- Title
- Optimizing tissue pathophysiology with computed tomography perfusion imaging in acute ischemic stroke
- Creator
- Chen, Chushuang
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Background: Ischemic stroke is the leading cause of adult disability in the developed world. When a blood vessel within the brain becomes occluded, there is a volume of tissue which immediately dies, the ischemic core, and a volume of tissue which is hypo-perfused and will die within hours if the occlusion is not removed, the ischemic penumbra. Salvage of the ischemic penumbra by reperfusion can be achieved with intravenous thrombolysis which activates the bodies’ anti-clotting system to dissolve a thrombus, or mechanical removal of the clot with thrombectomy. Computed tomography perfusion (CTP) is a clinically available brain imaging technique which not only assists with positively confirming the diagnosis of acute ischemic stroke, but also assists reperfusion therapy decision making in clinical practice by providing information about brain tissue viability (salvageable versus non-salvageable tissue). The volume of the ischemic core has been shown to be related to patient outcomes, and the volume of the penumbra has also been shown to relate to treatment response potential. However, the measurement of penumbra and infarct core with CTP can be varied due to different structural tissue compartments of the brain (grey matter and white matter) and different algorithms applied to post-processing of raw imaging (standard singular value deconvolution (sSVD) and standard singular value deconvolution with delay and dispersion correction(ddSVD). This thesis incorporated a series of studies, aimed to increase the precision and accuracy of the tissue pathophysiology measures in acute ischemic stroke with CTP and relate the relevant measurement of ischemic penumbra and infarct core to patient outcomes. Methods: This thesis included acute ischemic stroke patients from two data sets: (1) A previously collected data set of acute ischemic stroke patients admitted to the John Hunter Hospital within 6 hours of symptom onset, underwent baseline MRI within 1 hour of the initial CTP, and follow-up MRI at 24-hour. (2) Acute ischemic strokes patients recruited into the INternational Stroke Perfusion Imaging REgistry (INSPIRE). National Institutes of Health Stroke Scale (NIHSS) was performed at baseline and 24-hour to assess the stroke severity. A modified Rankin Score (mRS) was performed at day-90 post-stroke to evaluate patient outcomes. All perfusion imaging were post-processing with MIStar (Apollo Medical Imaging Technology, Melbourne, Australia) using sSVD and/or ddSVD as post-processing algorithms. Results: The first study in this thesis derived the optimal threshold of penumbra and infarct core for gray matter and white matter. This study demonstrated that separated tissue-specific thresholds for gray matter and white matter increased volumetric agreement with acute diffusion-weighted imaging. Gray matter had considerably higher infarct core thresholds than white matter. Furthermore, a single threshold, delay time (DT) >3seconds from ddSVD accurately defined penumbra in gray matter and white matter, as well as mixed measures of gray matter and white matter. The following three studies in this thesis aimed to relate the relevant measurement of penumbra and infarct core to patient outcomes. This thesis demonstrated that in acute ischemic stroke patients who received alteplase, after correcting for baseline infarct core volume, for each percentage of penumbral volumes that was salvaged, the odds of a patient having an excellent clinical outcome increased by 7.4%. Furthermore, the perfusion imaging mismatch classification with DT was the optimal mismatch criteria as a patient selection tool for reperfusion therapy, in large vessel occlusion patients who receive intravenous thrombolysis only and patients who receive endovascular thrombectomy. Lastly, this thesis also found that patients with larger baseline CTP infarct core (>30mL) and “proximal” large vessel occlusion, with poorer collaterals clearly benefited from complete reperfusion after endovascular thrombectomy compared to complete reperfusion after intravenous thrombolysis alone. However, more “distal” large vessel occlusion patients with smaller baseline infarct cores and better collaterals, did not have additional benefit from complete reperfusion after endovascular thrombectomy compared with intravenous thrombolysis alone. Conclusion: The findings of this thesis supported that CTP was able to accuratly and precicely define acute ischemic tissue pathophysiology. Moreover, the accurate measures of brain tissue viability were directly related to patient clinical outcome regardless of the type of treatment received (intravenous thrombolysis or thrombectomy), and the likelihood of the success of reperfusion therapy. Importantly, the relationship between the baseline tissue pathophysiology of the ischemic core and penumbra to patient outcomes was seen to be significantly different depending on treatment type.
- Subject
- ischemic stroke; penumbra; thrombolysis; thrombectomy; perfusion; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1406198
- Identifier
- uon:35602
- Rights
- Copyright 2019 Chushuang Chen
- Language
- eng
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View Details Download | ATTACHMENT01 | Thesis | 3 MB | Adobe Acrobat PDF | View Details Download | ||
View Details Download | ATTACHMENT02 | Abstract | 188 KB | Adobe Acrobat PDF | View Details Download |