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UBC Theses and Dissertations

Characterization of tumour vasculature with dynamic contrast enhanced MRI and Gd-hyperbranched polyglycerols McPhee, Kelly Catherine


Tumour tissue is highly heterogeneous with disordered vasculature that is characteristically highly permeable relative to other normal tissue blood vessels. Non-invasive investigation of tumour vasculature may be achieved using Dynamic Contrast Enhanced MRI (DCE-MRI). Pharmacokinetic modelling of contrast agent uptake can provide information about blood flow and vessel permeability, but modelling is limited due to the ability of typical contrast agents such as Gd-DTPA to extravasate and accumulate in tumour tissue. The hypothesis motivating this work is that DCE-MRI measurements with both high and low molecular weight contrast agent uptake will allow for improved interpretation of the tumour micro-environment. A new high molecular weight contrast agent comprised of hyperbranched polyglycerol (HPG) molecules doubly labelled with gadolinium and a fluorescent marker is characterized, and used along side a standard low molecular weight contrast agent, Gadovist (Bayer Healthcare). Histological data reveals that HPG extravasates slowly from vasculature, and remains near blood vessels over the time-frame of a DCE-MRI experiment. HPG was also found to accumulate in tumour tissue over days, peaking at 2-4 days. HPG was found to be inappropriate for pharmacokinetic modelling, due to relatively low enhancement in the DCE-MRI data. Parameter maps showing bolus arrival time of HPG throughout the tumour show increased sensitivity to necrosis relative to Gadovist. Initial area under the HPG-concentration time curve was found to be correlated with vascular density. Modelling of DCE-MRI data should be performed with a model appropriate to the tissue, contrast agent, and data available. While simpler models are not able to distinguish blood flow from permeability, data quality is not necessarily sufficient to justify the use of a more complex model. This problem is addressed in this work by modelling contrast agent uptake with system of increasingly complex models, and the Akaike information criterion was used to determine that a general two compartment exchange model was more appropriate than the extended Tofts model for pharmacokinetic modelling of DCE-MRI with a standard contrast agent.

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