Automated discrimination between very early Alzheimer disease and controls using an easy Z-score imaging system for multicenter brain perfusion single-photon emission tomography

Abstract

Background and purpose: In Alzheimer disease (AD), a peculiar regional cerebral blood flow (rCBF) abnormality has been reported in the posterior cingulate gyri and precunei, even at a very early stage. We performed a multicenter brain perfusion single-photon emission tomography (SPECT) study to evaluate the discrimination ability of an easy Z-score imaging system (eZIS) with a common normal data base between patients with very early AD at the stage of mild cognitive impairment and age-matched healthy controls.

Materials and methods: For a multicenter study, SPECT images of 40 patients with AD and 40 healthy volunteers were acquired from 4 gamma camera systems in 4 different institutions. Systematic differences of SPECT images between gamma cameras were corrected by using conversion maps calculated from the SPECT images of the same brain phantom. Receiver operating characteristic (ROC) analysis was performed to discriminate patients and controls by using a Z-score in the volume of interest (VOI), which had been defined as a region related to AD in subjects other than those in a multicenter study.

Results: Bilateral posterior cingulate gyri, precunei, and parietal cortices were defined as a VOI showing rCBF reduction in very early AD. A new indicator of rCBF abnormality in the VOI provided 86% accuracy for distinction of AD and healthy controls in the multicenter study. The area under the ROC curve was 0.934.

Conclusion: Because an eZIS can use a common normal data base by converting site-specific SPECT data to the core data, the eZIS was useful for automated diagnosis of very early AD in routine studies in multiple institutions.

Fig 1.

Maximum intensity projections of SPM2 results from group comparison of rCBF between patients with very early AD and age-matched healthy volunteers. Patients with very early AD showed significant decline of rCBF in bilateral posterior cingulate gyri, precunei, and inferior parietal cortices. Height threshold is <0.001, corrected for multiple comparisons.

Fig 2.

ROC curves with data conversion to the core SPECT data for discrimination between patients with probable AD at the very early stage of MCI and age-matched healthy volunteers in a multicenter study by using the 3 indicators of severity, extent, and ratio.

Fig 3.

Automated voxel-by-voxel Z-score analysis by comparison of a brain perfusion SPECT image of a 78-year-old man with probable AD and an MMSE score of 24 with the mean and SD of SPECT images of healthy volunteers after normalization to global mean cerebral blood flow values. Color-scaled Z-score maps ranging from 2.0 to 5.0 with extent threshold of 300 voxels are displayed by overlaying on transaxial sections and surface rendering of the spatially normalized MR imaging template. Red lines enclose a VOI with the most significant decline of rCBF in very early AD obtained from group comparison with healthy volunteers by SPM2. The severity, extent, and ratio are 2.18, 77.2%, and 3.56, respectively.