Cerebral vasomotor reactivity (CVR) testing

David Goldemund M.D.
Updated on 07/11/2023, published on 26/10/2023

Definition of cerebral vasomotor reactivity (CVR)

  • Cerebral Vasomotor Reactivity (CVR or CVMR) refers to changes in smooth muscle tone in the arterial wall in response to certain vasodilatory stimuli (commonly changes in PaCO2 or pH)
    • do not confuse with cerebral autoregulation, which means the ability of cerebral arterioles to maintain a constant cerebral blood flow (CBF) despite fluctuations in systemic blood pressure
    • CVR and cerebral autoregulation are two major mechanisms that regulate cerebral blood flow (CBF)
  • impaired CVR indicates compromised regulation of cerebral circulation and increased vulnerability of the brain to ischemic events
    • the annual risk of ischemic stroke is higher with impaired CVR (13.9% vs. 4.1%)   [Silvestrini, 2000]
    • impaired CVR is also associated with an increased risk of death; incident stroke does not affect this association, suggesting that lower CVR reflects a generally compromised vascular system [Portegies, 2013]
  • in cases of significant extracranial stenosis, CVR testing allows assessment of the collateral circulation status and the risk of hemodynamic failure; demonstration of impaired CVR may support the indication for CEA in asymptomatic individuals


  • cerebral blood flow is influenced by PaCO2 and pH
    • ↓PaCO2 (e.g. hyperventilation) CBF decreases (vasoconstriction → ↑peripheral resistance → decreased flow in proximal segments, e.g. M1)
    • ↑PaCO2 CBF increases (vasodilation → ↓ peripheral resistance → increased flow in proximal segments, e.g. M1)
  • when CVR is exhausted, vasodilatation is already maximal, and the decrease in perfusion pressure can no longer be compensated, resulting in an immediate decrease in cerebral blood flow (CBF)
  • in general, CVR can be defined as the difference between the cerebral blood flow velocity before and after the use of a vasodilating stimulus
Intracranial flow changes during apnoe and hyperpnoe

Methods to measure cerebrovascular reserve

  • Transcranial Doppler (TCD/TCCD) (Müller, 1995)
    • utilizes vasodilatory agents like hypercapnia or IV acetazolamide to stimulate cerebral vasodilation
    • TCD/TCCD measures blood flow velocity changes in response to these stimuli
  • acetazolamide-challenged methods
    • Positron Emission Tomography (PET)  Evaluation of CVR after acetazolamide administration in moyamoya disease. Vasculopathy of the right side was found more severe than the left. CVR was computed as the percentage ratio between ΔCBF and baseline CBF

      • provides high-resolution images and quantitative assessment of CVR
    • Arterial Spin Labeling (ASL) MRI (Zhao, 2022)
    • Single-photon emission Computed Tomography (SPECT)
      • lower resolution and less quantitative compared to PET
    • Blood Oxygen Level Dependent (BOLD) MRI
    • CT/MR perfusion (Kim, 2010)

Ultrasound Evaluation of CVR

  • measurement usually uses a transcranial ultrasound (TCD/TCCD) along with vasodilatory stimuli such as hypercapnia or acetazolamide
  • breath-holding and apnea/hyperventilation tests seem to be practical for rough assessing cerebral hemodynamics
  • the disadvantage of this method is that patients may not be able to tolerate breath-holding long enough to achieve hypercapnia
    • acetazolamide injection and CO2 inhalation test with capnometry are more accurate
  • patients should be examined in a comfortable supine position in a quiet room with standard room temperature

Breath-holding index (BHI)

  • the Breath-Holding Test is a simple method to measure CVR (noninvasive, well tolerated, reproducible)
  • baseline velocity (V1) is measured in the M1 segment of the MCA or BA
  • then the patient holds their breath as long as possible without taking a deep breath (t – time of apnea in seconds)
  • measure the velocity at the end of apnea (V2 – if hypercapnia is achieved, peripheral vasodilation with increased flow in the M1 segment of the MCA occurs)
  • determine the BHI using the following formula:
                  V2 – V1
BHI =   —————-   x   100
                   V1 x t
Normal finding (different cut-offs are reported in the literature):
  • 0.7-1.8 
  • 1.2 ± 0.6  (Widder, 2014)
  • most commonly 1.03-1.65 (Zavoreo 2003)

    • values slightly change with age Normal BHI values depend on age (Zavoreo, 2003)
  • 1.45 ± 0.50 ; PIV (percentage increase in flow velocity) values being 31.6 +/- 12.3% (Jiménez-Caballero, 2006)
Normal CVR (BHI 0.88, PIV 20%)

Apnoe/hyperventilation (BH/HV) test

  • designed to evaluate cerebral autoregulatory function by inducing both hypo- and hypercapnia
  • Vbaseline
  • V1 – PSV after 10-20s of breath-holding (↑ PSV in proximal MCA due to peripheral vasodilation)
  • V2 – PSV after 40s moderate hyperventilation (↓ PSV)
  • normal finding: change of V1/V2 against baseline >15-30% (values vary in the literature)
preserved  normal reaction
decreased  absent reaction to hypercapnia
exhausted  absent reaction to both hypo- and hypercapnia
paradoxical reaction reduced flow during hypercapnia (due to the steal phenomenon)
Flow changes with normal CVR

Acetazolamide test

  • acetazolamide is used as a vasodilator stimulant
    • reversible inhibitor of the enzyme carbonic anhydrase
    • increases CBF by dilating  the arterioles;  metabolic changes induced by acetazolamide include increased extracellular pCO2 and decreased extracellular pH
  • baseline velocity is obtained, commonly in the proximal MCA (V1)
  • IV injection of acetazolamide is administered to induce cerebral vasodilation, typically at a dose of 15-20 mg/kg
  • post-administration velocities (typically after 10-20 minutes)  (V2)
  • CVR is calculated as the percentage change in flow velocity between baseline and peak velocity after acetazolamide administration
    • increase of > 20-40% is generally considered normal CVR
    • increase of < 20% suggests impaired CVR


  • CVR refers to changes in smooth muscle tone in the arterial wall in response to vasodilatory agents (pH or PaCO2)
  • yes, CVR and CBF are directly related; reduced CVR generally implies the compromised ability to increase CBF
  • reduced CVR may indicate compromised cerebral blood flow regulation and elevated risk of ischemic events
  • CVR is often reduced post-stroke, increasing the vulnerability to further ischemic injury
  • CVR serves as an important prognostic marker in various cerebrovascular diseases, including chronic steno-occlusive disorders and stroke. Reduced CVR often indicates impaired autoregulatory capacity, signifying an increased risk for ischemic events
  • age, systemic blood pressure, medications, underlying cerebrovascular pathology (significant stenosis)
  • CVR is typically assessed using transcranial Doppler ultrasound, PET, SPECT, or special MRI sequences (ASL, BOLD), after exposure to a vasodilatory agent
  • CVR assessment is not yet routine but is increasingly used in specialized centers for evaluating cerebrovascular pathology

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Cerebral vasomotor reactivity (CVR)