Changes in synaptic density in the subacute phase after ischemic stroke: A ¹¹C-UCB-J PET/MR study

Area of Science:

• Neuroscience
• Radiology
• Neurology

Background:

• Functional brain alterations post-ischemic stroke are established via MRI and PET.
• Previous research lacked in vivo data on synaptic changes after stroke.
• Synaptic vesicle protein 2A (SV2A) imaging offers a novel method to assess presynaptic nerve terminal density.

Purpose of the Study:

• To investigate synaptic density changes in subacute ischemic stroke using 11C-UCB-J PET.
• To evaluate if synaptic loss is confined to the ischemic core or extends to other brain regions.
• To explore the potential of 11C-UCB-J PET for assessing synaptic alterations in stroke patients.

Main Methods:

• 16 ischemic stroke patients underwent 11C-UCB-J PET/MR imaging 21±8 days post-stroke.
• Regional 11C-UCB-J standardized uptake value ratio (SUVR) was measured.
• Comparisons were made between lesioned and non-lesioned tissues, affected and unaffected hemispheres, and cerebellar hemispheres, as well as against 40 healthy controls.

Main Results:

• A significant decrease in 11C-UCB-J SUVR was observed in the ischemic lesion compared to controls (ratio=0.67±0.28, p=0.00023).
• Reduced 11C-UCB-J SUVR was found in the affected hemisphere's non-lesioned tissue compared to the unaffected hemisphere (ΔSUVR=-0.17, p=0.0035).
• The contralesional cerebellum showed lower 11C-UCB-J SUVR than the ipsilesional cerebellum (ΔSUVR=-0.14, p=0.0048), with 8 patients exhibiting crossed cerebellar diaschisis.

Conclusions:

• 11C-UCB-J PET can detect reduced synaptic density in the ischemic tissue of subacute stroke patients.
• Synaptic alterations extend beyond the ischemic core, affecting remote brain regions.
• These findings highlight the potential of SV2A PET imaging for evaluating synaptic changes and diaschisis after stroke.