European Radiology

, Volume 26, Issue 8, pp 2578–2586 | Cite as

Changes and variability of proton density and T1 relaxation times in early multiple sclerosis: MRI markers of neuronal damage in the cerebral cortex

  • René-Maxime Gracien
  • Sarah C. Reitz
  • Stephanie Michelle Hof
  • Vinzenz Fleischer
  • Hilga Zimmermann
  • Amgad Droby
  • Helmuth Steinmetz
  • Frauke Zipp
  • Ralf Deichmann
  • Johannes C. Klein



Proton density (PD) and T1 relaxation time are promising quantitative MRI (qMRI) markers of neuronal damage in multiple sclerosis (MS). However, it is unknown whether cortical differences of these parameters between patients and controls exist in the early stages of disease. This study investigates cortical T1 and PD in early MS stages, hypothesizing that these are altered and display a high spatial variability.


Quantitative T1 and PD mapping was performed on 11 patients with clinically isolated syndrome (CIS)/early MS in remission and 11 healthy controls. The normal appearing cortical gray matter was extracted, lobar regions were identified, and mean values and standard deviations of both parameters were calculated within each region.


Increased PD was detected in MS/CIS patients in the cerebral cortex as a whole and all subregions, indicating an increase of water content. Increase of PD variability reached significance in the whole cortex and in the frontal and parietal regions. Longer T1 relaxation times and increased variability were found in the cerebral cortex in all regions studied, indicating a change of microstructural tissue composition that is spatially heterogeneous.


The data show spatially heterogeneous cortical involvement in early MS is reflected in T1 and PD qMRI.

Key Points

Cortical involvement in early MS is reflected in T1/PD quantitative MRI.

The changes are spatially heterogeneous.

Cortical damage goes beyond increased water content.


Multiple sclerosis Gray matter Diagnostic imaging Magnetic resonance imaging Demyelinating diseases 



Brain extraction tool


Band width


Clinically isolated syndrome


Cerebrospinal fluid


Expanded Disability Status Scale


Echo planar imaging


FMRIB automated segmentation tool


FMRIB’s integrated registration and segmentation tool


Fluid attenuated inversion recovery


Fast low angle shot




Gradient echo


FMRIB Software Library


Gray matter


Healthy controls


Montreal Neurological Institute


Magnetization prepared rapid acquisition of gradient echoes


Magnetic resonance imaging


Proton density


Percent units


Partial volume estimate


Quantitative magnetic resonance imaging


Region of interest


Relapsing-remitting Multiple Sclerosis




Echo time


Inversion time


Repetition time


Variable flip angle


White matter



The scientific guarantor of this publication is Johannes C Klein.

The authors of this manuscript declare no relationships with any companies relevant to this study:

Dr. RM Gracien went to a MS related training to London in 2013 sponsored by Roche.

Dr. H Steinmetz has received speaker’s honoraria from Bayer, Sanofi and Boehringer Ingelheim.

Dr. F Zipp has received research grants from Teva, Merck Serono, Novartis and Bayer as well as consultation fees from Teva, Merck Serono, Novartis, Bayer Healthcare, Biogen Idec Germany, ONO, Genzyme, Sanofi-Aventis and Octapharma. She has received travel compensation from the aforementioned companies.

Dr. JC Klein received speaker honoraria and travel reimbursement from Medtronic, AstraZeneca, Abbott Laboratories and AbbVie.

This study has received funding by the Bundesministerium für Bildung und Forschung [DLR 01GO0203; Brain Imaging Center Frankfurt] and the Deutsche Forschungsgemeinschaft [DFG CRC-TR 128; Drs Zipp and Deichmann].

One of the authors has significant statistical expertise.

This study was approved by the ethics committee of the State Medical Association of Rhineland-Palatine. Written informed consent was obtained from all healthy controls and patients in this study. Methodology: prospective, multicentre, observational study

Supplementary material

330_2015_4072_Fig5_ESM.jpg (2.5 mb)
Supplementary Figure 1

Data sets for a representative patient in the MNI 152 standard space (x = 5.00, y = 0.00, z = 15.00). Top: Acquired anatomical MP-RAGE data set. Middle: Calculated quantitative T1 map (T1 is given in ms). Bottom: Calculated quantitative PD map (PD is given in percent units, pu). (JPEG 2598 kb)


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Copyright information

© European Society of Radiology 2015

Authors and Affiliations

  • René-Maxime Gracien
    • 1
    • 2
  • Sarah C. Reitz
    • 1
    • 2
  • Stephanie Michelle Hof
    • 1
    • 2
  • Vinzenz Fleischer
    • 3
    • 4
  • Hilga Zimmermann
    • 3
    • 4
  • Amgad Droby
    • 4
  • Helmuth Steinmetz
    • 1
  • Frauke Zipp
    • 3
    • 4
  • Ralf Deichmann
    • 2
  • Johannes C. Klein
    • 1
    • 2
  1. 1.Department of NeurologyUniversity Hospital, Goethe UniversityFrankfurt/MainGermany
  2. 2.Brain Imaging CenterUniversity Hospital, Goethe UniversityFrankfurt/MainGermany
  3. 3.Department of NeurologyUniversity Hospital, Gutenberg UniversityMainzGermany
  4. 4.Neuroimaging Center (NIC) of the Focus Program Translational Neuroscience (FTN)University Hospital, Gutenberg UniversityMainzGermany

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