Prognostic Utility of Arterial Spin Labelling Magnetic Resonance Imaging in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review and Meta-Analysis

Abstract

Abstract Background Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. This systematic review and meta-analysis assessed the prognostic utility of arterial spin labelling (ASL) magnetic resonance imaging (MRI) in neonates with HIE. Materials and Methods We searched PubMed, Embase, Cochrane Library, Scopus, and Ovid for studies evaluating ASL MRI in full-term neonates with HIE. The primary outcome was the correlation between cerebral perfusion abnormalities and neurodevelopmental outcomes. Secondary outcomes included age at imaging, ASL sequence (pulsed ASL or pseudo-continuous ASL), MRI field strength (1.5T or 3T), and coil details. Two reviewers independently extracted data. Risk of bias was assessed using the Quality in Prognostic Studies (QUIPS) tool across six domains. Certainty of evidence was graded using GRADE. Meta-analyses were performed using a random-effects model with heterogeneity assessed via I 2 . Results Out of 168 screened records, five observational studies ( n  = 160 neonates) were included. Two studies had a moderate risk of bias (participation and prognostic factor measurement); three were low risk across all QUIPS domains. The pooled correlation between ASL perfusion and functional outcome was r  = 0.80 (95% confidence interval [CI]: 0.64–0.90; I 2  = 74%). Thalamic cerebral blood flow (CBF) was significantly higher in neonates with poor outcomes (pooled mean difference: –16.45 mL/100 g/min; 95% CI: –24.39 to –8.51; I 2  = 74%). Normalized CBF was higher in good outcome groups (mean difference: 0.44, 95% CI: 0.14–0.73; I 2  = 55%). Diagnostic performance showed pooled sensitivity: 0.87 (95% CI: 0.69–0.96), specificity: 1.00 (95% CI: 0.84–1.00), positive likelihood ratio: 18.99, negative likelihood ratio: 0.17, and diagnostic odds ratio: 117.54 (95% CI: 12.37–1116.8), with I 2  = 0% across diagnostic outcomes, though based on two studies. Conclusion ASL MRI showed promising associations between cerebral perfusion patterns and neurodevelopmental outcomes in neonatal HIE. An increased absolute thalamic CBF has been associated with adverse prognosis, while a preserved normalized CBF may reflect intact autoregulatory function and more favorable outcomes. However, these findings are correlational, and no causal inferences can be drawn from small, heterogeneous studies. The evidence is limited by the small number of studies, high heterogeneity, and publication bias. Larger multicenter studies with standardized protocols are required before ASL can be considered for routine prognostication.