medvisМедицинская визуализацияMedical Visualization1607-07632408-9516RDS-Media Ltd.10.24835/1607-0763-1256medvis-1256Research ArticleГОЛОВАHEADКоличественная оценка магнитной восприимчивости (QSM) в подкорковых структурах головного мозга как маркер нейродегенерации при ремиттирующем и вторично-прогрессирующем рассеянном склерозеQuantitative susceptibility mapping (QSM) in deep gray matter as a neurodegeneration marker in relapsing-remitting and secondary-progressive multiple sclerosishttps://orcid.org/0000-0003-4604-7288МатросоваМ. С.MatrosovaM. S.

Матросова Мария Сергеевна – аспирант, врач-рентгенолог

125367 Москва, Волоколамское шоссе, д. 80, стр. 1

Maria S. Matrosova – graduate student, Radiologist

80-1, Volokolamskoye shosse, Moscow 125367

kmari-s@yandex.ruhttps://orcid.org/0000-0002-1645-6526БрюховВ. В.BryukhovV. V.

Брюхов Василий Валерьевич – кандидат медицинских наук, старший научный сотрудник, врач-рентгенолог 

125367 Москва, Волоколамское шоссе, д. 80, стр. 1

Vasiliy V. Bryukhov – Cand. of Sci. (Med.), Senior Research Associate, Radiologist

80-1, Volokolamskoye shosse, Moscow 125367

abdomen@rambler.ruhttps://orcid.org/0000-0003-2676-452XПоповаЕ. В.PopovaE. V.

Попова Екатерина Валериевна – доктор медицинских наук, заведующая межокружного отделения рассеянного склероза ГБУЗ “ГКБ 24 ДЗМ”; доцент кафедры неврологии, нейрохирургии и медицинской генетики лечебного факультета ФГАОУ ВО РНИМУ им. Н.И. Пирогова

117997 Москва, ул. Островитянова, д. 1;  127015 Москва, ул. Писцовая, д. 10

Ekaterina V. Popova – Doct. of Sci. (Med.), Head of Multiple Sclerosis Сenter in Moscow City Clinical Hospital 24; Assistant Professor, Pirogov Russian National Research Medical University Department of Neurology, Neurosurgery and Medical Genetics

house 1, Ostrivityanova str., Moscow 117997; 10, Pistsovaya str., Moscow 127015

epopova1980@yandex.ruhttps://orcid.org/0000-0001-9831-8970БельскаяГ. Н.BelskayaG. N.

Бельская Галина Николаевна – доктор медицинских наук, профессор, заведующая многопрофильным клинико-диагностическим центром

125367 Москва, Волоколамское шоссе, д. 80, стр. 1

Galina N. Belskaya –Doct. of Sci. (Med.), Professor, Head of Multidisciplinary Clinical and Diagnostic Center

80-1, Volokolamskoye shosse, Moscow 125367

belskaya@neurology.ruhttps://orcid.org/0000-0003-3820-4554КротенковаМ. В.KrotenkovaM. V.

Кротенкова Марина Викторовна – доктор медицинских наук, главный научный сотрудник, руководитель отдела лучевой диагностики 

125367 Москва, Волоколамское шоссе, д. 80, стр. 1

Marina V. Krotenkova – Doct. of Sci. (Med.), Head of Department of Radiology, Main Researcher

80-1, Volokolamskoye shosse, Moscow 125367

krotenkova_mrt@mail.ruФГБНУ “Научный центр неврологии”РоссияResearch center of neurologyRussian FederationФГАОУ ВО “Российский национальный исследовательский медицинский университет им. Н.И. Пирогова” Минздрава России; ГБУЗ города Москвы “Городская клиническая больница № 24 ДЗ города Москвы”РоссияPirogov Russian National Research Medical University of the Ministry of Healthcare of the Russian Federation; City Clinical Hospital №24 of Moscow Healthcare DepartmentRussian Federation2023130520232721222Copyright © Матросова М.С., Брюхов В.В., Попова Е.В., Бельская Г.Н., Кротенкова М.В., 20232023Матросова М.С., Брюхов В.В., Попова Е.В., Бельская Г.Н., Кротенкова М.В.Matrosova M.S., Bryukhov V.V., Popova E.V., Belskaya G.N., Krotenkova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://medvis.rdsmedia.ru/jour/article/view/1256Цель исследования

Цель исследования: изучение изменений в распределении железа в веществе головного мозга с помощью методики магнитно-резонансной томографии (МРТ) – количественного картирования восприимчивости (quantitative susceptibility mapping – QSM) – в сопоставлении с клиническими данными у пациентов с рассеянным склерозом (РС).

