Quantitative cerebrovascular reactivity MRI in mice using acetazolamide challenge

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To develop a quantitative MRI method to estimate cerebrovascular reactivity (CVR) in mice. Methods: We described an MRI procedure to measure cerebral vasodilatory response to acetazolamide (ACZ), a vasoactive agent previously used in human clinical imaging. Vascular response was determined by cerebral blood flow (CBF) measured with phase-contrast or pseudo-continuous arterial spin labeling MRI. Vasodilatory input intensity was determined by plasma ACZ level using high-performance liquid chromatography. We verified the source of the CVR MRI signal by comparing ACZ injection to phosphate-buffered saline injection and noninjection experiments. Dose dependence and feasibility of regional CVR measurement were also investigated. Results: Cerebral blood flow revealed an exponential increase following intravenous ACZ injection, with a time constant of 1.62 min. In contrast, phosphate-buffered saline or noninjection exhibited a slow linear CBF increase, consistent with a gradual accumulation of anesthetic agent, isoflurane, used in this study. When comparing different ACZ doses, injections of 30, 60, 120, and 180 mg/kg yielded a linear increase in plasma ACZ concentration (p < 0.0001). On the other hand, CBF changes under these doses were not different from each other (p = 0.50). The pseudo-continuous arterial spin labeling MRI with multiple postlabeling delays revealed similar vascular responses at different postlabeling delay values. There was a regional difference in CVR (p = 0.005), with isocortex (0.81 ± 0.17%/[μg/ml]) showing higher CVR than deep-brain regions. Mice receiving multiple ACZ injections lived for a minimum of 6 months after the study without noticeable aberrant behavior or appearance. Conclusions: We demonstrated the proof-of-principle of a new quantitative CVR mapping technique in mice.

Original languageEnglish (US)
Pages (from-to)2233-2241
Number of pages9
JournalMagnetic resonance in medicine
Volume88
Issue number5
DOIs
StatePublished - Nov 2022

Keywords

  • acetazolamide
  • arterial spin labeling
  • cerebral blood flow
  • cerebrovascular reactivity
  • mouse
  • phase contrast

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint

Dive into the research topics of 'Quantitative cerebrovascular reactivity MRI in mice using acetazolamide challenge'. Together they form a unique fingerprint.

Cite this