Quantitative assessment of cerebral glucose metabolic rates after blood-brain barrier disruption induced by focused ultrasound using FDG-MicroPET

Feng Yi Yang*, Wen Yuan Chang, Jyh Cheng Chen, Lin Chien Lee, Yi Shun Hung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The goal of this study was to evaluate the pharmacokinetics of 18F-2-fluoro-2-deoxy-d-glucose (18F-FDG) and the expression of glucose transporter 1 (GLUT1) protein after blood-brain barrier (BBB) disruption of normal rat brains by focused ultrasound (FUS). After delivery of an intravenous bolus of ~37MBq (1mCi) 18F-FDG, dynamic positron emission tomography scans were performed on rats with normal brains and those whose BBBs had been disrupted by FUS. Arterial blood sampling was collected throughout the scanning procedure. A 2-tissue compartmental model was used to estimate 18F-FDG kinetic parameters in brain tissues. The rate constants Ki, K1, and k3 were assumed to characterize the uptake, transport, and hexokinase activity, respectively, of 18F-FDG. The uptake of 18F-FDG in brains significantly decreased immediately after the blood-brain barrier was disrupted. At the same time, the derived values of Ki, K1, and k3 for the sonicated brains were significantly lower than those for the control brains. In agreement with the reduction in glucose, Western blot analyses confirmed that focused ultrasound exposure significantly reduced the expression of GLUT1 protein in the brains. Furthermore, the effect of focused ultrasound on glucose uptake was transient and reversible 24h after sonication. Our results indicate that focused ultrasound may inhibit GLUT1 expression to decrease the glucose uptake in brain tissue during the period of BBB disruption.

Original languageEnglish
Pages (from-to)93-98
Number of pages6
JournalNeuroImage
Volume90
DOIs
StatePublished - 15 Apr 2014

Keywords

  • Blood-brain barrier disruption
  • F-FDG
  • Focused ultrasound
  • MicroPET
  • Pharmacokinetics

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