To ensure optimal assessment and interpretation of neuroimaging findings, MRI requests submitted to the neuroradiology team should include key clinical information about the patient: gestational age at birth, current postmenstrual and chronological age; relevant events since birth and their timing; any significant comorbidities; neurological signs, if present; and head circumference (including the corresponding percentile). It is also advisable to indicate any suspected clinical condition or specific lesion that needs to be ruled out, as this helps guide the selection of the most appropriate MRI protocol. Direct communication with the radiology team can further support this process.

Brain MRI without sedation is a safe procedure in neonates and, when performed appropriately, can produce high-quality images. However, this requires a well-defined imaging protocol and adequate training of the healthcare team. Whenever possible, this should be the preferred modality.

Table S1 in Appendix B outlines the nursing care required before, during, and after the MRI examination.

High-quality imaging is essential for obtaining accurate and clinically useful information. At a minimum, this requires a 1.5 T MRI scanner, along with a dedicated neonatal head coil. If this is not available, a multichannel head coil that allows proper positioning and centering of the neonate should be used.

The imaging protocol—including the choice of sequences and their parameters—must be optimized for the neonatal brain. It should enable the detection of a wide range of conditions and be tailored to the patient's clinical presentation and history. Although a basic neonatal protocol is shown in Table 1, additional sequences should be included as needed on an individual basis (Table 2).

This section, along with Tables 2 to 7 and Table S2 in the supplementary material, describes the neonatal neurological conditions in which MRI plays a key role in diagnosis and prognosis.

It also addresses two common neurological emergencies in which early diagnosis is essential: acute neonatal encephalopathy and neonatal seizures.

Acute neonatal encephalopathy is a clinical syndrome characterized by altered alertness or neurobehavior, which may be accompanied by abnormal tone or reflexes, abnormal movement patterns, and, in some cases, seizures. It is a descriptive umbrella term that indicates neurological dysfunction of the brain, without implying a single cause. The underlying etiology may be hypoxic-ischemic, infectious, genetic, or metabolic.

In any neonate with acute neonatal encephalopathy or seizures where a hypoxic-ischemic cause is not suspected, MRI should be performed as early as possible. The goal is to rapidly guide diagnosis and, in some cases, treatment. This initial scan does not preclude the need for repeat imaging later on, if necessary.

MRI is the gold standard for assessing the nature and severity of brain injury in hypoxic-ischemic encephalopathy (HIE), as well as for providing prognostic information.3

Hypoxic-ischemic injury is associated with characteristic lesion patterns (topographic distribution) that vary depending on gestational age, as well as the nature, severity, and timing of the insult.3,4 These injury patterns are strongly correlated with neurodevelopmental outcomes,4,5 making their accurate description in the MRI report essential (Table 3). Several MRI-based scoring systems with prognostic value? have been developed, primarily for research purposes, and require specific training. Although they can be useful, their use is not essential as long as the involvement of individual brain structures is described in sufficient detail.

In addition to the typical involvement of the cortex, basal ganglia, white matter, and brainstem, acute injury to the mammillary bodies has recently been described in the context of HIE. These lesions may be present alongside other brain injuries, but they have also been observed in neonates with otherwise normal imaging findings. Identifying and reporting these lesions is important, as they are associated with learning and memory difficulties at school age. Adequate visualization requires axial or coronal T2-weighted images with 2 mm slice thickness (Tables 2 and 3).4,6

Although CUS is routinely used in neonates with HIE, its sensitivity is limited--particularly for detecting cortical, cerebellar, and brainstem lesions–and its prognostic utility is also more restricted. Nonetheless, CUS is a complementary modality to MRI, allowing for early and serial evaluations and, thus, monitoring of brain injury over time. Spectral Doppler analysis of flow velocity waveforms can help detect patterns indicative of impaired cerebral autoregulation. A validated CUS scoring system is available and has been associated with neurodevelopmental outcomes in neonates with HIE.7

