Evidence map›Paper›PMID 33943045›Full record

ArticleAnnals of clinical and translational neurology2021

Quantitative signal properties from standardized MRIs correlate with multiple sclerosis disability.

Matthew R Brier, Abraham Z Snyder, Aaron Tanenbaum, Richard A Rudick, Elizabeth Fisher, Stephen Jones, Joshua S Shimony, Anne H Cross, Tammie L S Benzinger, Robert T Naismith

Open access · goldAbstract readMulticenter Study
In one paragraph

Article in Annals of clinical and translational neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 12 citations in OpenAlex.

  1. Aging and the Spectral Properties of Brain Hemodynamics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  2. Article
  3. Claustrum Volume Is Reduced in Multiple Sclerosis and Predicts Disability.Annals of clinical and translational neurology · 2025
    Article
  4. Observational
  5. Article
  6. Review
  7. "Brain age" predicts disability accumulation in multiple sclerosis.Annals of clinical and translational neurology · 2023
    Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Matthew R BrierDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.ORCID 0000-0001-5987-8705
Abraham Z SnyderMalinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.
Aaron TanenbaumDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Richard A RudickBiogen, Cambridge, Massachusetts, USA.
Elizabeth FisherBiogen, Cambridge, Massachusetts, USA.
Stephen JonesImaging Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Joshua S ShimonyMalinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.
Anne H CrossDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.ORCID 0000-0003-0829-7569
Tammie L S Benzinger *Malinckrodt Institute of Radiology, Washington University in St. Louis, St. Louis, Missouri, USA.
Robert T Naismith *Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Washington University in St. Louis · USBiogen (United States) · USCleveland Clinic · US

Funding

Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
Imaging CoreU19AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2010 to 2025
$53.9M
The natural history of AB accumulation in preclinical ADP01AG026276 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 2005 to 2025
$49.5M
Dominantly Inherited Alzheimer NetworkUF1AG032438 · NIA · WASHINGTON UNIVERSITY · PI BATEMAN, RANDALL J · 2014 to 2017
$21.6M
PET SPHINGOSINE-1-PHOSPHATE RECEPTOR 1 (S1PR1) RADIOTRACERS FOR MULTIPLE SCLEROSISR01NS103988 · NINDS · WASHINGTON UNIVERSITY · PI Tammie Lee Smith Benzinger, Zhude Tu · 2017 to 2026
$5.3M
PET Imaging of Neuroinflammation in Genetic Alzheimer's DiseaseR01AG052550 · NIA · WASHINGTON UNIVERSITY · PI Beau M Ances, Tammie Lee Smith Benzinger · 2018 to 2026
$4.2M
Quantification of Neuroinflammation inAlzheimer's Disease Using Diffusion BasisSpectrum ImagingR01AG054567 · NIA · WASHINGTON UNIVERSITY · PI BENZINGER, TAMMIE LEE SMITH, WANG, YONG · 2017 to 2021
$3.6M
NINDS CENTER CORE FOR BRAIN IMAGINGP30NS098577 · NINDS · WASHINGTON UNIVERSITY · PI HERSHEY, TAMARA G, MARCUS, DANIEL SCOTT · 2016 to 2019
$2.4M
WASHINGTON UNIVERSITY NEUROSURGERY RESIDENT RESEARCH EDUCATION PROGRAMR25NS090978 · NINDS · WASHINGTON UNIVERSITY · PI ZIPFEL, GREGORY J · 2015 to 2023
$2.1M
HIGH PERFORMANCE BIOMEDICAL IMAGING COMPUTER RESOURCESS10RR022984 · NCRR · WASHINGTON UNIVERSITY · PI PRIOR, FRED WILLIAM · 2009 to 2009
$1.9M
GPU COMPUTING RESOURCE TO ENABLE INNOVATION IN IMAGING AND NETWORK BIOLOGYS10OD018091 · OD · WASHINGTON UNIVERSITY · PI PAPPU, ROHIT V, PRIOR, FRED WILLIAM · 2014 to 2014
$598k
NCRR NIH HHS S10 RR022984NIA NIH HHS P01 AG003991NIA NIH HHS P01 AG026276NIA NIH HHS R01 AG052550NIA NIH HHS R01 AG054567NIA NIH HHS U19 AG032438NIA NIH HHS UF1 AG032438NIH HHS S10 OD018091NINDS NIH HHS P30 NS098577NINDS NIH HHS R25 NS090978
6 · The paper itself

Abstract

objectiveTo enable use of clinical magnetic resonance images (MRIs) to quantify abnormalities in normal appearing (NA) white matter (WM) and gray matter (GM) in multiple sclerosis (MS) and to determine associations with MS-related disability. Identification of these abnormalities heretofore has required specialized scans not routinely available in clinical practice.

methodsWe developed an analytic technique which normalizes image intensities based on an intensity atlas for quantification of WM and GM abnormalities in standardized MRIs obtained with clinical sequences. Gaussian mixture modeling is applied to summarize image intensity distributions from T1-weighted and 3D-FLAIR (T2-weighted) images from 5010 participants enrolled in a multinational database of MS patients which collected imaging, neuroperformance and disability measures.

resultsIntensity distribution metrics distinguished MS patients from control participants based on normalized non-lesional signal differences. This analysis revealed non-lesional differences between relapsing MS versus progressive MS subtypes. Further, the correlation between our non-lesional measures and disability was approximately three times greater than that between total lesion volume and disability, measured using the patient derived disease steps. Multivariate modeling revealed that measures of extra-lesional tissue integrity and atrophy contribute uniquely, and approximately equally, to the prediction of MS-related disability.

interpretationThese results support the notion that non-lesional abnormalities correlate more strongly with MS-related disability than lesion burden and provide new insight into the basis of abnormalities in NA WM. Non-lesional abnormalities distinguish relapsing from progressive MS but do not distinguish between progressive subtypes suggesting a common progressive pathophysiology. Image intensity parameters and existing biomarkers each independently correlate with MS-related disability.

Indexed as

AdultBiomarkersFemaleGray MatterHumansMagnetic Resonance ImagingMaleMiddle AgedMultiple SclerosisSeverity of Illness IndexWhite MatterBiomarkers

Identifiers

PMID33943045
PMCPMC8108425
OpenAlexW3157673618

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.