Application of False Discovery Rate Control in the Assessment of Decrease of FDG Uptake in Early Alzheimer Dementia

Lee, Dong Soo; Kang, Hyejin; Jang, Myung Jin; Cho, Sang Soo; Kang, Won Jun; Lee, Jae Sung; Kang, Eunjoo; Lee, Kang Uk; Woo, Jong In; Lee, Myung Chul

Abstract

PURPOSE
Determining an appropriate thresholding is crucial for PDG PET analysis since strong control of Type I error could fail to find pathological differences between early Alzheimer' disease (AD) patients and healthy normal controls. We compared the SPM results on FDG PET imaging of early AD using uncorrected p-value, random-field based corrected p-value and false discovery rate (FDR) control. MATERIALS AND METHODS: Twenty-eight patients (66+/-7 years old) with early AD and 18 age-matched normal controls (68+/-6 years old) underwent FDG brain PET. To identify brain regions with hypo-metabolism in group or individual patient compared to normal controls, group images or each patient's image was compared with normal controls using the same fixed p-value of 0.001 on uncorrected thresholding, random-field based corrected thresholding and FDR control. RESULTS: The number of hypo-metabolic voxels was smallest in corrected p-value method, largest in uncorrected p-value method and intermediate in FDG thresholding in group analysis. Three types of result pattern were found. The first was that corrected p-value did not yield any voxel positive but FDR gave a few significantly hypometabolic voxels (8/28, 29%). The second was that both corrected p-value and FDR did not yield any positive region but numerous positive voxels were found with the threshold of uncorrected p-values (6/28, 21%). The last was that FDR was detected as many positive voxels as uncorrected p-value method (14/28, 50%). CONCLUSIONS: FDR control could identify hypo-metabolic areas in group or individual patients with early AD. We recommend FDR control instead of uncorrected or random-field corrected thresholding method to find the areas showing hypometabolism especially in small group or individual analysis of FDG PET.