Magnetic resonance imaging (MRI) is a non-invasive, non-ionising technique which allows CVR mapping using contrasts related to CBF and/or CBV. Transcranial Doppler ultrasound is a practical alternative, but has a limited field of view that allows blood velocity measurements only in parts of single large vessels, which do not necessarily reflect local changes in tissue blood supply (Purkayastha and Farzaneh, 2012 McDonnell et al., 2013). Positron emission tomography (PET), single-photon emission computed tomography (SPECT) (Ogasawara et al., 2003) and computed tomography (CT) (Marion and Gerrit, 1991) have all been used to measure CVR, but involve ionising radiation and have low temporal resolution. Several imaging methods can assess haemodynamic changes induced by the vasodilatory stimulus. Vasodilation can be induced without modulating the composition of the inhaled gas or breathing pattern by injection of acetazolamide (ACZ), a carbonic anhydrase inhibitor that causes acidosis (Vagal et al., 2009). Several approaches exist to manipulate PaCO 2: inhalation of gas with fixed CO 2 concentration (e.g., CO 2-enriched air or carbogen), rebreathing the exhaled gas, EtCO 2 targeting manually or using a computer-controlled device (Fierstra et al., 2013). As PaCO 2 cannot easily be measured in vivo, end-tidal CO 2 (EtCO 2), the most recent maximal exhaled CO 2 partial pressure, is often used as a surrogate and can be measured by recording the CO 2 level in the exhaled gas using a gas monitor. Common stimuli include changes in arterial CO 2 partial pressure (PaCO 2) induced by voluntary modulations of the breathing pattern, including breath-holding, hyperventilation and paced breathing (Petersson and Glenny, 2014 Urback et al., 2017 Liu et al., 2019) or by inhalation of CO 2-enriched gas (Fierstra et al., 2013 Liu et al., 2019). The resulting decrease in pH relaxes smooth muscle cells lining the arteries and arterioles, thereby increasing their diameter.

Vasodilation occurs naturally as a mechanism of CBF auto-regulation, but can also be triggered by exogenous stimuli inducing extracellular and intracellular acidosis. Our survey of CVR measurement approaches and applications will help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations. General linear modelling of the MRI signal with end-tidal CO 2 as the regressor is the most frequently used method to compute CVR. Blood oxygen level dependent (BOLD) acquisitions with fixed inspired CO 2 gas or end-tidal CO 2 forcing stimulus are the most commonly used methods. CVR was investigated in many pathologies such as steno-occlusive diseases, dementia and small vessel disease and is generally lower in patients than in healthy controls. We summarised the acquisition methods, experimental parameters, hardware and CVR quantification approaches used, clinical populations investigated, and corresponding summary CVR measures. We systematically reviewed publications measuring CVR using MRI up to June 2020, identifying 235 relevant papers. MRI allows in vivo measurement of CVR but several different methods have been presented in the literature, differing in pulse sequence, hardware requirements, stimulus and image processing technique. CVR closely relates to the health of the vasculature and is therefore a key parameter for studying cerebrovascular diseases such as stroke, small vessel disease and dementias. Cerebrovascular reactivity (CVR) magnetic resonance imaging (MRI) probes cerebral haemodynamic changes in response to a vasodilatory stimulus.

Cerebrovascular reactivity definition