The influence of ethnicity on neuroimaging and clinical outcome post stroke

Aims To investigate and establish the optimal threshold of rCBF correlates with final infarct volume for Asian populations. Methods/Overaching design This is an observational non-interventional cohort study investigating the optimal ischemic threshold of rCBF comparing Australian and Indonesian ischemic stroke patients. It will be conducted at two main centres, 1) Geelong University Hospital, Australia and (2) National Brain Centre, Jakarta, Indonesia. We believe that the study design will adequately address the overarching aims of my PhD in the elucidation of an optimal relative rCBF threshold for Asian patients. The study in both centres will share the following protocol and will align to the following study design principles and data acquisition as follows: Patient data will be sourced from neuroimaging sequences, including computed tomography perfusion (CTP) rCBF initial ischemic core at presentation, Magnetic Resonance Imaging (MRI) Diffusion Weighted Imaging (DWI) within 72 hours to demonstrate the final infarct volume and CT angiography (CTA). Digital subtraction angiography (DSA) will be reviewed only for patients who proceed to endovascular clot retrieval. Ischemic core volumes will be modelled using different rCBF thresholds. These models provide the basis for comparing and matching the appropriate thresholds in both populations. Consent procedures and clinical waiver processes Jakarta: We will obtain patient consent from Jakarta for neuroimaging (CT perfusion, CT angiography (CTA) and MRI with diffusion weighted imaging (DWI). Either the Emergency Department doctors or neurologists on site will be responsible for obtaining consent from either the patient or from patient’s family. Geelong Neuroimaging (CT perfusion, CT angiography and MRI (with DWI) constitutes the current standard of care for all stroke patients. On this basis, consent is not required. Patient Participation - Inclusion and Exclusion Criteria Inclusion Criteria: 1. Ischemic Stroke up to 24 hours from ictal onset 2. Age >18 years old Exclusion Criteria: 1. intracerebral haemorrhage 2. Pregnant women 3. Asian population in Australia General data collection protocol The preliminary assessment protocol involves collection of patient specific data Standardised per site sourced from a sequence of clinical, observational and imaging Procedures. On arrival at the emergency department, general wards, and stroke unit patients are assessed by the Emergency Department doctors, neurological registrars or designated stroke neurologists: 1). Initial clinical assessment (for all patients including those who proceed to intravenous thrombolysis or endovascular thrombectomy) The following data will be collected in the Clinical Report Form (CRF) as baseline measurement: age, gender, time metrics, vascular risk factors, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (MRS), relevant medical history, current medications. 2). Stroke imaging sequence protocol The following imaging sequences will be performed for all study patients: non-contrast computed tomography (NCCT), CT angiogram, CT perfusion, MRI and digital subtraction angiography (only for those patients who proceed to ECR). NCCT NCCT is critical in its use in exclusion of intracerebral haemorrhage. It is less sensitive but remains useful in the detection of early ischemic changes which include obscuration of grey-white matter and basal ganglia, cortical sulcal effacement and focal parenchymal hypo attenuation[67]. CT angiogram CT angiogram provides information regarding the presence and location of large vessel occlusion. This allows for classification of patients into different stroke territories. In addition, intracranial atherosclerotic disease (ICAD) will be detected[81]. CT perfusion CT perfusion provides information regarding tissue at risk (represented by T Max +6) and predicted ischemic core (represented by rCBF)[75]. Data collected from CT perfusion therefore contributes to the basis of this PhD the characteristics and processing of which will be elaborated in the next section on methodology. MRI Diffusion Weighted Imaging (DWI) MRI (utilizing diffusion weighted imaging sequences, DWI) provides an internationally confirmed standard for quantification of the ischemic core at 24-72 hours[64, 72]. Digital subtraction angiography (DSA) DSA provides data on the degree of reperfusion after endovascular clot retrieval (ECR)/thrombectomy. Follow up clinical assessment 1. mRS and NIHSS at discharge will be collected to assess the improvement. 