Diffusion- and Tractography-Based Characterization of Tissue Damage Within and Surrounding Paramagnetic Rim Lesions in Multiple Sclerosis

Maryam Mohebbi; Jack A. Reeves; Dejan Jakimovski; Alexander Bartnik; Niels Bergsland; Fahad Salman; Ferdinand Schweser; Bianca Weinstock-Guttman; Robert Zivadinov; Michael G. Dwyer

doi:10.3174/ajnr.A8524

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FIG 1.
Examples of PRL (pink) and non-PRL T2 (light green) lesions on QSM and FLAIR images from 2 different pwMS.
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FIG 2.
Diffusion-based fiber tractography, specifically highlighting the tracts located within a 10-mm radius of the lesions (A and B are PRL tracts and C is non-PRL tracts). A, Colors represent the direction of diffusion—blue for superior-inferior, green for anterior-posterior, and red for left-right. B, Notably, tracts closer to the lesions correspond to lower FA values, as indicated by the accompanying color bar.
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FIG 3.
The result of tractography of PRL-connected tracts versus PRL-nonconnected tracts through the selection of different region types as presented in the Supplemental Data. A, PRL-nonconnected tracts along with ROIs and without the ROIs (a), which clearly shows a holelike area of the ROIs that are terminative regions, restricting the tracts from entering the regions. B, The PRL-connected tracts with and without ROIs (b). C, The same tracts from the coronal view. The color bar shows the FA value.

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Table 1:

Demographic and clinical characteristics of the study population

	All	PRL−	PRL +
	Overall (n = 115)	Overall (n = 66)	Overall (n = 49)
PRL number, mean ± SD	0.65 ± 1.90	–	1.52 ± 2.92
T2 LN, mean ± SD	19.5 ± 11.12	18.32 ± 12.6	20.85 ± 9.05
T2 LV^{^a}, mean ± SD, mL	10.94 ± 13.64	8.35 ± 10.59	13.92 ± 16.06
Sex
Female	88 (76.5%)	55 (83.3%)	33 (67.3%)
Male	27 (23.5%)	11 (16.7%)	16 (32.6%)
Age (yrs)
Mean ± SD	52.9 ± 11.8	54.4 ± 11.1	50.5 ± 12.6
Median [min, max]	53.2 [23.2, 75.2]	53.6 [23.2, 73.4]	52.2 [24.2, 75.2]
Disease (type of MS)
RRMS	78 (67.8%)	46 (69.7%)	33 (67.3%)
PMS	37 (32.1%)	20 (30.3%)	16 (32.6%)
Disease duration in years
Mean ± SD	19.5 ± 10.1	20.2 ± 9.81	18.5 ± 10.6
Median [min, max]	17.0 [5.00, 47.0]	18.0 [5.00, 47.0]	17.0 [5.00, 40.0]
EDSS
Mean ± SD	3.44 ± 2.05	3.19 ± 1.84	3.71 ± 2.27
Median [min, max]	3.00 [0, 9.00]	2.50 [0, 7.00]	3.00 [0, 9.00]
Missing	3 (2.6%)	2 (3.0%)	1 (2.1%)

↵a Overall T2 LVs before excluding non-PRLs within close vicinity of PRLs by using double-threshold.
Note:—LN indicates lesion number; EDSS = Expanded Disability Status Scale; PMS = progressive MS.

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Table 2:

Comparison of the diffusion parameters within the nearby tracts connected to all lesions (PRLs and non-PRLs) versus within the lesions themselves^{^a}

Metrics	Tracts	Within-Lesion	Cohen d	P Value	q-Value
FA, mean ± SD	0.383 ± 0.054	0.296 ± 0.052	1.38	<.001	0.001
QA, mean ± SD	0.326 ± 0.062	0.290 ± 0.058	0.76	<.001	0.001
MD, mean ± SD	1.092 ± 0.147	1.232 ± 0.218	−0.70	<.001	0.001
AD, mean ± SD	1.539 ± 0.184	1.572 ± 0.206	−0.24	.02	0.02
RD, mean ± SD	0.869 ± 0.140	1.018 ± 0.195	−0.89	<.001	0.001
Iso, mean ± SD	0.789 ± 0.226	0.836 ± 0.255	−0.77	<.001	0.001
RDI, mean ± SD	0.519 ± 0.094	0.535 ± 0.111	−0.41	<.001	0.001

↵a Paired t-tests and effect sizes were calculated within subjects who had at least 1 PRL (n = 49), P < .05 considered statistically significant. q-value represents the Benjamini-Hochberg FDR corrected P value at the table level.

