4.6 Review

Chronic inflammation in multiple sclerosis - seeing what was always there

Journal

NATURE REVIEWS NEUROLOGY
Volume 15, Issue 10, Pages 582-593

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/s41582-019-0240-y

Keywords

-

Funding

  1. Imperial College Healthcare Trust - National Institute for Health Research (NIHR) Biomedical Research Centre
  2. Edmond J. Safra Foundation
  3. NIHR
  4. Medical Research Council
  5. UK Dementia Research Institute
  6. Alzheimer's Society
  7. Alzheimer's Research UK
  8. Lily Safra
  9. MRC [UKDRI-5003, MC_PC_17114, MR/N026934/1, MR/M024903/1] Funding Source: UKRI

Ask authors/readers for more resources

Activation of innate immune cells and other compartmentalized inflammatory cells in the brains and spinal cords of people with relapsing-remitting multiple sclerosis (MS) and progressive MS has been well described histopathologically. However, conventional clinical MRI is largely insensitive to this inflammatory activity. The past two decades have seen the introduction of quantitative dynamic MRI scanning with contrast agents that are sensitive to the reduction in blood-brain barrier integrity associated with inflammation and to the trafficking of inflammatory myeloid cells. New MRI imaging sequences provide improved contrast for better detection of grey matter lesions. Quantitative lesion volume measures and magnetic resonance susceptibility imaging are sensitive to the activity of macrophages in the rims of white matter lesions. PET and magnetic resonance spectroscopy methods can also be used to detect contributions from innate immune activation in the brain and spinal cord. Some of these advanced research imaging methods for visualization of chronic inflammation are practical for relatively routine clinical applications. Observations made with the use of these techniques suggest ways of stratifying patients with MS to improve their care. The imaging methods also provide new tools to support the development of therapies for chronic inflammation in MS.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Review Multidisciplinary Sciences

The UK Biobank imaging enhancement of 100,000 participants:rationale, data collection, management and future directions

Thomas J. Littlejohns, Jo Holliday, Lorna M. Gibson, Steve Garratt, Niels Oesingmann, Fidel Alfaro-Almagro, Jimmy D. Bell, Chris Boultwood, Rory Collins, Megan C. Conroy, Nicola Crabtree, Nicola Doherty, Alejandro F. Frangi, Nicholas C. Harvey, Paul Leeson, Karla L. Miller, Stefan Neubauer, Steffen E. Petersen, Jonathan Sellors, Simon Sheard, Stephen M. Smith, Cathie L. M. Sudlow, Paul M. Matthews, Naomi E. Allen

NATURE COMMUNICATIONS (2020)

Review Clinical Neurology

E-health and multiple sclerosis

Paul M. Matthews, Valerie J. Block, Letizia Leocani

CURRENT OPINION IN NEUROLOGY (2020)

Article Radiology, Nuclear Medicine & Medical Imaging

Unbalanced SSFP for super-resolution in MRI

Peter J. Lally, Paul M. Matthews, Neal K. Bangerter

Summary: The technique presented in this study achieves rapid, low SAR super-resolution imaging by utilizing the off-resonance profile in SSFP, demonstrating its feasibility through Bloch simulations and synthetic phantoms. By proposing a k-space reconstruction approach to account for B-0 effects, high-resolution super-resolution images were successfully reconstructed from a test object at 9.4T, showcasing improved resolution capabilities with minimal RF power requirements.

MAGNETIC RESONANCE IN MEDICINE (2021)

Article Genetics & Heredity

Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect

Rafik Tadros, Catherine Francis, Xiao Xu, Alexa M. C. Vermeer, Andrew R. Harper, Roy Huurman, Ken Kelu Bisabu, Roddy Walsh, Edgar T. Hoorntje, Wouter P. te Rijdt, Rachel J. Buchan, Hannah G. van Velzen, Marjon A. van Slegtenhorst, Jentien M. Vermeulen, Joost Allard Offerhaus, Wenjia Bai, Antonio de Marvao, Najim Lahrouchi, Leander Beekman, Jacco C. Karper, Jan H. Veldink, Elham Kayvanpour, Antonis Pantazis, A. John Baksi, Nicola Whiffin, Francesco Mazzarotto, Geraldine Sloane, Hideaki Suzuki, Deborah Schneider-Luftman, Paul Elliott, Pascale Richard, Flavie Ader, Eric Villard, Peter Lichtner, Thomas Meitinger, Michael W. T. Tanck, J. Peter van Tintelen, Andrew Thain, David McCarty, Robert A. Hegele, Jason D. Roberts, Julie Amyot, Marie-Pierre Dube, Julia Cadrin-Tourigny, Genevieve Giraldeau, Philippe L. L'Allier, Patrick Garceau, Jean-Claude Tardif, S. Matthijs Boekholdt, R. Thomas Lumbers, Folkert W. Asselbergs, Paul J. R. Barton, Stuart A. Cook, Sanjay K. Prasad, Declan P. O'Regan, Jolanda van der Velden, Karin J. H. Verweij, Mario Talajic, Guillaume Lettre, Yigal M. Pinto, Benjamin Meder, Philippe Charron, Rudolf A. de Boer, Imke Christiaans, Michelle Michels, Arthur A. M. Wilde, Hugh Watkins, Paul M. Matthews, James S. Ware, Connie R. Bezzina

