Development and Validation of Cerebrovascular Reactivity Measurements

Cerebrovascular reactivity (CVR) refers to the responsiveness of cerebral vasculature to vasoactive stimuli. Specifically, CVR reflects the ability of cerebral vessels to dilate or constrict in response to challenges or maneuvers and is therefore an indicator of cerebrovascular reserve. This physiological parameter is thought to be an important index of the brain's vascular health, and provides vascular reserve information that is complementary to steady-state vascular parameters, such as cerebral blood flow (CBF) and cerebral blood volume (CBV). Increased CO2 (hypercapnia) and pH have direct and indirect effects on vascular smooth muscle cells (SMC) causing relaxation and subsequent vasodialation.

In the context of stroke, the ability to maintain CBF to hypoperfused tissue will determine the final infarct volume and subsequent clinical symptoms. CVR can be assessed using vasodilatory techniques and magnetic resonance imaging (MRI). CVR mapping requires a physiological challenge while monitoring the corresponding hemodynamic changes in the brain. We propose to develop and validate a non-invasive and clinically-applicable method to reliably measure tissue perfusion termed arterial spin labeling (ASL) to evaluate hemodynamic reserve.  We will evaluate existing methods of presentation the vasoactive stimuli including CO2 inhalation and breath hold. We hypothesize that the developed method will serve as a reliable prognostic marker of ischemic risk an provide complementary information to existing clinical neuroimaging methods for assessing acute stroke patients. We will approach our goal of developing and validating a measure of CVR with the following aims:

Specific Aim 1: Characterize the advantages and disadvantages of current vasoactive stimuli methods for inducing hypercapnia and causing vasodialation. CVR will be measured using pseudo-continuous ASL (pCASL) MRI at 3.0 T in healthy adults to:

1. Develop protocols for using pCASL MRI data acquisition to measure increasing arterial partial pressure of CO2 (pCO2) using both sequential gas delivery CO2 and breath hold
2. Determine sources of variation on the measured MRI signal for both techniques of inducing hypercapnia (sequential gas delivery CO2 & breath hold)

Specific Aim 2: Validate the established protocols against the gold standard method for CVR measurement and establish their repeatability.

1. Healthy subjects will be scanned using the developed MRI pCASL protocol as well as the gold standard of transcranial doppler (TCD).
2. Reliability of repeated CVR measures will be established by scanning healthy subjects twice using identical procedures. CVR maps of the brain will be generated using pCASL MRI during controlled changes in pCO2.

Impact: The results of this project will establish reliable protocols for measurement of CVR using a controlled cerebrovascular challenge. This developed technique will be used to examine autoregulatory function in the context of ischemic stroke including sex differences, cognitive function, and recovery trajectories.