Материал и методы

Материал и методы. В данное проспективное исследование вошло три группы пациентов: 47 пациентов с ремиттирующим РС (РРС), 20 – с вторично-прогрессирующим РС (ВПРС) и 39 здоровых добровольцев (группа контроля). Для всех пациентов были собраны анамнестические данные и проведена МРТ головного мозга, включающая последовательность мульти-эхо 3D Т2* GRE, после чего были получены карты QSM и рассчитана относительная магнитная восприимчивость в области подкорковых структур.

Результаты

Результаты. Были выявлены более высокие показатели магнитной восприимчивости в скорлупе у пациентов с ВПРС по сравнению с РРС, что может отражать избыточное накопление железа в данных структурах. При этом было выявлено понижение магнитной восприимчивости в подушке таламуса у пациентов с ВПРС, однако у части пациентов отмечалось ее резкое повышение при уменьшении объема подушки таламуса.

Заключение

Заключение. Повышение магнитной восприимчивости на карте QSM в области подкорковых структур головного мозга, преимущественно в области скорлупы, отражающее накопление железа, а также ее снижение в области подушки таламуса, являются более характерными для пациентов с ВПРС, что может иметь прогностическую значимость в оценке прогрессирования заболевания.

Purpose

Purpose. The aim of the study was to investigate changes in iron distribution in the brain of patients with multiple sclerosis (MS) using magnetic resonance imaging (MRI) technique – quantitative susceptibility mapping (QSM) – in comparison with clinical data.

Materials and methods

Materials and methods. Three groups of patients were included in this prospective study: 47 patients with relapsing-remitting MS (RRMS), 20 patients with secondary progressive MS (SPMS) and 39 healthy controls. For all patients we collected clinical data, including history of present illness (H&P) and disability degree, and performed brain MRI followed by QSM maps obtaining and assessing relative magnetic susceptibility in subcortical structures.

Results

Results. We found an increase in magnetic susceptibility in the heads of the caudate nuclei and in putamen in patients with SPMS as compared to RRMS. At the same time, a decrease in magnetic susceptibility in the thalamic pulvinar was detected in patients with MS in the long term, but a sharp hyperintensity in conjunction with decreasing volume was observed in some patients.

Conclusion

Conclusion. Increased magnetic susceptibility on the QSM in subcortical structures of the brain, reflecting iron content, is more typical for patients with SPMS, which may indicate the prognostic value of these changes.

