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Abstract

Objective:

We investigated the evolution of new multiple sclerosis (MS) lesions over time using frequency shifts of the magnetic resonance (MR) signal.

Methods:

Twenty patients with relapsing-remitting MS were serially scanned for 6 months at 1-month intervals. Maps of MR frequency shifts were acquired using susceptibility-weighted imaging. New lesions were identified by enhancement with gadolinium (Gd).

Results:

Forty new lesions were identified as areas of signal increase on Gd-enhanced scans. Up to 3 months before lesion appearance, the frequency in areas of future Gd enhancement was not detectably different from the frequency in normal-appearing white matter. Rapid increase in MR frequency was observed between 1 month before and 1 month after Gd enhancement. Two months postenhancement and later, the frequency stabilized and remained at a constantly increased level.

Conclusions:

These findings suggest that an increase in MR frequency does not simply reflect blood-brain barrier disruption or edema; rather, it reflects a change of tissue architecture as a consequence of new lesion formation. The data demonstrate that the MR frequency of focal MS lesions is increased before the lesions appear on conventional MRI. Unlike many other advanced imaging techniques, the images for frequency mapping can be rapidly acquired at high spatial resolution and standardized on most clinical scanners.

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Information & Authors

Information

Published In

Neurology®
Volume 81Number 3July 16, 2013
Pages: 211-218
PubMed: 23761621

Publication History

Received: August 9, 2012
Accepted: April 4, 2013
Published online: June 12, 2013
Published in print: July 16, 2013

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Disclosure

V. Wiggermann, E. Hernández Torres, I.M. Vavasour, G.R.W. Moore, C. Laule, A.L. MacKay, and D.K.B. Li report no disclosures. A. Traboulsee has received grant support from Roche Pharmaceuticals, Bayer Pharmaceuticals, and honoraria from Teva Innovation, Biogen Idec, EMD Serono, Sanofi-Genzyme, Chugai, and Roche Pharmaceuticals. A. Rauscher reports no disclosures. Go to Neurology.org for full disclosures.

Study Funding

This work was supported by the Multiple Sclerosis Society of Canada, the Natural Sciences and Engineering Research Council of Canada (402039-2011), the Deutscher Akademischer Austauschdienst (CA-EN-1265), and the CIHR New Investigator Award Program (261306). A.R. is recipient of a Canadian Institutes of Health Research New Investigator award. C.L. is the recipient of the Women Against MS End MS Research and Training Network Transitional Career Development Award from the MS Society of Canada. G.R.W.M. is supported by the Multiple Sclerosis Society of Canada. We acknowledge the continued research support at our site by Philips Healthcare.

Authors

Affiliations & Disclosures

Vanessa Wiggermann
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Enedino Hernández Torres, PhD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Irene M. Vavasour, PhD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) F. Hoffmann-la Roche Ltd. (2) TEVA Neuroscience
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Multiple Sclerosis Society of Canada
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
G.R. Wayne Moore, MD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
Member of the Medical Advisory Committee of the Multiple Sclerosis Society of Canada
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Teva: Honorarium for speaking at a neurology practicum in 2012.
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Schering.
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Berlex: Grant-in-aid of research.
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Multiple Sclerosis Society of Canada
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Cornelia Laule, PhD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
MS Society of Canada
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alex L. MacKay, DPhil
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Cornell University, $1000 honorarium plus travel, Jan 2011 Washington University, $1000 honorarium plus travel, Nov 2011
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
University of British Columbia, Professor
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Genzyme Corp, Advanced MRI measures of repair in Alemtuzimab treated patients, $35,000/yr, 2010-2014 Teva Innovation, Remyelination in multiple sclerosis, $46,000/yr, 2010-2014
Research Support, Government Entities:
1.
NSERC, Proton Magnetic Resonance of Biological Systems, $60,000/yr, 2010-2015 MS Society of Canada, Anatomical and functional MRI correlates of cognitive dysfunction in multiple sclerosis, $92,000/yr, 2010-2014
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
David K.B. Li, MD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
Served on the Scientific Advisory Board Hoffmann-La Roche, Nuron Biotherapeutics and Data Safety Monitoring Board for Opexa Therapeutics
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
Consortium of MS Centers
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Consultant to Genzyme
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
I am the Director of the UBC MS/MRI Research Group which has been contracted to perform central analysis of MRI scans for therapeutic trials with Angiotech, Bayer, Berlex-Schering, Bio-MS, Centocor, Daiichi Sankyo, Hoffmann-LaRoche, Merck-Serono, Schering-Plough, Teva Neurosciences, Sanofi-Aventis, Transition Therapeutics.
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Grant support from MS Society of Canada, Canadian Institute of Health Research
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Anthony Traboulsee, MD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
1. Roche Clinical Trial Steering Committee (2010 ongoing) 2. Merck Serono Data Safety Monitoring Board (2009 ongoing) 3. Neuron Data Safety Monitoring Board (2013 ongoing) 4. MS Society of Canada Minocycline in CIS Clinical Trial Steering Committee (2009 ongoing)
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
1. Teva Neuroscience 2. Biogen 3. EMD Serono 4. Sanofi Genzyme 5. Novartis
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Chugai Pharmaceuticals
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
1. Sanofi Genzyme 2. Roche 3. Bayer 4. Biogen
Research Support, Government Entities:
1.
1. Canadian Institute for Health Research (PI)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1. MS Society of Canada 2. Lotte Hecht Foundation 3. Vancouver General and UBC Hospital Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Alexander Rauscher, PhD
From the UBC MRI Research Centre (V.W., E.H.T., A.L.M., A.R.), Department of Radiology (V.W., E.H.T., I.M.V., C.L., A.L.M., D.K.B.L., A.R.), Department of Pathology & Laboratory Medicine (G.R.W.M., C.L.), International Collaboration for Repair Discoveries (G.R.W.M.), Department of Physics and Astronomy (A.L.M.), Brain Research Centre (A.L.M., D.K.B.L., A.T., A.R.), and Department of Medicine, Division of Neurology (A.T.), University of British Columbia, Vancouver, Canada.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1. Canadian Institutes of Health Research (201109MSH-261306-183304) 2. National Sciences and Engineering Research Council (402039-2011)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence to Dr. Rauscher: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Vanessa Wiggermann: data analysis, interpretation of results, statistical analysis, manuscript writing. Enedino Hernández Torres: data processing, data analysis, manuscript editing. Irene Vavasour: study design, data acquisition, revising manuscript. G.R. Wayne Moore: revising manuscript. Cornelia Laule: study coordination, study design, manuscript editing. Alex MacKay: involved in obtaining funding for project, study design, reviewing the manuscript. David Li: study design, interpretation of results, drafting/revising of manuscript. Anthony Traboulsee: recruitment of subjects, review and interpretation of results, development/revising of manuscript. Alexander Rauscher: concept, study design, design of data acquisition and data analysis, supervision of data analysis, interpretation of results, development and writing of manuscript.

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