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CerebrUS: diagnostic algorithm for perinatal brain injury

CerebrUS by eurUS.brain eurUS.brain lectures — ESPR

Ultrasound and newborn brain injury

Cerebrus stands for the cerebrum combined with cranial ultrasound (CUS). Ultrasound is the most used and most researched tool for imaging the newborn brain. This information targets clinicians with an active interest in newborn brain imaging, mainly performing cranial ultrasound themselves, including neuropaediatricians and paediatric radiologists. The descriptions may be useful for parents of any newborn infant with abnormal brain images, especially due to acquired injury.

(Multi)focal brain injury and imaging

The site guides you through a collection of disease descriptions, mainly lesions. The aim is to provide a comprehensive definition of newborn brain changes observed with imaging. Although the anchors are ultrasound scans, magnetic resonance imaging is added for completion. Extensive attention is paid to lesions like haemorrhage, stroke and infection. For ischaemic stroke, arterial and venous anatomy are displayed in extenso. Vascular anatomy is documented with doppler ultrasound. Both preterm and term brain injury are described. Neuropathology (still the gold standard of newborn brain disease) is from the literature, personal observations and from dr Stefanie Brock at UZ Brussel. The content is not based on products by artificial intelligence.

Neonatologists and diagnostic imaging

Clinical images are anonymised, collected during routine care in hospitals with a waiver for their use. Initial input is property of Paul Govaert, neonatology consultant in UZ Brussel, Belgium. The content is the result of collaboration between european neonatologists specialised in CUS, operating in group as eurUS.brain under the ESPR (European Society for Paediatric Research). Neuropathology (still the gold standard of newborn brain disease) is from the literature, personal observations and from dr Stefanie Brock at UZ Brussel. Every item has typical images (scans and graphics), contextual information and literature references. When graphics are adapted versions, the source is clearly indicated. The focus is on description of mechanisms behind newborn brain injury and their repercussion on imaging. When available long-term prognosis is added. The clinical neonatal background behind any item is provided in detail. Careful interpretation of the images should help to target diagnostic investigations, avoiding unnecessary excursions. Item summaries are by Sofia Spinedi, neonatologist in AOU Bologna.

How to navigate

Within an item navigation is by buttons that highlight on hovering and a general navigator bar on the left of the screen, containing the link to references for the item. Follow the arrow to the item that you want to explore for that region. Choose the brain region that is abnormal in your images ——> Select yellow region ——> Return to the home page (top of the page) at any time to select another item. In the search it may help to include the haemorrhagic nature of the lesion. Some lesions or imaging alterations defy classification: other entities.

Clues to antenatal onset

What are clues to the prenatal origin of a lesion? (1) a previous sib may have been affected, indicating a common noxious agent or a genetic disorder with vasculopathy, metabolic disorder or cardiac failure
(2) the maternal history may be highly suggestive
(3) anomalous fetal ultrasound (or MR) findings may have been observed
(4) fetal CTG and flow findings may be diagnostic
(5) typical clinical phenotypes may be indicative:
- seizures in the delivery room
- the fetal hypokinesia sequence
- fetofetal or fetomaternal transfusion
(6) postmortem evidence of antenatal damage may be found
(7) finally, early neonatal ultrasound imaging and confirmation with MRI or CT of a lesion antedating the delivery is the cornerstone of detection of fetal brain damage When a lesion is clearly of antenatal onset, the differential diagnosis differs from acute intrapartum or neonatal events.

