Additional file 1 of The identification and cognitive correlation of perfusion patterns measured with arterial spin labeling MRI in Alzheimer’s disease

Additional file 1: Supplementary Fig. 1. ROC curves of both global and relative regional CBF values for discrimination between patients with AD and NCs. The AUC value was 0.72 with a sensitivity of 65.63% and a specificity of 71.88% for global CBF, and was 0.998 (sensitivity 100.00% and specificity 96.88%), 1.00 (sensitivity 100.00% and a specificity 100.00%), 0.975 (sensitivity 96.88% and specificity 87.50%), 0.996 (sensitivity 96.88% and specificity 96.88%), and 0.979 (sensitivity 93.75% and specificity 96.88%) for right precuneus, left PCC, left angular, right inferior parietal lobule, and right inferior temporal gyrus, respectively. ROC: receiver operator characteristic; CBF: cerebral blood flow; AUC: area under the curve; PCC: posterior cingulate cortex. Supplementary Fig. 2. AD-related covariance patterns (grey matter vs perfusion) in the identification cohort at different levels of reliability at each voxel. Structural covariance pattern (ADRP-GM) was identified from a linear combination of the first 3 principal components (PCs: variance accounting for = 11.5%, 6.9% and 3.6% respectively) accounting for 14% of the total voxel × subject variance. Brain regions in the ADRP-perfusion (displayed at a threshold value with high reliability of P = 0.001 as reported in the manuscript) was compared with their counterparts in the ADRP-GM displayed at threshold values corresponding to low, moderate and high levels of reliability (P = 0.05, 0.01 and 0.001) following the bootstrap test with 1000 iterations. Supplementary Fig. 3. The overlap of regional topographies with decreased loading of ADRP-CBF and ADRP-GM identified from SSM/PCA in the identification cohort. Blue color indicates regions with decreased loading in CBF, orange color indicates regions with decreased loading in gray matter volume, and pink color indicates regions with overlap of decreased loading in CBF and gray matter volume. The structural changes were only observed in a few isolated areas of smaller anatomic extent compared with CBF changes, even at threshold values with the lowest reliability of P = 0.05. Supplementary Fig. 4. The overlap of regional changes in decreased CBF and gray matter atrophy without normalization for the differences in global value across all AD and healthy subjects in the identification cohort. Blue color indicates regions with decreased CBF, orange color indicates regions with gray matter atrophy and pink color indicates regions with overlap of decreased CBF and gray matter atrophy in AD patients compared to NCs. To rule out false positives that were more pronounced in the results without global normalization, a stringent threshold of 4.67 or 5.56 (both at P < 0.05, FWE-corrected) for decreased CBF or gray matter atrophy was used to overlay SPM maps onto a standard MRI brain template. Supplementary Fig. 5. The overlap of regional changes in relative decreased CBF and gray matter atrophy after ANCOVA normalization for the differences in global value across all AD and healthy subjects in the identification cohort. Blue color indicates regions with decreased CBF, orange color indicates regions with gray matter atrophy, and pink color indicates regions with overlap of decreased CBF and gray matter atrophy in AD patients compared to NCs. To better appreciate relevant brain regions involved in the results, a liberal threshold of 1.67 (P < 0.05, uncorrected) was used to overlay both SPM maps onto a standard MRI brain template. Supplementary Fig. 6. Brain regions of abnormal perfusion (AD vs NC) in the identification cohort using masks with different threshold. SPM analysis was repeated in the identification cohort using the brain mask at a compromise threshold (pGM ≥ 0.5). The same regions of relative hypo- and hyper-perfusion were identified (despite slightly smaller extent) as those found with the brain mask of pGM ≥ 0.3 used in the article. A threshold of 3.23 (P < 0.001, uncorrected) was used to overlay SPM maps onto a standard MRI brain template

Table_3_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R2 = 0.588; P Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Image_3_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.PDF

Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R2 = 0.588; P Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Table_1_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Image_1_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.PDF

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Table_2_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Image_2_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.PDF

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p

Image_4_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.PDF

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p