Elsevier

NeuroImage

Volume 64, 1 January 2013, Pages 32-42
NeuroImage

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

https://doi.org/10.1016/j.neuroimage.2012.08.071Get rights and content

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 4.0 mm for the left hemispheres (n = 7) and 3.2 mm 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.

Highlights

► Localized human perirhinal cortex using ex vivo MRI volumes ► Validated localization of perirhinal cortex with cytoarchitectural Nissl staining ► Mapped perirhinal labels from high resolution ex vivo to flattened spherical space ► Hausdorff distance measures were compared for right and left hemispheres. ► Cortical thickness showed differences between controls and Alzheimer's disease.

Introduction

The perirhinal cortex (Brodmann's area 35) is a multimodal cortical area that is located in the medial temporal lobe (MTL). A multimodal area receives input from more than one cortical association area and it is a region where information from different modalities converge (Jones and Powell, 1970, Van Hoesen and Pandya, 1975a). Perirhinal cortex is situated between the entorhinal cortex (Brodmann's area 28 and perirhinal's medial neighbor) and ectorhinal cortex (Brodmann's area 36 and perirhinal's lateral neighbor) in the mediolateral plane. The ectorhinal cortex (area 36) constitutes the perirhinal's anterior and lateral neighbor while the posterior parahippocampal cortex lies posterior to the perirhinal cortex.

Brodmann described the perirhinal cortex as a “transition between archipallium and neopallium” (Brodmann, 1909, Brodmann and Garey, 1994). Since then, the perirhinal cortex has undergone several name modifications. Braak and Braak coined the term ‘transentorhinal’ and succinctly described the mediolateral boundaries, but this description lacked the anterior-posterior entirety of the area (Braak and Braak, 1985). Perirhinal area 35 and transentorhinal are somewhat synonymous terms. To further complicate the situation for area 35, several investigators have lumped area 35 (perirhinal) and area 36 (ectorhinal) together and referred to it as perirhinal cortex (Suzuki and Amaral, 1994a, Suzuki and Amaral, 1994b), dropping the ectorhinal designation entirely and creating a very large area. Nonetheless, extensive rostrocaudal analyses with several histological stains have yielded the boundaries of the perirhinal cortex in the human brain, albeit including isocortical area 36 in the definition (Ding and Van Hoesen, 2010). To make matters even more confusing, perirhinal (area 35) and entorhinal (area 28) have also been grouped together and referred to as the rhinal cortex (Meunier et al., 1996, Murray and Mishkin, 1986). As a result, perirhinal cortex has three names and three different meanings in the current literature. Given that perirhinal cortex lies in the depths of two sulci (the rhinal sulcus anteriorly and the collateral sulcus anteriorly and posteriorly), and that perirhinal cortex has several names and designations, its location has been confounded with that of its neighbors. This complicated and convoluted scientific backdrop with respect to perirhinal is unfortunate, because imaging, cognitive, and behavioral neuroscientists rely on accurate neuroanatomical localization. When loose definitions occur anatomically, it is difficult to interpret functional findings and controversies can develop that are more semantic than substantive.

Regarding function, the perirhinal cortex plays a significant role in memory as has been demonstrated by several lines of evidence. Perirhinal cortex detects novel objects and denotes familiarity both in non-human primate studies and functional MRI (Buckley and Gaffan, 1998, Meunier et al., 1993, Meunier et al., 1996, Murray and Mishkin, 1986, Murray et al., 2005, Suzuki et al., 1993, Zola-Morgan et al., 1989). The perirhinal cortex receives inputs from a plethora of diverse cortices and its strongest output is projected to the entorhinal cortex, its medial neighbor, (Suzuki and Amaral, 1994a, Suzuki and Amaral, 1994b, Van Hoesen and Pandya, 1975a), which in turn projects to the hippocampus (Van Hoesen and Pandya, 1975b). Undeniably, all of these structures, entorhinal, perirhinal and hippocampus are well known for their role in memory (Brown and Aggleton, 2001, Murray et al., 2005). In fact, when the memory circuit fails as it does in Alzheimer's disease, the medial temporal lobe reveals a burden of neurofibrillary tangles and beta-amyloid plaques (Arnold et al., 1991a, Braak and Braak, 1991). Moreover, perirhinal cortex manifests neurofibrillary tangles in normal aging and Alzheimer's disease (AD) at its earliest pathological stages in the MTL (Braak and Braak, 1985, Knopman et al., 2003, Kordower et al., 2001, Solodkin and Van Hoesen, 1996, Van Hoesen et al., 2000). As the disease progresses, neurofibrillary tangles and amyloid plaques dominate the entire cerebral cortical landscape, and replace healthy neurons with dysfunctional tangled ones and extracellular deposits (Arnold et al., 1991a, Braak and Braak, 1991). This massive neuronal cell death throughout MTL (and beyond in later stages) causes significant atrophy that has been detected with in vivo MRI. Several groups have demonstrated that entorhinal and perirhinal show volumetric changes between normal aging and mild Alzheimer's disease (De Toledo-Morrell et al., 2000, Jack et al., 1997, Kaye et al., 1997, Killiany et al., 2000, Killiany et al., 2002, Xu et al., 2000) and the mesocortices represent the best indicators, and even more so, the predictors of converting to AD.