Clues during CUS

- a parenchymal hyperechoic lesion seen on admission immediately after birth is likely of antepartum origin

- after a few days clot in a ventricle begins to undergo lysis, giving rise to cavitation within; the coagulum starts to retract leaving irregular intraluminal structures with a dense ridge and a hypoechoic centre

- towards the end of the first week, following a sterile reaction to blood, the ependyma becomes hyperechoic and granular in some spots, a phenomenon that is to persist for weeks [Rypens et al. 1994]

- widening of the ventricle without bulky clot presence is an argument for subacute or chronic staging

- associated lesions in white matter, if cystic, can point to the subacute character of the event

- exceptionally haemorrhage in plexus choroideus or germinal matrix may evolve into a growing hygroma with a capsule analogous to that of a chronic subdural haematoma

- as a rule ischaemic echogenicities persist for several (≥ 2) weeks, whereas any haemorrhagic area should be cleared of most echoic foci in two to three weeks

Blood evolution stages

Stage	Feature
deoxyHb	early clot retraction, clot center hypoechoic change, fibrin strands
extracellular metHb	hypoechoic particulate cerebrospinal fluid, with motion during doppler imaging
intracellular metHb	hyperechoic ependyma w 2-4, clot with grey center and white border
hemosiderin	porencephaly; clot remnants for a few months; best seen in susceptibility weighted MR sequences

solid, hyperechoic

Disease entities

Deep grey matter

unilateral or asymmetrical
antenatal bilateral thalamic injury
(lenticulostriate) arteriopathy
peri- or postnatal injury to deep grey matter due to asphyxia
phosphate precipitation
kernicterus
hypernatremic dehydration
toxic injury (CO, …)
perinatal perforator stroke
bilateral symmetrical
deep grey matter haematoma
abscedation
thalamic lesions

Matrix

postnatal onset hyperechoic germinolysis
antenatal cystic germinolysis
germinal matrix haemorrhage
germinal matrix neuroepithelium

White matter

supratentorial white matter haematoma
antenatal porencephaly of venous type
leukomalacia due to asphyxia
medullary vein infarction
encephalitis, viral
preterm white matter injury
encephalitis, bacterial
air and precipitation

Midline

midline cavity
midline venous infarction
large cavum veli interpositi
arachnoid cyst
focal change
lipoma
cystic cavum Vergae
cystic cavum septi pellucidi
septal empyema

Hindbrain and cerebellum

posterior fossa hydranencephaly
antenatal damage to brainstem or spinal cord
cerebellar arterial ischaemic stroke
unilateral cerebellar atrophy or partial destruction
vanishing cerebellum (disorder of neurulation)
cerebellar abscedation
brainstem or cord haematoma
cerebellar leukomalacia
cerebellar haemorrhage
brainstem or cord arterial infarction
cerebellar agenesis
brainstem or cord injury due to asphyxia
cerebellar cleft or cortical dysplasia

Fluid spaces, ventricles and choroid plexus

intradural haematoma
changes in choroid plexus
extra-axial haematoma
antenatal clastic hydrocephalus
plexus hypertrophy
hydrocephalus/ventriculomegaly
subdural haematoma
intraventricular haemorrhage
plexus tumor
plexus pseudocyst
epidural haematoma
plexus haemorrhage or hygroma
ventriculitis

Cortex and other entities

tissue destruction by inborn error of metabolism
neurodegenerative disorder
parenchymal tumour
multicystic encephalopathy
schizencephaly
brain disruption sequence
hypoglycaemia
polymicrogyria
inflammatory vasculopathy
intra- or postpartum primary cortical injury due to asphyxia
arterial porencephaly
hydranencephaly
cerebral hemiatrophy
disorders of tight junction molecules
pial arterial ischaemic stroke
subpial/subarachnoid haematoma
basement membrane disorder
complex histological changes of the vessel wall
bacterial meningitis
watershed injury
PRES
focal cortical dysplasia/neuroectodermal disorder
intrapartum asphyxia
congenital brain tumour

Vessels

vascular anomaly
arteriopathy
venous haemorrhage
congenital anomaly of a large artery
arteries: 3D model
spasm or compression
arterial tortuosity
sinovenous thrombosis
deep veins
brain arteries
arterial ischaemic stroke
antenatal intracranial haemorrhage
intracranial haemorrhage
GMH/IVH

Veins are involved in many lesions, almost always haemorrhagic; the mechanistic approach to venous injury can yield findings that are important for management.

