The fornix sign: a potential sign for Alzheimer's disease based on diffusion tensor imaging

Abstract

Background: We investigated a simple imaging sign for Alzheimer's disease (AD), using diffusion tensor imaging (DTI). We hypothesized that a reduction in fractional anisotropy (FA) in the fornix could be utilized as an imaging sign.

Methods: Twenty-three patients with AD, 24 patients with amnestic mild cognitive impairment (aMCI), and 25 control participants (NC) underwent DTI at baseline and 1 year later. The diagnosis was reevaluated 1 year and 3 years after the initial scan. A color-scaled FA map was used to visually identify the FA reduction ("fornix sign"). We investigated whether the fornix sign could separate AD from NC, and could predict progression from aMCI to AD or NC to aMCI. We also quantified FA of the fornix to validate the fornix sign.

Results: The fornix sign was identical to the lack of any voxels with an FA > .52 within the fornix. The fornix sign differentiated AD from NC with specificity of 1.0 and sensitivity of .56. It predicted conversion from NC to aMCI with specificity of 1.0 and sensitivity of .67, and from aMCI to AD with specificity of .94 and sensitivity of .83.

Conclusion: The fornix sign is a promising predictive imaging sign of AD.

Figure 1

Example of the fornix sign. The axial (left), coronal (middle), and sagittal (right) slices of the color-scaled FA map are shown with the magnified view of the fornix (yellow rectangle). A: FA map of a cognitively normal 80-year-old woman without a fornix sign. The core part of the fornix appears yellow to red (FA 0.5 – 0.8). B: FA map of an 80-year-old woman with Alzheimer's disease with the fornix sign. The fornix appears green (FA < 0.5). FA, fractional anisotropy.

Figure 2

Color-scaled FA maps from 25 cognitively normal elderly participants. Sagittal and axial magnified views of the body of the fornix are shown (baseline image, left), and compared with the FA maps of one year later (follow-up image, right). Color scale is the same as that used in Fig. 1. The age of the participants at the baseline scan are shown in the second column to the left, with the participants’ identification number (#) in the leftmost column. Participants with an identification number marked by a red square developed aMCI one year after the baseline scan, and those with an identification number marked by a green square developed aMCI within three years after the baseline scan. The images with the fornix sign (both readers judged the fornix sign as “present”) are marked by a yellow rectangle, and the images with an “equivocal” fornix sign (the images with a split decision by the readers) are marked by a pink rectangle.

Figure 3

Color-scaled FA maps from 24 aMCI patients. Sagittal and axial magnified views of the body of the fornix are shown (baseline image, left), and compared with the FA maps of one year later (follow-up image, right). Color scale is the same as that used in Figs. 1 and 2. The ages of the participants at the baseline scan are shown in the second to the left column, with the participants’ identification number (#) in the leftmost column. Participants with an identification number marked by a red square developed AD one year after the baseline scan, and those with an identification number marked by a green square developed AD within three years after the baseline scan. The images with the fornix sign (both readers judged the fornix sign as “present”) are marked by a yellow rectangle, and the images with an “equivocal” fornix sign (the images with a split decision by the readers) are marked by a pink rectangle.

Figure 4

Color-scaled FA maps from 23 AD patients. Sagittal and axial magnified views of the body of the fornix are shown (baseline image, left), and compared with the FA maps of one year later (follow-up image, right). Color scale is the same as that used in Figs. 1 - 3. The ages of the participants at the baseline scan are shown in the second left column, with the participants’ identification number (#) in the leftmost column. The images with the fornix sign (both readers judged the fornix sign as “present”) are marked by a yellow rectangle, and the images with an “equivocal” fornix sign (the images with a split decision by the readers) are marked by a pink rectangle.

Figure 5

Scattergrams of the mean-FA and max-FA of the fornix. Points with an “absent” fornix sign are shown on the left side, and points with a “present” fornix sign are shown on the right side. Blue circles: cognitively normal control participants (NC); blue triangles: NC who later converted to amnestic mild cognitive impairment (aMCI); yellow circles: aMCI stable for three years; yellow triangles: aMCI who converted to Alzheimer's disease (AD); red circles: AD.

Figure 6

ROC curves drawn from FA values measured by three-dimensional region-of-interest analyses. Blue line: mean-FA of the fornix; green line: max-FA of the fornix; yellow line: mean-FA of the whole brain; red line: max-FA of the whole brain.