Browsing by Author "Sun, Hongfu"

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects
    (2018) Elkady, Ahmed M.; Cobzas, Dana; Sun, Hongfu; Blevins, Gregg; Wilman, Alan H.
    Background: Combined R2* and quantitative susceptibility (QS) has been previously used in cross‐sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. Purpose: We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. Study Type: Longitudinal (baseline and 2‐year follow‐up) retrospective study. Subjects: Twenty‐seven relapsing‐remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age‐matched healthy subjects. Field Strength/Sequence: 4.7T 10‐echo gradient‐echo acquisition. Assessment: Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. Statistical Tests: We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P = 0.1) to regress bulk and DARE measures with the follow‐up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. Results: Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease (r = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS (r = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS (r = 0.68; Q = 0.0005).Data Conclusion: DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age‐matched controls, respectively. Specific DARE measures of MS DGM correlated with follow‐up MSSS, and may reflect complex disease pathology.
  • Thumbnail Image
    Item
    Discriminative analysis of regional evolution of iron and myelin/calcium in deep gray matter of multiple sclerosis and healthy subjects
    (2018) Elkady, Ahmed M.; Cobzas, Dana; Sun, Hongfu; Blevins, Gregg; Wilman, Alan H.
    Combined R2* and quantitative susceptibility (QS) has been previously used in cross‐sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. Longitudinal (baseline and 2‐year follow‐up) retrospective study. Twenty‐seven relapsing‐remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age‐matched healthy subjects . Field Strength/Sequence: 4.7T 10‐echo gradient‐echo acquisition. Automatically segmented caudate nucleus (CN), thalamus (TH), putamen (PU), globus pallidus, red nucleus (RN), substantia nigra, and dentate nucleus were retrospectively analyzed to quantify regional volumes, bulk mean R2*, and bulk mean QS. DARE utilized combined R2* and QS localized changes to compute spatial extent, mean intensity, and total changes of DGM iron and myelin/calcium over 2 years. We used mixed factorial analysis for bulk analysis, nonparametric tests for DARE (α = 0.05), and multiple regression analysis using backward elimination of DGM structures (α = 0.05, P = 0.1) to regress bulk and DARE measures with the follow‐up Multiple Sclerosis Severity Score (MSSS). False detection rate correction was applied to all tests. Bulk analysis only detected significant (Q ≤ 0.05) interaction effects in RRMS CN QS (η = 0.45; Q = 0.004) and PU volume (η = 0.38; Q = 0.034). DARE demonstrated significant group differences in all RRMS structures, and in all PMS structures except the RN. The largest RRMS effect size was CN total R2* iron decrease (r = 0.74; Q = 0.00002), and TH mean QS myelin/calcium decrease for PMS (r = 0.70; Q = 0.002). DARE iron increase using total QS demonstrated the highest correlation with MSSS (r = 0.68; Q = 0.0005). DARE enabled discriminative assessment of specific DGM changes over 2 years, where iron and myelin/calcium changes were the primary drivers in RRMS and PMS compared to age‐matched controls, respectively. Specific DARE measures of MS DGM correlated with follow‐up MSSS, and may reflect complex disease pathology.
  • Thumbnail Image
    Item
    Five year iron changes in relapsing-remitting multiple sclerosis deep gray matter compared to healthy controls
    (2019) Elkady, Ahmed M.; Cobzas, Dana; Sun, Hongfu; Seres, Peter; Blevins, Gregg; Wilman, Alan H.
    Relapsing-Remitting MS (RRMS) Deep Grey Matter (DGM) 5 year changes were examined using MRI measures of volume, transverse relaxation rate (R2*) and quantitative magnetic susceptibility (QS). By applying Discriminative Analysis of Regional Evolution (DARE), R2* and QS changes from iron and non-iron sources were separated. 25 RRMS and 25 age-matched control subjects were studied at baseline and 5-year follow-up. Bulk DGM mean R2* and QS of the caudate nucleus, putamen, thalamus and globus pallidus were analyzed using mixed factorial analysis (α = 0.05) with sex as a covariate, while DARE employed non-parametric analysis to study regional changes. Regression/correlation analysis was performed with disease duration and MS Severity Score (MSSS). No significant change in Extended Disability Status Score was found over 5 years (baseline = 2.4 ± 1.2; follow-up = 2.8 ± 1.3). Significant time effects were found for R2* in the caudate (Q = 0.000008; η2 = 0.36), putamen (Q = 0.0000007; η2 = 0.43), and globus pallidus (Q = 0.0000007; η2 = 0.43), while significant longitudinal effects were only found for QS in the putamen (Q = 0.002; η2 = 0.22). Significant bulk interaction was only found for thalamus volume (Q = 0.02; η2 = 0.20). Iron decrease was the only detected significant effect using DARE, and the highest significant DARE effect size was mean thalamus R2* iron decrease (Q = 0.002; η2 = 0.26). No significant correlations or regressions were demonstrated with clinical measures. Thalamic atrophy was the only bulk effect that demonstrated different rates of changes over 5 years compared to age-matched controls. DARE Iron decrease in regions of the caudate, putamen, and thalamus were prominent features in stable RRMS over 5 years.
