Research ArticleCLINICAL INVESTIGATIONS

Comparison of 18F-FDG PET and Optimized Voxel-Based Morphometry for Detection of Alzheimer's Disease: Aging Effect on Diagnostic Performance

Ichiro Matsunari, Miharu Samuraki, Wei-Ping Chen, Daiseke Yanase, Nozomi Takeda, Kenjiro Ono, Mitsuhiro Yoshita, Hiroshi Matsuda, Masahito Yamada and Seigo Kinuya
Journal of Nuclear Medicine December 2007, 48 (12) 1961-1970; DOI: https://doi.org/10.2967/jnumed.107.042820

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    Flow chart of optimized VBM. After affine registration and transformation, original T1 images are segmented. Segmented gray-matter images are further spatially normalized using a study-specific gray-matter template (left image of priors). Normalization parameters are then applied to the original T1 images; this is followed by the second segmentation using priors representing tissue probability maps that had been generated from group 1 subjects. Finally, segmented gray-matter images with or without modulation are smoothed for subsequent statistical analysis.

  • FIGURE 2. 
    FIGURE 2. 

    Maximum-intensity projections of SPM2 results for significant decline in adjusted 18F-FDG uptake (upper) or gray-matter density by optimized VBM without modulation (middle) and optimized VBM with modulation (lower) in AD patients as compared with age-matched healthy volunteers. Height threshold < 0.05, corrected for multiple comparisons; extent threshold was set to 50 voxels.

  • FIGURE 3. 
    FIGURE 3. 

    ROC curves for discrimination between AD patients and healthy volunteers obtained from PET and VBMs when thresholding at averaged values of positive z scores as measure of hypometabolism or atrophy. Solid line indicates 18F-FDG PET; dashed line indicates optimized VBM without modulation (OPT); fine dot line indicates optimized VBM with modulation (MOD).

  • FIGURE 4. 
    FIGURE 4. 

    ROC curves for discrimination between AD patients and healthy volunteers in younger subgroup (left) and older subgroup (right) obtained from PET and VBM when thresholding at averaged values of positive z scores as measure of hypometabolism or atrophy. Solid line indicates 18F-FDG PET; dashed line indicates optimized VBM without modulation (OPT); fine dot line indicates optimized VBM with modulation (MOD).

  • FIGURE 5. 
    FIGURE 5. 

    Comparison of 18F-FDG PET and VBM z-score maps from 81-y-old woman (age of onset, 71 y; MMSE score, 22) and 53-y-old man (age of onset, 50 y; MMSE score, 26) with probable AD. Automated voxel-by-voxel z-score analysis was performed by comparison of relative 18F-FDG uptake or gray-matter concentration/volume for patient with mean and SD of 18F-FDG or gray-matter images of healthy volunteers. Color-scaled z-score maps ranging from 2.0 to 6.0 were displayed by overlaying on transaxial sections of anatomically standardized MRI of patient. By definition, positive z scores indicate more severe hypometabolism in PET or atrophy in VBM. Averaged values of positive z scores of the older patient in predefined regions were 2.66 for PET, 3.16 for optimized VBM without modulation, and 3.00 for optimized VBM with modulation, whereas those of the younger patient were 2.85, 0.09, and 0.29, respectively.

  • FIGURE 6. 
    FIGURE 6. 

    Maximum-intensity projections of SPM2 results for significant decline in adjusted 18F-FDG uptake (upper) or gray-matter density by optimized VBM without modulation (middle) and optimized VBM with modulation (lower) in early-onset (left) and late-onset (right) AD patients as compared with age-matched healthy volunteers. Height threshold < 0.001, uncorrected for multiple comparisons; extent threshold was set to 50 voxels.

Tables

  • TABLE 1

    Clinical Characteristics of Subjects

    Group 1Group 2
    CharacteristicAD (n = 27)Healthy (n = 40)AD (n = 34)Healthy (n = 50)
    Sex (M/F)12/1520/2016/1824/26
    Age* (y)68.6 ± 6.866.5 ± 7.668.4 ± 10.767.7 ± 9.1
    Onset of AD* (y)66.3 ± 6.9—65.3 ± 10.9—
    Disease duration* (y)2.4 ± 1.9—3.1 ± 4.5—
    MMSE score*22.0 ± 3.329.2 ± 0.822.1 ± 3.829.3 ± 0.8

    • ↵* Data are expressed as mean ± SD.

    • MMSE = Mini-Mental State Examination.

  • TABLE 2

    Location and Peaks of Significant Decrease in Relative 18F-FDG Uptake (Normalized to Global Mean of Whole Brain), Gray-Matter Concentration, and Gray-Matter Volume in AD Patients Compared with Healthy Volunteers

    Coordinate
    Structurexyzt value
    18F-FDG PET
     R/L posterior cingulate gyrus4−502212.85
     R/L precuneus0−70308.81
     L angular gyrus−46−68428.95
     R angular gyrus50−68407.57
     R precentral gyrus346686.12
     R hippocampus−20−40−25.84
     R thalamus14−18145.04
     R frontal gyrus5422365.57
     L temporal gyrus−62−38−165.50
    Optimized VBM
     R hippocampus (posterior portion)26−36−27.45
     L hippocampus (posterior portion)−20−3606.26
     R pallidum160−26.17
     R hippocampus (anterior portion)18−4−165.94
     R thalamus14−10165.69
     L parahippocampal gyrus−16−2−185.66
    Optimized VBM with modulation
     R hippocampus32−36−26.43
     R parahippocampal gyrus14−2−205.75
     R pallidum180−25.67
     R hippocampus26−10−185.58
     L hippocampus−28−4025.51
     L parahippocampal gyrus−140−225.18
     L thalamus−12−20205.10
     R caudate14−18225.03
     R thalamus14−28184.94
  • TABLE 3

    Average z Scores of 18F-FDG PET and Optimized VBM in Group 2 Subjects

    Subject18F-FDG PETOptimized VBMOptimized VBM with modulationP value*
    AD2.69 ± 1.25†1.62 ± 0.871.25 ± 070<0.001
    Healthy0.75 ± 0.310.74 ± 0.380.57 ± 0.37<0.05
    P value‡<0.0001<0.0001<0.0001

    • ↵* P value by repeated-measures ANOVA.

    • ↵† P < 0.001 vs. either VBM or VBM with modulation.

    • ↵‡ P value by Wilcoxon rank sum test.

  • TABLE 4

    Average z Scores of 18F-FDG PET and Optimized VBM in Early-Onset Subgroup

    Subgroup18F-FDG PETOptimized VBMOptimized VBM with modulationP value*
    AD3.30 ± 1.40†1.23 ± 0.620.87 ± 0.52<0.001
    Healthy0.69 ± 0.300.65 ± 0.400.44 ± 0.29<0.05
    P value‡<0.00010.00430.0084

    • ↵* P value by repeated-measures ANOVA.

    • ↵† P < 0.001 vs. either VBM or VBM with modulation.

    • ↵‡ P value by Wilcoxon rank sum test.

  • TABLE 5

    Average z Scores of 18F-FDG PET and Optimized VBM in Late-Onset Subgroup

    Subgroup18F-FDG PETOptimized VBMOptimized VBM with modulationP value*
    AD2.20 ± 0.89†1.93 ± 0.931.54 ± 0.69<0.05
    Healthy0.81 ± 0.310.82 ± 0.360.67 ± 0.40NS
    P value‡<0.0001<0.0001<0.0001

    • ↵* P value by repeated-measures ANOVA.

    • ↵† P < 0.05 vs. VBM with modulation.

    • ↵‡ P value by Wilcoxon rank sum test.

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