Skip to main content

18F-florbetapir PET/MRI for quantitatively monitoring demyelination and remyelination in acute disseminated encephalomyelitis

Dear Editor,

Acute disseminated encephalomyelitis (ADEM) is one of the most important inflammatory demyelinating disorders of the central nervous system [1]. Magnetic resonance imaging (MRI) is essential for the diagnosis and follow-up of demyelinating disease. However, conventional MRI measurement cannot provide a direct quantitative assessment of demyelination and remyelination [2]. Advanced MRI techniques such as magnetization transfer imaging [3] or myelin water fraction [4] are increasingly popular as research tools but have not yet been standardized for widespread clinical application.

Positron emission tomography (PET) is a noninvasive technique for quantitative imaging of biochemical and physiological processes. Amyloid PET tracer 11C-PiB has been studied for the quantitative assessment of myelin content in preclinical [5, 6] and clinical studies [7,8,9,10]. However, the short half-life of carbon-11 limits the use of 11C-PiB in clinical practice. Therefore, some fluorine-18-labeled amyloid tracers including 18F-florbetaben [11, 12] and 18F-florbetapir [13] have been investigated as imaging marker for quantification of myelin loss in patients with multiple sclerosis (MS). Our recent study also showed that myelin histology correlated quantitatively with 18F-florbetapir binding in demyelinated lesions [14]. Nevertheless, the ability of fluorine-18-labeled amyloid tracers for assessing remyelination has not yet been demonstrated. In addition, as MRI is more sensitive than computed tomography (CT) in the detection of demyelinated lesion, a hybrid PET/MRI can obtain more reliable semi-quantitative measurements of tracer uptake than PET/CT. Consequently, we for the first time, to our knowledge, present a case of hybrid PET/MRI with 18F-florbetapir for quantitatively monitoring demyelination and remyelination in a 59-year-old female patient with ADEM.

The patient admitted to our hospital because of acute onset of confusion, impaired short-term memory, muscle weakness, and positive Babinski sign on the left side for 4 days. She has no similar attack in the past. She had upper respiratory infection history 1 week prior her symptoms started. Her mini-mental state examination (MMSE) score was 18, and expanded disability status scale (EDSS) score was 7. On admission, cerebral spinal fluid (CSF) examination indicated protein elevation and lymphocytic pleocytosis. Oligoclonal band was negative in CSF. Serum and CSF antibodies against aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) were all negative. T1-weighted MRI with gadolinium showed disseminated subcortical lesions with marginal mild enhancement and central “black hole” (Additional file 1), suggesting destruction of blood-brain barrier and axonal loss.

On pre-treatment PET/MRI, T2 FLAIR image demonstrated multifocal hyperintense lesions (Fig. 1a, c, e, white arrow) in damaged white matter (DWM). Registered to T2 FLAIR image, the volume of interest in the largest five DWM lesions was manually delineated on PET images, and the cerebellum was used as the reference region for the standardized uptake value relative ratios (SUVR) (Additional file 1). We found that the 18F-florbetapir binding (Fig. 1b, d, f) in DWM (mean SUVR = 0.74 ± 0.04) was significantly lower than that in normal-appearing white matter (NAWM) (mean SUVR = 0.97 ± 0.03) indicating a myelin loss in DWM.

Fig. 1

Demyelination and remyelination in five representative lesions on pre- and post-treatment 18F-florbetapir PET/MRI. af Pre-treatment PET/MRI showed multifocal hyperintense lesions (white arrow) with decreased 18F-florbetapir uptake (SUVR = 0.75, 0.75, 0.78, 0.67, and 0.77). gl Five months later, reduced hyperintense lesions with increased 18F-florbetapir uptake (SUVR = 0.85, 0.82, 0.80, 0.80 and 0.86) were observed on post-treatment PET/MRI

Based on her medical history, clinical manifestations and PET/MRI findings, the diagnosis of ADEM was made. The patient then received the course of intravenous immunoglobulin at 0.4 g/kg/day for 5 days and intravenous methylprednisolone 500 mg/day for 5 days followed by a tapering dose of prednisone. Five months later, she had normal muscle strength on the left side. Her MMSE score returned to 29, and EDSS score improved to 1. Repeated lumbar puncture showed normal cell count and protein level. Consistent with the improvements in clinical symptoms and scoring, post-treatment PET/MRI showed a reduction of the hyperintense lesions (Fig. 1g, i, k) and an increased but still lower than normal 18F-florbetapir uptake (Fig. 1h, j, l) in DWM (mean SUVR = 0.82 ± 0.03) reflecting an incomplete remyelination.

With this letter, we would like to suggest that 18F-florbetapir PET as an additional supplement to conventional MRI has good potential for quantitative assessment of the progression of demyelinating disease such as ADEM, MS, and neuromyelitis optica, and it may be considered in the future for evaluation of efficacy of new treatments which promote remyelination [15]. However, the sensitivity and specificity of 18F-florbetapir PET/MRI needs to be further evaluated in a larger group of patients.

Availability of data and materials

All data generated or analyzed during this study are included in this published article [and its supplementary information files].


  1. 1.

