Abstract: We identified four randomised controlled trials, using different intraoperative imaging technologies: iMRI (2 trials including 58 and 14 participants, respectively); fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) (1 trial, 322 participants); and neuronavigation (1 trial, 45 participants). We identified one ongoing trial assessing iMRI with a planned sample size of 304 participants for which results are expected to be published around autumn 2018. We identified no trials for ultrasound. Meta-analysis was not appropriate due to differences in the tumours included (eloquent versus non-eloquent locations) and variations in the image guidance tools used in the control arms (usually selective utilisation of neuronavigation). There were significant concerns regarding risk of bias in all the included studies. All studies included people with high-grade glioma only. Extent of resection was increased in one trial of iMRI (risk ratio (RR) of incomplete resection 0.13, 95% confidence interval (CI) 0.02 to 0.96; 1 study, 49 participants; very low-quality evidence) and in the trial of 5-ALA (RR of incomplete resection 0.55, 95% CI 0.42 to 0.71; 1 study, 270 participants; low-quality evidence). The other trial assessing iMRI was stopped early after an unplanned interim analysis including 14 participants, therefore the trial provides very low-quality evidence. The trial of neuronavigation provided insufficient data to evaluate the effects on extent of resection. Reporting of adverse events was incomplete and suggestive of significant reporting bias (very low-quality evidence). Overall, reported events were low in most trials. There was no clear evidence of improvement in overall survival with 5-ALA (hazard ratio 0.83, 95% CI 0.62 to 1.07; 1 study, 270 participants; low-quality evidence). Progression-free survival data were not available in an appropriate format for analysis. Data for quality of life were only available for one study and suffered from significant attrition bias (very low-quality evidence). Intra-operative imaging technologies, specifically iMRI and 5-ALA, may be of benefit in maximising extent of resection in participants with high grade glioma. However, this is based on low to very low quality evidence, and is therefore very uncertain. The short- and long-term neurological effects are uncertain. Effects of image-guided surgery on overall survival, progression-free survival, and quality of life are unclear. A brief economic commentary found limited economic evidence for the equivocal use of iMRI compared with conventional surgery. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly. Further research, including studies of ultrasound-guided surgery, is needed.

Plain-language summary: Our search strategy is up to date as of July 2017. We found four trials looking at three different types of tools to help improve the amount of tumour that is removed. The tumour being evaluated was high-grade glioma. Imaging interventions used during surgery included: • magnetic resonance imaging (iMRI) during surgery to assess the amount of remaining tumour; • fluorescent dye (5-aminolevulinic acid) to mark out the tumour; or • imaging before surgery to map out the location of a tumour, which was then used at the time of surgery to guide the surgery (neuronavigation). All the studies had compromised methods, which could mean their conclusions were biased. Other studies were funded by the manufacturers of the image guidance technology being evaluated. We found low- to very low-quality evidence that use of image-guided surgery may result in more of the tumour being removed surgically in some people. The short- and long-term neurological effects are uncertain. We did not have the data to determined whether any of the evaluated technologies affect overall survival, time until disease progression, or quality of life. There was very low-quality evidence for neuronavigation, and we identified no trials for ultrasound guidance. In terms of costs, a non-systematic review of economic studies suggested that compared with standard surgery use of image-guided surgery has an uncertain effect on costs and that 5-aminolevulinic acid was more costly than conventional surgery. Evidence for intraoperative imaging technology for use in removing brain tumours is sparse and of low to very low quality. Further research is needed to assess three main questions. 1. Is removing more of the tumour better for the patient in the long term? 2. What are the risks of causing a patient to have worse symptoms by taking out more of the tumour? 3. How does resection affect a patient's quality of life?