Keywords: Multiple Sclerosis, Multiple Sclerosis, Disease Duration; Substantia nigra; Iron; Swallow tail sign; Quantitative susceptibility mapping
Motivation: Regionally progressive iron deposition has not been indicated in the substantia nigra (SN), which is the main impaired region in relapsing-remitting multiple sclerosis (RRMS).
Goal(s): To study the iron accumulation in substantia nigra (SN) subdivisions and “swallow tail sign” in RRMS patients with different DDs.
Approach: Quantitative susceptibility mapping (QSM) values were measured in the anterior and posterior SN at different levels.
Results: QSM values of the SN were higher in RRMS patients with 5-10 years DDs than controls. There were significantly positive correlations between “swallow tail sign” scores and QSM values of the caudal pSN in the patients with long DDs.
Impact: This is a preliminary study providing objective evidence of the iron-related progression of SN subregions in RRMS patients with different DDs, and abnormal “swallow tail sign” may provide an additional imaging maker for MS patients.
1. Ricigliano VAG, Morena E, Colombi A, et al. Choroid plexus enlargement in inflammatory multiple sclerosis: 3.0-T MRI and translocator protein PET evaluation.Radiology. 2021;301:166-177
2. Zeng C, Du S, Han Y, et al. Optic radiations are thinner and show signs of iron deposition in patients with long-standing remitting-relapsing multiple sclerosis: an enhanced T2*-weighted angiography imaging study.Eur Radiol. 2018;28:4447-4454.
3. Dal-Bianco A, Grabner G, Kronnerwetter C, et al.Long-term evolution of multiple sclerosis iron rim lesions in 7 T MRI.Brain. 2021;144:833-847.
4. Dal-Bianco A, Grabner G, Kronnerwetter C, et al. A distinct hibiscus sabdariffa extract prevents iron neurotoxicity, a driver of multiple sclerosis pathology. Cells. 2022;11:440.
5. Carandini T, Mancini M, Bogdan I, et al. In vivo evidence of functional disconnection between brainstem monoaminergic nuclei and brain networks in multiple sclerosis. Mult Scler Relat Disord. 2021;56:103224.
6. Yarnykh VL, Krutenkova EP, Aitmagambetova G, et al.Iron-insensitive quantitative assessment of subcortical gray matter demyelination in multiple sclerosis using the macromolecular proton fraction.AJNR Am J Neuroradiol. 2018;39:618-625.
7. Blazejewska AI, Al-Radaideh AM, Wharton S, et al.Increase in the iron content of the substantia nigra and red nucleus in multiple sclerosis and clinically isolated syndrome: a 7 Tesla MRI study.J Magn Reson Imaging. 2015;41:1065-1070.
8. Weber CE, Ebert A, Platten M, et al. Susceptibility-weighted 3T MRI of the swallow tail sign in multiple sclerosis: a case-control study. J Neuroimaging. 2020;30:766-768.
9. Blazejewska AI, Al-Radaideh AM, Wharton S, et al. Increase in the iron content of the substantia nigra and red nucleus in multiple sclerosis and clinically isolated syndrome: a 7 Tesla MRI study. J Magn Reson Imaging. 2015;41:1065-1070.
10. Bergsland N, Zivadinov R, Schweser F, et al.Ventral posterior substantia nigra iron increases over 3 years in Parkinson's disease.Mov Disord. 2019;34:1006-1013.
Figure 1: The section showing the red nucleus (RN) with the largest radius was selected for the rostral level (A), and the section at the level inferior to the RN was selected for the caudal level (B). The anterior SN (aSN) (yellow) and posterior SN (pSN) (blue) were separated along a line that splits the whole SN ROIs in half. Each SN was divided into rostral aSN, rostral pSN, caudal aSN, and caudal pSN.
Figure 2: Normal and abnormal “swallow tail sign” on SWI. The normal nigrosome-1 in the posterior part of the bilateral SN showed tail wedge or “water drop” hyperintensity on SWI, and its appearance was like a swallow tail, and the score was 0.
Fgirue 3: The nigrosome-1 hyperintensity was disappeared. It was an abnormal “swallow tail sign” and was scored as 1.
Figure 4: Intergroup differences in the bilateral QSM values in subregions of SN. # represents the comparisons between the MS groups and HC. #, ##, ### indicate P < 0.05, P < 0.01 and P < 0.001. While * represents those between MS subgroups. ** and * indicate P < 0.01 and P < 0.05, respectively, which are regarded as statistically significant.