Legend

A indicates that the lesion needs to correspond with an arterial template V indicates that the lesion may be related to a large vein

References

Group publications

Alarcón A, Carreras N, Muehlbacher T, Casas-Alba D, Arena R, Roca-Llabrés P, Navarro-Morón J, de Vries LS, Govaert P; EurUS.Brain group. Foetal disruptive brain injuries: Diagnosing the underlying pathogenetic mechanisms with cranial ultrasonography. Dev Med Child Neurol. 2025 Nov;67(11):1383-1408. doi: 10.1111/dmcn.16380. Epub 2025 Jul 13. PMID: 40653787; PMCID: PMC12521638.
Licht-van der Stap RG, de Vries LS, Alarcon A, Govaert P, Steggerda SJ; EurUS.Brain group. Cranial ultrasound in neonatal brain infections. Dev Med Child Neurol. 2025 Aug;67(8):986-1003. doi: 10.1111/dmcn.16279. Epub 2025 Feb 25. PMID: 39996578; PMCID: PMC12237230.
Valverde E, Ybarra M, Bravo MC, Dudink J, Govaert P, Horsch S, Steggerda S, Pellicer A; EurUS.Brain Group. State-of-the-art cranial ultrasound in clinical scenarios for infants born at term and near-term. Dev Med Child Neurol. 2025 Mar;67(3):322-347. doi: 10.1111/dmcn.16133. Epub 2024 Oct 21. PMID: 39432744.
Govaert P, Arena R, Dudink J, Steggerda S, Agut T, Marissens G, Hoebeek F; EurUS.Brain group. Developmental anatomy of the thalamus, perinatal lesions, and neurological development. Dev Med Child Neurol. 2025 Jan;67(1):15-34. doi: 10.1111/dmcn.15992. Epub 2024 Jun 14. PMID: 38875159.
Horsch S, Schwarz S, Arnaez J, Steggerda S, Arena R, Govaert P; EurUS.Brain group. Cerebral Doppler imaging in neonates: A guide for clinical application and diagnosis. Dev Med Child Neurol. 2024 Dec;66(12):1570-1589. doi: 10.1111/dmcn.15998. Epub 2024 Jun 28. PMID: 38940604.
Bravo MC, Lubian S, Horsch S, Cabañas F, de Vries LS; EurUS.Brain group. Neonatal ventriculomegaly: Pathophysiology and management guided with cranial ultrasonography. Dev Med Child Neurol. 2024 Nov;66(11):1419-1431. doi: 10.1111/dmcn.15955. Epub 2024 May 15. PMID: 38747316.
Arena R, Gallini F, De Rose DU, Conte F, Giraldi L, Pianini T, Perri A, Catenazzi P, Orfeo L, Vento G, Govaert P. Brain Growth Evaluation Assessed with Transfontanellar (B-GREAT) Ultrasound. Old and New Bedside Markers to Estimate Cerebral Growth in Preterm Infants: a Pilot Study. Am J Perinatol. 2024 Mar;41(4):488-497. doi: 10.1055/a-1704-1716. Epub 2021 Nov 23. PMID: 34814194.
Govaert P, Roehr CC, Gressens P. Cranial ultrasound by neonatologists. Pediatr Res. 2020 Mar;87(Suppl 1):1-2. doi: 10.1038/s41390-020-0779-8. PMID: 32218540; PMCID: PMC7098880.
Dudink J, Jeanne Steggerda S, Horsch S; eurUS.brain group. State-of-the-art neonatal cerebral ultrasound: technique and reporting. Pediatr Res. 2020 Mar;87(Suppl 1):3-12. doi: 10.1038/s41390-020-0776-y. PMID: 32218539; PMCID: PMC7098885.
Annink KV, de Vries LS, Groenendaal F, Vijlbrief DC, Weeke LC, Roehr CC, Lequin M, Reiss I, Govaert P, Benders MJNL, Dudink J. The development and validation of a cerebral ultrasound scoring system for infants with hypoxic-ischaemic encephalopathy. Pediatr Res. 2020 Mar;87(Suppl 1):59-66. doi: 10.1038/s41390-020-0782-0. PMID: 32218538; PMCID: PMC7098882.
Fumagalli M, Parodi A, Ramenghi L, Limperopoulos C, Steggerda S; eurUS.brain group. Ultrasound of acquired posterior fossa abnormalities in the newborn. Pediatr Res. 2020 Mar;87(Suppl 1):25-36. doi: 10.1038/s41390-020-0778-9. PMID: 32218537; PMCID: PMC7098891.
Camfferman FA, de Goederen R, Govaert P, Dudink J, van Bel F, Pellicer A, Cools F; eurUS.brain group. Diagnostic and predictive value of Doppler ultrasound for evaluation of the brain circulation in preterm infants: a systematic review. Pediatr Res. 2020 Mar;87(Suppl 1):50-58. doi: 10.1038/s41390-020-0777-x. PMID: 32218536; PMCID: PMC7098887.
Parodi A, Govaert P, Horsch S, Bravo MC, Ramenghi LA; eurUS.brain group. Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res. 2020 Mar;87(Suppl 1):13-24. doi: 10.1038/s41390-020-0780-2. PMID: 32218535; PMCID: PMC7098890.
Agut T, Alarcon A, Cabañas F, Bartocci M, Martinez-Biarge M, Horsch S; eurUS.brain group. Preterm white matter injury: ultrasound diagnosis and classification. Pediatr Res. 2020 Mar;87(Suppl 1):37-49. doi: 10.1038/s41390-020-0781-1. PMID: 32218534; PMCID: PMC7098888.
Govaert P, Triulzi F, Dudink J. The developing brain by trimester. Handb Clin Neurol. 2020;171:245-289. doi: 10.1016/B978-0-444-64239-4.00014-X. PMID: 32736754.

