Microvascular ultrasound imaging of the neonatal brain: a scoping review

Abstract Microvascular changes in the developing neonatal brain often precede clinically detectable injury. Advanced ultrasound techniques such as microvascular Doppler (MVD), contrast-enhanced ultrasound (CEUS), and super-resolution ultrasound (SRUS) offer the potential for bedside assessment of microvascular flow and perfusion without sedation, organotoxic contrast agents, or ionising radiation. Using Joanna Briggs Institute methodology and PRISMA-ScR guidance, MEDLINE, EMBASE, Web of Science, trial registries, and grey literature were searched for original in vivo neonatal studies reporting microvascular or perfusion data using MVD, CEUS, or SRUS-based approaches. Extracted data included study metadata, population characteristics, ultrasound systems and protocols, and key feasibility, safety, and performance outcomes. Of 3028 screened records, 23 studies met the inclusion criteria (1 SRUS, 8 CEUS, 14 MVD). Using SonoVue/Lumason microbubbles, the CEUS studies reported 163 neonatal brain scans in 91 neonates (25 +3 to 41 +4 weeks’ gestation). A total of 263 infants were studied across 14 MVD studies. All studies demonstrated safe ultrasound techniques that can be used to assess brain perfusion and cerebrovascular pathologies in preterm and term neonates, particularly in understanding changes in cerebral microvasculature, mainly in infants with hypoxic–ischaemic encephalopathy (HIE), neurovascular, and congenital cardiac conditions. Conclusions : Advanced ultrasound techniques show promise as adjuncts in neonatal neuroimaging, enabling assessment of perfusion and microvascular haemodynamics. Future clinical translation would require standardised protocols, normative datasets, longitudinal outcome linkage, governance and training standards, and diagnostic effectiveness. What is Known: • Conventional cranial ultrasound is indispensable in neonatal care but predominantly demonstrates anatomical structures. Doppler ultrasound provides macrovascular surrogates and does not directly quantify tissue perfusion .• Microvascular dysfunction is a fundamental antecedent to most neonatal brain injuries yet remains largely undetectable to current bedside imaging . What is New: • This scoping review synthesises in vivo neonatal evidence for microvascular ultrasound techniques for bedside assessment .• Evidence to date supports feasibility across diverse neonatal groups and thus readiness for mechanistic evaluation in health and disease .• Translational progress is limited by small cohorts, a lack of normative reference datasets, and limited linkage with longitudinal outcomes .