Measurement of physiological variables by dynamic Gd-DTPA enhanced MRI
Abnormal angiogenesis is characterised by the alteration of physiological variables such as capillary permeability and fractional volume of the extravascular extracellular space. The aim of the work presented in this thesis was to investigate the feasibility of non-invasive measurement of these physiological variables through quantitative analysis of dynamic Gd-DTPA enhanced MRI (DEMRI) acquired using standard imaging hardware within a clinical setting. A method for quantitative analysis of DEMRI (QDEMRI) was developed and implemented on a standard personal computer platform using a set of programs written in the C programming language. The method includes pharmacokinetic modelling of Gd-DTPA kinetics based on the modification of existing approaches and moving-window algorithms for the measurement of black-box quantifiers of DEMRI. The measurements were performed in two angiogenesis dependent diseases: breast cancer and rheumatoid arthritis (RA). In a study involving QDEMRI analysis of 59 primary invasive breast carcinomas, a significant relationship between capillary permeability-related QDEMRI variables and tumour grade was found. In a randomised controlled study of early RA in metacarpophalangeal joints, a significant reduction in the QDEMRI variable which reflects fractional volume of the extravascular extracellular space was found three months after the start of therapy in 20 patients treated with methotrexate and intra-articular methylprednisolone injections, whereas it remained constant in a control group of 17 patients who were treated with slow-acting methotrexate only. A significant reduction in the permeability-related QDEMRI variable was detected in 17 patients treated with leflunomide four months after the start of treatment whilst it remained unchanged in 17 patients treated with methotrexate in a randomised controlled study of established RA of the knee joint. The results obtained in this work indicate that the proposed QDEMRI method can be used in its present form to monitor treatment-induced changes in angiogenesis dependent diseases. Further work is needed to render these measurements fully independent of DEMRI acquisition settings and allow the evaluation of individual lesions.