рассеянный склерозмагнитно-резонансная томографияжелезоколичественное картирование восприимчивостивторично-прогрессирующий рассеянный склероз.multiple sclerosismagnetic resonance imagingironquantitative susceptibility mappingsecondary progressive multiple sclerosis.ReferencesThompson A. J., Banwell B. L., Barkhof F., Carroll W. M., Coetzee T., Comi G., Correale J., Fazekas F., Filippi M., Freedman M. S., Fujihara K., Galetta S. L., Hartung H. P., Kappos L., Lublin F. D., Marrie R. A., Miller A. E., Miller D. H., Montalban, X., Mowry E. M., … Cohen J. A. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17 (2): 162–173. https://doi.org/10.1016/S1474-4422(17)30470-2Thompson A. J., Banwell B. L., Barkhof F., Carroll W. M., Coetzee T., Comi G., Correale J., Fazekas F., Filippi M., Freedman M. S., Fujihara K., Galetta S. L., Hartung H. P., Kappos L., Lublin F. D., Marrie R. A., Miller A. E., Miller D. H., Montalban, X., Mowry E. M., … Cohen J. A. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17 (2): 162–173. https://doi.org/10.1016/S1474-4422(17)30470-2Walton C., King R., Rechtman L., Kaye W., Leray E., Marrie R. A., Robertson N., La Rocca N., Uitdehaag B., van der Mei I., Wallin M., Helme A., Angood Napier C., Rijke N., Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Multiple Sclerosis Journal. 2020; 26 (14): 1816–1821. https://doi.org/10.1177/1352458520970841Walton C., King R., Rechtman L., Kaye W., Leray E., Marrie R. A., Robertson N., La Rocca N., Uitdehaag B., van der Mei I., Wallin M., Helme A., Angood Napier C., Rijke N., Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Multiple Sclerosis Journal. 2020; 26 (14): 1816–1821. https://doi.org/10.1177/1352458520970841Ontaneda D., Thompson A. J., Fox R. J., Cohen J. A. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet (London, England). 2017; 389 (10076): 1357–1366. https://doi.org/10.1016/S0140-6736(16)31320-4Ontaneda D., Thompson A. J., Fox R. J., Cohen J. A. Progressive multiple sclerosis: prospects for disease therapy, repair, and restoration of function. Lancet (London, England). 2017; 389 (10076): 1357–1366. https://doi.org/10.1016/S0140-6736(16)31320-4Zhang Y., Salter A., Jin S., Culpepper W.J. 2nd, Cutter G.R., Wallin M., Stuve O. Disease-modifying therapy prescription patterns in people with multiple sclerosis by age. Ther Adv Neurol Disord. 2021; 14: 17562864211006499. https://doi.org/10.1177/17562864211006499Zhang Y., Salter A., Jin S., Culpepper W.J. 2nd, Cutter G.R., Wallin M., Stuve O. Disease-modifying therapy prescription patterns in people with multiple sclerosis by age. Ther Adv Neurol Disord. 2021; 14: 17562864211006499. https://doi.org/10.1177/17562864211006499Guan Y., Jakimovski D., Ramanathan M., Weinstock-Guttman B., Zivadinov R. The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging. Neural Regen Res. 2019; 14(3): 373-386. https://doi.org/10.4103/1673-5374.245462Guan Y., Jakimovski D., Ramanathan M., Weinstock-Guttman B., Zivadinov R. The role of Epstein-Barr virus in multiple sclerosis: from molecular pathophysiology to in vivo imaging. Neural Regen Res. 2019; 14(3): 373-386. https://doi.org/10.4103/1673-5374.245462Dendrou C.A., Fugger L., Friese M.A. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015; 15 (9): 545-58. https://doi.org/10.1038/nri3871Dendrou C.A., Fugger L., Friese M.A. Immunopathology of multiple sclerosis. Nat Rev Immunol. 