Elsevier

Pediatric Neurology

Volume 82, May 2018, Pages 36-43
Pediatric Neurology

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

https://doi.org/10.1016/j.pediatrneurol.2018.02.004Get rights and content

Abstract

Background

Deviation of mean arterial blood pressure (MAP) from the range that optimizes cerebral autoregulatory vasoreactivity (optimal MAP) could increase neurological injury from hypoxic-ischemic encephalopathy (HIE). We tested whether a global magnetic resonance imaging (MRI) brain injury score and regional diffusion tensor imaging (DTI) are associated with optimal MAP in neonates with HIE.

Methods

Twenty-five neonates cooled for HIE were monitored with the hemoglobin volume index. In this observational study, we identified optimal MAP and measured brain injury by qualitative and quantitative MRIs with the Neonatal Research Network (NRN) score and DTI mean diffusivity scalars. Optimal MAP and blood pressure were compared with brain injury.

Results

Neonates with blood pressure measurements within optimal MAP during rewarming had less brain injury by NRN score (P = 0.040). Longer duration of MAP within optimal MAP during hypothermia correlated with higher mean diffusivity in the anterior centrum semiovale (P = 0.008) and pons (P = 0.002). Blood pressure deviation below optimal MAP was associated with lower mean diffusivity in cerebellar white matter (P = 0.033). Higher optimal MAP values related to lower mean diffusivity in the basal ganglia (P = 0.021), the thalamus (P = 0.006), the posterior limb of the internal capsule (P = 0.018), the posterior centrum semiovale (P = 0.035), and the cerebellar white matter (P = 0.008). Optimal MAP values were not associated with the NRN score.

Conclusions

The NRN score and the regional mean diffusivity scalars detected injury with mean arterial blood pressure deviations from the optimal MAP. Higher optimal MAP and lower mean diffusivity may be related because of cytotoxic edema and limited vasodilatory reserve at low MAP in injured brain. DTI detected injury with elevated optimal MAP better than the NRN score.

Introduction

Neuroprotective treatment for hypoxic-ischemic encephalopathy (HIE) has focused on therapeutic hypothermia, but this protection is incomplete as nearly half of hypothermia-treated survivors develop moderate to severe disabilities.1, 2 Cerebral autoregulation maintains blood flow across fluctuations in blood pressure. Cerebral vasoreactivity describes the vasodilatory and vasoconstrictive responses to changes in blood pressure that mediate cerebral blood flow autoregulation. Dysfunctional vasoreactivity and autoregulation during resuscitation,3 hypothermia,4 and rewarming5, 6 may contribute to secondary brain injury and poor neurological outcomes in HIE.

The blood pressure range with optimized autoregulatory vasoreactivity—the optimal mean arterial blood pressure (MAP)—can be identified using the hemoglobin volume index (HVx) from near-infrared spectroscopy.7, 8, 9, 10 Conceptually, optimal MAP is located in the center of the blood pressure-cerebral blood flow autoregulation plateau. Vasoreactivity decreases and autoregulation becomes progressively more dysfunctional as blood pressure deviates from optimal MAP. Using optimal MAP as a hemodynamic goal to optimize autoregulatory vasoreactivity in individual neonates reflects a precision medicine approach that contrasts with using generalized blood pressure goals, such as those based on gestational age, that assume similar hemodynamic needs among all neonates. We previously demonstrated a relationship between blood pressure relative to optimal MAP and brain injury on magnetic resonance imaging (MRI)5, 11, 12 and neurodevelopmental outcomes6 in a small cohort of babies with HIE.

Both conventional MRI and diffusion tensor imaging (DTI) can map brain injury. The qualitative National Institute of Child Health and Human Development (NICHD) Neonatology Research Network (NRN) brain injury score analyzes conventional T1- and T2-weighted images to combine subcortical, basal ganglia, thalamus, internal capsule, watershed, and cerebral injuries into one global injury score. A higher NRN score predicts death or disability.13 The NRN score is a standardized, reproducible, qualitative global brain injury scoring system that can be used across institutions in multicenter studies because it uses conventional sequences. Quantitative brain injury can be evaluated with DTI mean diffusivity (MD) scalars. MD identifies compromised microstructural integrity in brain parenchyma after hypoxic-ischemic injury. Region of interest (ROI) analysis can be performed in specific anatomic locations.

In the current study, we extend our prior work5, 6, 11, 12 to validate the relationships between blood pressure, optimal MAP, and brain injury using qualitative and quantitative MRIs with the NRN brain injury score2 and DTI MD scalars in neonates younger than 10 days. We hypothesized that both the NRN score and MD scalars would detect relationships between blood pressure deviation from optimal MAP and brain injury in newborns with HIE. We also hypothesized that absolute values of optimal MAP would be associated with brain injury severity.

Section snippets

Materials and Methods

This observational study was conducted in the Johns Hopkins University neonatal intensive care unit (NICU) with institutional review board approval. We sequentially screened all neonates with HIE admitted to the NICU between September 2010 and July 2015. Written informed consent was obtained from the parents until May 2013, when near-infrared spectroscopy (NIRS) monitoring became the standard of care for HIE treatment at our hospital. The institutional review board then granted a waiver of

Results

We screened 122 neonates with HIE. Forty-seven (39%) did not meet eligibility criteria because of the following: unreliable arterial blood pressure tracing (16), parents did not consent to the study (nine), the patient was transferred out of the NICU for potential extracorporeal membrane oxygenation (six), technical difficulties (five), death before HVx monitoring could be started (five), inadequate resources (three), coagulopathy (one), complex cardiac disease (one), or parents did not speak

Discussion

In an observational pilot study of newborns treated with hypothermia for HIE, we identified relationships between blood pressure regulation relative to optimal MAP and brain injury measured by the global NRN score and regional MD scalars. Greater duration of blood pressure within optimal MAP was related to less injury by NRN score and higher MD in the ACS and the pons. Blood pressure deviation below optimal MAP was associated with lower MD in cerebellar white matter. Higher optimal MAP values

Conclusions

We observed significant relationships between blood pressure deviation from the MAP range with most robust cerebral autoregulatory vasoreactivity and brain injury measured by qualitative and quantitative MRIs. MD scalars from DTI MRI identified detailed relationships between optimal MAP and regional injury that the NRN score did not. Higher optimal MAP and lower MD in multiple brain regions may be related to cytotoxic edema with limited vasodilatory reserve at low blood pressure. Future

Conflicts of interest

JKL, FJN, and RC-V received research support from Medtronic for a separate study. JKL was also a paid advisory board member for Medtronic. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Medtronic had no role in the current study's design, data collection and analysis, interpretation of the results, writing, or decision to submit our manuscript for publication.

Dedication

We dedicate this manuscript to the Poretti family in loving memory of Dr. Andrea Poretti (AP).

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    Funding: This work was supported by the National Institutes of Health, Bethesda, MD, USA (grant numbers R01HD070996 [FJN], R01HD074593 [FJN], R01NS060703 [RCK], and K08NS080984 [JKL]), and the Sutland-Pakula Endowment for Neonatal Research (RC-V).

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