A diagnostic index based on quantitative susceptibility mapping and voxel-based morphometry may improve early diagnosis of Alzheimer's disease

Abstract

Objectives: Voxel-based morphometry (VBM) is widely used to quantify the progression of Alzheimer's disease (AD), but improvement is still needed for accurate early diagnosis. We evaluated the feasibility of a novel diagnosis index for early diagnosis of AD based on quantitative susceptibility mapping (QSM) and VBM.

Methods: Thirty-seven patients with AD, 24 patients with mild cognitive impairment (MCI) due to AD, and 36 cognitively normal (NC) subjects from four centers were included. A hybrid sequence was performed by using 3-T MRI with a 3D multi-echo GRE sequence to obtain both a T1-weighted image for VBM and phase images for QSM. The index was calculated from specific voxels in QSM and VBM images by using a linear support vector machine. The method of voxel extraction was optimized to maximize diagnostic accuracy, and the optimized index was compared with the conventional VBM-based index using receiver operating characteristic analysis.

Results: The index was optimal when voxels were extracted as increased susceptibility (AD > NC) in the parietal lobe and decreased gray matter volume (AD < NC) in the limbic system. The optimized proposed index showed excellent performance for discrimination between AD and NC (AUC = 0.94, p = 1.1 × 10^-10) and good performance for MCI and NC (AUC = 0.87, p = 1.8 × 10^-6), but poor performance for AD and MCI (AUC = 0.68, p = 0.018). Compared with the conventional index, AUCs were improved for all cases, especially for MCI and NC (p < 0.05).

Conclusions: In this preliminary study, the proposed index based on QSM and VBM improved the diagnostic performance between MCI and NC groups compared with the VBM-based index.

Key points: • We developed a novel diagnostic index for Alzheimer's disease based on quantitative susceptibility mapping (QSM) and voxel-based morphometry (VBM). • QSM and VBM images can be acquired simultaneously in a single sequence with little increasing scan time. • In this preliminary study, the proposed diagnostic index improved the discriminative performance between mild cognitive impairment and normal control groups compared with the conventional VBM-based index.

Keywords: Alzheimer disease; Diagnosis, computer-assisted; Early diagnosis; Iron; Magnetic resonance imaging.