Quantitative measurements of cerebral hemodynamics using magnetic resonance imaging

Cerebral ischemia is a vascular disorder that is characterized by the reduction of blood supply to the brain, resulting in impaired metabolism and finally death of brain cells. Cerebral ischemia is a major clinical problem associated with global morbidity and mortality rates of about 30%. Clinical management of cerebral ischemia relies heavily on perfusion analysis using dynamic susceptibility contrast MRI (DSC-MRI). DSC-MRI analysis is performed using mathematical models that simulate the underlying vascular physiology of brain. Cerebral perfusion is calculated using perfusion imaging and is used as a marker of tissue health status; low perfusion being an indicator of impaired tissue metabolism.
In addition to measurement of cerebral perfusion, it is possible to quantify the blood flow variation within the capillary network referred to as cerebral microvascular hemodynamics. It has been hypothesized that microvascular hemodynamics are closely associated with tissue oxygenation and that hemodynamics might undergo a considerable amount of variation to maintain normal tissue metabolism under conditions of ischemic stress. However with DSC-MRI perfusion imaging, quantification of cerebral hemodynamics still remains a big challenge.
Singular Value Decomposition (SVD) is currently a standard methodology for estimation of cerebral perfusion with DSC-MRI in both research and clinical settings. It is a robust technique for quantification of cerebral perfusion, however, the quantification of hemodynamic information cannot be achieved with SVD methods because of the non-physiological behaviour of SVD in microvascular hemodynamic estimation. SVD is sensitive to the noise in the MR signal which appears in the calculated microvascular hemodynamics, thus making it difficult to interpret for pathophysiological significance. Other methods, including model-based approaches or methods based on likelihood estimation, stochastic modeling and Gaussian processes, have been proposed. However, none of these have become established as a means to study tissue hemodynamics in perfusion imaging. Possibly because of the associated constrains in these methodologies that limited their sensitivity to hemodynamic variation in vivo.
The objective of the research presented in this thesis is to develop and to evaluate a method to perform a quantitative estimation of cerebral hemodynamics using DSC-MRI. A new Control Point Interpolation (CPI) method has been developed to perform a non-parametric analysis for DSC-MRI. The CPI method was found to be more accurate in estimation of cerebral perfusion than the alternative methods. Capillary hemodynamics were calculated by estimating the transit time distribution of the tissue capillary network using the CPI method. The variations in transit time distribution showed quantitative differences between normal tissue and tissue under ischemic stress. The method has been corrected for the effects of macrovascular bolus dispersion and tested over a larger clinical cohort of patients with atherosclerosis. CPI method is thus a promising method for quantifying cerebral hemodynamics using perfusion imaging. CPI method is an attempt to evaluate the use of quantitative hemodynamic information in diagnostic and prognostic monitoring of patients with ischemia and vascular diseases.