Optimizing statistical parametric mapping analysis of 18F-FDG PET in children

Abstract

Background: Statistical parametric mapping (SPM) procedure is an objective tool to analyze 18F-fluoro-2-deoxy-d-glucose-positron-emission tomography (FDG-PET) images and a useful complement to visual analysis. However, SPM requires a comparison to control data set that cannot be obtained in healthy children for ethical reasons. Using adults as controls showed some limitations. The purpose of the present study was to generate and validate a group of pseudo-normal children as a control group for FDG-PET studies in pediatrics.

Methods: FDG-PET images of 47 children (mean ± SD age 10.2 ± 3.1 years) with refractory symptomatic (MRI-positive, n = 20) and cryptogenic (MRI-negative, n = 27) focal epilepsy planned for surgery were analyzed using visual and SPM analysis. Performances of SPM analysis were compared using two different control groups: (1) an adult control group consisting of healthy young adults (n = 25, 30.5 ± 5.8 years, adult PET template) and (2) a pediatric pseudo-control group consisting of patients (n = 24, 10.6 ± 3.1 years, children PET template) with refractory focal epilepsy but with negative MRI and with PET considered normal not only on visual analysis but also on SPM.

Results: Among the 47 children, visual analysis succeeded detecting at least one hypometabolic area in 87% of the cases (interobserver kappa = 0.81). Regarding SPM analysis, the best compromise between sensitivity and specificity was obtained with a threshold of p less than 0.001 as an extent of more than 40 voxels. There was a significant concordance to detect hypometabolic areas between both SPM analyses [kappa (K) = 0.59; p < 0.005] and between both SPM and visual analyses (K = 0.45; p < 0.005), in symptomatic (K = 0.74; p < 0.005) as in cryptogenic patients (K = 0.26; p < 0.01). The pediatric pseudo-control group dramatically improved specificity (97% vs. 89%; p < 0.0001) by increasing the positive predictive value (86% vs. 65%). Sensitivity remained acceptable although it was not better (79% vs. 87%, p = 0.039). The main impact was to reduce by 41% the number of hypometabolic cortical artifacts detected by SPM, especially in the younger epileptic patients, which is a key point in clinical practice.

Conclusions: This age-matched pseudo-control group is a way to optimize SPM analysis of FDG-PET in children with epilepsy. It might also be considered for other brain pathologies in pediatrics in the future.

Figure 1

Flow chart.

Figure 2

Cortical location of the hypometabolic areas.X axis presents the number of hypometabolic areas using visual analysis (n = 86) and of hypometabolic clusters (true hypometabolic areas and artifacts) using SPM-P (n = 83) and SPM-A (n = 120), according to their regional location on the cortex: F, frontal; C, central or opercular; P, parietal; T, temporal or insular; O, occipital. Y axis presents the number of hypometabolic areas among the 470 regions visually analyzed (47 patients, ten regions/patient). Notice that visual analysis is equal or superior to SPM to identify a hypometabolic area in any region, and both SPM procedures are quite equivalent to identify a true hypometabolic cluster in any region, but SPM-A identifies more artifacts than SPM-P, particularly in the frontal and temporal cortices, the most frequent hypometabolic locations.

Figure 3

Hypometabolic artifacts observed in patient group using SPM-A and SPM-P analysis. Hypometabolic artifacts observed in patient group (n = 47) using SPM-A analysis (adult control group) and SPM-P analysis (pediatric pseudo-control group). X axis presents the ages (in years). Y axis presents the number of hypometabolic artifacts (false positive results) using SPM-A (lozenges) and SPM-P (circles) analysis. The broken line represents the number of patients at the different ages. Notice that artifacts are observed less frequently using SPM-P than SPM-A, and none was found in patients under 6 years old using SPM-P.

Figure 4

Comparative results using SPM-A, SPM-P, and visual analyses. Comparative results using SPM-A (adult control group), SPM-P (pediatric pseudo-control group) and visual analyses in a 4 year old patient. In this 4-year-old patient with positive MRI and seizure onset zone (SOZ) in the left insula, visual analysis (image C) shows a left insular hypometabolic area (axial slice). SPM-P (image B, SPM glass brain) identifies a hypometabolic cluster in the same area. SPM-A (image A, SPM glass brain) also identifies this cluster, but also shows several additional hypometabolic artifacts mainly located within the frontal cortex, ipsi- and contralaterally.