2. mRS at day 90 will be collected by phone call or during clinical visit. Our preliminary participant inclusion and assessment protocol involves collection of patient specific data; standardised per site sourced from a sequence of clinical, observational and imaging procedures The imaging protocol and associated imaging and data analytical sequence is as follows: Initially a non-contrast-enhanced head CT and/or a CT angiogram will be combined with a Perfusion CT scan. CT perfusion scanning parameters and data acquisition General principles Whole-brain perfusion CT is routinely accomplished using CT systems with a purpose designed data acquisition and wide detector array 8-16 cm system (DAS). Time-resolved scans are used to track the flow of iodinated contrast media through the brain with multiple images (20-40) acquired over the same region of interest (ROI) of target anatomy. Patients are required to remain still during the examination in order to avoid motion misregistration. The examination couch may remain stationary during the entire examination or move back and forth to enable acquisition of date in the required imaging planes dictated by underlying engineering principles. Acquisitions are repeated at specified time intervals (e.g. every second to every 2-3 seconds) for a predetermined duration (e.g. 40-90 seconds). Thick image sections are acquired to minimize image noise and optimize the useful signal to noise (SRN) ratio (section widths are generally set at 5-10 mm). Data are used to generate colour maps of hemodynamic significance, for example cerebral blood volume (CBV) and cerebral blood flow (CBF), mean transit time (MTT) and time to peak (TPP). Dose Management 80 kVp is an international standard that is recognised to increase iodine signal brightness and maintain low radiation dosage per single scan (i.e. one tube rotation). The time interval between scans, and hence the total number of scans over the examination duration, is set carefully, taking into an account the requirements of the analysis algorithm. Dose (tube current) modulation is not generally used, as it interferes with the calculation of the CBV and CBF parameters. Our imaging protocols adopted in Geelong and Jakarta have been designed to align with international standards and guidelines consequently there is technical and clinical standardisation of the imaging techniques performed in both centres. While it is acknowledged that there are differences in the technical design and specifications of commercial imaging systems. We have ensured that our data standardisation and management processes align with (DICOM) standards consequently our pre and post processing of DICOM data in the (RAPID) software is considered compatible between both sites providing the required levels of accuracy and compatibility for comparative analysis. Data acquisition technical specifications per site: Jakarta specific CT perfusion protocol CTP (Model: Phillips ICT 256) 1. Total volume contrast of injection 40 mL Iodine based contrast medium is given with injection rate of bolus at 6mls/sec. 2. The injector and the scanner are started at the same time. 3. Images are acquired every 1.5 seconds for 70 seconds, thus obtaining 35 sets of data. 4. Perfusion coverage is 8cm. 5. Images will be constructed which are 5 mm thick. 6. Total of 640 images will be produced. 7. We use 80kVp and 100mAs for the perfusion. 8. CTP series will be auto sent (by series) to RAPID for post-processing Geelong specific CT perfusion protocol CT Perfusion (Model: Philips ICT Scanner 256) 1. Total volume of 50 mL of Iodine based contrast medium is given as an injection bolus at a rate of 6mL/sec. 2. The injector and the scanner are started at the same time. 3. Images are acquired every 2 seconds for 70 seconds, thus obtaining 35 sets of data. 4. Perfusion coverage is 8cm. 5. Images are 10mm thick and produce 8 images per acquisition. 6. Total of 280 images will be produced. 7. We use 80kVp and 80mAs for the perfusion. 8. CTP series will be auto sent (by series) to RAPID for processing CT Carotid Angiography CTA: (Model: Phillips ICT 256) Jakarta’s Protocol 1. A total volume of 65-75ml of Iodine based contrast is given as an injection bolus at a rate of 5mls/sec. 2. Bolus tracking is used to start the scan. 3. A single image will be taken through the aortic arch and place a ROI in the descending aorta. 4. Wait for 15 seconds after the injection and then take monitoring scans through the arch. When the contrast reaches a predetermined threshold level of 150HU it indicates the beginning of the scan. 5. Generate a thin data set with slice thickness of 0.9 mm. 6. Multiplanar (MPR) images will be created in several planes that are 4mm thickness. 7. 120kVp will be used for angiography. 8. Radiation dose: 31.9 mGy(DLP:801.2 mGycm) Geelong’s Protocol (Model: Philips ICT Scanner 256) 1. A total volume of 65-75ml of Iodine based contrast is given as an injection bolus at a rate of 5mls/sec. 2. Bolus tracking is used to start the scan. 3. A single image will be taken through the aortic arch and place a ROI in the descending aorta. 4. Wait 15 seconds after the injection and then take monitoring scans through the arch. When the contrast reaches a predetermined threshold level of 150HU it indicates the beginning of the scan. 5. Generate a thin data set with slice thickness of 0.8mm. 6.