PET-guided MR Spectroscopy in Alzheimer's disease

Abstract

Objectives: To determine if the level of metabolites in MR Spectroscopy (MRS) is a representative marker of underlying pathological changes identified in PET images in Alzheimer's disease (AD).

Methods: We performed PET-guided MRS in cases of probable AD, Mild Cognitive Impairment (MCI) and healthy controls (HC). All participants were imaged by ¹¹ C-Pittsburgh Compound B (¹¹C-PiB) and ¹⁸ F-fluorodeoxy-glucose (¹⁸F-FDG)-PET followed by 3T MRS. PET images were assessed both visually and using standardized uptake value ratios (SUVR). MRS voxels were placed in regions with maximum abnormality on amyloid (Aβ+s) and FDG (hypometabolic) areas on PET scans. Corresponding normal areas were selected in controls. The ratios of total N-acetyl group (tNA), myoinositol(mI), choline(Chol), glutamate+glutamine (Glx) over Creatine (Cr) were compared between these regions.

Results: Aβ+ regions had significantly higher (p=0.02) mI/Cr and lower tNA/Cr (p=0.02), while in hypometabolic areas only tNA/Cr was reduced (p=0.003). Multiple regression analysis adjusting for sex, age and education showed mI/Cr was only associated with ¹¹C-PiB SUVR (p<0.0001). tNA/Cr, however was associated with both PiB (p=0.0003) and ¹⁸F-FDG SUVR (p=0.006). The level of mI/Cr was not significantly different between MCI and AD (p=0.28) but tNA/Cr showed significant decline from HC to MCI to AD (p=0.001, p=0.04).

Interpretation: mI/Cr has significant temporal and spatial associations with Aβ and could be potentially considered as a disease state biomarker. tNA is an indicator of early neurodegenerative changes and might have a role as disease stage biomarker and also as a valuable surrogate marker for treatment response. This article is protected by copyright. All rights reserved.

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