Cot-side functional imaging in neonates for early neurodevelopment monitoring using functional ultrasound (fUS) connectivity imaging and the combination of fUS with diffuse optical tomography (fUS-DOT): A feasibility study

The newborn infant, particularly those born preterm, is vulnerable to brain injury resulting in lifelong neurodevelopmental sequalae. Conventional structural brain imaging correlates poorly with later individual neurodevelopmental trajectories. Therefore, assessing brain integrity with functional (particularly functional connectivity (FC)) neuroimaging, would be beneficial, as studies showed correlation between early FC assessment and later neurodevelopmental outcomes. However, these tools are absent of neonatal clinical settings, probably either due to lack of portability or restricted access to the deep structures. In this proof of concept (poc) work, we show that functional ultrasound imaging (fUS) has key characteristics for this challenge: including portability, sensitivity and spatiotemporal resolution. fUS can monitor fine grain brain activity in deep cerebral nuclei, detect changes in FC dynamics at different developmental stages, with capabilities for 3D imaging. Furthermore, we present a multimodal poc combining fUS with high-density diffuse optical tomography (HD-DOT). The results demonstrate correlation between fUS and HD-DOT signals in spatially overlapping areas of the brain. The complementary fields of view of fUS (in depth) and HD-DOT (shallow cortex) could enable for the first time cot-side whole brain assessment of FC. In the future, a system combining fUS and HD-DOT could be developed as a clinical tool to monitor the developing brain in high-risk infants.