Abstract
BackgroundMulticentre clinical trials evaluating the role of 18F-Fluoroethyl-l-tyrosine (18F-FET) PET as a diagnostic biomarker in glioma management have highlighted a need for standardised methods of data analysis. 18F-FET uptake normalised against background in the contralateral brain is a standard imaging technique to delineate the biological tumour volume (BTV). Quantitative analysis of 18F-FET PET images requires a consistent and robust background activity. Currently, defining background activity involves the manual selection of an arbitrary region of interest, a process that is subject to large variability. This study aims to eliminate methodological errors in background activity definition through the introduction of a semiautomated method for region of interest selection. A new method for background activity definition, involving the semiautomated generation of mirror-image (MI) reference regions, was compared with the current state-of-the-art method, involving manually drawing crescent-shape (gCS) reference regions. The MI and gCS methods were tested by measuring values of background activity and resulting BTV of 18F-FET PET scans of ten patients with recurrent glioblastoma multiforme generated from inputs provided by seven readers. To assess intra-reader variability, each scan was evaluated six times by each reader. Intra- and inter-reader variability in background activity and BTV definition was assessed by means of coefficient of variation.ResultsCompared to the gCS method, the MI method showed significantly lower intra- and inter-reader variability both in background activity and in BTV definition.ConclusionsThe proposed semiautomated MI method minimises intra- and inter-reader variability, providing a valuable approach for standardisation of 18F-FET PET quantitative parameters.Trial registration ANZCTR, ACTRN12618001346268. Registered 9 August 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374253
Highlights
Multicentre clinical trials evaluating the role of 18F-Fluoroethyl-l-tyrosine (18F-FET) PET as a diagnostic biomarker in glioma management have highlighted a need for standardised methods of data analysis. 18F-FET uptake normalised against background in the contralateral brain is a standard imaging technique to delineate the biological tumour volume (BTV)
The important role of 18F-Fluoroethyl-l-tyrosine (18F-FET) PET imaging in the management of glioma patients is becoming widely recognised around the world by associations such as the European Association of Neuro Oncology, the European Association of Nuclear Medicine (EANM) and the Response Assessment in Neuro Oncology working group [1,2,3,4]. 18F-FET PET imaging has proven useful in the diagnosis of primary tumour lesions, the differentiation between chemoradiationrelated changes and tumour recurrence at follow-up, the assessment of response to treatment with certain anticancer drugs and patients’ prognosis [1]
Guided crescent‐shape volume of interest (VOI) The use of the guided crescent-shape (gCS) method for background activity assessment resulted in a median intra-reader coefficient of variation (CoV) of 1.72% for contralateral reference (CTRL) SUVmean and 6.77% for BTV, and in a median inter-reader CoV of 2.80% for CTRL SUVmean and 14.37% for BTV (Tables 1 and 2)
Summary
Multicentre clinical trials evaluating the role of 18F-Fluoroethyl-l-tyrosine (18F-FET) PET as a diagnostic biomarker in glioma management have highlighted a need for standardised methods of data analysis. 18F-FET uptake normalised against background in the contralateral brain is a standard imaging technique to delineate the biological tumour volume (BTV). There is a need to standardise methods for data acquisition and analysis, to enable correlations and comparisons of results from different sites Evaluation metrics of such trials are often determined via PET tracer uptake measures, such as standard uptake values (SUV) and tumour-to-brain ratio (TBR), where TBR is defined as the ratio between activity in the tumour lesion and activity in a background reference region in the healthy, contralateral part of the brain. A recent study by Unterrainer et al [6] has demonstrated that adding guidelines to the definition of a crescent-shaped VOI in the contralateral hemisphere including grey and white matter significantly reduces intra- and inter-reader variability in the measurement of reference background activity, providing a first important step towards the standardisation of background activity assessment for clinical application This method still requires significant manual reader input, which remains time-consuming and a source of methodological error. This method does not account for the presence of multiple tumour lesions in the generation of the FET TBR map and, of the BTVCS, as FET TBR map generation is solely determined by the manually drawn CTRLCS VOI defined by the reader
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