Neurovascular coupling methods in healthy individuals using transcranial doppler ultrasonography: A systematic review and consensus agreement

Abstract

Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments. Medline (Ovid), Scopus, Web of Science, EMBASE (Ovid) and CINAHL were searched using a predefined search strategy (PROSPERO: CRD42019153228), generating 6006 articles. Included studies contained TCD-based assessments of NVC in healthy adults. Study quality was assessed using a checklist, and findings were synthesised narratively. 76 studies (2697 participants) met the review criteria. There was significant heterogeneity in the participant position used (e.g., seated vs supine), in TCD equipment, and vessel insonated (e.g. middle, posterior, and anterior cerebral arteries). Larger, more significant, TCD-based NVC responses typically included a seated position, baseline durations >one-minute, extraneous light control, and implementation of previously validated protocols. In addition, complementary, combined position, vessel insonated and stimulation type protocols were associated with more significant NVC results. Recommendations are detailed here, but further investigation is required in patient populations, for further optimisation of TCD-based NVC assessments.

Keywords: Healthy; narrative summary; neurovascular coupling; systematic review; transcranial Doppler ultrasonography.

Figure 1.

Representative TCD-based NVC assessment set-up and results. The centre panel display a representative photo of an individual wearing a multimodal headcap consisting of bilateral transcranial Doppler ultrasound (TCD), functional near-infrared spectroscopy (fNIRS) (an optional multimodal addition to TCD), and electroencephalography (EEG) with peripheral monitoring for systemic influences of carbon dioxide (CO₂) via capnography, heart rate (HR) via electrocardiography (ECG), and blood pressure (BP) via finger photoplethysmography corrected for heart level. The top left panels demonstrate an individual completing a visual “Where’s Waldo?” task with both eyes closed and eyes opened instructions. The bottom left panels display the representative middle cerebral artery velocity (MCAv) and posterior cerebral artery velocity (PCAv) during the visual task via TCD and the oxygenated haemoglobin (HbO), deoxygenated haemoglobin (HbR), and total haemoglobin (THb) responses via fNIRS in the motor and occipital cortices. The top right panels demonstrate an individual completing a visually-cued motor finger tapping task during period of rest and active motor engagement. The bottom right panels display the representative MCAv and PCAv responses during the motor task via TCD and the HbO, HbR, and THb responses via fNIRS in the motor and occipital cortices.

Figure 2.

Prisma flow diagram for narrative synthesis.

Figure 3.

Summary of key study characteristics. a = TCD equipment used. b = Artery insonated. c = Resting period duration. d = Outcome metrics observed.