  • Thumbnail Image
    Item
    Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter
    (2017) Elkady, Ahmed M.; Cobzas, Dana; Sun, Hongfu; Blevins, Gregg; Wilman, Alan H.
    To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls.R2*/QS maps were computed using a 4.7T 10‐echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing‐remitting (RR), 40 secondary‐progressive (SP), 13 primary‐progressive (PP) MS patients, and 75 controls. Sparse classification for R2*/QS maps of segmented caudate nucleus (CN), putamen (PU), thalamus (TH), and globus pallidus (GP) structures produced localized maps of iron/myelin in MS patients relative to controls. Paired t‐tests, with age as a covariate, were used to test for statistical significance (P ≤ 0.05).In addition to DGM structures found significantly different in patients compared to controls using whole region analysis, singular sparse analysis found significant results in RRMS PU R2* (P = 0.03), TH R2* (P = 0.04), CN QS (P = 0.04); in SPMS CN R2* (P = 0.04), GP R2* (P = 0.05); and in PPMS CN R2* (P = 0.04), TH QS (P = 0.04). All sparse regions were found to conform to an iron accumulation pattern of changes in R2*/QS, while none conformed to demyelination. Intersection of sparse R2*/QS regions also resulted in RRMS CN R2* becoming significant, while RRMS R2* TH and PPMS QS TH becoming insignificant. Common iron‐associated volumes in MS patients and their effect size progressively increased with advanced phenotypes.A localized technique for identifying sparse regions indicative of iron or myelin in the DGM was developed. Progressive iron accumulation with advanced MS phenotypes was demonstrated, as indicated by iron‐associated sparsity and effect size.
  • Thumbnail Image
    Item
    Progressive iron accumulation across multiple sclerosis phenotypes revealed by sparse classification of deep gray matter
    (2017) Elkady, Ahmed M.; Cobzas, Dana; Sun, Hongfu; Blevins, Gregg; Wilman, Alan H.
    Purpose: To create an automated framework for localized analysis of deep gray matter (DGM) iron accumulation and demyelination using sparse classification by combining quantitative susceptibility (QS) and transverse relaxation rate (R2*) maps, for evaluation of DGM in multiple sclerosis (MS) phenotypes relative to healthy controls. Materials and Methods: R2*/QS maps were computed using a 4.7T 10-echo gradient echo acquisition from 16 clinically isolated syndrome (CIS), 41 relapsing-remitting (RR), 40 secondary-progressive (SP), 13 primary-progressive (PP) MS patients, and 75 controls. Sparse classification for R2*/QS maps of segmented caudate nucleus (CN), putamen (PU), thalamus (TH), and globus pallidus (GP) structures produced localized maps of iron/myelin in MS patients relative to controls. Paired t-tests, with age as a covariate, were used to test for statistical significance (P ≤ 0.05).Results: In addition to DGM structures found significantly different in patients compared to controls using whole region analysis, singular sparse analysis found significant results in RRMS PU R2* (P = 0.03), TH R2* (P = 0.04), CN QS (P = 0.04); in SPMS CN R2* (P = 0.04), GP R2* (P = 0.05); and in PPMS CN R2* (P = 0.04), TH QS (P = 0.04). All sparse regions were found to conform to an iron accumulation pattern of changes in R2*/QS, while none conformed to demyelination. Intersection of sparse R2*/QS regions also resulted in RRMS CN R2* becoming significant, while RRMS R2* TH and PPMS QS TH becoming insignificant. Common iron-associated volumes in MS patients and their effect size progressively increased with advanced phenotypes. Conclusion: A localized technique for identifying sparse regions indicative of iron or myelin in the DGM was developed. Progressive iron accumulation with advanced MS phenotypes was demonstrated, as indicated by iron-associated sparsity and effect size.