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Updated: Apr 18, 2026
Positron Emission Tomography Imaging for In Vivo Measuring of Myelin Content in the Lysolecithin Rat Model of Multiple Sclerosis
Published on: February 28, 2021
Increased PET 11C-PBR28 binding in multiple sclerosis normal-appearing white matter correlates with MRI measures of
Irene M Vavasour1, Nasim Vafai2, Philippe Beauchemin3
1Radiology, University of British Columbia, Vancouver, Canada; International Collaboration on Repair Discoveries (ICORD), University of British Columbia, Vancouver, Canada.
Introduction:
The Positron Emission Tomography (PET) tracer 11C-PBR28 binds to the Translocator Protein (TSPO), a marker of activated microglia. Advanced Magnetic Resonance (MR) techniques are sensitive to different tissue properties such as myelin (myelin water fraction, MWF; magnetisation transfer ratio, MTR; radial diffusivity, RD; choline, tCho), axons (axial diffusivity, AD; n-acetylaspartate, tNAA) and gliosis (myo-inositol, mI).
Objective:
To compare 11C-PBR28 binding across MS subtypes and investigate the correlation between 11C-PBR28 binding and advanced MR measures in normal-appearing white matter (NAWM) and lesions.
Methods:
Twelve people living with MS (7 relapsing-remitting MS (RRMS) and 5 progressive MS (PMS)) and 6 healthy controls (HC) were scanned with PET and MRI. A 70-minute 11C-PBR28 PET session was used to determine the non-displaceable binding potential (BPND). Advanced 3T MR included myelin water imaging, diffusion tensor imaging and spectroscopy. Mean measurements were extracted from lesion and NAWM masks.
Results:
Within NAWM, 11C-PBR28 binding was different between groups (BPND HC=0.70, RRMS=0.72, PMS=0.79; p = 0.03) and lesions exhibited lower BPND (NAWM=0.75, lesion=0.63; p = 0.0002). Lesions also had lower MWF (NAWM=0.13, lesion=0.08) and MTR (NAWM=41.5, lesion=33.5), and higher AD (NAWM=1.05, lesion=1.41) and RD (NAWM=0.50, lesion=0.83) than NAWM (all p < 0.0001). In NAWM, correlations were found between PBR-BPND and MWF (R=-0.71, p = 0.001) and MTR (R=-0.68, p = 0.003).
Conclusions:
Increased inflammation and gliosis indicated by elevated 11C-PBR28 binding in NAWM are associated with demyelination (decreased MWF and MTR), especially in PMS. The ability to measure and monitor diffuse inflammation could help evaluate therapies designed to target whole brain immune activity and more specifically microglia.
Insights
Positron Emission Tomography (PET) tracer 11C-PBR28 shows increased binding in normal-appearing white matter (NAWM) in progressive MS (PMS). This inflammation correlates with demyelination, suggesting PET can monitor diffuse brain immune activity.
Area of Science:
- Neuroimaging
- Neuroinflammation
- Multiple Sclerosis (MS) research
Background:
- 11C-PBR28 PET tracer targets Translocator Protein (TSPO), a marker for activated microglia.
- Advanced Magnetic Resonance (MR) techniques assess tissue properties like myelin, axons, and gliosis.
Purpose of the Study:
- Compare 11C-PBR28 binding across MS subtypes.
- Correlate 11C-PBR28 binding with advanced MR measures in normal-appearing white matter (NAWM) and lesions.
Main Methods:
- 12 MS patients (RRMS, PMS) and 6 healthy controls (HC) underwent PET and 3T MRI scans.
- 11C-PBR28 PET measured non-displaceable binding potential (BPND).
- Advanced MR included myelin water imaging, diffusion tensor imaging, and spectroscopy.
Main Results:
- 11C-PBR28 binding (BPND) was higher in PMS NAWM than HC and RRMS (p=0.03).
- Lesions showed lower BPND, myelin water fraction (MWF), and magnetisation transfer ratio (MTR), with higher axial and radial diffusivity (AD, RD) than NAWM (all p<0.0001).
- NAWM 11C-PBR28 BPND correlated with decreased MWF (R=-0.71) and MTR (R=-0.68) (p<0.003).
Conclusions:
- Elevated 11C-PBR28 binding in NAWM indicates inflammation and gliosis, particularly in PMS.
- This inflammation is linked to demyelination (reduced MWF/MTR), especially in progressive MS.
- 11C-PBR28 PET may help evaluate therapies targeting whole-brain immune activity and microglia.
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