Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI

Abstract

The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important for normal memory function. Specifically, perirhinal cortex is involved in the detection of novel objects and manifests neurofibrillary tangles in Alzheimer's disease very early in disease progression. We scanned ex vivo brain hemispheres at standard resolution (1 mm × 1 mm × 1 mm) to construct pial/white matter surfaces in FreeSurfer and scanned again at high resolution (120 μm × 120 μm × 120 μm) to determine cortical architectural boundaries. After labeling perirhinal area 35 in the high resolution images, we mapped the high resolution labels to the surface models to localize area 35 in fourteen cases. We validated the area boundaries determined using histological Nissl staining. To test the accuracy of the probabilistic mapping, we measured the Hausdorff distance between the predicted and true labels and found that the median Hausdorff distance was 4.0mm for the left hemispheres (n=7) and 3.2mm for the right hemispheres (n=7) across subjects. To show the utility of perirhinal localization, we mapped our labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and found decreased cortical thickness measures in mild cognitive impairment and Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our ex vivo probabilistic mapping of the perirhinal cortex provides histologically validated, automated and accurate labeling of architectonic regions in the medial temporal lobe, and facilitates the analysis of atrophic changes in a large dataset for earlier detection and diagnosis.

Figure 1

Anterior-posterior coronal slices that demonstrate perirhinal cortex in ex vivo MRI. Several ex vivo MRI slices demonstrate detection of perirhinal cortex (area 35) throughout its rostrocaudal extent in one selected case (67 year old, male). Note the vertical columnar structures in 35a and the oblique wedge in entire area 35 that indicate perirhinal cortex. White carets represent the medial and lateral borders in panels A–L.

Figure 2

Histological validation of perirhinal cortex in ex vivo MRI. High resolution FLASH image (100 μm isotropic) that reveals columnar contrast in area 35a medially and lighter contrast superficially and laterally in area 35b in (A). The corresponding histological slice is illustrated in (B) with boxed insets for higher magnification photos of area 35a and area 35b respectively in (C) and (D). Black arrows point to the columns in perirhinal 35a and dotted lines in infragranular lamina represent the medial portion of the oblique wedge observed in ex vivo MRI in (C). With the collateral sulcus fundus on the left, (D) shows the histological slice of area 35b and the lateral portion of the oblique wedge. The asterisk (*) denotes layer V in area 35b. Magnification bar = 5 mm in (A) and (B). Magnification bar = 500 μm in (C) and (D).

Figure 3

Fourteen cases were labeled on high resolution ex vivo MRI volumes and mapped to respective individual surface maps. Each inflated brain shows the location of perirhinal cortex (area 35) for each case labeled in white.

Figure 4

Average probabilistic maps for perirhinal cortex. Each case label was mapped onto an existing template - fsaverage - where labels overlapped to show high probability of localization in this ventromedial view. Yellow represents 100% overlap among cases.

Figure 5

Median Hausdorff distance in perirhinal cortex. The Hausdorff distance was computed from the manual labels and the mapped label. The mean distance was 4.0 mm for left hemisphere and 3.2 mm for the right hemisphere and the Hausdorff distance was slightly more variable in left than right hemispheres.

Figure 6

Cortical thickness measures for ADNI subjects in left and right hemispheres in controls, mild cognitive impairment and Alzheimer's disease. The black bars represent perirhinal cortex (area 35) and the gray bars represent entorhinal cortex (area 28). Note the perirhinal cortex is thinner than the entorhinal cortex in each group but shows the same pattern of atrophy as entorhinal cortex. Error bars represent standard error of the mean for each group.