Functional MRI using intravascular contrast agents: detrending of the relative cerebrovascular (rCBV) time course

Adam J Schwarz1, Torsten Reese, Alessandro Gozzi

  • 1Department of Neuroimaging, Centre of Excellence for Drug Discovery (Psychiatry), GlaxoSmithKline Medicines Research Centre, Verona, Italy. adam.j.schwarz@gsk.com

Insights

Accurate interpretation of animal fMRI requires detrending to correct for contrast agent washout. A constrained mono-exponential washout model fit provides a robust and efficient method for this analysis.

Area of Science:

  • Neuroimaging
  • Pharmacology
  • Biophysics

Background:

  • Pharmacological fMRI in animal models uses blood pool contrast agents to measure cerebral blood volume changes.
  • Background signal drift from contrast agent washout can confound interpretation of neural activation signals.
  • Time-course detrending is crucial for accurate analysis when signal drift is significant.

Purpose of the Study:

  • To evaluate detrending methods for estimating background signal drift caused by contrast agent washout in animal fMRI.
  • To identify a robust approach for correcting signal drift in pharmacological fMRI experiments.

Main Methods:

  • Comparison of different detrending approaches, including constant background approximation, unconstrained fits, and a constrained fit of a mono-exponential washout model.
  • Application of methods to fMRI studies in rats investigating responses to rapid pharmacological challenges (cocaine, amphetamine).

Main Results:

  • A constrained fit of a mono-exponential washout model demonstrated higher accuracy than constant background approximation and unconstrained fits.
  • The constrained fitting approach enabled accurate estimation of contrast agent washout.
  • Shorter baseline periods were required with the constrained fitting method compared to unconstrained extrapolation.

Conclusions:

  • Constrained mono-exponential washout model fitting is a robust and accurate detrending method for pharmacological fMRI in rats.
  • This approach improves the interpretation of functional responses to rapid pharmacological challenges.
  • The method reduces overall experiment duration by allowing shorter baseline recordings.