Flett, A; (2012) Focal and diffuse myocardial fibrosis quantification by cardiovascular magnetic resonance. Doctoral thesis , UCL (University College London).

Abstract

The ratio of cell to interstitial volume is a property of normal organs and tissues which changes in disease through cell loss and/or interstitial expansion. Interstitial expansion consists of increased intercellular water associated with increased collagen in focal or diffuse fibrosis, or deposition of pathological material, such as amyloid. Focal fibrosis: Cardiovascular magnetic resonance (CMR) using the late gadolinium enhancement technique has established itself as the gold standard method for the imaging of focal fibrosis. There is no consensus on the method of its objective quantification. In this thesis the techniques used to quantify focal fibrosis in a variety of diseases are analysed and a ‘clear winner’ technique identified. The contribution of focal fibrosis to exercise intolerance in hypertrophic cardiomyopathy is explored, revealing that it is the strongest of the known non-invasive exercise predictors. Diffuse fibrosis: Diffuse myocardial fibrosis (DMF) is a ubiquitous process accelerated by all disease processes. Until now DMF has been a covert entity – known to be present from biopsy and post mortem study but not quantifiable non-invasively. Here is developed the first accurate non-invasive clinically validated method for the measurement of diffuse myocardial fibrosis which we name equilibrium contrast CMR. It is safe and easily performed as an extension to a normal CMR scan. Clinically, measurement of DMF is shown to be important in severe aortic stenosis. EQ-CMR measured DMF was the best predictor of baseline exercise performance and symptoms and was the only variable to predict response to surgery. LVH regression early after aortic valve replacement is shown to be cellular rather than fibrosis resolution. Preliminary data are reported demonstrating that DMF is present in a variety of other cardiological disease states and varying interstitial volumes are shown in four different organs. These data highlight the huge potential of this technique – not only in cardiology but throughout the body. In addition, DMF quantification is likely to be important in disease and therapeutic response monitoring, prognostication and as a biomarker for research.

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