Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis

Abstract

PiB uptake in the cortex in late MS is not different from normal age-matched controls. PiB uptake in the WM in late MS may be a marker of the large network structures' integrity such as those involved in visuospatial performance.

A new frontier for amyloid PET imaging: multiple sclerosis

“…After computation of voxel-wise maps of the distribution of volume ratios reflecting myelin content, the authors calculated dynamic indices of global myelin content, demyelination and remyelination in each patient. A progressive reduction in 11 C-PiB binding from the NAWM to MS lesions, reflecting a decline in myelin content was demonstrated and dynamic remyelination was inversely correlated with clinical disability [23]. These findings support the role of AMY-PET with 11 C-PiB in the evaluation of remyelination potential at the single-subject level.…”

“…These studies demonstrated that AMY-PET detects decreased activity in black hole areas in T1weighted MR images and in WM lesions in T2-weighted MR images, suggesting that amyloid tracer uptake decreases with demyelination. 11 C-PiB has been shown to bind more strongly to NAWM than to perilesional tissue and lesions, in line with the relative loss of myelin in these regions [22][23][24]. Furthermore, longitudinal data support the hypothesized ability of 11 C-PiB to capture demyelination and remyelination in single lesions over time.…”

“…The hypothesis that AMY-PET tracers can bind to myelin was first investigated in vitro and ex vivo by means of 11 C-Pittsburgh compound-B ( 11 C-PiB) and autoradiography in human brain [22][23][24]. These studies demonstrated that AMY-PET detects decreased activity in black hole areas in T1weighted MR images and in WM lesions in T2-weighted MR images, suggesting that amyloid tracer uptake decreases with demyelination.…”

White Matter Reference Region in PET Studies of 11C-Pittsburgh Compound B Uptake: Effects of Age and Amyloid-β Deposition

“…Studies using MRI to measure white matter hyperintensity have proposed that cerebral small-vessel disease can lead to reduced Ab clearance and to increased cerebral GM 11 C-PiB in AD (33,34). However, white matter hyperintensity measurements in studies of WM 11 C-PiB uptake have found reduction in binding (35) and that WM lesions can reduce WM 11 C-PiB binding in cognitively impaired (36) as well as in multiple sclerosis patients (37).…”

Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers

“…For all indices high between-patient variability of myelin content change was highlighted during follow up and dynamic remyelination was demonstrated to inversely correlate with clinical disability scales. The association of cognitive function in late MS with cortical and WM PiB binding has also been assessed in another group of 24 MS patients identified within the population-based Mayo Clinic Study of Aging (Zeydan et al 2018). In that study Zeydan and colleagues found no difference in global cortical PiB standardized uptake value ratios between MS and controls.…”