Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Dr. Ting-Yim Lee

Abstract

CT Perfusion (CTP) provides measurement of perfusion at the capillary level which can be used to characterize tissue viability, and blood-brain-barrier (BBB) compromise. Using CTP, the goals of this research are to: 1) select patients that will benefit from acute stroke treatment, and 2) determine if pre-stroke neuroprotection reduces stroke severity.

Chapter two investigates the cerebral blood volume (CBV) parameter in a small acute ischemic stroke (AIS) patient set. Overestimation of the acute CBV defect is caused by incomplete wash-out of the CT contrast due to a shortened CTP acquisition time (“truncation artifact”).

In chapter three we examine the prognostic reliability of the acute CBV defect to predict infarct core and penumbra in AIS. We determine that hypervolemia, the “truncation artifact” and recanalization are all important variables which affect the relationship between the acute CBV defect volume and the final infarct volume.

Chapter four implements a novel porcine model of ischemic stroke using the transient vasoconstrictor, endothelin-1. Using this model, we show that the CTP-cerebral blood flow (CBF) parameter is as good as MR-DWI for acute infarct core delineation, and the CBF/CBV mismatch may not indicate penumbral tissue in the acute stroke setting.

In Chapter five, it we show that vascular integrity measured with the CTP-BBB permeability surface area product (PS) is a strong predictor of sub-acute bleeding in the brain (hemorrhagic transformation).

Chapter six shows that different rates of CT contrast extravasation exist for primary intracerebral hemorrhage (ICH) patients with/without the CTA-Spot Sign and/or post-contrast leakage. Furthermore, early rates of extravasation are correlated with sub-acute hematoma expansion.

Chapter seven describes the development of an improved, reproducible and survivable rabbit large clot embolic model (RLCEM) of cerebral ischemia for testing treatment options for AIS. We demonstrate that pre-stroke treatment with dipyridamole provides a neurovascular advantage post stroke onset.

In summary, the current uses of CTP imaging in acute stroke include: 1) quantifying ischemia to define infarct core and penumbra in AIS, 2) predicting hemorrhagic transformation of AIS, 3) predicting hematoma expansion in primary ICH, and 4) assessing treatment response in animal models of stroke to facilitate new drug development.


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