Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental NeurologyАнналы клинической и экспериментальной неврологии2075-54732409-2533Eco-Vector22610.17816/psaic226TechnologiesТехнологииUnknownState-of-the-art neuroimaging techniques in pathogenesis of multiple sclerosisСовременные методы визуализации в патогенезе рассеянного склерозаBryukhovV. V.БрюховВасилий Валерьевич
Russian Federation
abdomen@rambler.ruKulikovaS. N.КуликоваСофья Николаевна
Russian Federation
abdomen@rambler.ruhttps://orcid.org/0000-0003-3820-4554KrotenkovaMarina V.КротенковаМарина Викторовна
Russian Federation

D. Sci. (Med.), Head, Neuroradiology department

д.м.н., рук. отд. лучевой диагностики

abdomen@rambler.ruPeresedovaA. V.ПереседоваA. В.
Russian Federation
abdomen@rambler.ruZavalishinI. A.ЗавалишинИ. A.
Russian Federation
abdomen@rambler.ruResearch Center of NeurologyФГБНУ «Научный центр неврологии»0909201373475402022017Copyright ©; 2013, Bryukhov V.V., Kulikova S.N., Krotenkova M.V., Peresedova A.V., Zavalishin I.A.Copyright ©; 2013, Bryukhov V.V., Kulikova S.N., Krotenkova M.V., Peresedova A.V., Zavalishin I.A.2013Bryukhov V.V., Kulikova S.N., Krotenkova M.V., Peresedova A.V., Zavalishin I.A.Bryukhov V.V., Kulikova S.N., Krotenkova M.V., Peresedova A.V., Zavalishin I.A.https://creativecommons.org/licenses/by/4.0https://annaly-nevrologii.com/pathID/article/view/226

Magnetic resonance imaging (MRI) is one of the main methods of multiple sclerosis (MS) diagnostic, differential diagnostic and disease course monitoring. Conventional MRI techniques have low sensitivity in the assessment of diffuse damage of normal appearing white matter and focal/diffuse damage of grey matter which are of great interest in MS. Advanced MRI techniques allow to get over these limitations and to obtain more specific information about MS pathogenesis. Thus MR-spectroscopy metabolites analysis helps to assess inflammation, myelin structure, remyelination and axonal loss or dysfunction, i.e. lets us see pathochemical changes in MS. Demyelination and axonal loss differentiation is possible due to MR magnetization transfer technique and also diffusion tensor imaging, which characterize water diffusion in the brain tissue restricted by cell membranes and axonal cytoskeleton. Grey matter damage could be assessed using sequences with one or two inverted impulses and morphometric analysis of atrophy. Functional MRI performance using different paradigms characterizes cortical reorganization in response to functional injury. Vascular aspects of MS are also widely discussed nowadays. MR-perfusion and susceptibility weighted imaging allow assessing perfusion and venous flowing changes. State-of-the art neuroimaging methods let us perform detailed analysis of tissue damage in MS including the cell level, obtain more precise information about functional, metabolic and pathologic features, therapy influence on the inflammatory reactions and neuroprotection. Perspective use of high-field MR scanners (more than 1.5 T) will lead to the increase of sensitivity of different pathologic mechanisms detection.

Магнитно-резонансная томография (МРТ) при рассеянном склерозе (РС) является основным инструментальным методом диагностики, дифференциальной диагностики и мониторирования течения процесса. Для традиционных последовательностей МРТ характерна низкаячувствительность для оценки диффузного поражения внешне неизменного белого вещества и очаговых/диффузных изменениях в сером веществе, которым уделяется большое внимание при РС. Новые МРТ методики позволяют преодолевать эти ограничения, способствуют уточнению различных аспектов патогенеза. Так, анализ содержания ряда метаболитов при МР-спектроскопии способствует оценке воспаления, состояния миелина, ремиелинизации и аксонального/нейронального повреждения или дисфункции, т.е. позволяет визуализировать патохимические изменения при РС. Для дифференцировки демиелинизации и аксонального повреждения используется МРТ визуализация с переносом намагниченности, а также диффузионная тензорная МРТ, отражающая нарушения диффузии молекул воды, ограниченной клеточными мембранами и аксональным цитоскелетом. Для оценки поражения серого вещества головного мозга используются последовательности с одним и двумя инвертирующими импульсами и морфометрический анализ атрофических процессов. При РС рассматривается влияние кортикальной реорганизации на восстановление функций, что изучается путем проведения функциональной МРТ (фМРТ) с использованием различных парадигм. Активно обсуждается роль сосудистого фактора в патогенезе РС. МРТ перфузия и визуализация с получением изображений, взвешенных по магнитной восприимчивости, особенно чувствительная к нарушениям венозного кровотока, позволяют уточнить роль снижения церебральной перфузии, а также венозных изменений. Современные методы визуализации дают возможность детально оценить поражение при РС, в т.ч. и на клеточном уровне, уточнить функциональные, метаболические, патофизиологические особенности, могут способствовать оценке влияния терапии на иммуновоспалительные реакции и нейропротекцию. Использование высокопольныхМР-томографов (более 1,5 Т) в перспективе будет способствовать повышению чувствительности выявления различных механизмов патологических процессов.