2015; 15 (9): 545-58. https://doi.org/10.1038/nri3871Uher T., Krasensky J., Malpas C., Bergsland N., Dwyer M.G., Kubala Havrdova E., Vaneckova M., Horakova D., Zivadinov R., Kalincik T. Evolution of Brain Volume Loss Rates in Early Stages of Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021; 8 (3): e979. https://doi.org/10.1212/NXI.0000000000000979Uher T., Krasensky J., Malpas C., Bergsland N., Dwyer M.G., Kubala Havrdova E., Vaneckova M., Horakova D., Zivadinov R., Kalincik T. Evolution of Brain Volume Loss Rates in Early Stages of Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2021; 8 (3): e979. https://doi.org/10.1212/NXI.0000000000000979Stankiewicz J.M., Weiner H.L. An argument for broad use of high efficacy treatments in early multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2019; 7 (1): e636. https://doi.org/10.1212/NXI.0000000000000636Stankiewicz J.M., Weiner H.L. An argument for broad use of high efficacy treatments in early multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2019; 7 (1): e636. https://doi.org/10.1212/NXI.0000000000000636Giovannoni G., Butzkueven H., Dhib-Jalbut S., Hobart J., Kobelt G., Pepper G., Sormani M.P., Thalheim C., Traboulsee A., Vollmer T. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016; Suppl 1: S5-S48. https://doi.org/10.1016/j.msard.2016.07.003Giovannoni G., Butzkueven H., Dhib-Jalbut S., Hobart J., Kobelt G., Pepper G., Sormani M.P., Thalheim C., Traboulsee A., Vollmer T. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016; Suppl 1: S5-S48. https://doi.org/10.1016/j.msard.2016.07.003Filippi M., Rocca M.A., Ciccarelli O., De Stefano N., Evangelou N., Kappos L., Rovira A., Sastre-Garriga J., Tintorè M., Frederiksen J.L., Gasperini C., Palace J., Reich D.S., Banwell B., Montalban X., Barkhof F.; MAGNIMS Study Group. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016; 15 (3): 292-303. https://doi.org/10.1016/S1474-4422(15)00393-2Filippi M., Rocca M.A., Ciccarelli O., De Stefano N., Evangelou N., Kappos L., Rovira A., Sastre-Garriga J., Tintorè M., Frederiksen J.L., Gasperini C., Palace J., Reich D.S., Banwell B., Montalban X., Barkhof F.; MAGNIMS Study Group. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016; 15 (3): 292-303. https://doi.org/10.1016/S1474-4422(15)00393-2Traboulsee A., Simon J.H., Stone L., Fisher E., Jones D.E., Malhotra A., Newsome S.D., Oh J., Reich D.S., Richert N., Rammohan K., Khan O., Radue E.W., Ford C., Halper J., Li D. Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis. AJNR Am J Neuroradiol. 2016; 37 (3): 394-401. https://doi.org/10.3174/ajnr.A4539Traboulsee A., Simon J.H., Stone L., Fisher E., Jones D.E., Malhotra A., Newsome S.D., Oh J., Reich D.S., Richert N., Rammohan K., Khan O., Radue E.W., Ford C., Halper J., Li D. Revised Recommendations of the Consortium of MS Centers Task Force for a Standardized MRI Protocol and Clinical Guidelines for the Diagnosis and Follow-Up of Multiple Sclerosis. AJNR Am J Neuroradiol. 2016; 37 (3): 394-401. https://doi.org/10.3174/ajnr.A4539Брюхов В.В., Куликова С.Н., Кротенкова М.В., Переседова А.В., Завалишин И.А. Современные методы визуализации в патогенезе рассеянного склероза. Анналы клинической и экспериментальной неврологии. 2017; 7 (3): 47-54. https://doi.org/10.17816/psaic226.Bryukhov V.V., Kulikova S.N., Krotenkova M.V., Peresedova A.V., Zavalishin I.A. State-of-the-art neuroimaging techniques in pathogenesis of multiple sclerosis. Annals of Clinical and Experimental Neurology. 2017; 7 (3): 47-54. https://doi.org/10.17816/psaic226 (In Russian)Mahad D.H., Trapp B.D., Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015; 14 (2): 183-93. https://doi.org/10.1016/S1474-4422(14)70256-XMahad D.H., Trapp B.D., Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol. 2015; 14 (2): 183-93. https://doi.org/10.1016/S1474-4422(14)70256-XFrischer J.M., Bramow S., Dal-Bianco A., Lucchinetti C.F., Rauschka H., Schmidbauer M., Laursen H., Sorensen P.S., Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009; 132 (5): 1175-89. https://doi.org/10.1093/brain/awp070Frischer J.M., Bramow S., Dal-Bianco A., Lucchinetti C.F., Rauschka H., Schmidbauer M., Laursen H., Sorensen P.S., Lassmann H. