A probabilistic atlas of locus coeruleus pathways to transentorhinal cortex for connectome imaging in Alzheimer's disease

• Published in: NeuroImage (Orlando, Fla.) Vol. 223; p. 117301
• Main Authors: Sun, Wei, Tang, Yuchun, Qiao, Yuchuan, Ge, Xinting, Mather, Mara, Ringman, John M., Shi, Yonggang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2020; Elsevier Limited; Elsevier
• Subjects: Adult; Algorithms; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Alzheimer's disease; Atlases as Topic; Brain stem; Connectome - methods; Diffusion Tensor Imaging; Entorhinal Cortex - diagnostic imaging; Entorhinal Cortex - pathology; Female; Humans; Image Processing, Computer-Assisted - methods; Locus coeruleus; Locus Coeruleus - diagnostic imaging; Locus Coeruleus - pathology; Magnetic resonance imaging; Male; Medical imaging; Neural networks; Neural Pathways - diagnostic imaging; Neural Pathways - pathology; Neurodegenerative diseases; Neuroimaging; Norepinephrine; Pathology; Protocol; Quality control; Software; Tau protein
• ISSN: 1053-8119; 1095-9572; 1095-9572
• DOI: 10.1016/j.neuroimage.2020.117301

According to the latest Braak staging of Alzheimer's disease (AD), tau pathology occurs earliest in the brain in the locus coeruleus (LC) of the brainstem, then propagates to the transentorhinal cortex (TEC), and later to other neocortical regions. Recent animal and in vivo human brain imaging research also support the trans-axonal propagation of tau pathology. In addition, neurochemical studies link norepinephrine to behavioral symptoms in AD. It is thus critical to examine the integrity of the LC-TEC pathway in studying the early development of the disease, but there has been limited work in this direction. By leveraging the high-resolution and multi-shell diffusion MRI data from the Human Connectome Project (HCP), in this work we develop a novel method for the reconstruction of the LC-TEC pathway in a cohort of 40 HCP subjects carefully selected based on rigorous quality control of the residual distortion artifacts in the brainstem. A probabilistic atlas of the LC-TEC pathway of both hemispheres is then developed in the MNI152 space and distributed publicly on the NITRC website. To apply our atlas on clinical imaging data, we develop an automated approach to calculate the medial core of the LC-TEC pathway for localized analysis of connectivity changes. In a cohort of 138 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we demonstrate the detection of the decreased fiber integrity in the LC-TEC pathways with increasing disease severity.