Abstract
BackgroundDiffusion- and perfusion-weighted MRI are valuable tools for measuring the cellular and vascular properties of brain tumours. This has been well studied in adult patients, however, the biological features of childhood brain tumours are unique, and paediatric-focused studies are less common. We aimed to assess the diagnostic utility of apparent diffusion coefficient (ADC) values derived from diffusion-weighted imaging (DWI) and cerebral blood flow (CBF) values derived from arterial spin labelling (ASL) in paediatric brain tumours.MethodsWe performed a meta-analysis of published studies reporting ADC and ASL-derived CBF values in paediatric brain tumours. Data were combined using a random effects model in order to define typical parameter ranges for different histological tumour subtypes and WHO grades. New data were also acquired in a ‘validation cohort’ at our institution, in which ADC and CBF values in treatment naïve paediatric brain tumour patients were measured, in order to test the validity of the findings from the literature in an un-seen cohort. ADC and CBF quantification was performed by two radiologists via manual placement of tumour regions of interest (ROIs), in addition to an automated approach to tumour ROI placement.ResultsA total of 14 studies met the inclusion criteria for the meta-analysis, constituting data acquired in 542 paediatric patients. Parameters of interest were based on measurements from ROIs placed within the tumour, including mean and minimum ADC values (ADCROI-mean, ADCROI-min) and the maximum CBF value normalised to grey matter (nCBFROI-max). After combination of the literature data, a number of histological tumour subtype groups showed significant differences in ADC values, which were confirmed, where possible, in our validation cohort of 32 patients. In both the meta-analysis and our cohort, diffuse midline glioma was found to be an outlier among high-grade tumour subtypes, with ADC and CBF values more similar to the low-grade tumours. After grouping patients by WHO grade, significant differences in grade groups were found in ADCROI-mean, ADCROI-min, and nCBFROI-max, in both the meta-analysis and our validation cohort. After excluding diffuse midline glioma, optimum thresholds (derived from ROC analysis) for separating low/high-grade tumours were 0.95 × 10−3 mm2/s (ADCROI-mean), 0.82 × 10−3 mm2/s (ADCROI-min) and 1.45 (nCBFROI-max). These thresholds were able to identify low/high-grade tumours with 96%, 83%, and 83% accuracy respectively in our validation cohort, and agreed well with the results from the meta-analysis. Diagnostic power was improved by combining ADC and CBF measurements from the same tumour, after which 100% of tumours in our cohort were correctly classified as either low- or high-grade (excluding diffuse midline glioma).ConclusionADC and CBF values are useful for differentiating certain histological subtypes, and separating low- and high-grade paediatric brain tumours. The threshold values presented here are in agreement with previously published studies, as well as a new patient cohort. If ADC and CBF values acquired in the same tumour are combined, the diagnostic accuracy is optimised.
Highlights
Brain tumours represent the most common solid tumour of childhood, and one of the highest causes of paediatric cancer-related mortality (Pollack, 1994)
Our inclusion criteria were as follows: (1) arterial spin labelling (ASL) or diffusion-weighted imaging (DWI) was used to measure cerebral blood flow (CBF) or apparent diffusion coefficient (ADC) values respectively, in treatment naïve paediatric brain tumours; (2) subsequent histological confirmation of tumour subtype was performed, with the exception of optic pathway glioma and diffuse midline glioma, in which tissue sampling is not generally used for diagnosis; (3) imaging parameters were obtained from tumour regions of interest (ROIs) avoiding large blood vessels, necrotic, cystic and haemorrhagic regions; (4) studies reported ADCROI-mean, and/or ADCROI-min values, or maximum normalised CBF values for the tumour, the latter being normalised to normal appearing grey matter in the same patient
ADCmean, ADCmin, and nCBFmax were measured over the entire tumour volume for comparison
Summary
Brain tumours represent the most common solid tumour of childhood, and one of the highest causes of paediatric cancer-related mortality (Pollack, 1994). After combination of the literature data, a number of histological tumour subtype groups showed significant differences in ADC values, which were confirmed, where possible, in our validation cohort of 32 patients In both the meta-analysis and our cohort, diffuse midline glioma was found to be an outlier among high-grade tumour subtypes, with ADC and CBF values more similar to the low-grade tumours. After excluding diffuse midline glioma, optimum thresholds (derived from ROC analysis) for separating low/high-grade tumours were 0.95 × 10−3 mm2/s (ADCROI-mean), 0.82 × 10−3 mm2/s (ADCROI-min) and 1.45 (nCBFROI-max) These thresholds were able to identify low/high-grade tumours with 96%, 83%, and 83% accuracy respectively in our validation cohort, and agreed well with the results from the meta-analysis. If ADC and CBF values acquired in the same tumour are combined, the diagnostic accuracy is optimised
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