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009; 132 (5): 1175-89. https://doi.org/10.1093/brain/awp070Lublin F.D., Reingold S.C., Cohen J.A., Cutter G.R., Sørensen P.S., Thompson A.J., Wolinsky J.S., Balcer L.J., Banwell B., Barkhof F., Bebo B. Jr, Calabresi P.A., Clanet M., Comi G., Fox R.J., Freedman M.S., Goodman A.D., Inglese M., Kappos L., Kieseier B.C., Lincoln J.A., Lubetzki C., Miller A.E., Montalban X., O'Connor P.W., Petkau J., Pozzilli C., Rudick R.A., Sormani M.P., Stüve O., Waubant E., Polman C.H. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014; 83 (3): 278-86. https://doi.org/10.1212/WNL.0000000000000560Lublin F.D., Reingold S.C., Cohen J.A., Cutter G.R., Sørensen P.S., Thompson A.J., Wolinsky J.S., Balcer L.J., Banwell B., Barkhof F., Bebo B. Jr, Calabresi P.A., Clanet M., Comi G., Fox R.J., Freedman M.S., Goodman A.D., Inglese M., Kappos L., Kieseier B.C., Lincoln J.A., Lubetzki C., Miller A.E., Montalban X., O'Connor P.W., Petkau J., Pozzilli C., Rudick R.A., Sormani M.P., Stüve O., Waubant E., Polman C.H. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014; 83 (3): 278-86. https://doi.org/10.1212/WNL.0000000000000560Хачанова Н.В., Бойко А.Н., Бахтиярова К.З., Власов Я.В., Евдошенко Е.П., Сиверцева С.А., Шмидт Т.Е., Шумилина М.В. Рекомендации экспертного совещания «Вторично-прогрессирующий рассеянный склероз: нерешенные вопросы и перспективы». Неврология, нейропсихиатрия, психосоматика. 2019; 11 (4): 172-175. https://doi.org/10.14412/2074-2711-2019-4-172-175Khachanova N.V., Boyko A.N., Bakhtiyarova K.Z., Vlasov Y.V., Evdoshenko E.P., Sivertseva S.A., Schmidt T.E., Shumilina M.V. Recommendations from the Expert Meeting «Secondary progressive multiple sclerosis: unresolved issues and prospects». Neurology, Neuropsychiatry, Psychosomatics. 2019; 11 (4): 172-175. https://doi.org/10.14412/2074-2711-2019-4-172-175 (In Russian)Steenwijk M.D., Daams M., Pouwels P.J., J Balk L., Tewarie P.K., Geurts J.J., Barkhof F., Vrenken H. Unraveling the relationship between regional gray matter atrophy and pathology in connected white matter tracts in long-standing multiple sclerosis. Hum Brain Mapp. 2015; 36 (5): 1796-807. https://doi.org/10.1002/hbm.22738Steenwijk M.D., Daams M., Pouwels P.J., J Balk L., Tewarie P.K., Geurts J.J., Barkhof F., Vrenken H. Unraveling the relationship between regional gray matter atrophy and pathology in connected white matter tracts in long-standing multiple sclerosis. Hum Brain Mapp. 2015; 36 (5): 1796-807. https://doi.org/10.1002/hbm.22738Кротенкова И.А., Брюхов В.В., Переседова А.В., Кротенкова М.В. Атрофия центральной нервной системы при рассеянном склерозе: данные МРТ-морфометрии. Журнал неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски. 2014; 114 (10 2): 50 56Krotenkova I.A., Briukhov V.V., Peresedova A.V., Krotenkova M.V. Atrophy of the central nervous system in multiple sclerosis: MRI-morphometry results. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2014; 114 (10 2): 50 56. (In Russian)Кротенкова И.А., Брюхов В.В., Захарова М.Н., Морозова С.Н., Кротенкова М.В., Аскарова Л.Ш. Атрофия головного и спинного мозга у пациентов с ремиттирующим рассеянным склерозом: 3-летнее динамическое исследование. Лучевая диагностика и терапия. 2017; (1): 35-39. https://doi.org/10.22328/2079-5343-2017-1-35-39Krotenkova I.A., Bryukhov V.V., Zakharova M.N., Morozova S.N., Krotenkova M.V., Askarova L.S. Brain and spine atrophy in relapsing remitting multiple sclerosis: a 3-year follow-up study. Diagnostic radiology and radiotherapy. 