Multilevel classification of Alzheimer’s and Mild Cognitive Impairment patients by using Diffusion Tensor Imaging data
Ranganatha Sitaram1, Josué Luiz Dalboni da Rocha2,3, Ivanei Bramati4, Gabriel Coutinho4, and Fernanda Tovar Moll4

1Institute for Medical and Biological Engineering and Department of Psychiatry, Pontificia Universidad Católica de Chile, Santiago, Chile, 2Biomedical Engineering, University of Florida, Gainesville, FL, United States, 3University of Florida, Gainesville, FL, United States, 4Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, Brazil, Rio de Janeiro, Brazil

Synopsis

The proposed novel approach is based on three levels of analyses of DTI data: 1) voxel level analysis of Fractional Anisotropy, 2) connection level based on fiber tracks between brain regions, and 3) network level based connections among multiple brain regions. This novel approach was applied to differentiate between AD, MCI and controls. We achieved accuracy of 93% between AD and controls, 90% between AD and MCI. Main discriminative areas were Hippocampal Cingulum and Parahippocampal Gyrus. The results suggest that our multilevel DTI analysis not only informs difference between brain conditions, but also shows strong potential as diagnostic tool.

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disease that current treatments are only symptomatic and restricted to reduce the progression rate of mental deterioration (Hong-Qi et al., 2012). AD may affect people in different ways, but the most common first symptom is the inability to remember new information (Alzheimer’s Association, 2012). The transitional stage in which the patient’s cognitive functions are not considered normal, but the patient does not meet the criteria for the dementia is called Mild Cognitive Impairment (MCI). MCI is associated with high risk for development of AD, with conversion rates between 10% and 15% per year (Petersen et al., 2001). There is no reliable method for early diagnosis of AD. Diffusion Tensor Imaging (DTI) is a highly promising imaging technique, whose development may provide much earlier evidences of the disease than neuropsychological symptoms (Várkuti, 2011).

Purpose

Following the hypothesis that DTI measures can potentially be used in the early diagnosis of dementia, this study aims to discriminate AD, MCI patients and healthy volunteers through a multilevel DTI approach. We propose this approach to evaluate whether fractional anisotropy (voxel level), axonal tractography (connection level) and graph theory (network level) are good discriminators of the disease in study.

Methods

AD, MCI patients and healthy volunteers (15 from each), matching age and education level, were recruited. T1 and DTI were acquired at Institute D’or (Brazil) on a Philips 3T scanner. T1 was acquired by gradient recalled echo, with repetition time = 7.16msec, echo time = 3.41msec, flip angle = 8, matrix = 480x480 with resolution 0.5mm x 0.5mm, 340 slices of 0.5mm. DTI was acquired using spin echo, with repetition time = 5620msec, echo time = 65msec, flip angle = 90, matrix = 96x96 with resolution 2.5mm x 2.5mm, 60 slices of 2.5mm, 32 directions and b-value=1000sec/mm2. The images were preprocessed by realignment, coregistration and normalization by SPM, segmentation and reconstruction by DSI Studio. Fractional Anisotropy (FA) was used for voxel level analysis. Tractography (Kreher et al., 2008) was performed at DSI Studio, considering the whole brain as seed, with FA=0.1, maximum angle = 60, step size = 1.25mm, length constraint from 25 to 100mm. The connectivity matrix, with each Brodmann area (BA) as node, was used for connection level analysis. Degree, Clustering coefficient, Efficiency, Betweenness centrality and Vulnerability of each connectivity matrix was extracted for network level analysis. Leave-One-Out Cross-Validation was performed, including feature seletion (Fisher Score - FS), training and classification (Support Vector Machine).

Results

At voxel level, the two biggest clusters are inside both parahippocampal gyrus (Figure 2) and hippocampal cingulum (Figure 3). At hippocampal cingulum, accuracy reached 93% between AD and controls, and 87% between AD and MCI. At parahippocampal gyrus, accuracy reached 90% between AD and controls, and 90% between AD and MCI. At connection level (BAs as nodes), top 1 edge obtained the highest classification, reaching 83% for AD versus controls and 70% for AD versus MCI. Top 1 discriminating edge was the connection between BA 10 and 32 (Figure 4). At network level, top 4 feature set achieved the highest accuracy, reaching 80% for AD versus controls and 70% for both MCI versus AD. Top 4 features includes BA 34 (entorhinal cortex), BA 20 (inferior temporal gyrus), BA 42 (posterior transversal temporal area) and BA 46 (dorsolateral prefrontal cortex) (Figure 5).

Discussion & Conclusions

Based on the results, we can indicate that a stage of specific FA alterations inside hippocampal cingulum and parahippocampal gyrus is good a biomarker for AD. These findings in parahippocampal gyrus are in accordance to indications from previous studies (Dyrba et al., 2013). Parahippocampal gyrus is involved in visual memory (Epstein and Kanwisher, 1998). Hippocampal cingulum is the hippocampal formation’s portion of cingulum (Nir et al., 2013). These results indicate that our approach has strong potential for clinical diagnosis of AD and MCI.

Acknowledgements

No acknowledgement found.

References

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Figures

Simplified dataflow of the multilevel DTI approach applied for AD diagnosis.

Sagittal (left-superior), coronal (right-superior) and transversal (inferior) views of voxels (black) whose Fisher Score (AD versus controls) are higher than 1. Gray region inside the brain is parahippocampal gyrus.

Left view (left) and right view (right) of voxels whose Fisher Score (AD versus controls) are higher than 1 (red) inside bilateral portion of cingulum which inside hippocampal formation (yellow).

Sagittal view of BA 10 (green) and BA 32 (blue).

Sagittal view of BA 20 (green), BA 34 (blue), BA 42 (yellow) and BA 46 (red).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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