Voxel‐Wise Co‐analysis of Macro‐ and Microstructural Brain Alteration in Mild Cognitive Impairment and Alzheimer's Disease Using Anatomical and Diffusion MRI

Abstract

Background and Purpose To determine if a voxel-wise “co-analysis” of structural and diffusion tensor magnetic resonance imaging (MRI) together reveals additional brain regions affected in mild cognitive impairment (MCI) and Alzheimer’s Disease (AD) than voxel-wise analysis of the individual MRI modalities alone. Methods Twenty-one patients with MCI, 21 patients with AD, and 21 cognitively normal healthy elderly were studied with MRI. Maps of deformation and fractional anisotropy (FA) were computed and used as dependent variables in univariate and multivariate statistical models. Results Univariate voxel-wise analysis of macrostructural changes in MCI showed atrophy in the right anterior temporal lobe, left posterior parietal/precuneus region, WM adjacent to the cingulate gyrus, and dorsolateral prefrontal regions, consistent with prior research. Univariate voxel-wise analysis of microstructural changes in MCI showed reduced FA in the left posterior parietal region extending into the corpus callosum, consistent with previous work. The multivariate analysis, which provides more information than univariate tests when structural and FA measures are correlated, revealed additional MCI-related changes in corpus callosum and temporal lobe. Conclusion These results suggest that in corpus callosum and temporal regions macro- and microstructural variations in MCI can be congruent, providing potentially new insight into the mechanisms of brain tissue degeneration.

White matter alterations in early‐stage Alzheimer's disease: A tract‐specific study

“…Consistent with previous DTI studies [8] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , our results demonstrated that subjects with MCI had significantly decreased FA and increased MD and Dr in the white matter. With relatively stable Da, the differences in FA and MD were mostly driven by the increase in Dr, suggesting deterioration in the axonal membrane and/or myelin sheathes [6] .…”

White matter alterations in early‐stage Alzheimer's disease: A tract‐specific study

“…Consistent with previous DTI studies [8] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , our results demonstrated that subjects with MCI had significantly decreased FA and increased MD and Dr in the white matter. With relatively stable Da, the differences in FA and MD were mostly driven by the increase in Dr, suggesting deterioration in the axonal membrane and/or myelin sheathes [6] .…”

Combining Structural Magnetic Resonance Imaging and Visuospatial Tests to Classify Mild Cognitive Impairment

“…In fact their contribution to the classification power is always higher than that of MRI and standard cognitive tests feature sets. This is clearly depicted by the results in Table 2 and Figure 1, especially looking at the third row of For MRI, the analysis of Kernel weights reveals a picture of brain regions that is only partially in agreement with expectations based on previous knowledge from studies of MCI converters vs healthy subjects [59][60][61]. This is most likely due to the high variability of results through the different cross validation folds (see following discussion and Supplementary Material on SVM for more details), to the small cohort of participants and to the overshadowing of some Kernels (regions) by others Kernels (regions) containing the same patterns of information [49].…”

Deformation-based morphometry: a sensitive imaging approach to detect radiation-induced brain injury?

“…The causal relationships between macrostructural and microstructural modifications in the brain have been widely studied in recent years, particularly in aging and neurodegenerative diseases. However, it is difficult to conclude because the results are very controversial: some studies reported that the diffusion metrics and cerebral volume changes derived from JD values are congruent [ 45 , 46 ] while others concluded that they are independent [ 47 , 48 ]. Regarding a potential link between macrostructural changes and brain vascularization, there are few studies in the literature.…”

White matter alterations in early‐stage Alzheimer's disease: A tract‐specific study

“…Consistent with previous DTI studies [8] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , our results demonstrated that subjects with MCI had significantly decreased FA and increased MD and Dr in the white matter. With relatively stable Da, the differences in FA and MD were mostly driven by the increase in Dr, suggesting deterioration in the axonal membrane and/or myelin sheathes [6] .…”

Combining Structural Magnetic Resonance Imaging and Visuospatial Tests to Classify Mild Cognitive Impairment

“…In fact their contribution to the classification power is always higher than that of MRI and standard cognitive tests feature sets. This is clearly depicted by the results in Table 2 and Figure 1, especially looking at the third row of For MRI, the analysis of Kernel weights reveals a picture of brain regions that is only partially in agreement with expectations based on previous knowledge from studies of MCI converters vs healthy subjects [59][60][61]. This is most likely due to the high variability of results through the different cross validation folds (see following discussion and Supplementary Material on SVM for more details), to the small cohort of participants and to the overshadowing of some Kernels (regions) by others Kernels (regions) containing the same patterns of information [49].…”

Deformation-based morphometry: a sensitive imaging approach to detect radiation-induced brain injury?

“…The causal relationships between macrostructural and microstructural modifications in the brain have been widely studied in recent years, particularly in aging and neurodegenerative diseases. However, it is difficult to conclude because the results are very controversial: some studies reported that the diffusion metrics and cerebral volume changes derived from JD values are congruent [ 45 , 46 ] while others concluded that they are independent [ 47 , 48 ]. Regarding a potential link between macrostructural changes and brain vascularization, there are few studies in the literature.…”

White matter alterations in early‐stage Alzheimer's disease: A tract‐specific study

“…Consistent with previous DTI studies [8] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , our results demonstrated that subjects with MCI had significantly decreased FA and increased MD and Dr in the white matter. With relatively stable Da, the differences in FA and MD were mostly driven by the increase in Dr, suggesting deterioration in the axonal membrane and/or myelin sheathes [6] .…”

Combining Structural Magnetic Resonance Imaging and Visuospatial Tests to Classify Mild Cognitive Impairment

“…In fact their contribution to the classification power is always higher than that of MRI and standard cognitive tests feature sets. This is clearly depicted by the results in Table 2 and Figure 1, especially looking at the third row of For MRI, the analysis of Kernel weights reveals a picture of brain regions that is only partially in agreement with expectations based on previous knowledge from studies of MCI converters vs healthy subjects [59][60][61]. This is most likely due to the high variability of results through the different cross validation folds (see following discussion and Supplementary Material on SVM for more details), to the small cohort of participants and to the overshadowing of some Kernels (regions) by others Kernels (regions) containing the same patterns of information [49].…”

Deformation-based morphometry: a sensitive imaging approach to detect radiation-induced brain injury?

“…The causal relationships between macrostructural and microstructural modifications in the brain have been widely studied in recent years, particularly in aging and neurodegenerative diseases. However, it is difficult to conclude because the results are very controversial: some studies reported that the diffusion metrics and cerebral volume changes derived from JD values are congruent [ 45 , 46 ] while others concluded that they are independent [ 47 , 48 ]. Regarding a potential link between macrostructural changes and brain vascularization, there are few studies in the literature.…”