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Title: Micro-computed tomography for high resolution soft tissue imaging : applications in the normal and failing heart
Author: Stephenson, Robert
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2013
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The normal structure and function of the heart, the common pathological changes that cause abnormal function and the interventions proposed to improve or restore its function are fundamentally based on cardiac anatomy. Therefore in all these areas a detailed and accurate understanding of 3D structure is essential. However there is still disparity over some aspects of the form and function of the healthy heart. Furthermore, in heart failure (HF) the transition from compensated to decompensated HF is poorly understood, and details of ventricular, and particularly atrial, remodelling and their effects on cardiac function are yet to be fully elucidated. In addition little is known on how the 3D morphology of the cardiac conduction system is affected in disease, and further knowledge is required on the structural substrates for arrhythmogenesis associated with HF. Here we have developed contrast enhanced micro-CT for soft tissue imaging, allowing non-invasive high resolution (~5 µm attainable) differentiation of multiple soft tissue types including; muscle, connective tissue and fat. Micro-CT was optimised for imaging of whole intact mammalian hearts and from these data we reveal novel morphological and anatomical detail in healthy hearts and in hearts after experimental HF (volume and pressure overload). Remodelling of the myocardium in HF was dramatic with significant hypertrophy and dilatation observed in both atria and ventricles. The atria showed a 67% increase in myocardial volume, with the left atrium showing a 93% increase. The pectinate muscle: wall thickness ratio was significantly increased in both atria (p=<0.05), and total cavity volume of the atria was increased by 119% (p=<0.05). An 84% (p=<0.05) and 28% (p=<0.01) increase in myocardial volume was seen in the right and left ventricles (RV and LV) respectively. The LV cavity increased to 231% of control (p=<0.001). Regional remodelling occurred in the LV with the base and mid-wall of the heart undergoing eccentric hypertrophy and the apex undergoing mixed hypertrophy. Longitudinal in vivo analysis by echocardiography revealed progressive loss of function pre termination (41% reduction in fractional shortening, p=< 0.001). We have imaged the major regions of the cardiac conduction system (CCS) in single intact hearts and we present the data as high resolution 3D renderings. This is the first time that such data has been shown for any species. In HF all regions of the CCS underwent dramatic morphological changes, with all regions undergoing hypertrophy and stretch. The sinoatrial node showed an 85% increase in volume (p=0.08) and 51% increase in surface area (p=<0.05). The atrioventricular node increased in both volume (52% p=< 0.05) and 3D length (14% p=< 0.05). The free running Purkinje fibre network showed an 85% increase in volume (p=<0.05); 3D filament analysis revealed the free running length was increased by 62% (p=<0.05), and was strongly correlated with the increase in LV cavity volume. Applying a novel technique for the extraction of 3D fibre orientation from micro-CT data we showed that significant changes occur in HF. The technique was first validated in skeletal muscle and then applied to the heart. Fibre orientation in the ventricles was consistent with previous findings, and novel insight into the complex and heterogeneous fibre orientation of the atria and their accompanying muscle bands was obtained. In HF significant changes in fibre orientation were seen in regions of dilatation; in the LV fibres became more vertical at the endocardium and this coincided with a reduction in the transverse angle; in the transmural mid-wall of both the LV and interventricular septum the percentage of circumferential fibres was reduced, and fibres became more disordered. Based on changes in morphology and 3D fibre orientation we present the idea of regional specific compensated and decompensated HF in the presence of volume and pressure overload. Data presented here provides new information on remodelling of the heart in HF, giving insight into the mechanisms underlying the contractile and electrical pathologies associated with HF.
Supervisor: Jarvis, Jonathan; Corno, Antonio; Jeffery, Nathan Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine