Imaging biomarkers for detection and longitudinal monitoring of ventricular abnormalities from birth to childhood

Table 1 Summary of key imaging biomarkers for hydrocephalus assessment and their clinical applicability

Biomarker	Benefits	Applicability
Levene’s index	Tailored for neonates (≤ 40 weeks of gestational age); correlates with gestational age. Useful for defining early intervention thresholds (e.g., > 4 mm above the 97th percentile)	Used in preterm infants via transfontanellar ultrasound. Requires population-specific nomograms
Thalamo-occipital distance	Assesses posterior ventricular dilation. Pathological values vary by population and age (e.g., > 24 mm is considered pathological in some studies)	Measured via parasagittal ultrasound or MRI. Complements anteriorly focused indices
Evans’ index	Simple and quick measurement; considers cranial size proportionality. Widely used in clinical practice	Applicable in MRI, CT, and transfontanellar ultrasound. Lacks standardized pediatric cut-off values
Cella media index	Relates ventricular size to brain tissue volume. Normal values > 4; correlates with third ventricle size	Applied in MRI/CT. Useful for assessing global ventricular dilation
Fronto-occipital horn ratio	Evaluates global ventricular dilation (includes frontal and occipital horns). The mean value in healthy individuals is approximately 0.37; a value above 0.44 indicates pathology	Validated in MRI, CT, and ultrasound. Age-independent reference ranges
Bicaudate index	Focuses on frontal horn size; useful for assessing ventricular symmetry	Limited to MRI/CT (technical challenges in ultrasound). Less reliable in asymmetry or congenital malformations
Anteroposterior lateral ventricle index	Measures the anteroposterior ventricular diameter relative to intracranial size. Has potential for detecting subtle pathological changes	Used in MRI/CT (axial plane reconstruction based on the AC-PC line). Not yet validated in pediatric populations, but it shows promise
Volumetric analysis	Quantifies total CSF volume; detects progressive changes that may be missed by linear indices. Shows better correlation with functional impairment	Requires high-resolution MRI and specialized software. Limited by cost and clinical workflow constraints

CSF: Cerebrospinal fluid; MRI: Magnetic resonance imaging; CT: Computed tomography; AC-PC: Anterior commissure-posterior commissure.