Clinical translation of MRI-based brain iron assessment in multiple sclerosis



Tissue loss in the thalamus is one of the earliest imaging hallmarks of multiple sclerosis. This has been recognized for some time, yet the current lack of non-invasive methods to study tissue alterations on the cellular and molecular level in the various sub-regions of the deep gray matter presents a major challenge in understanding and targeting the biological mechanisms that may be associated with or precede neurodegeneration. This inability to study these mechanisms has been a major obstacle in developing treatments for multiple sclerosis.
Dr. Schweser is one of the pioneering developers of Quantitative Susceptibility Mapping (QSM), a sophisticated MRI technique that allows for the quantification of magnetic susceptibility in the brain and other organs. This technology was developed at the Medical Physics Group led by Dr. Jürgen Reichenbach. Magnetic tissue susceptibility MRI provides a unique opportunity to assess tissue iron in a clinical setting. Dr. Schweser's pioneering work has opened up a new avenue of exploration in the medical field.
Iron is an essential co-factor in various biochemical pathways. Its deprivation from glial cells in the normal-appearing white matter is a pathological hallmark of multiple sclerosis that has been implicated in neuronal injury. It was recently observed that the thalamus of patients with multiple sclerosis shows a progressive decline in magnetic susceptibility. Other research suggests that a similar phenomenon may exist in other deep gray matter regions.

We are currently undertaking a comprehensive investigation into the population and subject-level dynamics of iron homeostasis imaging markers in the deep gray matter (DGM) of individuals with multiple sclerosis (MS). Our research aims to determine whether disease progression is associated with iron-related oligodendroglia dysfunction in the DGM. We anticipate that this research will have a significant impact on the field, as it will open up new avenues for the development of effective treatments to combat the progression of MS, ultimately improving public health.

Publications


Toward online reconstruction of quantitative susceptibility maps: Superfast dipole inversion


F. Schweser, A. Deistung, K. Sommer, J. Reichenbach


Magnetic resonance in medicine, 2013


Establishing MRI phase , abnormal MRI phase , and volume behavior in the subcortical deep gray matter of healthy individuals


J. Hagemeier, M. Dwyer, N. Bergsland, F. Schweser, C. Magnano, M. Heininen-Brown, D. Ramasamy, E. Carl, C. Kennedy, Mariya Cherneva, R. Melia, P. Polak, A. Deistung, J. Reichenbach, R. Zivadinov


2012


Non-invasive Investigation of the Compartmentalization of Iron in the Human Brain


F. Schweser, J. Sedlacik, A. Deistung, J. Reichenbach


2012


Quantitative susceptibility mapping (QSM) as a means to measure brain iron? A post mortem validation study


C. Langkammer, F. Schweser, N. Krebs, A. Deistung, W. Goessler, E. Scheurer, K. Sommer, G. Reishofer, K. Yen, F. Fazekas, S. Ropele, J. Reichenbach


NeuroImage, 2012


Longitudinal Evaluation of Brain Iron Depositions in a Patient With Confirmed c19orf12 Mutation Using R2* Relaxometry and Quantitative Susceptibility Mapping


U. Löbel, A. Meyer-Osores, J. Sedlacik, F. Schweser, R. Grosse, A. Deistung, J. Reichenbach, A. Schulz, M. Hartig, A. Kohlschütter


2013


Effect of Age on MRI Phase Behavior in the Subcortical Deep Gray Matter of Healthy Individuals


J. Hagemeier, M. Dwyer, N. Bergsland, F. Schweser, C. Magnano, M. Heininen-Brown, D. Ramasamy, E. Carl, C. Kennedy, R. Melia, P. Polak, A. Deistung, J. Geurts, J. Reichenbach, R. Zivadinov


American Journal of Neuroradiology, 2013


Improved deep gray matter segmentation using anatomical information from quantitative susceptibility maps


F. Schweser, Xiang Feng, Rosa Mach Batlle, D. Güllmar, A. Deistung, M. Dwyer, R. Zivadinov, J. Reichenbach


2013


Effects of diet on brain iron levels among healthy individuals: an MRI pilot study


J. Hagemeier, Olivia Tong, M. Dwyer, F. Schweser, M. Ramanathan, R. Zivadinov


Neurobiology of Aging, 2015


Quantitative Susceptibility Mapping Indicates a Disturbed Brain Iron Homeostasis in Neuromyelitis Optica – A Pilot Study


T. Doring, Vanessa Granado, F. Rueda, A. Deistung, J. Reichenbach, G. Tukamoto, E. Gasparetto, F. Schweser


PloS one, 2016


Cerebral Microbleeds in Multiple Sclerosis Evaluated on Susceptibility-weighted Images and Quantitative Susceptibility Maps: A Case-Control Study.


