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Published on: June 26, 2013
Network Neurodegeneration in Alzheimer's Disease via MRI Based Shape Diffeomorphometry and High-Field Atlasing
Michael I Miller1, J Tilak Ratnanather1, Daniel J Tward1
1Center for Imaging Science, Johns Hopkins University , Baltimore, MD , USA ; Institute for Computational Medicine, Johns Hopkins University , Baltimore, MD , USA ; Department of Biomedical Engineering, Johns Hopkins University , Baltimore, MD , USA.
Abstract:
This paper examines MRI analysis of neurodegeneration in Alzheimer's Disease (AD) in a network of structures within the medial temporal lobe using diffeomorphometry methods coupled with high-field atlasing in which the entorhinal cortex is partitioned into eight subareas. The morphometry markers for three groups of subjects (controls, preclinical AD, and symptomatic AD) are indexed to template coordinates measured with respect to these eight subareas. The location and timing of changes are examined within the subareas as it pertains to the classic Braak and Braak staging by comparing the three groups. We demonstrate that the earliest preclinical changes in the population occur in the lateral most sulcal extent in the entorhinal cortex (alluded to as transentorhinal cortex by Braak and Braak), and then proceeds medially which is consistent with the Braak and Braak staging. We use high-field 11T atlasing to demonstrate that the network changes are occurring at the junctures of the substructures in this medial temporal lobe network. Temporal progression of the disease through the network is also examined via changepoint analysis, demonstrating earliest changes in entorhinal cortex. The differential expression of rate of atrophy with progression signaling the changepoint time across the network is demonstrated to be signaling in the intermediate caudal subarea of the entorhinal cortex, which has been noted to be proximal to the hippocampus. This coupled to the findings of the nearby basolateral involvement in amygdala demonstrates the selectivity of neurodegeneration in early AD.
Insights
Early Alzheimer's Disease (AD) neurodegeneration begins in the entorhinal cortex, specifically its lateral regions, and progresses medially, aligning with Braak staging. Network analysis reveals changes at substructure junctures in the medial temporal lobe.
Area of Science:
- Neuroimaging
- Neuropathology
- Medical image analysis
Background:
- Alzheimer's Disease (AD) is a progressive neurodegenerative disorder.
- Medial temporal lobe structures are critical for memory and are affected early in AD.
- Understanding the precise spatial and temporal progression of neurodegeneration is crucial for early diagnosis and intervention.
Purpose of the Study:
- To analyze neurodegeneration in the medial temporal lobe network in Alzheimer's Disease using advanced MRI techniques.
- To map the location and timing of neurodegenerative changes within specific subareas of the entorhinal cortex.
- To correlate these changes with established neuropathological staging (Braak and Braak).
Main Methods:
- High-field (11T) MRI and diffeomorphometry were used to analyze neurodegeneration.
- The entorhinal cortex was partitioned into eight subareas for detailed analysis.
- Morphometry markers were indexed to template coordinates for three subject groups: controls, preclinical AD, and symptomatic AD.
- Changepoint analysis was employed to examine the temporal progression of atrophy across the network.
Main Results:
- Earliest preclinical AD changes were observed in the lateral entorhinal cortex (transentorhinal cortex), progressing medially, consistent with Braak staging.
- Network changes occurred at the junctures of medial temporal lobe substructures.
- Changepoint analysis indicated the earliest temporal progression of atrophy in the intermediate caudal subarea of the entorhinal cortex.
- Neurodegeneration showed selectivity, affecting the entorhinal cortex and basolateral amygdala.
Conclusions:
- The study confirms the medial temporal lobe network's involvement in early Alzheimer's Disease.
- Findings support the Braak and Braak staging hypothesis regarding the progression of neurodegeneration.
- The entorhinal cortex, particularly its intermediate caudal subarea, is a key region for early AD detection and understanding disease initiation.
