Abstract

AimUnderstanding neuroinflammation after acute ischemic stroke is a crucial step on the way to an individualized post-stroke treatment. Microglia activation, an essential part of neuroinflammation, can be assessed using [18F]GE-180 18 kDa translocator protein positron emission tomography (TSPO-PET). However, the commonly used 60–90 min post-injection (p.i.) time window was not yet proven to be suitable for post-stroke neuroinflammation assessment. In this study, we compare semi-quantitative estimates derived from late time frames to quantitative estimates calculated using a full 0–90 min dynamic scan in a mouse photothrombotic stroke (PT) model.Materials and MethodsSix mice after PT and six sham mice were included in the study. For a half of the mice, we acquired four serial 0–90 min scans per mouse (analysis cohort) and calculated standardized uptake value ratios (SUVRs; cerebellar reference) for the PT volume of interest (VOI) in five late 10 min time frames as well as distribution volume ratios (DVRs) for the same VOI. We compared late static 10 min SUVRs and the 60–90 min time frame of the analysis cohort to the corresponding DVRs by linear fitting. The other half of the animals received a static 60–90 min scan and was used as a validation cohort. We extrapolated DVRs by using the static 60–90 min p.i. time window, which were compared to the DVRs of the analysis cohort.ResultsWe found high linear correlations between SUVRs and DVRs in the analysis cohort for all studied 10 min time frames, while the fits of the 60–70, 70–80, and 80–90 min p.i. time frames were the ones closest to the line of identity. For the 60–90 min time window, we observed an excellent linear correlation between SUVR and DVR regardless of the phenotype (PT vs. sham). The extrapolated DVRs of the validation cohort were not significantly different from the DVRs of the analysis group.ConclusionSimplified quantification by a reference tissue ratio of the late 60–90 min p.i. [18F]GE-180 PET image can replace full quantification of a dynamic scan for assessment of microglial activation in the mouse PT model.

Highlights

  • Stroke is the second leading cause of death worldwide and one of the leading causes of disability [1]

  • Even though the influence of the neuroinflammatory response to stroke outcome in humans is yet to be determined, individual measures of neuroinflammation can assist in patient selection for immune interventions

  • In an experimental stroke model, we investigated the relationship between the VT ratio (DVR) in the lesion area and the normal cortex tissue calculated from a long 0–90 min p.i. [18F]GE-180 PET scan by using Logan plot with an imagederived blood input function (IDIF) and the standardized uptake value ratio (SUVR) in the same regions estimated from one of the late 10 min time frames

Read more

Summary

Introduction

Stroke is the second leading cause of death worldwide and one of the leading causes of disability [1]. Treatment dedicated to improving post-stroke recovery remains unresolved. One of potential targets for such treatment is post-stroke neuroinflammation due to its long-lasting nature and the presence of multiple effectors that can be targeted [2, 3]. None of the so far conducted trials testing immunomodulatory therapies have been able to consistently demonstrate a beneficial function of such approaches on post-stroke recovery. There can be several possible reasons for these failures, one of which is the fact that previous studies did not take into account individual patients’ differences in the extent of the neuroinflammatory response. Even though the influence of the neuroinflammatory response to stroke outcome in humans is yet to be determined, individual measures of neuroinflammation can assist in patient selection for immune interventions

Objectives
Methods
Results
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call