Automated segmentation of medial temporal lobe subregions on in vivo T1-weighted MRI in early stages of Alzheimer's disease.

Long Xie,Laura E M Wisse,Jose V Manjón,John Pluta,David A Wolk,Paul A Yushkevich,For The Alzheimer's Disease Neuroimaging Initiative ,Hongzhi Wang,Virgine Piskin,Robin De Flores,Sandhitsu R Das,Song‐Lin Ding

doi:10.1002/hbm.24607

Abstract

Medial temporal lobe (MTL) substructures are the earliest regions affected by neurofibrillary tangle pathology-and thus are promising biomarkers for Alzheimer's disease (AD). However, automatic segmentation of the MTL using only T1-weighted (T1w) magnetic resonance imaging (MRI) is challenging due to the large anatomical variability of the MTL cortex and the confound of the dura mater, which is commonly segmented as gray matter by state-of-the-art algorithms because they have similar intensity in T1w MRI. To address these challenges, we developed a novel atlas set, consisting of 15 cognitively normal older adults and 14 patients with mild cognitive impairment with a label explicitly assigned to the dura, that can be used by the multiatlas automated pipeline (Automatic Segmentation of Hippocampal Subfields [ASHS-T1]) for the segmentation of MTL subregions, including anterior/posterior hippocampus, entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36, and parahippocampal cortex on T1w MRI. Cross-validation experiments indicated good segmentation accuracy of ASHS-T1 and that the dura can be reliably separated from the cortex (6.5% mislabeled as gray matter). Conversely, FreeSurfer segmented majority of the dura mater (62.4%) as gray matter and the degree of dura mislabeling decreased with increasing disease severity. To evaluate its clinical utility, we applied the pipeline to T1w images of 663 ADNI subjects and significant volume/thickness loss is observed in BA35, ERC, and posterior hippocampus in early prodromal AD and all subregions at later stages. As such, the publicly available new atlas and ASHS-T1 could have important utility in the early diagnosis and monitoring of AD and enhancing brain-behavior studies of these regions.

Highlights

The medial temporal lobe (MTL) is the target of several neurodegenerative pathologies, most notably of neurofibrillary tangle (NFT) pathology which is thought to first affect the transentorhinal cortex, before it spreads to the entorhinal cortex and cornu ammonis region (CA) 1 of the hippocampus (Braak and Braak, 1995, 1991)
We evaluated the performance of our pipeline in scans from Alzheimer’s disease neuroimaging initiative (ADNI) phases GO and 2 by comparing MTL subregional volumes and thickness in amyloid negative controls with individuals with preclinical AD, prodromal AD and AD dementia
To demonstrate clinical utility of the proposed pipeline, we compared the volume and thickness measures extracted using the proposed pipeline between patients and controls using a large dataset from the ADNI and compared this with FreeSurfer (Section 3.3)

Summary

Introduction

The medial temporal lobe (MTL) is the target of several neurodegenerative pathologies, most notably of neurofibrillary tangle (NFT) pathology which is thought to first affect the transentorhinal cortex, before it spreads to the entorhinal cortex and cornu ammonis region (CA) 1 of the hippocampus (Braak and Braak, 1995, 1991). A recent in vivo MRI study showed selective atrophy in Brodmann area 35 (BA35), a region that approximates the transentorhinal region, in individuals with preclinical Alzheimer’s disease (AD) compared to controls (Wolk et al, 2017) These subregions are of interest because they are thought to subserve different cognitive functions, such as recollection and familiarity (Wolk and Dickerson, 2011; Yonelinas et al, 2007), and are part of two dissociable MTL networks, where the anterior hippocampus, entorhinal cortex (ERC) and perirhinal cortex (PRC) are part of the anterior MTL network and the posterior hippocampus and parahippocampal cortex (PHC) are part of the posterior MTL (Ranganath and Ritchey, 2012). T1-weighted images often have higher resolution in the through-plane direction which helps in better resolving the folding and branching of sulci, important for the segmentation of these MTL cortical regions

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Discussion

Conclusion