Use of T1-weighted/T2-weighted magnetic resonance ratio to elucidate changes due to amyloid β accumulation in cognitively normal subjects

Abstract

The ratio of signal intensity in T1-weighted (T1w) and T2-weighted (T2w) magnetic resonance imaging (MRI) was recently proposed to enhance the sensitivity of detecting changes in disease-related signal intensity. The objective of this study was to test the effectiveness of T1w/T2w image ratios as an easily accessible biomarker for amyloid beta (Aβ) accumulation. We performed the T1w/T2w analysis in cognitively normal elderly individuals. We applied [¹¹C] Pittsburgh Compound B (PiB)-PET to the same individuals, and Aβ deposition was quantified by its binding potential (PiB-BP_ND). The subjects were divided into low and high PiB-BP_ND groups, and group differences in regional T1w/T2w values were evaluated. In the regions where we found a significant group difference, we conducted a correlation analysis between regional T1w/T2w values and PiB-BP_ND. Subjects with high global cortical PiB-BP_ND showed a significantly higher regional T1w/T2w ratio in the frontal cortex and anterior cingulate cortex_. We found a significant positive relationship between the regional T1w/T2w ratio and Aβ accumulation. Moreover, with a T1w/T2w ratio of 0.55 in the medial frontal regions, we correctly discriminated subjects with high PiB-BP_ND from the entire subject population with a sensitivity of 84.6% and specificity of 80.0%. Our results indicate that early Aβ-induced pathological changes can be detected using the T1w/T2w ratio on MRI. We believe that the T1w/T2w ratio is a prospective stable biological marker of early Aβ accumulation in cognitively normal individuals. The availability of such an accessible marker would improve the efficiency of clinical trials focusing on the initial disease stages by reducing the number of subjects who require screening by Aβ-PET scan or lumbar puncture.

Keywords: 11C–labeled Pittsburgh Compound B ([11C]PiB); AD, Alzheimer's disease; Alzheimer's disease (AD); Amyloid-β (Aβ); Aβ, amyloid beta; BP, binding potential; CSF, cerebrospinal fluid; FWHM, full-width at half maximum; MRI, magnetic resonance imaging; PET, positron emission tomography; PiB, Pittsburgh Compound B; PiB-BPND, PiB-BP estimates relative to non-displaceable (ND) binding; Positron emission tomography (PET); ROC, receiver operating characteristic; T1-weighted/T2-weighted magnetic resonance ratio images; T1w, T1-weighted; T2w, T2-weighted; VOI, volumes of interest.

Graphical abstract

Fig. 1

Images of voxel-based maps showing greater T1w/T2w ratios in the region of the medial frontal cortex in the high PiB-BP_ND group compared to the low PiB-BP_ND group. p < 0.001, uncorrected. The statistical parametric mapping projections were superimposed on representative sagittal (x = 4), transaxial (z = − 8) and coronal (y = 60) magnetic resonance images.

Fig. 2

Scatter plots of the relationships among the T1w/T2w ratios, regional PiB-BP_ND values, and the global cortical mean PiB-BP_ND values. We found significant positive correlations among the regional T1w/T2w ratios, regional PiB-BP_ND values, and global cortical mean PiB-BP_ND values. Fitted lines (solid) with 95% confidence intervals (dashed lines) are shown in each plot. p < 0.05; ρ, Spearman's ρ; VOI, volume of interest.

Fig. 3

Scatter plot of the T1w/T2w ratios in the medial frontal region of the low and high PiB-BP_ND groups. With a T1w/T2w ratio of 0.55, we correctly predicted 11 of 13 high PiB-BP_ND group members and 20 of 25 low PiB-BP_ND group members.

Fig. 4

Receiver operating characteristic curve for the T1w/T2w ratio. With the T1w/T2w ratio of 0.55, Youden index [sensitivity – (1-specificity)] shows a maximum value of 0.65 (sensitivity = 0.846, specificity = 0.800) at the cutpoint shown by asterisk.