Summary: The study found a strong genetic correlation between hypertrophic and dilated cardiomyopathies and left ventricular traits, with opposing genetic effects in the two cardiomyopathies. The research also supported a causal association between increased left ventricular contractility and hypertrophic cardiomyopathy risk.

NATURE GENETICS (2021)

Article Multidisciplinary Sciences

SARS-CoV-2 antibody prevalence in England following the first peak of the pandemic

Helen Ward, Christina Atchison, Matthew Whitaker, Kylie E. C. Ainslie, Joshua Elliott, Lucy Okell, Rozlyn Redd, Deborah Ashby, Christl A. Donnelly, Wendy Barclay, Ara Darzi, Graham Cooke, Steven Riley, Paul Elliott

Summary: The REACT-2 study in England found that by mid-July 2020, around 6% of adults had been infected with SARS-CoV-2, with healthcare workers and individuals of Black or South Asian ethnicity disproportionately affected. Although different ethnicities had similar infection fatality ratios, higher hospitalization and mortality rates in minority ethnic groups may be due to higher rates of infection rather than differential disease experience or care.

NATURE COMMUNICATIONS (2021)

Article Engineering, Electrical & Electronic

Tensor Dropout for Robust Learning

Arinbjorn Kolbeinsson, Jean Kossaifi, Yannis Panagakis, Adrian Bulat, Animashree Anandkumar, Ioanna Tzoulaki, Paul M. Matthews

Summary: CNNs achieve high performance with deep, over-parametrized neural architectures, but lack robustness and generalization abilities. Tensor layers provide better inductive biases through multi-linear structure, and tensor dropout is a technique to improve generalization for image classification and phenotypic trait prediction tasks. Superior performance and improved robustness are demonstrated in experiments, validating the theoretical validity and regularizing effect of tensor dropout.

IEEE JOURNAL OF SELECTED TOPICS IN SIGNAL PROCESSING (2021)

Article Radiology, Nuclear Medicine & Medical Imaging

Preclinical evaluation of (S)-[18F]GE387, a novel 18-kDa translocator protein (TSPO) PET radioligand with low binding sensitivity to human polymorphism rs6971

Nisha K. Ramakrishnan, Matthew Hird, Stephen Thompson, David J. Williamson, Luxi Qiao, David R. Owen, Allen F. Brooks, Peter J. H. Scott, Sergio Bacallado, John T. O'Brien, Franklin Aigbirhio

Summary: This study evaluated the two enantiomers of [F-18]GE387, showing that (S)-[F-18]GE387 has favorable kinetics in healthy subjects and can distinguish inflamed brain regions in neuroinflammation models, while also demonstrating low sensitivity to TSPO polymorphism in human brain tissue.

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2021)

Article Neurosciences

Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain

Erik Nutma, Emeline Gebro, Manuel C. Marzin, Paul van der Valk, Paul M. Matthews, David R. Owen, Sandra Amor

Summary: The expression of TSPO in the human central nervous system may reflect cell density rather than activation status of microglia/macrophages. This has implications for interpreting TSPO PET signals in MS and other CNS diseases, highlighting the limitations of extrapolating TSPO biology from rodents to humans.
Article Biochemistry & Molecular Biology

Astrocyte reactivity with late-onset cognitive impairment assessed in vivo using 11C-BU99008 PET and its relationship with amyloid load

Valeria Calsolaro, Paul M. Matthews, Cornelius K. Donat, Nicholas R. Livingston, Grazia D. Femminella, Sandra Silva Guedes, Jim Myers, Zhen Fan, Robin J. Tyacke, Ashwin V. Venkataraman, Robert Perneczky, Roger Gunn, Eugenii A. Rabiner, Steve Gentleman, Christine A. Parker, Philip S. Murphy, Paul B. Wren, Rainer Hinz, Magdalena Sastre, David J. Nutt, Paul Edison

Summary: This study utilized a novel PET tracer, C-11-BU99008, to investigate astrocyte reactivity associated with Alzheimer's disease, revealing significantly increased astrocyte reactivity in older cognitively impaired and Alzheimer's disease patients, particularly in cortical regions.

