LA MEJORA CONTINUA DE LOS PROCESOS DE LA EMPRESA

4.1.2.1 Patient recruitment

The project was approved by the Australian Capital Territory health human research ethics committee and the Australian National University human research ethics committee (Approval references ETH11.09.1014 and 2010-392 respectively). Informed consent was obtained from each patient or from next of kin if the patient was unable to give informed consent as a result of their brain injury.

All patients were recruited within 24 hours of suffering an ischaemic stroke in the territory perfused by the middle cerebral artery (MCA). Recruitment was limited to MCA strokes because this territory consists largely of tissue from which good MR spectra can generally be obtained. Furthermore, MCA strokes are the single most common class of ischaemic stroke [18]. Patients were excluded if they were under 18 years of age, if they had any known contraindications to MRI, or if they could not receive their first MRI within 24 hours of stroke onset (or time last known well for patients with an unknown stroke onset).

4.1.2.2 Imaging

The study design called for each patient to undergo a total of 5 MR examinations, with the first of these being conducted as soon as practical after stroke onset, subsequent

examinations were conducted every 24 hours after the initial examination. All

examinations were conducted on the 1.5T Siemens Magnatom Avanto MRI scanner at the Canberra Hospital.

The protocol for the first MR examination involved Diffusion-weighted imaging (DWI), which shows acute ischaemia very effectively [22] in 3 planes. These triplanar images were then used to guide the location of 3 single-voxel MR spectroscopy (MRS) acquisitions identical to those carried out on healthy volunteers in Chapters 3.2 and 3.3. The first MRS voxel was located within the infarct, recognisable as a region hyper-intensity on the DWI. The second voxel was positioned in tissue as close to the infarct as possible (peri-infarct), while avoiding structures such as the skull or ventricles that would have degraded the

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quality of the spectrum. The final spectrum was positioned in the contralateral hemisphere, as close as practical to the ‘mirror image’ of the infarct voxel.

Perfusion-weighted imaging (requiring an injection of gadolinium-based contrast agent) was performed after the acquisition of the final MR spectrum to provide a cerebral blood flow value for the purposes of future finite element modelling (see chapters 5.1 and 5.2). If patients were unable to receive the gadolinium contrast agent for any reason (most

commonly because of poor kidney function [202]) they were still enrolled in the study and the PWI scan was simply omitted from the scanning protocol. Consideration was given to conducting the PWI before the MRS acquisitions, and using the PWI/DWI mismatch to identify penumbra for voxel placement. Unfortunately, the MRI scanner being used did not have this capability, as the PWI scans had to be post-processed off-site. Therefore, the PWI was conducted after the MRS scans in order to reduce the risk of the gadolinium in the patient’s blood affecting the MR spectra [203].

The second and subsequent MR examinations all began with a 3 dimensional fluid attenuated inversion recovery (FLAIR) scan. This is a form of T2-weighted imaging (See Appendix 1) which shows sub-acute ischaemia very effectively and produces clearer anatomical images than DWI. The 3 dimensional FLAIR data were then post-processed into 3 plane images, similar to the 3 plane diffusion-weighted images used in the first scan. These triplanar images were used to position 3 MRS voxels. The MRS voxels were manually positioned as close as possible to the location of the 3 voxels acquired in the first MR examination. PWI and DWI were not conducted during these examinations.

4.1.2.3 Other data collection

The severity of each patient’s stroke symptoms was assessed using the national institute of health stroke scale (NIHSS) [204, 205]. Relevant information such as time of symptom onset, age, medications, risk factors and previous ischaemic events was obtained from the patient’s medical notes and from bedside interviews conducted with the patients or their relatives. The patient’s tympanic temperature was recorded at the end of each MR examination.

Patient outcome was recorded by means of the modified Rankin score, which was assessed via telephone interview 90 days after the patient’s stroke. Both the NIHSS and the

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modified Rankin score are very common assessment tools in stroke studies [204, 206, 207] and using these tools made comparison to previous studies easier. Furthermore, while this study was never designed to recruit enough patients to derive meaningful conclusions about the effects of regional brain temperature on outcome, by recording the NIHSS and modified Rankin score the door was left open for these data to be included in a subsequent larger data set or meta-analysis.

4.1.2.4 Data processing

MRS data were processed in the manner described in chapter 2.1, and the amplitude- weighted temperature was calculated for each voxel (see chapters 3.2 and 3.3). These temperatures were recorded in a spreadsheet for further analysis. The raw data from each PWI scan was burned onto a DVD and sent to Dr Andrew Bivard at John Hunter Hospital in Newcastle, NSW, for processing on the MIStar software package (Apollo Medical Imaging, Melbourne, Vic). Unfortunately, absolute CBF values are difficult to determine accurately using the PWI scans available at Canberra Hospital. Therefore, MIStar was used to map the relative CBF (CBF values relative to the average value across the entire patient’s brain) and the relative CBF value corresponding to each MRS voxel was recorded.

No statistical analysis was carried out as the sample size obtained was too small for such analysis to yield meaningful results.

4.1.3 Results