VALIDATION, OPTIMIZATION, AND IMAGE PROCESSING OF SPIRAL CINE DENSE MAGNETIC RESONANCE IMAGING FOR THE QUANTIFICATION OF LEFT AND RIGHT VENTRICULAR MECHANICS

Recent evidence suggests that cardiac mechanics (e.g. cardiac strains) are better measures of heart function compared to common clinical metrics like ejection fraction. However, commonly-used parameters of cardiac mechanics remain limited to just a few measurements averaged over the whole left ventricle. We hypothesized that recent advances in cardiac magnetic resonance imaging (MRI) could be extended to provide measures of cardiac mechanics throughout the left and right ventricles (LV and RV, respectively). Displacement Encoding with Stimulated Echoes (DENSE) is a cardiac MRI technique that has been validated for measuring LV mechanics at a magnetic field strength of 1.5 T but not at higher field strengths such as 3.0 T. However, it is desirable to perform DENSE at 3.0 T, which would yield a better signal to noise ratio for imaging the thin RV wall. Results in Chapter 2 support the hypothesis that DENSE has similar accuracy at 1.5 and 3.0 T. Compared to standard, clinical cardiac MRI, DENSE requires more expertise to perform and is not as widely used. If accurate mechanics could be measured from standard MRI, the need for DENSE would be reduced. However, results from Chapter 3 support the hypothesis that measured cardiac mechanics from standard MRI do not agree with, and thus cannot be used in place of, measurements from DENSE. Imaging the thin RV wall with its complex contraction pattern requires both three-dimensional (3D) measures of myocardial motion and higher resolution imaging. Results from Chapter 4 support the hypothesis that a lower displacement-encoding frequency can be used to allow for easier processing of 3D DENSE images. Results from Chapter 5 support the hypothesis that images with higher resolution (decreased blurring) can be achieved by using more spiral interleaves during the DENSE image acquisition. Finally, processing DENSE images to yield measures of cardiac mechanics in the LV is relatively simple due to the LV’s mostly cylindrical geometry. Results from Chapter 6 support the hypothesis that a local coordinate system can be adapted to the geometry of the RV to quantify mechanics in an equivalent manner as the LV. In summary, cardiac mechanics can now be quantified throughout the left and right ventricles using DENSE cardiac MRI

The role of myocardial fibrosis in outcome following mitral valve repair in degenerative mitral regurgitation

Primary degenerative mitral regurgitation (MR) is a disease of increasing prevalence. Its optimal management is surgical repair, but surgery timings remain controversial. Current guidelines that suggest ‘watchful-waiting’ have been criticised for promoting rescue surgery after the establishment of symptoms or left ventricular (LV) dysfunction. Conversely, non-selective early surgical approaches result in unnecessary surgery for some patients. Myocardial fibrosis has been hypothesised to accumulate in MR, leading to eventual overt LV dysfunction. This thesis examines this hypothesis, assesses the prognostic impact of myocardial fibrosis, and determines its value as a biomarker for optimising the timing of surgery. In a prospective multicentre study of severe MR patients, I provide definitive histological evidence for the presence of myocardial fibrosis, before the onset of symptoms. Due to its patchy nature, non-invasive quantification of fibrosis on cardiac magnetic resonance (CMR) was a superior marker of preoperative myocardial function and symptom burden. However, neither histology- nor CMR-derived fibrosis correlated with postoperative outcomes. Despite successful surgery, symptomatic patients continued to possess worse cardiopulmonary exercise (CPET) performance and symptom burden quantified via patient-response questionnaires (PROMs) compared to asymptomatic patients, providing additional support for the benefits of early surgery. Further evaluation of surveillance CPET and PROMs is indicated for patients in whom early surgery is clinically inappropriate