MOLECULAR PSYCHIATRY (2021)

Article Multidisciplinary Sciences

Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

George Zhang Wei, Katherine A. Martin, Peter Yuli Xing, Ruchi Agrawal, Luke Whiley, Thomas K. Wood, Sophia Hejndorf, Yong Zhi Ng, Jeremy Zhi Yan Low, Janet Rossant, Robert Nechanitzky, Elaine Holmes, Jeremy K. Nicholson, Eng-King Tan, Paul M. Matthews, Sven Pettersson

Summary: This study demonstrates that the tryptophan metabolite indole produced by gut microbes can influence neurogenesis in the adult hippocampus through a specific signaling pathway. The effects of indole on neural progenitor cells include cell cycle exit, terminal differentiation, and maturation into neurons with longer and more branched neurites, highlighting a potential therapeutic opportunity for brain aging-related mechanisms.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Article Biology

Alcohol consumption in the general population is associated with structural changes in multiple organ systems

Evangelos Evangelou, Hideaki Suzuki, Wenjia Bai, Raha Pazoki, He Gao, Paul M. Matthews, Paul Elliott

Summary: The study found a monotonous association between higher alcohol consumption and lower normalized brain volume, as well as correlations with increased left ventricular mass and liver fat content. These results suggest that there is no safe threshold for alcohol consumption and call for a reevaluation of current public health guidelines.

ELIFE (2021)

Article Clinical Neurology

Diverse human astrocyte and microglial transcriptional responses to Alzheimer's pathology

Amy M. Smith, Karen Davey, Stergios Tsartsalis, Combiz Khozoie, Nurun Fancy, See Swee Tang, Eirini Liaptsi, Maria Weinert, Aisling McGarry, Robert C. J. Muirhead, Steve Gentleman, David R. Owen, Paul M. Matthews

Summary: The study reveals significant differences in gene expression in astrocytes and microglia in the brains of AD patients, correlated with amyloid-beta or pTau expression. There are distinct gene expression patterns in the two cell types and pathologies, but common gene sets exist in each cell type. Additionally, different sub-clusters are found in astrocytes and microglia, characterized by transcriptional signatures related to either homeostatic functions or disease pathology.

ACTA NEUROPATHOLOGICA (2022)

Article Clinical Neurology

Boosting the diagnostic power of amyloid-β PET using a data-driven spatially informed classifier for decision support

Ashwin V. Venkataraman, Wenjia Bai, Alex Whittington, James F. Myers, Eugenii A. Rabiner, Anne Lingford-Hughes, Paul M. Matthews

Summary: A data-driven, spatially informed classifier was developed to improve the diagnostic power of amyloid PET in Alzheimer's disease. This classifier significantly increased the accuracy and sensitivity of AD scans, showcasing the importance of considering spatial variation in Aβ PET signal for optimal interpretation of scans.

ALZHEIMERS RESEARCH & THERAPY (2021)

Article Medicine, General & Internal

OPTIMISE: MS study protocol: a pragmatic, prospective observational study to address the need for, and challenges with, real world pharmacovigilance in multiple sclerosis

Ruth Dobson, Matthew Craner, Ed Waddingham, Aleisha Miller, Ana Cavey, Stewart Webb, Cheryl Hemingway, Jeremy Hobart, Nikos Evangelou, Neil Scolding, David Rog, Richard Nicholas, Monica Marta, Camilla Blain, Carolyn Anne Young, Helen L. Ford, Paul M. Matthews

Summary: The study aims to characterize and compare the incidence and risk of serious adverse events in MS patients treated with DMTs. The OPTIMISE:MS database allows for electronic data capture and secure data transfer. Ethical permission has been obtained and results will be disseminated through publication, with participants' consent for sharing anonymized data for further research use.

BMJ OPEN (2021)

Proceedings Paper Computer Science, Artificial Intelligence

Subject-Specific Lesion Generation and Pseudo-Healthy Synthesis for Multiple Sclerosis Brain Images

Berke Doga Basaran, Mengyun Qiao, Paul A. Matthews, Wenjia Bai

Summary: In this study, a foreground-based generative method is proposed to model local lesion characteristics and generate synthetic lesions and pseudo-healthy images. The method can also be used for data augmentation in training brain image segmentation networks.

SIMULATION AND SYNTHESIS IN MEDICAL IMAGING, SASHIMI 2022 (2022)

No Data Available