Important references

Darrow, V.C., Alvord, E.C. jr, Mack, L.A., Hodson, W.A. (1988) 'Histologic evolution of the reactions to hemorrhage in the premature human infant's brain. A combined ultrasound and autopsy study and a comparison with the reaction in adults.' American Journal of Pathology, 130, 44-58.

Ghazi-Birry H, Brown W, Moody D, Challa V, Block S, and Reboussin D (1977) Human Germinal Matrix: Venous Origin of Hemorrhage and Vascular Characteristics. AJNR Am J Neuroradiol 18:219-229.

Larroche, J.-Cl. (1977) 'Developmental pathology of the neonate.' North-Holland : Elsevier.

Marin-Padilla, M. (1996) 'Developmental neuropathology and impact of perinatal brain damage. I: Hemorrhagic lesions of neocortex.' Journal of Neuropathology and Experimental Neurology, 55, 758-773.

Moody, D.M., Brown, W.R., Challa, V.R., Block, S.M. (1994) 'Alkaline phosphatase histochemical staining in the study of germinal matrix hemorrhage and brain vascular morphology in a very-low-birth-weight neonate.' Pediatric Research, 35, 424-430.

Paneth, N., Rudelli, R., Kazam, E., Monte, W. (1994) Brain Damage in the Preterm Infant. Clinics in Developmental Medicine No. 131. London: Mac Keith Press.

Pape, K.E., Wigglesworth, J.S. (1979) Haemorrhage, Ischaemia and the Perinatal Brain. Clinics in Developmental Medicine No. 69/70. London: Spastics International Medical Publications.

Rypens F, Avni EF, Dussaussois L, David P, Vermeylen D, Van Bogaert P, Matos C (1994) Hyperechoic thickened ependyma: sonographic demonstration and significance in neonates. Pediatr Radiol 24:550–553.

Schmidt, H. (1965) Untersuchungen zur Pathogenese und Ätiologie der geburtstraumatischen Hirnschädigungen Früh- und Reifgeborener. Jena: Gustav Fisher Verlag. References to the current item in alphabetical order.

Cerebrus