Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial
Background Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by cha...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Oberta de Catalunya (UOC) |
| Repositorio: | O2, repositorio institucional de la UOC |
| OAI Identifier: | oai:openaccess.uoc.edu:10609/153475 |
| Acceso en línea: | https://hdl.handle.net/10609/153475 http://doi.org/10.1016/j.ynirp.2024.100216 |
| Access Level: | acceso abierto |
| Palabra clave: | multiple sclerosis deep grey matter thalamusIron quantitative susceptibility mapping |
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oai:openaccess.uoc.edu:10609/153475 |
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España |
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| dc.title.none.fl_str_mv |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| title |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| spellingShingle |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial Williams, Thomas multiple sclerosis deep grey matter thalamusIron quantitative susceptibility mapping |
| title_short |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| title_full |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| title_fullStr |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| title_full_unstemmed |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| title_sort |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trial |
| dc.creator.none.fl_str_mv |
Williams, Thomas John, Nevin Alex Calvi, Alberto Bianchi, Alessia De Angelis, Floriana Doshi, Anisha Wright, Sarah Shatila, Madiha C. Yiannakas, Marios Chowdhury, Fatima Stutters, Jon Ricciardi, Antonio Prados Carrasco, Ferran MacManus, David Grussu, Francesco Karsa, Anita Samson, Becky Battiston, Marco Gandini Wheeler-Kingshott, Claudia A.M. Shmueli, Karin Beveridge, Judy |
| author |
Williams, Thomas |
| author_facet |
Williams, Thomas John, Nevin Alex Calvi, Alberto Bianchi, Alessia De Angelis, Floriana Doshi, Anisha Wright, Sarah Shatila, Madiha C. Yiannakas, Marios Chowdhury, Fatima Stutters, Jon Ricciardi, Antonio Prados Carrasco, Ferran MacManus, David Grussu, Francesco Karsa, Anita Samson, Becky Battiston, Marco Gandini Wheeler-Kingshott, Claudia A.M. Shmueli, Karin Beveridge, Judy |
| author_role |
author |
| author2 |
John, Nevin Alex Calvi, Alberto Bianchi, Alessia De Angelis, Floriana Doshi, Anisha Wright, Sarah Shatila, Madiha C. Yiannakas, Marios Chowdhury, Fatima Stutters, Jon Ricciardi, Antonio Prados Carrasco, Ferran MacManus, David Grussu, Francesco Karsa, Anita Samson, Becky Battiston, Marco Gandini Wheeler-Kingshott, Claudia A.M. Shmueli, Karin Beveridge, Judy |
| author2_role |
author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
multiple sclerosis deep grey matter thalamusIron quantitative susceptibility mapping |
| topic |
multiple sclerosis deep grey matter thalamusIron quantitative susceptibility mapping |
| description |
Background Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration. However, it currently remains unknown whether susceptibility is abnormal in older progressive MS cohorts, and whether it correlates with disability. Objectives To investigate differences in mean regional susceptibility in deep grey matter between people with secondary progressive multiple sclerosis (SPMS) and healthy controls; to examine in patients the relationships between deep grey matter susceptibility and clinical and imaging measures of disease severity. Methods Baseline data from a subgroup of the MS-STAT2 trial (simvastatin vs. placebo in SPMS, NCT03387670) were included. The subgroup underwent clinical assessments and an advanced MRI protocol at 3T. A cohort of age-matched healthy controls underwent the same MRI protocol. Susceptibility maps were reconstructed using a robust QSM pipeline from multi-echo 3D gradient-echo sequence. Regions of interest (ROIs) in the thalamus, globus pallidus and putamen were segmented from 3D T1-weighted images, and lesions segmented from 3D fluid-attenuated inversion recovery images. Linear regression was used to compare susceptibility from ROIs between patients and controls, adjusting for age and sex. Where significant differences were found, we further examined the associations between ROI susceptibility and clinical and imaging measures of MS severity. Results 149 SPMS (77% female; mean age: 53 yrs; median Expanded Disability Status Scale (EDSS): 6.0 [interquartile range 4.5–6.0]) and 33 controls (52% female, mean age: 57) were included. Thalamic susceptibility was significantly lower in SPMS compared to controls: mean (SD) 28.6 (12.8) parts per billion (ppb) in SPMS vs. 39.2 (12.7) ppb in controls; regression coefficient: −12.0 [95% confidence interval: −17.0 to −7.1], p < 0.001. In contrast, globus pallidus and putamen susceptibility were similar between both groups. In SPMS, a 10 ppb lower thalamic susceptibility was associated with a +0.13 [+0.01 to +0.24] point higher EDSS (p < 0.05), a −2.4 [−3.8 to −1.0] point lower symbol digit modality test (SDMT, p = 0.001), and a −2.4 [−3.7 to −1.1] point lower Sloan low contrast acuity, 2.5% (p < 0.01). Lower thalamic susceptibility was also strongly associated with a higher T2 lesion volume (T2LV, p < 0.001) and lower normalised whole brain, deep grey matter and thalamic volumes (all p < 0.001). Conclusions The reduced thalamic susceptibility found in SPMS compared to controls suggests that thalamic iron concentrations are lower at this advanced stage of the disease. The observed relationships between lower thalamic susceptibility and more severe physical, cognitive and visual disability suggests that reductions in thalamic iron may correlate with important mechanisms of clinical disease progression. Such mechanisms appear to intimately link reductions in thalamic iron with higher T2LV and the development of thalamic atrophy, encouraging further research into QSM-derived thalamic susceptibility as a biomarker of disease severity in SPMS. |