Brain MRI is the imaging modality of choice for establishing both the diagnosis of neonatal arterial ischemic stroke (NAIS)8 and its prognosis, based on: (1) the arterial territory predominantly affected, (2) the extent of the infarction, and (3) the anatomical or functional structures involved (Table 4).9–12

Until MRI can be performed, CUS may be used to detect NAIS, particularly middle cerebral artery infarction, provided it is performed ?24 hours after the event by an experienced operator with appropriate equipment.13

In cases where the neonatal MRI is inconclusive or when unexpected motor development is observed, repeat brain MRI with diffusion tensor imaging -based tractography at around 3 months of age can provide a more accurate prediction of neurodevelopmental outcomes14 (Table 4).

Conventional MRI combined with venography has a sensitivity of nearly 100% for detecting cerebral venous sinus thrombosis (CVST) in pediatric patients, although sensitivity is somewhat lower in neonates.15 MRI with venography should be performed urgently when CVST is suspected, as it also facilitates characterization of associated lesions. CUS has shown high specificity for the diagnosis of CVST16 and helps reduce false positives in MRI assessment.

MRI and CUS are complementary modalities for both diagnosis and follow-up, particularly for monitoring vessel recanalization.

Cerebral venous infarction most often results from obstruction of a cerebral vein and, less commonly, from hemorrhagic transformation of a neonatal arterial ischemic stroke. Venous infarctions are readily distinguished by their hemorrhagic nature and by their location within regions drained by deep medullary veins.

MRI studies are essential for diagnosis, with susceptibility-weighted imaging (SWI) playing a particularly important role. The prognosis of cerebral venous infarction depends on its location and on the structures involved within the lesion area.

Brain dysmaturation (secondary to sustained abnormalities in cerebral blood flow and metabolism during gestation), cumulative ischemia-reperfusion injury and acquired brain damage (eg, ischemic or hemorrhagic stroke) are the main pathogenic mechanisms involved in neurodevelopmental disorders detected in infants with congenital heart disease.17–19

While all neonates with congenital heart disease should be monitored with frequent CUS examinations, CUS must be specifically performed at the following time points: (1) at birth, to assess brain maturation and for the presence of prenatal lesions; (2) after each surgery or interventional procedure, to rule out complications; (3) if seizures or other neurologic manifestations develop; and (4) if there is acute hemodynamic deterioration. Whenever the sonographic findings are abnormal or inconclusive, the evaluation should be completed with MRI.

Cranial ultrasound and MRI are complementary tools in the study of congenital cytomegalovirus infection of the central nervous system (CNS).20,21 Cranial ultrasound is superior to MRI for detection of calcifications and lenticulostriate vasculopathy. All neonates with cytomegalovirus infection who are symptomatic or with abnormal CUS findings should undergo brain MRI to assess the extension of WM injury and rule out cortical or cerebellar malformations.22

Although there are no studies in which antiviral treatment was assigned based on the severity of the imaging findings, scores of 2 or 3 on neuroimaging severity scales generally constitute an indication for treatment (Table 5). For detailed information on the antiviral treatment protocol, we refer the reader to the applicable guidelines.25

Table 6 summarizes the neuroimaging findings associated with other CNS infections.

Assessment with MRI is indicated in newborns with complicated meningitis or abnormal findings on the CUS. The optimal timing for MRI depends on the clinical condition of the patient and the changes in sonographic features over time. Magnetic resonance imaging is more reliable for diagnosis of extra-axial bacterial empyema.26,27

There are limited data on the correlation of neuroimaging findings with subsequent neurological outcomes, so the prognosis must be individualized and made with caution, taking into account all the clinical information for the patient, as opposed to just the imaging data.

Meningoencephalitis secondary to enterovirus, parechovirus, herpesvirus or rotavirus infection typically involves the WM (Table 6). In the case of abnormal WM echogenicity on the CUS or presence of neurologic manifestations, diffusion-weighted imaging would be indicated within a week of onset to assess for the characteristic pattern of these infections in the neonatal period: restricted diffusion typically involving periventricular and subcortical WM (and frequently frontal WM), corpus callosum, internal and external capsule, pyramidal tracts and cerebral peduncles, sparing the basal ganglia and cerebellum. Punctate ischemic lesions are also frequently detected (Table 6).

