Vascular artefacts in fMRI of early visual cortex: The effects of resolution and field strength

Large draining veins residing on the cortical surface are recognised as a major problem in fMRI measurements, leading to the displacement, distortion, and reduction in spatial localisation of signals. This is detrimental to the application of fMRI in advanced human brain imaging, such as in retinotopic mapping, where the BOLD signal becomes obscured by the artefacts from nearby draining veins (venous artefacts). There is consensus that at an increased magnetic field strength, the sensitivity to the contributions from these draining veins reduces, which promises the ability to capture measurements at greater sensitivity and specificity. With the advent of fMRI hardware and technologies, there is a great interest in understanding cortical layer-specific neuronal response that had been previously obscured due to the domination of signal change caused by venous artefacts. This forms the basis of support for fMRI at ultra-high magnetic field strength, with the conventional wisdom that the reduced sensitivity to macrovasculature (including draining veins) that comes with higher magnetic field strength can increase the sensitivity to underlying responses that closely reflect neuronal activation. However, this is debatable. Instead, there are instances where human neuronal response profiles displayed a pattern that seemed indicative of synaptic activities even without using ultra-high magnetic field strength. Recent trends in moving to ultra-high magnetic field strengths, especially for depth-dependent fMRI, beget the questions – is ultra-high magnetic field strength really necessary, and can it resolve the artefacts from draining veins? To elucidate these questions, this thesis aims to test the venous artefact and its impact on underlying signals across spatial resolutions and magnetic field strengths, focusing on the quality of the retinotopic organisation of the early visual cortex. The first experimental study was conducted to test the venous artefact and its impact on fMRI signals across the grey matter using high-resolution (isotropic resolution of 1 mm) fMRI images collected at 3 T. Using two surface reconstruction packages, the findings established that venous artefact occurs at the cortical surface and spreads within the grey matter. In this study, the ability of high-resolution fMRI at 3 T to conduct depth-dependent analyses was demonstrated. The second experimental study delves into the role of spatial resolution in the depth-dependent analysis of venous artefacts and their impact. The 1 mm 3 T fMRI images were spatially smoothed to simulate two additional sets of lower-effective resolution images. Here, the results found consistency in the venous artefact but a reduction in the venous effects. This suggests that at lower spatial resolutions, the venous artefact exists, but its impact on underlying signals is concealed. The third experiment incorporates two sets of 7 T fMRI images, with spatial resolutions of 1.6 mm and 0.8 mm, to test the venous artefacts at ultra-high magnetic field strength. The results showed evidence that venous artefacts remained prominent at 7 T. This study was extended into a comparative study by including the 3 T fMRI images used in the first study. Here, the generalisability of the venous artefact was established at 3 T and 7 T, as well as across various spatial resolutions. Finally, the fourth experiment explored a non- BOLD contrast, postulated to be less sensitive to contributions from the draining veins. In this study, VASO-fMRI was conducted with a spatial resolution of 1.1 mm and at 7 T to test the venous artefact and its impact. A reduction in the venous artefact and its impact was demonstrated. However, VASO images were found insufficient to inform the retinotopic organisation of the early visual cortex due to higher noise and lower signals, but they can be beneficial when used in conjunction with BOLD images. In summary, this thesis established the competence of high-resolution fMRI at 3 T for depth-dependent analysis. This suggests that the artefacts arising from draining veins can be avoided by avoiding surfaces or locations that are in proximity to these veins. Furthermore, this thesis sheds light on the generalisability of the venous artefact across magnetic field strengths and spatial resolutions. Finally, the results from the VASO-fMRI study demonstrated how VASO retinotopic mapping could benefit BOLD retinotopic mapping, especially when the BOLD response is highly polluted with macrovasculature

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

This was an investigator initiated study funded by Nestle Health Sciences through an unrestricted research grant, and by a National Institute for Health Research (UK) Professorship held by RP. The study was sponsored by Queen Mary University of London