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Whole brain white matter histogram analysis of diffusion tensor imaging data detects microstructural damage in mild
Giovanni Giulietti1, Mario Torso1, Laura Serra1
1Neuroimaging Laboratory, IRCCS Santa Lucia Foundation, Rome, Italy.
Background:
Amnestic mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). However, the clinical conversion from MCI to AD is unpredictable. Hence, identification of noninvasive biomarkers able to detect early changes induced by dementia is a pressing need.
Purpose:
To explore the added value of histogram analysis applied to measures derived from diffusion tensor imaging (DTI) for detecting brain tissue differences between AD, MCI, and healthy subjects (HS).
Study Type:
Prospective.
Population/Subjects:
A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS).
Field Strength:
3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT); inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging (DTI).
Assessment:
Normal-appearing white matter (NAWM) masks were obtained using the T1 -weighted volumes for tissue segmentation and T2 -weighted images for removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50, C75), which were compared between groups. Receiver operating characteristic (ROC) and area under ROC curves (AUC) were calculated. To confirm our results, the same analysis was repeated on the ADNI dataset.
Statistical Tests:
One-way analysis of variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis.
Results:
For the local cohort, C25 of AXD had the maximum capability of group discrimination with AUC of 0.80 for "HS vs. patients" comparison and 0.74 for "AD vs. others" comparison. For the ADNI cohort, MV of AXD revealed the maximum group discrimination capability with AUC of 0.75 for "HS vs. patients" comparison and 0.75 for "AD vs. others" comparison.
Data Conclusion:
AXD of NAWM might be an early marker of microstructural brain tissue changes occurring during the AD course and might be useful for assessing disease progression.
Level Of Evidence:
1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017.
Insights
Axial diffusivity (AXD) in normal-appearing white matter (NAWM) can help distinguish between Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy individuals. This diffusion tensor imaging (DTI) measure shows promise as an early biomarker for neurodegeneration.
Area of Science:
- Neuroimaging
- Radiology
- Neurology
Background:
- Amnestic mild cognitive impairment (MCI) represents a transitional phase between normal aging and Alzheimer's disease (AD).
- Predicting the clinical progression from MCI to AD remains challenging.
- There is a critical need for noninvasive biomarkers to detect early dementia-related brain changes.
Purpose of the Study:
- To investigate the utility of histogram analysis of diffusion tensor imaging (DTI) metrics for differentiating brain tissue characteristics.
- To compare DTI-derived measures between Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy subjects (HS).
Main Methods:
- Prospective study involving a local cohort and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
- Diffusion tensor imaging (DTI) was performed on 3T MRI scanners.
- Histogram analysis of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) in normal-appearing white matter (NAWM) was conducted.
Main Results:
- In the local cohort, the 25th percentile (C25) of AXD demonstrated the highest discrimination capability (AUC 0.80 for HS vs. patients).
- In the ADNI cohort, the mean value (MV) of AXD showed the strongest group discrimination (AUC 0.75 for HS vs. patients and AD vs. others).
- These findings were validated across both independent datasets.
Conclusions:
- Axial diffusivity (AXD) in normal-appearing white matter (NAWM) may serve as an early indicator of microstructural brain changes in Alzheimer's disease (AD).
- AXD analysis holds potential for monitoring disease progression in AD and MCI.
- Histogram-based DTI metrics offer valuable insights into early neurodegenerative processes.