2017; (1): 35-39. https://doi.org/10.22328/2079-5343-2017-1-35-39 (In Russian)Cortese R., Collorone S., Ciccarelli O., Toosy A.T. Advances in brain imaging in multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2019. https://doi.org/10.1177/1756286419859722Cortese R., Collorone S., Ciccarelli O., Toosy A.T. Advances in brain imaging in multiple sclerosis. Therapeutic Advances in Neurological Disorders. 2019. https://doi.org/10.1177/1756286419859722Belaidi A.A., Bush A.I. Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics. J. Neurochem. 2016; 139: 179-197. https://doi.org/10.1111/jnc.13425Belaidi A.A., Bush A.I. Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics. J. Neurochem. 2016; 139: 179-197. https://doi.org/10.1111/jnc.13425Rouault T. Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci. 2013; 14: 551–564. https://doi.org/10.1038/nrn3453Rouault T. Iron metabolism in the CNS: implications for neurodegenerative diseases. Nat Rev Neurosci. 2013; 14: 551–564. https://doi.org/10.1038/nrn3453Ward R.J., Zucca F.A., Duyn J.H., Crichton R.R., Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014; 13 (10): 1045–1060. doi:10.1016/S1474-4422(14)70117-6Ward R.J., Zucca F.A., Duyn J.H., Crichton R.R., Zecca L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 2014; 13 (10): 1045–1060. doi:10.1016/S1474-4422(14)70117-6Gaasch J.A., Lockman P.R., Geldenhuys W.J., Allen D.D., Van der Schyf C.J. Brain Iron Toxicity: Differential Responses of Astrocytes, Neurons, and Endothelial Cells. Neurochem Res. 2007; 32: 1196–1208. https://doi.org/10.1007/s11064-007-9290-4Gaasch J.A., Lockman P.R., Geldenhuys W.J., Allen D.D., Van der Schyf C.J. Brain Iron Toxicity: Differential Responses of Astrocytes, Neurons, and Endothelial Cells. Neurochem Res. 2007; 32: 1196–1208. https://doi.org/10.1007/s11064-007-9290-4Li G., Wu R., Tong R., Bo B., Zhao Y., Gillen K.M., Spincemaille P., Ku Y., Du Y., Wang Y., Wang X., Li J. Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease. Mov Disord. 2020; 35: 1787-1795. https://doi.org/10.1002/mds.28141Li G., Wu R., Tong R., Bo B., Zhao Y., Gillen K.M., Spincemaille P., Ku Y., Du Y., Wang Y., Wang X., Li J. Quantitative Measurement of Metal Accumulation in Brain of Patients With Wilson's Disease. Mov Disord. 2020; 35: 1787-1795. https://doi.org/10.1002/mds.28141Bagnato F., Hametner S., Yao B., van Gelderen P., Merkle H., Cantor F.K., Lassmann H., Duyn J.H. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011; 134 (12): 3602-15. https://doi.org/10.1093/brain/awr278Bagnato F., Hametner S., Yao B., van Gelderen P., Merkle H., Cantor F.K., Lassmann H., Duyn J.H. Tracking iron in multiple sclerosis: a combined imaging and histopathological study at 7 Tesla. Brain. 2011; 134 (12): 3602-15. https://doi.org/10.1093/brain/awr278Gillen K.M., Mubarak M., Park C., Ponath G., Zhang S., Dimov A., Levine-Ritterman M., Toro S., Huang W., Amici S., Kaunzner U.W., Gauthier S.A., Guerau-de-Arellano M., Wang Y., Nguyen T.D., Pitt D. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021; 8 (4): 877-886. https://doi.org/10.1002/acn3.51338Gillen K.M., Mubarak M., Park C., Ponath G., Zhang S., Dimov A., Levine-Ritterman M., Toro S., Huang W., Amici S., Kaunzner U.W., Gauthier S.A., Guerau-de-Arellano M., Wang Y., Nguyen T.D., Pitt D. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Ann Clin Transl Neurol. 2021; 8 (4): 877-886. https://doi.org/10.1002/acn3.51338Zhang Y., Gauthier S.A., Gupta A., Chen W., Comunale J., Chiang G., Zhou D., Askin G., Zhu W., Pitt D., Wang Y.F. Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation. AJNR Am J Neuroradiol. 2016; 37: 1629 - 1635. https://doi.org/10.3174/ajnr.A4825Zhang Y., Gauthier S.A., Gupta A., Chen W., Comunale J., Chiang G., Zhou D., Askin G., Zhu W., Pitt D., Wang Y.F. Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation. AJNR Am J Neuroradiol. 