| publishDate |
2024 |
| dc.date.none.fl_str_mv |
2024 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/10609/153475 http://doi.org/10.1016/j.ynirp.2024.100216 |
| url |
https://hdl.handle.net/10609/153475 http://doi.org/10.1016/j.ynirp.2024.100216 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
NeuroImage: Reports, 2024, 4(3) info:eu-repo/grantAgreement/MS-STAT2/NCT03387670/ |
| dc.rights.none.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Elsevier B.V. |
| publisher.none.fl_str_mv |
Elsevier B.V. |
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reponame:O2, repositorio institucional de la UOC instname:Universitat Oberta de Catalunya (UOC) |
| instname_str |
Universitat Oberta de Catalunya (UOC) |
| reponame_str |
O2, repositorio institucional de la UOC |
| collection |
O2, repositorio institucional de la UOC |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869423206634356736 |
| spelling |
Investigating the relationship between thalamic iron concentration and disease severity in secondary progressive multiple sclerosis using quantitative susceptibility mapping: Cross-sectional analysis from the MS-STAT2 randomised controlled trialWilliams, ThomasJohn, Nevin AlexCalvi, AlbertoBianchi, AlessiaDe Angelis, FlorianaDoshi, AnishaWright, SarahShatila, MadihaC. Yiannakas, MariosChowdhury, FatimaStutters, JonRicciardi, AntonioPrados Carrasco, FerranMacManus, DavidGrussu, FrancescoKarsa, AnitaSamson, BeckyBattiston, MarcoGandini Wheeler-Kingshott, Claudia A.M.Shmueli, KarinBeveridge, Judymultiple sclerosisdeep grey matterthalamusIronquantitative susceptibility mappingBackground Deep grey matter pathology is a key driver of disability worsening in people with multiple sclerosis. Quantitative susceptibility mapping (QSM) is an advanced magnetic resonance imaging (MRI) technique which quantifies local magnetic susceptibility from variations in phase produced by changes in the local magnetic field. In the deep grey matter, susceptibility has previously been validated against tissue iron concentration. However, it currently remains unknown whether susceptibility is abnormal in older progressive MS cohorts, and whether it correlates with disability. Objectives To investigate differences in mean regional susceptibility in deep grey matter between people with secondary progressive multiple sclerosis (SPMS) and healthy controls; to examine in patients the relationships between deep grey matter susceptibility and clinical and imaging measures of disease severity. Methods Baseline data from a subgroup of the MS-STAT2 trial (simvastatin vs. placebo in SPMS, NCT03387670) were included. The subgroup underwent clinical assessments and an advanced MRI protocol at 3T. A cohort of age-matched healthy controls underwent the same MRI protocol. Susceptibility maps were reconstructed using a robust QSM pipeline from multi-echo 3D gradient-echo sequence. Regions of interest (ROIs) in the thalamus, globus pallidus and putamen were segmented from 3D T1-weighted images, and lesions segmented from 3D fluid-attenuated inversion recovery images. Linear regression was used to compare susceptibility from ROIs between patients and controls, adjusting for age and sex. Where significant differences were found, we further examined the associations between ROI susceptibility and clinical and imaging measures of MS severity. Results 149 SPMS (77% female; mean age: 53 yrs; median Expanded Disability Status Scale (EDSS): 6.0 [interquartile range 4.5–6.0]) and 33 controls (52% female, mean age: 57) were included. Thalamic susceptibility was significantly lower in SPMS compared to controls: mean (SD) 28.6 (12.8) parts per billion (ppb) in SPMS vs. 39.2 (12.7) ppb in controls; regression coefficient: −12.0 [95% confidence interval: −17.0 to −7.1], p < 0.001. In contrast, globus pallidus and putamen susceptibility were similar between both groups. In SPMS, a 10 ppb lower thalamic susceptibility was associated with a +0.13 [+0.01 to +0.24] point higher EDSS (p < 0.05), a −2.4 [−3.8 to −1.0] point lower symbol digit modality test (SDMT, p = 0.001), and a −2.4 [−3.7 to −1.1] point lower Sloan low contrast acuity, 2.5% (p < 0.01). Lower thalamic susceptibility was also strongly associated with a higher T2 lesion volume (T2LV, p < 0.001) and lower normalised whole brain, deep grey matter and thalamic volumes (all p < 0.001). Conclusions The reduced thalamic susceptibility found in SPMS compared to controls suggests that thalamic iron concentrations are lower at this advanced stage of the disease. The observed relationships between lower thalamic susceptibility and more severe physical, cognitive and visual disability suggests that reductions in thalamic iron may correlate with important mechanisms of clinical disease progression. Such mechanisms appear to intimately link reductions in thalamic iron with higher T2LV and the development of thalamic atrophy, encouraging further research into QSM-derived thalamic susceptibility as a biomarker of disease severity in SPMS.Elsevier B.V.202520252024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/10609/153475http://doi.org/10.1016/j.ynirp.2024.100216reponame:O2, repositorio institucional de la UOCinstname:Universitat Oberta de Catalunya (UOC)InglésNeuroImage: Reports, 2024, 4(3)info:eu-repo/grantAgreement/MS-STAT2/NCT03387670/Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttps://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:openaccess.uoc.edu:10609/1534752026-05-28T12:42:01Z |
| score |
15,812455 |