Currently, standard clinical MRI scans are acquired with voxels that are approximately 1–2 mm and are thus unable to resolve cortical architecture detail. A recent field has emerged called ‘ex vivo imaging’ where an autopsy brain is scanned allowing for the acquisition of ultra-high resolution images due to a number of factors that increase image SNR dramatically (e.g. no sample motion, optimal coil loading, exceptionally long scan sessions, reduced distance of the coils from the sample). Generating probabilistic maps based on ex vivo imaging has become a reliable method used to predict location and cortical boundaries because it can be validated with histological ground truth (Fischl et al., 2009). Ex vivo probability maps have improved upon global volumetric registration such as the Talairach atlas or relying on cortical folding patterns in an ad hoc manner, which can be problematic in higher order associative areas where the sulcal pattern is quite variable.

Our goal was to define the perirhinal cortex (area 35) in ex vivo MRI, validate the MRI-based labeling with Nissl staining, and build a probabilistic atlas for this area in FreeSurfer (http://surfer.nmr.mgh.harvard.edu/fswiki). In this study, we utilized probabilistic mapping based on high resolution ex vivo imaging to predict the location of the perirhinal cortex in the human brain, validated them with histological assays and applied our mesocortical (i.e. entorhinal and perirhinal) labels to the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to assess cortical thickness in these vulnerable areas in the MTL in aging, mild cognitive impairment and Alzheimer's disease.

Section snippets

Ex vivo samples

We collected 14 autopsied brain hemispheres from the Massachusetts General Hospital Autopsy Service (Massachusetts General Hospital, Boston MA) and the Framingham Heart Study and Boston University Alzheimer's Disease Center (Veterans Administration Medical Center, Bedford, VA). Each case was pathologically screened for overt neurological diagnoses such as strokes or significant atrophy and none was reported. Hemisphere laterality was evenly divided in our ex vivo sample set with seven left

Boundaries of perirhinal cortex

Several cortical architectural features defined the perirhinal cortex in MRI FLASH images. First, modularity was revealed by alternating light and dark intensity that was observed in the perirhinal area 35a. Second, dark signal was observed in the superficial layers in areas 35a and 35b, but this dark signal was only observed in infragranular layers in area 35a. Thus, the dark signal formed an oblique wedge throughout the anterior-posterior extent of the perirhinal cortex. The superficial

Discussion

In this report, we identified the location of the perirhinal cortex (Brodmann's area 35) using high resolution ex vivo MRI, validated the perirhinal cortex with histological analysis and applied surface based registration to our labeled perirhinal cortices to quantify the variability between subjects. We then utilized the labels to predict perirhinal cortex location in ADNI in vivo subjects and applied it to determine cortical thickness in controls, mild cognitive impairment patients and AD

Conclusion

Understanding cortical areas that traverse more than one gyrus or sulcus is an important task and critical in the assessment of normal brain function as well as disease states. Several imaging studies have utilized a volumetric approach to evaluate and predict the state of atrophy in the MTL in AD. As quantitative measures evolve in imaging from global atrophy to specific metrics such as cortical thickness, it is important to accurately assess each anatomical area in healthy controls,

Acknowledgments

We would like to thank those who donated tissue; their generous donation made this work possible. We extend special thanks to Brad Dickerson for reading this manuscript and helpful comments. Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758), the National Institute on Aging (AG022381) and (AG028521),

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    Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in the analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

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