2016; 37: 1629 - 1635. https://doi.org/10.3174/ajnr.A4825Wisnieff C., Ramanan S., Olesik J., Gauthier S., Wang Y., Pitt D. Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron. Magn Reson Med. 2015; 74 (2): 564-70. https://doi.org/10.1002/mrm.25420Wisnieff C., Ramanan S., Olesik J., Gauthier S., Wang Y., Pitt D. Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron. Magn Reson Med. 2015; 74 (2): 564-70. https://doi.org/10.1002/mrm.25420Wang Y., Spincemaille P., Liu Z., Dimov A., Deh K., Li J., Zhang Y., Yao Y., Gillen K.M., Wilman A.H., Gupta A., Tsiouris A.J., Kovanlikaya I., Chiang G.C., Weinsaft J.W., Tanenbaum L., Chen W., Zhu W., Chang S., Lou M., Kopell B.H., Kaplitt M.G., Devos D., Hirai T., Huang X., Korogi Y., Shtilbans A., Jahng G.H., Pelletier D., Gauthier S.A., Pitt D., Bush A.I., Brittenham G.M., Prince M.R. Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care. J Magn Reson Imaging. 2017; 46 (4): 951-971. https://doi.org/10.1002/jmri.25693Wang Y., Spincemaille P., Liu Z., Dimov A., Deh K., Li J., Zhang Y., Yao Y., Gillen K.M., Wilman A.H., Gupta A., Tsiouris A.J., Kovanlikaya I., Chiang G.C., Weinsaft J.W., Tanenbaum L., Chen W., Zhu W., Chang S., Lou M., Kopell B.H., Kaplitt M.G., Devos D., Hirai T., Huang X., Korogi Y., Shtilbans A., Jahng G.H., Pelletier D., Gauthier S.A., Pitt D., Bush A.I., Brittenham G.M., Prince M.R. Clinical quantitative susceptibility mapping (QSM): Biometal imaging and its emerging roles in patient care. J Magn Reson Imaging. 2017; 46 (4): 951-971. https://doi.org/10.1002/jmri.25693Chen W., Zhu W., Kovanlikaya I., Kovanlikaya A., Liu T., Wang S., Salustri C., Wang Y. Intracranial calcifications and hemorrhages: characterization with quantitative susceptibility mapping. Radiology. 2014; 270 (2): 496-505. https://doi.org/10.1148/radiolChen W., Zhu W., Kovanlikaya I., Kovanlikaya A., Liu T., Wang S., Salustri C., Wang Y. Intracranial calcifications and hemorrhages: characterization with quantitative susceptibility mapping. Radiology. 2014; 270 (2): 496-505. https://doi.org/10.1148/radiolLiu C., Wei H., Gong N.J., Cronin M., Dibb R., Decker K. Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications. Tomography. 2015; 1 (1): 3-17. https://doi.org/10.18383/j.tom.2015.00136Liu C., Wei H., Gong N.J., Cronin M., Dibb R., Decker K. Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications. Tomography. 2015; 1 (1): 3-17. https://doi.org/10.18383/j.tom.2015.00136Schweser F., Hagemeier J., Dwyer M.G., Bergsland N., Hametner S., Weinstock-Guttman B., Zivadinov R. Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI. Hum Brain Mapp. 2021; 42 (5): 1463-1474. https://doi.org/10.1002/hbm.25306Schweser F., Hagemeier J., Dwyer M.G., Bergsland N., Hametner S., Weinstock-Guttman B., Zivadinov R. Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI. Hum Brain Mapp. 2021; 42 (5): 1463-1474. https://doi.org/10.1002/hbm.25306Yu F.F., Chiang F.L., Stephens N., Huang S.Y., Bilgic B., Tantiwongkosi B., Romero R. Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging. Neuroradiology. 2019; 61 (1): 71-79. https://doi.org/10.1007/s00234-018-2137-7Yu F.F., Chiang F.L., Stephens N., Huang S.Y., Bilgic B., Tantiwongkosi B., Romero R. Characterization of normal-appearing white matter in multiple sclerosis using quantitative susceptibility mapping in conjunction with diffusion tensor imaging. Neuroradiology. 2019; 61 (1): 71-79. https://doi.org/10.1007/s00234-018-2137-7Kaunzner U.W., Kang Y., Zhang S., Morris E., Yao Y., Pandya S., Hurtado Rua S.M., Park C., Gillen K.M., Nguyen T.D., Wang Y., Pitt D., Gauthier S.A. