Neurodevelopmental disorders (NDD) affect how the brain develops and can lead to lifelong difficulties with movement, learning, behavior, and thinking. Every year, around one million newborns in Europe are affected by these conditions. Some babies are at higher risk of NDD due to factors such as being born extremely premature, having poor growth in the womb, experiencing a lack of oxygen at birth, or having a family history of severe NDD. However, predicting which babies will develop these disorders is currently very challenging because there are no reliable early indicators (biomarkers) to detect them.
The CONEXUS study is testing a new type of brain imaging technology called functional ultrasound imaging (fUS) to see if it can help assess brain function in newborns at high risk of NDD. This technique measures brain activity by detecting small changes in blood flow, similar to an ultrasound scan but using advanced imaging technology. Researchers believe this method, known as fC-fUS imaging, could help identify early signs of neurodevelopmental disorders.
Preliminary studies have shown that fUS imaging can detect brain activity changes in newborns, such as differences between sleep states or during epileptic seizures. The CONEXUS study will expand on this by improving the imaging technology and testing it in a larger group of newborns, including those born prematurely, those with restricted growth, those who needed cooling treatment after birth due to lack of oxygen, and those at risk for autism spectrum disorder (ASD).
The study is being conducted in multiple hospitals in France over five years, involving newborn intensive care, pediatrics, and child psychiatry teams. It is a feasibility study, meaning researchers aim to test whether this imaging technique is practical and effective for use in newborns. Babies will have short, painless fUS scans that focus on brain regions involved in movement, hearing, vision, and attention.
Ultimately, the goal of CONEXUS is to demonstrate that fC-fUS imaging can help doctors understand early brain development and identify signs of neurodevelopmental disorders before symptoms appear. If successful, this technique could improve early diagnosis, allowing doctors to start treatment sooner and improve long-term outcomes for affected children. This research has the potential to transform neonatal care by providing a new tool for detecting and monitoring brain function in newborns.
Children of gestational age> 36 WA + 0 days
with neonatal anoxo-ischemic encephalopathy
treated with controlled therapeutic hypothermia (group G2)
Siblings with at least one child with signs of autism spectrum disorder
Person subject to a judicial safeguard measure (guardianship, curatorship or safeguard of justice)
Known malformative pathology;
Known chromosomal abnormality;
Known allergy to silicone
Single group
Imaging Time
DevicefUS: transfontanellar functional ultrasound imaging, performed using the CONEXUS system. fUS-EEG: transfontanellar functional ultrasound imaging, performed using the CONEXUS system, performed simultaneously with an EEG examination. The fUS examinations consist of recording brain activity for a few minutes in one of the imaging planes (Posterior Coronal, Median Coronal, Frontal Coronal, Right Para-sagittal, Right/Left Para-sagittal, 3-plane Antero-posterior Coronal) including structures involved in brain functional connectivity networks (somatosensory, auditory, visual, salience). These fUS examinations are conducted to perform longitudinal follow-up of patients in the 5 different groups.
Feasibility of acquiring quantitative brain functional connectivity assessment using fUS data in 4 groups (G1 to G4) of newborns at high risk of neurodevelopmental disorder and a control group of term newborns.
Each fUS acquisition, for each patient, each acquisition time point, each imaging plane, consists of a succession of fUS images recorded over a duration ranging from 5 to 10 minutes. The acquisition will be considered successful if at least 50% of the fUS images do not show motion artifacts (criterion used in our preliminary studies) (validity criterion) and if vascular structures are visible at a depth \>50% of the maximum depth (sensitivity criterion). If these two criteria are met, we can then average the fUS signal over the functional areas and calculate a correlation matrix.
Feasibility of longitudinal quantification of fUS connectivity of preterm (from birth to equivalent term age) and term newborns in different connectivity networks
Static connectivity matrices are calculated for specific imaging planes via signals averaged over predefined functional areas (including: thalamus, precentral gyrus, postcentral gyrus, temporal lobe, Heschl's gyrus, insula, anterior and posterior cingulate cortex, frontal lobe, striatum, amygdala, visual cortex V1 V2) within an fUS acquisition. These matrices are compared after Fisher transformation via an ANOVA (Analysis of variance) and post hoc student test with correction (significance levels 95%)
Potential correlation between fUS connectivity assessment and neuropsychological assessment at 2 years within the groups of newborns at high risk of neurodevelopmental disorder
Quantitative connectivity assessment of the preterm newborn group will be compared to the Brunet-Lézine neurodevelopmental score at 2 years, to identify a potential correlation.
Feasibility of acquisition of 3D vascular atlases specific to fUS imaging in order to document the evolution of cerebrovascular structures in newborns at high risk of neurodevelopmental disorder and term newborns
No statistical analysis and no quantitative metrics, the measurement is of documentary value.
Quantify potential correlates between fUS and EEG data thanks to the simultaneous fUS-EEG clinical recordings in newborns at high risk of neurodevelopmental disorder and term newborns.
Comparison of connectivity between different sleep phases. The occurrences of different connectivity states will be evaluated for each group in the two sleep phases and tested via an ANOVA and post hoc Tukey's test, as for secondary outcome measure 2.
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