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Table 3:

Comparison of diffusion parameters between PRLs versus non-PRLs, within the lesions^{^a}

Metrics	PRLs	Non-PRLs	Cohen d	P Value	q-Value
Total LV,^{^b} mean ± SD, mL	0.459 ± 1.25	8.33 ± 11.03	–	<.001	0.008
FA, mean ± SD	0.279 ± 0.047	0.302 ± 0.056	−0.30	.04	0.16
QA, mean ± SD	0.283 ± 0.067	0.219 ± 0.056	−0.13	.38	0.43
MD, mean ± SD	1.232 ± 0.218	1.186 ± 0.112	0.16	.26	0.35
AD, mean ± SD	1.581 ± 0.265	1.560 ± 0.135	0.07	.63	0.63
RD, mean ± SD	1.058 ± 0.200	0.999 ± 0.115	0.20	.15	0.26
Iso, mean ± SD	0.855 ± 0.257	0.818 ± 0.220	0.28	.09	0.24
RDI, mean ± SD	0.542 ± 0.112	0.529 ± 0.086	0.22	.16	0.26

↵a Paired t-test was calculated within subjects who had at least 1 PRL (n = 49), P < .05 considered statistically significant. q-value represents the Benjamini-Hochberg FDR corrected P value at the table level.
↵b Non-PRL T2 LVs after excluding non-PRL T2 lesions overlapping or confluent with PRLs.

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Table 4:

Comparison of diffusion metrics between PRL-connected and non-PRL T2-lesion connected tracts near lesions^{^a}

Metrics	PRL Connected	Non-PRL T2 Lesion Connected	Cohen d	P Value	q-Value
Total LV,^{^b} mean ± SD, mL	0.459 ± 1.25	8.33 ± 11.03	–	< .001	0.004
FA, mean ± SD	0.354 ± 0.047	0.391 ± 0.056	–0.56	< .001	0.004
QA, mean ± SD	0.315 ± 0.067	0.328 ± 0.056	–0.17	.27	0.36
MD, mean ± SD	1.092 ± 0.218	1.101 ± 0.112	–0.04	.75	0.75
AD, mean ± SD	1.496 ± 0.265	1.562 ± 0.135	–0.23	.10	0.16
RD, mean ± SD	0.890 ± 0.200	0.871 ± 0.115	0.09	.51	0.58
Iso, mean ± SD	0.814 ± 0.257	0.766 ± 0.220	0.43	.007	0.02
RDI, mean ± SD	0.534 ± 0.112	0.508 ± 0.086	0.37	.02	0.04

↵a Paired t-test was calculated within subjects who had at least 1 PRL (n = 49), P < .05 considered statistically significant. q-value represents the Benjamini-Hochberg FDR corrected P value at the table level.
↵b Non-PRL T2 LVs after excluding non-PRL T2 lesions adjacent to PRLs.

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Table 5:

Comparison of diffusion metrics in PRL-connected versus PRL-nonconnected tracts (surrounding white matter)^{^a}

Metrics	PRL Connected	PRL Nonconnected Surrounding Tracts	Cohen d	P Value	q-Value
FA, mean ± SD	0.354 ± 0.047	0.354 ± 0.048	0.00	.98	0.98
QA, mean ± SD	0.315 ± 0.067	0.298 ± 0.062	0.44	.003	0.02
MD, mean ± SD	1.092 ± 0.218	1.077 ± 0.225	0.11	.45	0.63
AD, mean ± SD	1.496 ± 0.265	1.467 ± 0.256	0.19	.21	0.46
RD, mean ± SD	0.890 ± 0.200	0.881 ± 0.213	0.06	.68	0.79
Iso, mean ± SD	0.814 ± 0.257	0.799 ± 0.248	0.39	.26	0.46
RDI, mean ± SD	0.534 ± 0.112	0.523 ± 0.107	0.41	.21	0.46

↵a Paired t-test was calculated within subjects who had at least 1 PRL (n = 49), P < .05 considered statistically significant. q-value represents the Benjamini-Hochberg FDR corrected P value at the table level.