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Novel ex vivo MRI atlas of the medial temporal lobe can be used to characterize structural changes due to Alzheimer’s disease pathology
Author(s) -
Ravikumar Sadhana,
Wisse Laura,
Xie Long,
Ittyerah Ranjit,
Das Sandhitsu R.,
Detre John A.,
Grossman Murray,
Lavery Madigan,
Lim Sydney A.,
Irwin David J.,
Schuck Theresa,
Trojanowski John Q.,
ArtachoPerula Emilio,
Martin Maria Mercedes Iniguez de Onzono,
Lee Eddie B.,
Mizsei Gabor,
Tisdall Dylan M.,
del Mar Arroyo Jimenez Maria,
Munoz Monica,
Gonzalez Jose Carlos Delgado,
Parada Marta Corcoles,
de la Rosa Prieto Carlos,
Sanchez Sandra Cebada,
Prabhakaran Karthik,
del Pilar Marcos Rabal Maria,
Romero Francisco Javier Molina,
Robinson John L.,
Wolk David A.,
Insausti Ricardo,
Yushkevich Paul A.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.041279
Subject(s) - neuropathology , temporal lobe , ex vivo , pathology , neuroscience , medicine , neuroimaging , alzheimer's disease , brain atlas , disease , in vivo , psychology , biology , epilepsy , microbiology and biotechnology
Background Finding effective biomarkers that can support early‐stage clinical trials is a major challenge in Alzheimer’s Disease (AD). MRI measures of structural change in the medial temporal lobe (MTL) have proven to be sensitive to change in the early stages of AD. However, other frequently comorbid non‐AD factors (e.g. cerebrovascular disease, TDP‐43 pathology) also cause changes in the MTL. For MRI biomarkers to detect changes specifically linked to AD pathology , patterns of structural change must be linked to the underlying neuropathology. To provide this linkage, we use ex vivo imaging with pathologically derived ratings of AD and non‐AD pathology to study the localized effects of the disease on MTL structure. We hypothesize that such an analysis can be used to define MTL “hotspots” where in vivo measures will be more sensitive to disease progression in preclinical AD than current state of the art biomarkers. Method Ex vivo MTL specimens from 24 donors were scanned at 0.2x0.2x0.2mm 3 on 9.4T MRI. The specimens contain varying degrees of pathology spanning the spectrum of AD and common co‐morbid non‐AD pathologies. For 21 specimens, a pathologist provided semi‐quantitative ratings of tau and TDP‐43 severity (Table 1). Extending on techniques developed in our prior work, a computational atlas of the MTL was built via groupwise registration of all specimens’ MRI scans (Adler et al, 2018; Ravikumar et al, 2020). The atlas was used to investigate the correlation between tau pathology and cortical thickness. Result The developed atlas achieves excellent groupwise alignment and captures anatomical variability in the MTL despite its complex geometry (Figure 1). Correlation analysis between tau pathology and atrophy (correcting for age and TDP‐43) reveals significant clusters near the transentorhinal region and subiculum (Figure 2). Conclusion These correlation patterns are consistent with the early Braak stages and resemble results from a previous study which looked at the association between in vivo tau PET measures and atrophy (Das et al, 2019) (Figure 3). In future work, our novel ex vivo atlas will be leveraged to study variability in the distribution of tau pathology in 3D, by mapping quantitative serial pathology images into the atlas space (Figure 4).