    Young NP, Weinshenker BG, Lucchinetti CF. Acute disseminated encephalomyelitis: current understanding and controversies. Semin Neurol. 2008;28(1):84–94.

    Article  PubMed  Google Scholar 

  2. 2.

    Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. The Lancet Neurol. 2018;17(2):162–73.

    Article  PubMed  Google Scholar 

  3. 3.

    McCreary CR, Bjarnason TA, Skihar V, Mitchell JR, Yong VW, Dunn JF. Multiexponential T2 and magnetization transfer MRI of demyelination and remyelination in murine spinal cord. NeuroImage. 2009;45(4):1173–82.

    Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Zhang J, Kolind SH, Laule C, MacKay AL. Comparison of myelin water fraction from multiecho T2 decay curve and steady-state methods. Magn Reson Med. 2015;73(1):223–32.

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Stankoff B, Freeman L, Aigrot MS, Chardain A, Dolle F, Williams A, et al. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-(1)(1)C]-2-(4′-methylaminophenyl)- 6-hydroxybenzothiazole. Ann Neurol. 2011;69(4):673–80.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Faria Dde P, Copray S, Sijbesma JW, Willemsen AT, Buchpiguel CA, Dierckx RA, et al. PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C] MeDAS, [11C] CIC and [11C]PIB. Eur J Nucl Med Mol Imaging. 2014;41(5):995–1003.

    Article  PubMed  Google Scholar 

  7. 7.

    Bodini B, Veronese M, Garcia-Lorenzo D, Battaglini M, Poirion E, Chardain A, et al. Dynamic imaging of individual remyelination profiles in multiple sclerosis. Ann Neurol. 2016;79(5):726–38.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Goodheart AE, Tamburo E, Minhas D, Aizenstein HJ, McDade E, Snitz BE, et al. Reduced binding of Pittsburgh Compound-B in areas of white matter hyperintensities. NeuroImage Clinical. 2015;9:479–83.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Zeydan B, Lowe VJ, Schwarz CG, Przybelski SA, Tosakulwong N, Zuk SM, et al. Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis. Mult Scler. 2018;24(6):739–49.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Glodzik L, Rusinek H, Li J, Zhou C, Tsui W, Mosconi L, et al. Reduced retention of Pittsburgh compound B in white matter lesions. Eur J Nucl Med Mol Imaging. 2015;42(1):97–102.

    Article  PubMed  Google Scholar 

  11. 11.

    Matias-Guiu JA, Cabrera-Martin MN, Matias-Guiu J, Oreja-Guevara C, Riola-Parada C, Moreno-Ramos T, et al. Amyloid PET imaging in multiple sclerosis: an (18)F-florbetaben study. BMC Neurol. 2015;15:243.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Matias-Guiu JA, Cabrera-Martin MN, Cortes-Martinez A, Pytel V, Moreno-Ramos T, Oreja-Guevara C, et al. Amyloid PET in pseudotumoral multiple sclerosis. Mult Scler Relat Disord. 2017;15:15–7.

    Article  PubMed  Google Scholar 

  13. 13.

    Pietroboni AM, Carandini T, Colombi A, Mercurio M, Ghezzi L, Giulietti G, et al. Amyloid PET as a marker of normal-appearing white matter early damage in multiple sclerosis: correlation with CSF beta-amyloid levels and brain volumes. Eur J Nucl Med Mol Imaging. 2019;46(2):280–7.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Zhang M, Hugon G, Bouillot C, Bolbos R, Langlois JB, Billard T, et al. Evaluation of myelin radiotracers in the lysolecithin rat model of focal demyelination: beware of pitfalls! Contrast Media Mol Imaging. 2019;2019:9294586.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Plemel JR, Liu WQ, Yong VW. Remyelination therapies: a new direction and challenge in multiple sclerosis. Nat Rev Drug Discov. 2017;16(9):617–34.

    CAS  Article  PubMed  Google Scholar 

Download references


We thank Prof. Kung Hank F from University of Pennsylvania, Philadelphia, USA, and Prof. Lin Zhu from Beijing Normal University, Beijing, China, for kindly supplying the florbetapir probe precursor for us and synthesis technical support.


This work was supported by NSFC (81671241), Shanghai Shuguang Program (18SG15), and Shanghai Pujiang Program (18PJD030).

Author information




SC, JL, and BL designed the study. MZ performed the image analysis. MZ and SC wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sheng Chen.

Ethics declarations

Ethics approval and consent to participate

All procedures performed in this study were approved by the Ethics Committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine.

Consent for publication

Consent for publication has been obtained from the patient.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Additional file 1:

Figure S1. T1 weighted MR with gadolinium in the patient with ADEM before treatment. It showed disseminated subcortical lesions (white arrow) with marginal mild enhancement and central “black hole”, suggesting destruction of blood-brain barrier and axonal loss. Table S1. SUVR of the VOIs in the representative DWMs, NAWMs and right cerebellum. Figure S2. Change of SUVR in the five DWM lesions between pre-treatment and post-treatment.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, M., Liu, J., Li, B. et al. 18F-florbetapir PET/MRI for quantitatively monitoring demyelination and remyelination in acute disseminated encephalomyelitis. EJNMMI Res 9, 96 (2019).

Download citation