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Alzheimer Disease: Evaluation of a Functional MR Imaging Index as a Marker¹

¹ From the Biophysics Research Institute (S.J.L., Z.L., G.W.), Division of BioStatistics (M.J.Z.), and Department of Neurology (M.F., P.G.A.), Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. Received July 30, 2001; revision requested September 25; final revision received March 21, 2002; accepted April 12. Supported in part by the Extendicare Foundation, the Dana Foundation, and National Institutes of Health research grants DA10214, MH51358, and RR00058. Address correspondence to S.J.L. (e-mail: sjli@mcw.edu).

View larger version (52K): [in a new window]   Figure 1. Extraction of an SLF component in a voxel time course from the human hippocampus in a 70-year-old male control subject. A, Sagittal T1-weighted MR image, acquired with the spoiled GRE pulse sequence (24/5, flip angle of 45°, section thickness of 1.1 mm), depicts the hippocampal region. B, Representative voxel time course obtained with GRE echo-planar MR imaging (2,000/40, section thickness of 7 mm, field of view of 24 cm, in-plane resolution of 3.75 mm with 64 x 64 image matrix). C, The corresponding SLF component extracted from the voxel time course. The numbers in B and C are image numbers (x axes) and arbitrary signal intensities (y axes). The arrow in B points to the voxel time course from the hippocampus region.

View larger version (38K): [in a new window]   Figure 2. A, Representative image from the 12 sagittal spoiled GRE MR images (parameters in Figure 1) obtained in a 70-year-old male control subject contains a portion of the hippocampus, the white masked areas in the Talairach space. Hippocampus voxels for the calculation of the COSLOF index were determined with software (25). B, Histogram of cross-correlation coefficients obtained in the hippocampus region of this control subject () and an age-matched male probable AD patient (). These two histograms are significantly different. The mean of the correlation coefficients is defined as the COSLOF index, which is used to quantitatively measure functional synchrony.

View larger version (42K): [in a new window]   Figure 3. A, Representative sagittal spoiled GRE MR image (parameters in Figure 1), in the same control subject as in Figure 2, contains the primary visual cortex (white masked area). The primary visual cortex was determined on the basis of the gray matter bank, along with the calcarine fissure from the occipital pole to the intersection between the parieto-occipital sulcus and calcarine fissure (gray line in the white masked areas). B, Histograms of cross-correlation coefficients obtained from the primary visual cortex region in this control subject () and an age-matched male probable AD patient (). These two histograms largely overlap each other and are not significantly different, which suggests less impaired functional synchrony in the visual cortex region in probable AD patients.

View larger version (18K): [in a new window]   Figure 4. Scatterplot shows that the exponential-class curve significantly fits the relationship between MMSE scores and the COSLOF index among nine control subjects (), 10 AD patients (), and five MCI subjects (). The results suggest that the lower the COSLOF index value, the higher the risk for the development of AD. A further longitudinal study with MCI subjects is necessary to confirm such a suggestion.

View larger version (20K): [in a new window]   Figure 5. Line graph depicts the receiver operating characteristic curve with SDs (error bars) and shows the relationship between sensitivity and specificity of the COSLOF index test. On the basis of the curve, if we accept a 10% false-positive rate, then the COSLOF index test will provide an 80% true-positive rate. This test was conducted with 10 AD patients, five MCI subjects, and nine age-matched elderly control subjects.