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain. 2019; 142 (1): 133-145. https://doi.org/10.1093/brain/awy296Kaunzner U.W., Kang Y., Zhang S., Morris E., Yao Y., Pandya S., Hurtado Rua S.M., Park C., Gillen K.M., Nguyen T.D., Wang Y., Pitt D., Gauthier S.A. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain. 2019; 142 (1): 133-145. https://doi.org/10.1093/brain/awy296Liu J., Liu T., de Rochefort L., Ledoux J., Khalidov I., Chen W., Tsiouris A.J., Wisnieff C., Spincemaille P., Prince M.R., Wang Y. Morphology enabled dipole inversion for quantitative susceptibility mapping using structural consistency between the magnitude image and the susceptibility map. Neuroimage. 2012; 59 (3): 2560-8. https://doi.org/10.1016/j.neuroimage.2011.08.082Liu J., Liu T., de Rochefort L., Ledoux J., Khalidov I., Chen W., Tsiouris A.J., Wisnieff C., Spincemaille P., Prince M.R., Wang Y. Morphology enabled dipole inversion for quantitative susceptibility mapping using structural consistency between the magnitude image and the susceptibility map. Neuroimage. 2012; 59 (3): 2560-8. https://doi.org/10.1016/j.neuroimage.2011.08.082Wang Y., Liu T. Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker. Magn Reson Med. 2015; 73 (1): 82-101. https://doi.org/10.1002/mrm.25358Wang Y., Liu T. Quantitative susceptibility mapping (QSM): Decoding MRI data for a tissue magnetic biomarker. Magn Reson Med. 2015; 73 (1): 82-101. https://doi.org/10.1002/mrm.25358Burgetova A., Dusek P., Vaneckova M., Horakova D., Langkammer C., Krasensky J., Sobisek L., Matras P., Masek M., Seidl Z. Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis. AJNR Am J Neuroradiol. 2017; 38 (6): 1079-1086. https://doi.org/10.3174/ajnr.A5166Burgetova A., Dusek P., Vaneckova M., Horakova D., Langkammer C., Krasensky J., Sobisek L., Matras P., Masek M., Seidl Z. Thalamic Iron Differentiates Primary-Progressive and Relapsing-Remitting Multiple Sclerosis. AJNR Am J Neuroradiol. 2017; 38 (6): 1079-1086. https://doi.org/10.3174/ajnr.A5166Papathanasiou A., Messinis L., Zampakis P., Panagiotakis G., Gourzis P., Georgiou V., Papathanasopoulos P. Thalamic atrophy predicts cognitive impairment in relapsing remitting multiple sclerosis. Effect on instrumental activities of daily living and employment status. J Neurol Sci. 2015; 358 (1-2): 236-42. https://doi.org/10.1016/j.jns.2015.09.001Papathanasiou A., Messinis L., Zampakis P., Panagiotakis G., Gourzis P., Georgiou V., Papathanasopoulos P. Thalamic atrophy predicts cognitive impairment in relapsing remitting multiple sclerosis. Effect on instrumental activities of daily living and employment status. J Neurol Sci. 2015; 358 (1-2): 236-42. https://doi.org/10.1016/j.jns.2015.09.001Прахова Л.Н., Богдан А.А., Ильвес А.Г., Магонов Е.П., Савинцева Ж.И., Трофимова Т.Н. Особенности развития нейродегенерации таламуса у больных рассеянным склерозом. Лучевая диагностика и терапия. 2015; (4): 35-41. https://doi.org/10.22328/2079-5343-2015-4-35-41Prakhova L.N., Bogdan A.A., Ilves A.G., Magonov E.P., Savintseva Z.I., Trofimova T.N. Features of thalamic neurodegeneration in patients with multiple sclerosis. Diagnostic radiology and radiotherapy. 2015; (4): 35-41. https://doi.org/10.22328/2079-5343-2015-4-35-41 (In Russian)Zivadinov R., Schweser F., Dwyer M.G., Pol S. Detection of Monocyte/Macrophage and Microglia Activation in the TMEV Model of Chronic Demyelination Using USPIO-Enhanced Ultrahigh-Field Imaging. J Neuroimaging. 2020; 30 (6): 769-778. https://doi.org/10.1111/jon.12768Zivadinov R., Schweser F., Dwyer M.G., Pol S. Detection of Monocyte/Macrophage and Microglia Activation in the TMEV Model of Chronic Demyelination Using USPIO-Enhanced Ultrahigh-Field Imaging. J Neuroimaging. 2020; 30 (6): 769-778. https://doi.org/10.1111/jon.12768

The authors declare that there are no conflicts of interest present.