Abstract
Magnetic resonance imaging (MRI) based diffusion tensor imaging (DTI) can assess white matter (WM) integrity through several metrics, such as fractional anisotropy (FA), axial/radial diffusivities (AxD/RD), and mode of anisotropy (MA). Standard DTI is susceptible to the effects of extracellular free water (FW), which can be removed using an advanced free-water DTI (FW-DTI) model. The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer’s disease (AD). Data were obtained from the Open Access Series of Imaging Studies (OASIS-3) database and included both healthy controls (HC) and mild-to-moderate AD. With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Widespread higher AxD and RD were observed with standard DTI; however, the FW index, indicative of AD-associated neurodegeneration, was significantly elevated in these regions in AD, highlighting the potential impact of free water contributions on standard DTI in neurodegenerative pathologies. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. In conclusion, FW-DTI better reflects the underlying pathology of AD and improves the accuracy of DTI metrics related to WM integrity in Alzheimer’s disease.
Highlights
Using free water (FW)-diffusion tensor imaging (DTI), improved consistency was observed in fractional anisotropy (FA), axial diffusivity (AxD), and radial diffusivity (RD), and the complementary FW index was higher in the Alzheimer’s disease (AD) group as expected
The FW correction method has shown promise in many neurological diseases of the WM21,24–27, those with neurodegenerative aspects; we demonstrate that the application of FW correction in AD improves the accuracy and sensitivity of the resulting DTI metrics
This study demonstrates that the implementation of a FW correction algorithm for DTI improves both the sensitivity and specificity of derived DTI metrics by removing partial volume effects (PVEs), and better captures underlying
Summary
The purpose of this study was to compare standard and FW-DTI metrics in the context of Alzheimer’s disease (AD). Database and included both healthy controls (HC) and mild-to-moderate AD With both standard and FW-DTI, decreased FA was found in AD, mainly in the corpus callosum and fornix, consistent with neurodegenerative mechanisms. Using FW-DTI, improved consistency was observed in FA, AxD, and RD, and the complementary FW index was higher in the AD group as expected. With both standard and FW-DTI, higher values of MA coupled with higher values of FA in AD were found in the anterior thalamic radiation and cortico-spinal tract, most likely arising from a loss of crossing fibers. While much of the pathologic evidence of AD is found in gray matter, it is well recognized that concomitant white matter (WM) alterations occur in the brains of AD populations, suggesting an expanded role for WM-based biomarkers in A
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