R. Zivadinov, D. Ramasamy, R. Benedict, P. Polak, J. Hagemeier, C. Magnano, M. Dwyer, N. Bergsland, N. Bertolino, B. Weinstock-Guttman, C. Kolb, D. Hojnacki, D. Utriainen, E. Haacke, F. Schweser


Radiology, 2016


Quantitative Susceptibility Mapping Study of Deep Gray Matter Iron at 3T in Large Cohort of Multiple Sclerosis Patients (P4.162)


J. Hagemeier, Schweser Ferdinand, M. Dwyer, P. Polak, N. Bergsland, B. Weinstock-Guttman, R. Zivadinov


2016


Evolution of Brain Iron Levels in Multiple Sclerosis: A 2-Year Longitudinal Quantitative Susceptibility Mapping Study at 3T (P4.163)


J. Hagemeier, F. Schweser, M. Dwyer, P. Polak, N. Bergsland, B. Weinstock-Guttman, R. Zivadinov


2016


Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals


J. Hagemeier, M. Ramanathan, F. Schweser, M. Dwyer, F. Lin, N. Bergsland, B. Weinstock-Guttman, R. Zivadinov


NeuroImage: Clinical, 2017


Brain Iron at Quantitative MRI Is Associated with Disability in Multiple Sclerosis.


R. Zivadinov, E. Tavazzi, N. Bergsland, J. Hagemeier, F. Lin, M. Dwyer, E. Carl, C. Kolb, D. Hojnacki, D. Ramasamy, J. Durfee, B. Weinstock-Guttman, F. Schweser


Radiology, 2018


Mapping of thalamic magnetic susceptibility in multiple sclerosis indicates decreasing iron with disease duration: A proposed mechanistic relationship between inflammation and oligodendrocyte vitality


F. Schweser, Ana Luiza Raffaini Duarte Martins, J. Hagemeier, F. Lin, Jannis Hanspach, B. Weinstock-Guttman, S. Hametner, N. Bergsland, M. Dwyer, R. Zivadinov


NeuroImage, 2018


Targeting Iron Dyshomeostasis for Treatment of Neurodegenerative Disorders


N. Bergsland, E. Tavazzi, F. Schweser, D. Jakimovski, J. Hagemeier, M. Dwyer, R. Zivadinov


CNS Drugs, 2019


Trajectories of magnetic susceptibility in the pulvinar provide further evidence for accelerated decline of thalamic iron in multiple sclerosis.


Salman F, Zivadinov R, Bergsland N, Dwyer MG, Weinstock-Guttman B, Schweser F


Proc Intl Soc Mag Reson Med, 2020, p. 1385


Decreasing brain iron in multiple sclerosis: The difference between concentration and content in iron MRI


F. Schweser, J. Hagemeier, M. Dwyer, N. Bergsland, S. Hametner, B. Weinstock-Guttman, R. Zivadinov


Human brain mapping, 2020


Decline of both iron concentration and iron content within the thalamus of patients with multiple sclerosis over two years.


Salman F, Bergsland N, Dwyer MG, Weinstock-Guttman B, Zivadinov R, Schweser F


Proc Intl Soc Mag Reson Med, 2021, p. 2805


Temporal evolution of the concentration and content of tissue iron in the pulvinar of patients with multiple sclerosis.


Salman F, Bergsland N, Dwyer M, Weinstock-Guttman B, Zivadinov R, Schweser F


Joint Workshop on MR phase, magnetic susceptibility and electrical properties mapping, Lucca, Italy, 2022


Temporal evlution of iron concentration and content in the pulvinar of patients with MS.


Salman F, Bergsland N, Dwyer MG, Weinstock-Guttman B, Zivadinov R, Schweser F


15th Annual Buffalo Neuroscience Research Day, Buffalo, NY, 2022


Two Novel Brain Iron Networks Explain Aging-related Variation in Deep Gray Matter


Reeves J, Bergsland N, Jakimovski D, Salman F, Damm J, Meineke N, Dwyer MG, Zivadinov R, Schweser F


American Academy of Neurology (AAN), Seattle, WA, 2022, p. 1950


Susceptibility networks reveal independent patterns of brain iron abnormalities in multiple sclerosis


Jack A. Reeves, N. Bergsland, M. Dwyer, G. Wilding, D. Jakimovski, Fahad Salman, B. Süle, Nicklas Meineke, B. Weinstock-Guttman, R. Zivadinov, F. Schweser


NeuroImage, 2022