18F-florbetapir PET/MRI for quantitatively monitoring myelin loss and recovery in patients with multiple sclerosis: A longitudinal study

Abstract

Background Amyloid positron emission tomography (PET) can measure in-vivo demyelination in patients with multiple sclerosis (MS). However, the value of 18 F-labeled amyloid PET tracer, 18 F-florbetapir in the longitudinal study for monitoring myelin loss and recovery has not been confirmed. Methods From March 2019 to September 2020, twenty-three patients with MS and nine healthy controls (HCs) underwent a hybrid PET/MRI at baseline and expanded disability status scale (EDSS) assessment, and eight of 23 patients further underwent follow-up PET/MRI. The distribution volume ratio (DVR) and standard uptake value ratio (SUVR) of 18 F-florbetapir in damaged white matter (DWM) and normal-appearance white matter (NAWM) were obtained from dynamic and static PET acquisition. Diffusion tensor imaging-derived parameters were also calculated. Data were expressed as mean ± standard deviation with 99% confidence interval (99%CI). Finding The mean DVR (1.08 ± 0.12, 99%CI [1.02 ~ 1.14]) but not the mean SUVR of DWM lesions was lower than that of NAWM in patients with MS (1.25 ± 0.10, 99%CI [1.20 ~ 1.31]) and HCs (1.29 ± 0.08, 99%CI [1.23 ~ 1.36]). A trend toward lower mean fractional anisotropy (374.95 ± 45.30 vs. 419.07 ± 4.83) and higher mean radial diffusivity (0.45 ± 0.05 vs. 0.40 ± 0.01) of NAWM in patients with MS than those in HCs was found. DVR decreased in DWM lesions with higher MD (rho = -0.261, 99%CI [-0.362 ~ -0.144]), higher AD (rho = -0.200, 99%CI [-0.318 ~ -0.070]) and higher RD (rho = -0.198, 99%CI [-0.313 ~ -0.075]). Patients’ EDSS scores were reduced ( B = 0.04, 99%CI [-0.005 ~ 0.084]) with decreased index of global demyelination in the longitudinal study. Interpretation Our exploratory study suggests that dynamic 18 F-florbetapir PET/MRI may be a very promising tool for quantitatively monitoring myelin loss and recovery in patients with MS. Funding Shanghai Pujiang Program, Shanghai Municipal Key Clinical Specialty, Shanghai Shuguang Plan Project, Shanghai Health and Family Planning Commission Research Project, Clinical Research Plan of SHDC, French-Chinese program "Xu Guangqi".

Characteristics of cerebral blood flow in an Eastern sample of multiple sclerosis patients: A potential quantitative imaging marker associated with disease severity

“…Our previous study demonstrated that dynamic 18 F-florberapir PET is a promising tool for quantitatively monitoring myelin loss and recovery and correlates closely with changes in EDSS (14,26). DTI can be used to assess CNS tissue integrity and provide information on microstructure changes of DWM and NAWM in MS patients (14). Previous studies have shown that brain perfusion changes MS patients with different CBF values showed different clinical severity.…”

“…Furthermore, some quantitative imaging techniques are more sensitive to subtle alterations within or outside lesions compared with conventional MRI. Our previous study demonstrated that dynamic 18 F-florberapir PET is a promising tool for quantitatively monitoring myelin loss and recovery and correlates closely with changes in EDSS (14,26). DTI can be used to assess CNS tissue integrity and provide information on microstructure changes of DWM and NAWM in MS patients (14).…”

The Role of Molecular Imaging as a Marker of Remyelination and Repair in Multiple Sclerosis

“…This has marked them as strong candidates with the potential to serve as real-world clinical surrogates for myelin assessment [ 32 ]. Several studies have demonstrated F-florbetapir’s ability to assess demyelination in MS patients [ 24 , 32 , 33 , 34 ]. Recently, Zhang et al carried out the first longitudinal study examining F-florbetapir’s ability to monitor myelination status in MS, and showed promising results.…”

“…F-florbetapir is less affected by lesion size and successfully differentiates between demyelination and inflammatory edema, usually indistinguishable on MRI. Moreover, the Expanded Disability Status Scale (EDSS) measuring MS-related disability and myelin changes was correlated with F-florbetapir but not with PiB [ 33 ]. This marks F-florbetapir as a promising tool for the future monitoring of the myelin status in MS patients [ 35 ].…”

Comparison of 11C-Pittsburgh Compound B and 18F-Flutemetamol White Matter Binding in PET

“…Although advanced MRI techniques such as diffusion tensor imaging are widely used in evaluating white matter (WM) integrity, they are not specific measures of myelin. Over the last decade, PET ligands have been utilized to study myelin kinetics (1- 10,12). PET ligands are also being used to understand the underlying mechanisms such as neuroinflammation, neurodegeneration, microglia activation and myelin kinetics (12,13).…”