The evolution of abnormal imaging findings varies, with a tendency toward normalization in some cases and progression to multicystic encephalomalacia and gliosis in others. For this reason, acute-phase neuroimaging findings offer little prognostic value, and repetition of MRI 2–3 weeks later is recommended to assess for the presence of residual WM lesions.

Severe, sustained, or repeated hypoglycemia can cause brain injury, especially involving the WM (including parenchymal hemorrhage) and cortex, but also the thalamus and globus pallidus.28 The blood glucose levels and episode durations associated with brain injury vary from patient to patient. Although it is not always the case, glucose levels that are low enough to cause brain injury are frequently accompanied by acute neurologic impairment and, in some cases, seizures.

Cranial ultrasound can detect changes in WM or basal nuclei echogenicity suggestive of injury. This requires confirmation by MRI. Normal CUS findings (especially if the assessment did not include images acquired through the posterior fontanelle) do not rule out occipital or posterior parietal injury. Therefore, in cases of severe and sustained hypoglycemia or in the presence of neurologic, MRI should be performed, even in patients with normal CUS findings.28

The serum bilirubin levels that can cause brain injury–most commonly in the globus pallidus and subthalamic nucleus, though periventricular white matter involvement has also been reported29–depend on gestational age, postnatal age, and the presence of comorbidities. Most neonates who later develop neurodevelopmental disorders have a history of acute encephalopathy during the neonatal period, although in preterm infants the signs are subtler and more difficult to recognize.

CUS has low sensitivity for detecting basal ganglia injury, and normal CUS findings do not rule it out. Brain MRI should be performed in the neonatal period in all neonates with a history of encephalopathy, and considered on an individual basis in those who required exchange transfusion or did not pass newborn hearing screening, depending on additional risk factors.

Injury to the globus pallidus may not become apparent until several weeks or months later, therefore repeat MRI may be useful, especially in infants with unexpectedly abnormal psychomotor development.29,30

The diagnosis of neurometabolic disorders, which are hereditary metabolic disorders that predominantly affect the CNS, is based on biochemical and genetic tests. Neuroimaging plays an important role in the differential diagnosis by guiding metabolic and genetic testing and early treatment.31

When the affected metabolic pathways are active in the fetus and are not compensated via placental clearance, there are prenatal manifestations, typically anomalies of brain development that are often similar to the lesions caused by congenital infections.32 These cases are usually detected during gestation, and the urgency of neuroimaging after birth is based on the clinical condition of the neonate and whether a definitive prenatal diagnosis has been made.

Cranial ultrasound is the first-line imaging modality for early detection of cysts, calcifications, lenticulostriate vasculopathy, structural abnormalities, edema and changes in echogenicity in the WM and diencephalic structures. However, MRI is the most sensitive and specific imaging modality for neurometabolic disorders.

When the onset is postnatal, they generally manifest with progressive acute encephalopathy, often accompanied by seizures, and therefore constitute a neurologic emergency. They can sometimes be misdiagnosed as sepsis or HIE. Combined with the clinical presentation and the findings of the physical examination, history-taking and first-line tests, the pattern of CNS injury on MRI can contribute greatly to the differential diagnosis, so MRI should be performed as soon as possible (Appendix B, Table S2).31,33

Serial CUS is the optimal screening method for the detection and follow-up of injury associated with prematurity, and the care of preterm neonates in the neonatal unit should always include serial CUS since, although most cases of intraventricular hemorrhage and cystic WM lesions occur within 2 weeks of birth, they may develop later, especially if the neonate experiences sepsis, enterocolitis, recurrent apnea… If neonates are discharged before they reach term-equivalent age, a follow-up ultrasound examination should be scheduled for approximately 40 weeks of postmenstrual age.

Tables 2 and 7 outline the indications and interpretation of brain MRI.34–38