that can be quantifiably tuned based on these structural observations. This will be achieved through detailed experiments using ex vivo rheology, development of new image-based rheology using 7T MRI, and computational biomechanical modelling.

Understanding the health and function of heart muscle is critical to the assessment of a range of cardiac pathologies. Diseases of the heart often lead to fundamental alterations in structures of the heart. For example, in hypertrophic cardiomyopathy the myocardium of the heart experiences significant concentric remodelling, increased muscle mass, restructuring of the cardiomyocyte, fibrosis of the extracellular matrix and myocardial disarray. Other conditions, such as myocardial ischemia similarly alter the structure of the heart due to regional ischemic events that lead to death of the muscle and areas of fibrotic scar tissue. A spectrum of imaging modalities have been introduced that provide some insight into the structural characteristics of the heart. These include invasive modalities (confocal imaging and histology of excised samples) as well as non-invasive in vivo modalities (LGE imaging, T2 imaging, in vivo DTI and elastography using MRI). However, the capacity to quantify the impact of these structural changes on the biomechanics of the heart muscle remains an unmet need.

The aim of this PhD is to characterize the complex multiscale structure of the myocardium and establish biomechanical models that can be quantifiably tuned based on these structural observations. This will be achieved through detailed experiments using ex vivo rheology, development of new image-based rheology using 7T MRI, and computational biomechanical modelling.

Year 1
The main goals of year 1 will be to develop an ex-vivo imaging rheology rig and conduct phantom experiments in bench-top triaxial rigs using controlled hydrogel and polymer materials. The imaging rheology rig will merge hardware developed at the Institute for Biomechanics at TU Graz with elastography measurements. The rig will be developed for use in 7T preclinical MRI systems. Sequences will be used to acquire structural information (LGE, DTI, MRE) and 3D deformation fields, enabling a comprehensive assessment of the biomechanics and structure of tissues ex vivo. In addition, work will begin on developing collagen hydrogels and polymers with defined structural anisotropy. These samples will be fabricated under controlled conditions, enabling quantification of structure through microscopy (SHG) as well as biomechanical testing. These results will provide a foundation for defining structurally based biomechanical models.

Year 2
The main goal of year 2 will be to acquire comprehensive ex vivo rheology on porcine myocardium. Experiments will be conducted using the imaging rheology rig and samples will be subsequently imaged using second harmonic imaging. These results will be used to develop a structurally based biomechanical model of the passive porcine myocardium.

Year 3
The main goal of year 3 will be to acquire comprehensive ex vivo rheology on human myocardium samples collected in Paris / University of Michigan Ann Arbor. Experiments will be conducted using the imaging rheology rig and samples will be subsequently imaged using second harmonic imaging. These results will be used adapt the porcine myocardial model. Additionally, structural imaging will be correlated with noninvasive imaging data in order to adapt biomechanical models based on these MRI imaging sources exclusively.

Year 4
The main goal of year 4 will be to use the models developed to simulate heart function using patient data acquired at KCL. This will represent a proof of concept using detailed imaging to quantify rheology and tune patient-specific biomechanical models.

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