Experimental Protocols and Analysis Methods for Real-Time Assessment of Cardiac Metabolism

Student thesis: Doctoral ThesisDoctor of Philosophy


Cardiovascular disease remains the primary cause of death worldwide. Medical imaging plays a critical and increasing role in both its diagnosis and characterisation. Recent advances in hyperpolarised 13C Magnetic Resonance (MR) allow, for example, imaging an injected molecule and its downstream metabolites to uncover biochemical changes in the myocardium. On the other hand, radionuclide imaging using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) has significantly higher sensitivity than MR, but the signals from injected tracers and their metabolites are indistinguishable. All these imaging modalities are able to produce dynamic data containing information of the kinetics of their respective tracers. In order to relate the measured signal or activity to the underlying physiological or biochemical processes mathematical models have to be used. In this thesis, experimental protocols have been developed and semi-quantitative and quantitative methods have been evaluated for the analysis of hyperpolarised 13C dynamic time-series and time-activity curves of PET tracers acquired ex vivo from Langendorff perfused rat hearts. A number of compartmental models were explored to fit in vitro and ex vivo hyperpolarised 13C time-series acquired for pyruvate and its downstream metabolites to derive apparent rates of the enzymatic reactions involved in pyruvate metabolic pathways. Compartmental modelling was also used in combination with Monte Carlo simulations to explore the detection limits of transmural cardiac ischemia in vivo in small rodents using hyperpolarised 13C spectroscopic imaging. The feasibility of using a model free maximum entropy/nonlinear least square method (MEM/NLS) for the kinetic analysis of hyperpolarised 13C dynamic data was explored in this thesis for the first time and validated using Monte Carlo simulations and experimental hyperpolarised 13C in vitro time-series. Finally, the feasibility of extending the analysis methods validated for in vivo PET experiments (spectral-based algorithm, Patlak graphical plot and the semi-quantitative index RATIO) to the kinetic analysis of time-activity curves of PET tracers acquired ex vivo was also assessed in this thesis.
Date of Award2014
Original languageEnglish
Awarding Institution
  • King's College London
SupervisorThomas Eykyn (Supervisor) & Richard Southworth (Supervisor)

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