multiple sclerosismagnetic resonance imagingpathogenesisрассеянный склерозмагнитно-резонансная томографияпатогенезЗавалишин И.А., Переседова А.В., Кротенкова М.В. и др. Кортикальная реорганизация при рассеянном склерозе. Анналы клинич. и эксперим. неврологии 2008; 2: 28–34.Куликова С.Н., Брюхов В.В., Переседова А.В. и др. Диффузионная тензорная магнитно-резонансная томография и трактография при рассеянном склерозе: обзор литературы. Журнал неврологии и психиатрии им. С.С. Корсакова. 2012 (2); 112: 52–59.Adhya S., Johnson G., Herbert J. et al. Pattern of hemodynamic impairment in multiple sclerosis: dynamic susceptibility contrast perfusion MR imaging at 3.0 T. Neuroimage 2006; 33 (4): 1029–1035.Amato M.P., Portaccio E., Stromillo M.L. et al. Cognitive assessment and quantitative magnetic resonance metrics can help to identify benign multiple sclerosis. Neurology 2008; 71: 632.Bö L., Vedeler C.A., Nyland H. et al. Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Multiple Sclerosis 2003; 9: 323–31.Brex P.A., Jenkins R., Fox N.C. et al. Detection of ventricular enlargement in patients at the earliest clinical stage of MS. Neurology, 2000; 54: 1689–91.Brooks D.J., Leenders K.L., Head G. et al. Studies on regional cerebral oxygen utilisation and cognitive function in multiple sclerosis. J. Neurol. Neurosurg Psychiatry 1984; 47: 1182 –1191.Brownell B., Hughes J.T. The distribution of plaques in the cerebrum in multiple sclerosis. J Neurol Neurosurg Psychiatry 1962; 25: 315–320.Budde M.D., Kim J.H., Liang H.F. et al. Toward accurate diagnosis of white matter pathology using diffusion tensor imaging. Magn Reson Med 2007; 57: 688.Cassol E., Ranjeva J-P., Ibarrola D. et al. Diffusion tensor imaging in multiple sclerosis: a tool for monitoring changes in normal-appearing white matter. Mult Scler 2004; 10: 188–196.Dalton C.M., Chard D.T., Davies G.R. et al. Early development of multiple sclerosis is associated with progressive grey matter atrophy in patients presenting with clinically isolated syndromes. Brain, 2004; 127: 1101–07.Dawson J.W. The histology of multiple sclerosis. Trans R Soc Edinburgh 1916; 50: 517–740.Dietemann J.L., Beigelman C., Rumbach L. et al. Multiple sclerosis and corpus callosum atrophy: relationship of MRI findings to clinical data. Neuroradiology, 1988; 30: 478–80.Doepp F., Paul F., Valdueza J.M. et al. No cerebrocervical venous congestion in patients with multiple sclerosis. Ann. Neurol., 2010; 68: 173–183.Dousset V., Grossman R.I., Ramer K.N. et al. Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging. Radiology 1992; 182: 483–491.Fernando K.T., McLean M.A., Chard D.T. et al. Elevated white matter myo-inositol in clinically isolated syndromes suggestive of multiple sclerosis. Brain 2004; 127: 1361.Filippi M., Tortorella C., Rovaris M. et al. Changes in the normal appearing brain tissue and cognitive impairment in multiple sclerosis. J. Neurol. Neurosurg Psychiatry 2000; 68: 157.Fink F., Klein J., Lanz M. et al. Comparison of diffusion tensorbased tractography and quantified brain atrophy for analyzing demyelination and axonal loss in MS. J Neuroimaging 2009; 20: 1–11.Fox N.C., Jenkins R., Leary S.M. et al. Progressive cerebral atrophy in MS: a serial study using registered, volumetric MRI. Neurology, 2000; 54: 807–812.Fox R.J., Beall E., Bhattacharyya P. et al. Advanced MRI in multiple sclerosis: current status and future challenges. Neurol. Clin. 2011;29: 357–380.Gallo A., Rovaris M, Riva R. et al. Diffusion tensor magnetic resonance imaging detects normal-appearing white matter damage unrelated to short-term disease activity in patients at the earliest clinical stage of multiple sclerosis . Arch Neurol 2005; 62 (5): 803–808.Gass A., Barker G.J., Kidd D. et al. Correlation of magnetization transfer ratio with disability in multiple sclerosis. Ann. Neurol 1994; 36: 62–67.Ge Y., Grossman R.I., Babb J.S. et al. Age-related total gray matter and white matter changes in normal adult brain. Part II. Quantitative magnetization transfer ratio histogram analysis. AJNR, 2002; 23: 1334–1341.Ge Y., Law M., Johnson G. et al. Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity. AJNR Am. J. Neuroradiol. 2005; 26: 1539–1547.Geurts J.J., Pouwels P.J., Uitdehaag B.M. et al. Intracortical lesions in multiple sclerosis: improved detection with 3D double inversionrecovery MR imaging. Radiology 2005; 236: 254–260.Griffin C.M., Chard D.T., Ciccarelli O. et al. Diffusion tensor imaging in early relapsing-remitting multiple sclerosis. Mult Scler 2001; 7: 290–297.Haselhorst R., Kappos L., Bilecen D. et al. Dynamic susceptibility contrast MR imaging of plaque development in multiple sclerosis: application of an extended blood-brain barrier leakage correction. J. Magn. Reson. Imaging 2000; 11: 495–505.He J., Inglese M., Li B.S. et al. Relapsing-remitting multiple sclerosis: metabolic abnormality in nonenhancing lesions and normal appearing white matter at MR imaging: initial experience. Radiology 2005; 234: 211.Horsfield M.A., Lai M., Webb S.L. et al. Apparent diffusion coefficient in benign and secondary progressive multiple sclerosis by nuclear magnetic resonance. Magn Reson Med 1996; 36: 393–400.Jones D.K. The effect of gradient sampling schemes on measures derived from diffusion tensor MRI: a Monte Carlo study. Magn Reson Med 2004; 51: 807.Kidd D., Barkhof F., McConnell R. et al. Cortical lesions in multiple sclerosis. Brain 1999; 122: 17–26.Kutzelnigg A., Lucchinetti C.F., Stadelmann C. et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 2005; 128: 2705–2712.Law M., Saindane A.M., Ge Y. et al. Microvascular abnormality in relapsing-remitting multiple sclerosis: perfusion MR imaging findings in normal-appearing white matter. Radiology. 2004; 231: 645–652.Lin X., Tench C.R., Morgan P.S. et al. ‘Importance sampling’ in MS: use of diffusion tensor tractography to quantify pathology related to specifi c impairment. J Neurol Sci 2005; 237: 13–19.Lycke J., Wikkelso C., Bergh A.C. et al. Regional cerebral blood flow in multiple sclerosis measured by single photon emission tomography with technetium-99m hexamethylpropyleneamine oxime.Eur. Neurol. 1993; 33(2): 163–167.Mader I., Seeger U., Weissert R. et al. Proton MR spectroscopy with metabolitenulling reveals elevated macromolecules in acute multiple sclerosis. Brain 2001; 124: 953.Mayer C.A., Pfeilschifter W., Lorenz M.W. et al. The perfect crime? CCSVI not leaving a trace in MS. J. Neurol. Neurosurg.Psychiatry. 2011; 82 (4): 436–440.Mesaros S., Rovaris M., Pagani E. et al. A magnetic resonance imaging voxel-based morphometry study of regional gray matter atrophy in patients with benign multiple sclerosis . Arch Neurol 2008; 65 (9):1223–1230.Miller D.H., Barkhof F., Frank J.A. et al.Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain, 2002; 125: 1676–1695.Newcombe J., Hawkins C.P., Henderson C.L. et al. Histopathology of multiple sclerosis lesions detected by magnetic resonance imaging in unfixed postmortem central nervous system tissue. Brain 1991; 114: 1013–1023.Pantano P., Mainero C., Iannetti G.D. et al. Contribution of corticospinal tract damage to cortical motor reorganization after a single clinical attack of multiple sclerosis. Neuroimage 2002; 17 (4): 1837–1843.Paolillo A., Giugni E., Bozzao A. et al. Fast spin echo and fast fluid attenuated inversion recovery sequences in multiple sclerosis. Radiol Med 1997; 93: 686–691.Peterson J.W., Bo L., Mork S.J. et al. Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 2001; 50: 389–400.Pierpaoli C., Jezzard P., Basser P.J. et al. Diffusion tensor MR imaging of the human brain. Radiology 1996; 201: 637–648.Prineas J.W., Barnard R.O., Kwon E.E. et al. Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 1993; 33: 137–151.Rashid W., Hadjiprocopis A., Davies G. et al. Longitudinal evaluation of clinically early relapsing-remitting multiple sclerosis with diffusion tensor imaging. J Neurol 2008; 255: 390–397.Rocca M.A., Mastronardo G., Rodegher M. et al. Long-term changes of magnetization transfer-derived measures from patients with relapsing-remitting and secondary progressive multiple sclerosis. AJNR Am J Neuroradiol 1999; 20: 821–827.Rocca M.A., Absinta M., Valsasina P. et al. Abnormal connectivity of the sensorimotor network in patients with MS: a multicenter fMRI study. Hum Brain Mapp. 2009 Aug; 30(8): 2412-2425.Sajja B.R., Wolinsky J.S., Narayana P.A. Proton magnetic resonance spectroscopy in multiple sclerosis. Neuroimaging Clin N Am 2009; 19: 45.Sastre-Garriga J., Ingle G.T., Chard D.T. et al. Grey and white matter volume changes in early primary progressive multiple sclerosis: a longitudinal study. Brain, 2005; 128: 1454–1460.Song S.K., Yoshino J., Le T.Q. et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage 2005; 26: 132.Srinivasan R., Sailasuta N., Hurd R. et al. Evidence of elevated glutamate in multiple sclerosis using magnetic resonance spectroscopy at 3 T. Brain 2005; 128: 1016.Sun X., Tanaka M., Kondo S. et al. Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study. Ann. Nucl. Med. 1998; 12 (2): 89–94.Swank R.L., Roth J.G., Woody D.C. Jr. Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis. Neurol Res 1983; 5: 37–59.Tartaglia M.C., Narayanan S., De Stefano N. et al. Choline is increased in prelesional normal appearing white matter in multiple sclerosis. J Neurol 2002; 249: 1382.Valsasina P., Rocca M.A., Absinta M. et al. A multicentre study of motor functional connectivity changes in patients with multiple sclerosis. Eur J Neurosci. 2011 Apr; 33 (7): 1256–1263.van Waesberghe J.H.T.M., Kamphorst W., De Groot C.J.A. et al. Axonal loss in MS lesions: MRI insights into substrates of disability. Ann Neurol 1999; 46: 747–754.van Walderveen M.A.A., Kamphorst W., Scheltens P. et al. Histopathologic correlate of hypointense lesions on T1-weighted spinecho MRI in multiple sclerosis. Neurology 1998; 50: 1282–1285.Vercellino M., Plano F., Votta B. et al. Grey matter pathology in multiple sclerosis. J Neuropathol Exp Neurol 2005; 64: 1101–1107.Verstraete E. et al. Motor network degeneration in amyotrophic lateral sclerosis: a structural and functional connectivity study. 2010. PLoS One 5: e13664.Voxel-based morphometric study of ageing in 465 normal adult human brains. C.D. Good. A. Neur. Image. 2001. Vol. 14; 1: 21–36.Xu J., Kobayashi S., Yamaguchi S. et al. Gender effects on age-related changes in brain structure. AJNR, 2000; 21: 112–118.Zamboni P., Galeotti R., Menegatti E. et al. A prospective open-label study of endovascular treatment of chronic cerebrospinal venous insufficiency. J. Vasc. Surg. 2009a; 50: 1348–1358 e1-3.Zamboni P., Galeotti R., Menegatti E. et al. Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 2009b; 80: 392–399.