Table 3 Imaging assessments of mechanisms

Cerebral blood flow

Cerebral artery: MCA

2 MHz TCD: flow dynamics

Nasal canula: monitor the end-tidal pressure of carbon dioxide

After 5 min. of stable phase the mean middle cerebral blood flow velocity (MCAVmean) is obtained

Cerebrovascular conductance index (CVC) = MCAVmean divided by mean arterial blood pressure [6].

Cerebral cortex

Cerebral perfusion is evaluated using Arterial Spin Labelling (ASL) MRI. This is followed by cortical segmentation to determine the boundaries of white and grey matter by thresholding tissue probability maps. The Desikan–Killiany is also used to calculate the mean ASL perfusion for each cerebral lobe, as well as the morphometrics of the T1 segmented volumes of grey, white, cerebrospinal fluid, and nonbrain tissues using the FreeSurfer software package [28, 64].

Carotid arteries and MCA

Ultrasound for measuring blood flow velocity, Pulsatility index and Resistive index [103]

Arterial stiffness

Medium to small cerebral arteries

4D flow MRI is used for measuring global cerebral arterial pulse wave velocity which a novel MRI-based marker for cerebral stiffness [74].

Peripheral arteries via extracranial carotid and femoral arteries concurrently

Tonometry sensors: Carotid-femoral pulse wave velocity for arterial stiffness calculated via semi-automated systems [6].

Carotid arteries

Ultrasound with a Wall Track System with vessel wall moving detector

Stiffness is assessed based on the distensibility of the carotid vessels. The distension of a vessel is defined as the change in diameter in systole divided by diastolic diameter during one cardiac cycle. Using semi- automated systems, the following measurement of stiffness could be obtained: distensibility coefficient (DC), stiffness index, compliance coefficient (CC), Peterson’s modulus, B stiffness, and Young’s elastic modulus [77].

Microvascular endothelial function

Peripheral arteries via the index finger

Finger plethysmography using pulse amplitude tonometry

RHI = ratio of the average amplitude after and before occlusion in both the right and left fingers, as well as at the baseline level

RHI is automatically calculated by software [6].

Cerebrovascular reactivity (CVR)

Occipital lobes of the brain

CVR to visual stimuli is assessed using BOLD-weighted echo-planar imaging with visual stimuli displayed on a screen inside the MRI scanner, which the participant views using a mirror mounted on the head coil [57]. The same metric of CVR could be acquired on BOLD-MRI following CO₂ inhalation [9, 61, 114].

Brain-feeding arteries

CVR to vasodilatory stimulus using ASL-MRI is defined as the percentage of rise in blood flow following the intravenous administration of acetazolamide [58]. The same metric of CVR could be acquired on ASL following CO₂ inhalation [60, 118].

CVR to vasodilatory stimulus via breath-holding on BOLD-fMRI [59, 65]

Intracranial artery: MCA

Transcranial doppler ultrasound measures CVR to Breath-holding, [116] and CO₂ inhalation [62, 119, 135].

Intracranial artery: MCA

Near-infrared spectroscopy (NIRS) could measure CO₂ -induced vasoreactivity changes [63].

Cerebral autoregulation

Brain tissues (grey matter supplied by internal carotid arteries (ICAs) and the basilar artery

Autoregulation is assessed using MRI with ASL quantified for pre-and-15 min-post administration of acetazolamide intravenously [58].

Diffusivity and glymphatic function

The periarterial spaces of the neuroparenchyma

Diffusion tensor imaging (DTI) is used to measure the along perivascular space index (ALPS index) to reflect glymphatic function [90, 91].

DTI also assesses the fractional anisotropy, apparent diffusion coefficient maps (for mean diffusivity and radial diffusivity) to evaluate the integrity of the neuroparenchyma [69, 72, 89, 96].

Blood brain barrier (BBB) leakage

The neurovasculature, and neuroparenchyma

Dynamic contrast-enhanced (DCE) MRI is used to quantify BBB permeability (leakage volume and rate) [31, 86, 88].

Neurovascular uncoupling

The nerves and neurovasculature

Resting state functional MR measures blood oxygen level-dependent (BOLD) signals, which reflect changes in blood flow and oxygenation. Arterial spin labelling MRI for examining brain functional connectivity, neural activity and blood flow dynamics [28, 71].

Cerebral autoregulation

Cerebral basal arteries including the middle cerebral artery (MCA) and posterior cerebral artery (PCA)

Cerebral blood flow velocity (CBFV) was recorded in MCA and PCA with 2 MHz transducers attached to a head band. Continuous arterial blood pressure (ABP) and heart rate recording are done with a finger plethysmograph. Dynamic cerebral autoregulation is determined using transfer function analysis of slow 0.1 Hz oscillations of ABP and CBFV induced by regular breathing at 6/minute over 180 s [73].