Diffusion Tensor Imaging Detects Occult Cerebellar Injury in Severe Neonatal Hypoxic-Ischemic Encephalopathy

Abstract

Background: Despite the benefits of whole-body hypothermia therapy, many infants with hypoxic-ischemic encephalopathy (HIE) die or have significant long-term neurodevelopmental impairment. Prospectively identifying neonates at risk of poor outcome is essential but not straightforward. The cerebellum is not classically considered to be a brain region vulnerable to hypoxic-ischemic insults; recent literature suggests, however, that the cerebellum may be involved in neonatal HIE. In this study, we aimed to assess the microstructural integrity of cerebellar and linked supratentorial structures in neonates with HIE compared to neurologically healthy neonatal controls. Methods: In this prospective cohort study, we performed a quantitative diffusion tensor imaging (DTI) analysis of the structural pathways of connectivity, which may be affected in neonatal cerebellar injury by measuring fractional anisotropy (FA) and mean diffusivity (MD) within the superior, middle, and inferior cerebellar peduncles, dentate nuclei, and thalami. All magnetic resonance imaging (MRI) studies were grouped into 4 categories of severity based on a qualitative evaluation of conventional and advanced MRI sequences. Multivariable linear regression analysis of cerebellar scalars of patients and controls was performed, controlling for gestational age, age at the time of MRI, and HIE severity. Spearman rank correlation was performed to correlate DTI scalars of the cerebellum and thalami. Results: Fifty-seven (23 females, 40%) neonates with HIE and 12 (6 females, 50%) neonatal controls were included. There were 8 patients (14%) in HIE severity groups 3 and 4 (injury of the basal ganglia/thalamus and/or cortex). Based on a qualitative analysis of conventional and DTI images, no patients had evidence of cerebellar injury. No significant differences between patients and controls were found in the FA and MD scalars. However, FA values of the middle cerebellar peduncles (0.294 vs. 0.380, p < 0.001) and MD values of the superior cerebellar peduncles (0.920 vs. 1.007 × 10^-3 mm/s², p = 0.001) were significantly lower in patients with evidence of moderate or severe injury on MRI (categories 3 and 4) than in controls. In patients, cerebellar DTI scalars correlated positively with DTI scalars within the thalami. Conclusion: Our results suggest that infants with moderate-to-severe HIE may have occult injury of cerebellar white-matter tracts, which is not detectable by the qualitative analysis of neuroimaging data alone. Cerebellar DTI scalars correlate with thalamic measures, highlighting that cerebellar injury is unlikely to occur in isolation and may reflect the severity of HIE. The impact of concomitant cerebellar injury in HIE on long-term neurodevelopmental outcome warrants further study.

Cerebral Autoregulation and Conventional and Diffusion Tensor Imaging Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy

“…Although the cerebellum is not classically considered a highly vulnerable region in HIE, cerebellar injury is known to occur in HIE. 20–23 Cerebellar injury may be difficult to detect in some situations because occult cerebellar white matter injury may be detectable by DTI but not conventional qualitative MRI. The incidence and specific characteristics of cerebellar injury that may predict adverse neurodevelopmental outcome in HIE deserve further study.…”

The Role of Diffusion Tensor Imaging in Detecting Hippocampal Injury Following Neonatal Hypoxic‐Ischemic Encephalopathy

“…A 1.5-Tesla clinical MRI scanner (Aera, Siemens, Erlangen, Germany) was used to obtain all brain MRI images using our previously described standard protocol which is optimized for neonatal brain imaging. 23 MR sequences included isotropic 3-dimensional T1-weighted and axial T2-weighted imaging, susceptibility-weighted imaging, and a single-shot spin echo, echo-planar axial DTI sequence with diffusion gradients along 20 noncollinear directions (effective low and high b value of 0, respectively, 800 seconds/mm2). Uniform DTI parameters were used to ensure consistency between patients and controls, and protocols were consistent throughout the study period.…”

Diffusion tensor imaging in neonatal encephalopathy: a systematic review

“…In all, 19 studies were included in our final list for review, which included DTI data from 557 NE infants and 112 healthy controls 15–33. These studies all met the guidelines outlined in the STROBE statement13 in regard to quality and bias.…”