Iron and Volume in the Deep Gray Matter: Association with Cognitive Impairment in Multiple Sclerosis

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Fig 1.
Scan demonstrating deep gray matter structure segmentation. FMRIB's Integrated Registration and Segmentation Tool was applied to the 3D high-resolution T1WI to segment the DGM. Pulvinar (yellow and red) was segmented using a semiautomated contouring technique.

Table 1:

Demographic characteristics, neuropsychological test scores, and mean phase of the low-phase voxels across subcortical deep gray matter structures

Note:—NC indicates healthy control; DMT, disease-modifying therapy; EDSS, Expanded Disability Status Scale; NS, not significant.
↵a P value is based on 1-way ANOVA.
↵b n = 68 for calculation of DMT duration as only 68 were on therapy.
↵c n = 83 for calculation of mean EDSS as 2 patients were not assessed during their clinical visit.
↵d P value is based on 1-way ANCOVA, controlling for age and years of education. Age, education, disease duration, and DMT duration data are given as mean years ± SD. Lesion volume is given as mean milliliters ± SD. NP test data for the SDMT, PASAT, DKEFS-CS, CVLT2, and BVMT-R are given as mean test score ± standard deviation. MP-LPV data in the thalamus, caudate nucleus, putamen, globus pallidus, and pulvinar structures are given as radians ± SD.

Table 2:

Partial correlation of structure volume and mean phase of the low-phase voxels to neuropsychological tests in patients with multiple sclerosis

	SDMT		PASAT		DKEFS-CS		CVLT2		BVMT-R
	r	P	r	P	r	P	r	P	r	P
Volume^{^a}
Thalamus	0.548	<.001	0.354	.001	0.422	<.001	0.313	.004	0.415	<.001
Caudate nucleus	0.470	<.001	0.357	.001	0.409	<.001	0.257	.019	0.348	.001
Putamen	0.516	<.001	0.405	<.001	0.429	<.001	0.382	<.001	0.518	<.001
Globus pallidus	0.449	<.001	0.296	.007	0.348	.001	NS		0.282	.010
Pulvinar	0.279	.011	0.275	.012	0.309	.005	0.221	.044	0.327	.003
MP-LPV^{^b}
Caudate nucleus	0.240	.030	0.232	.036	NS		NS		NS
Putamen	0.368	.001	NS		0.252	.022	NS		0.238	.031
Globus pallidus	NS		NS		NS		NS		0.235	.033
Pulvinar	0.244	.027	NS		0.255	.021	NS		0.251	.023

Table 4:

Summary of hierarchical linear regressions predicting neuropsychological test scores

NP Test	Independent Variable (Final Standardized Beta, P Value)	R²	R² Change	Model P Value	F Change	F Change P Value
SDMT
Block 1	Age (−0.115, .238), Ed (0.146, .125)	0.064	0.064	.068	2.780	NS
Block 2	Putamen LPV volume (0.012, .929)	0.082	0.018	.074	1.609	NS
Block 3	Putamen MP-LPV (0.154, .241)	0.206	0.124	.001	12.515	.001
Block 4	Putamen volume (0.468, <.001)	0.333	0.127	<.001	15.028	<.001
PASAT
Block 1	Age (0.112, .318), Ed (0.175, .096)	0.033	0.033	.255	1.388	NS
Block 2	Caudate n. LPV volume (0.009, .941)	0.042	0.010	.318	0.806	NS
Block 3	Caudate n. MP-LPV (0.120, .304)	0.094	0.052	.092	4.564	.036
Block 4	Caudate n. volume (0.319, .009)	0.169	0.075	.011	7.093	.009
DKEFS-CS
Block 1	Age (−0.081, .444), Ed (0.191, .078)	0.058	0.058	.085	2.544	NS
Block 2	Pulvinar LPV volume (0.161, .365)	0.072	0.013	.109	1.142	NS
Block 3	Pulvinar MP-LPV (0.160, .373)	0.132	0.061	.022	5.577	.021
Block 4	Pulvinar volume (0.214, .123)	0.158	0.026	.017	2.43	NS
CVLT2
Block 1	Age (−0.207, .049), Ed (0.158, .122)	0.093	0.093	.018	4.212	.018
Block 2	Putamen LPV volume (0.066, .661)	0.133	0.040	.009	3.710	NS
Block 3	Putamen MP-LPV (0.019, .894)	0.164	0.031	.006	2.942	NS
Block 4	Putamen volume (0.333, .012)	0.228	0.064	.001	6.589	.012
BVMT-R
Block 1	Age (−0.144, .175), Ed (0.083, .437)	0.042	0.042	.172	1.798	NS
Block 2	Pulvinar LPV volume (0.221, .213)	0.076	0.034	.092	2.981	NS
Block 3	Pulvinar MP-LPV (0.146, .413)	0.134	0.058	.02	5.365	.023
Block 4	Pulvinar volume (0.222, .109)	0.162	0.028	.014	2.625	NS