Changes in synaptic density in the subacute phase after ischemic stroke: A¹¹C-UCB-J PET/MR study

Abstract

Functional alterations after ischemic stroke have been described with Magnetic Resonance Imaging (MRI) and perfusion Positron Emission Tomography (PET), but no data on in vivo synaptic changes exist. Recently, imaging of synaptic density became available by targeting synaptic vesicle protein 2 A, a protein ubiquitously expressed in all presynaptic nerve terminals. We hypothesized that in subacute ischemic stroke loss of synaptic density can be evaluated with 11C-UCB-J PET in the ischemic tissue and that alterations in synaptic density can be present in brain regions beyond the ischemic core. We recruited ischemic stroke patients to undergo 11C-UCB-J PET/MR imaging 21 ± 8 days after stroke onset to investigate regional 11C-UCB-J SUVR (standardized uptake value ratio). There was a decrease (but residual signal) of 11C-UCB-J SUVR within the lesion of 16 stroke patients compared to 40 healthy controls (ratiolesion/controls = 0.67 ± 0.28, p = 0.00023). Moreover, 11C-UCB-J SUVR was lower in the non-lesioned tissue of the affected hemisphere compared to the unaffected hemisphere (ΔSUVR = −0.17, p = 0.0035). The contralesional cerebellar hemisphere showed a lower 11C-UCB-J SUVR compared to the ipsilesional cerebellar hemisphere (ΔSUVR = −0.14, p = 0.0048). In 8 out of 16 patients, the asymmetry index suggested crossed cerebellar diaschisis. Future research is required to longitudinally study these changes in synaptic density and their association with outcome.

Impact of meningeal uptake and partial volume correction techniques on [18F]MK-6240 binding in aMCI patients and healthy controls

“…Detailed demographics for the aMCI patients can be found in 1 and for the HC. 24 The study was conducted at the University Hospital Leuven, Belgium, approved by the local Ethics Committee (University Hospitals Leuven/KU Leuven) and each subject signed a written informed consent before enrollment. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.…”

Synaptic Vesicle Glycoprotein 2A: Features and Functions

“…SV2A PET was used to evaluate changes of synaptic density in damaged brain tissue after ischemic stroke, resulting in a decrease of SV2A density in the lesioned area compared to healthy controls and in a lower [ 11 C]UCB-J signal in the non-lesioned regions of the affected hemisphere compared to the unaffected one ( Michiels et al, 2021b ).…”

In Vivo Detection of Neurofibrillary Tangles by 18 F-MK-6240 PET/MR in Patients With Ischemic Stroke

“…The results of synaptic vesicle protein 2A PET in the subacute phase after ischemic stroke of this study population have been published previously. 16…”