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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