Near-infrared spectroscopy versus magnetic resonance imaging to study brain perfusion in newborns with hypoxic–ischemic encephalopathy treated with hypothermia
Introduction
Hypoxic–ischemic encephalopathy (HIE) remains the most common cause of brain injury in term newborns. Induced hypothermia is currently the only existing treatment to minimize brain injury in these newborns, with decreased death and disability rates at 12–18 months and beyond (Azzopardi et al., 2009, Eicher et al., 2005, Gluckman et al., 2005, Jacobs et al., 2007, Shankaran et al., 2005, Shankaran et al., 2012). However, some newborns still develop brain injury despite this treatment (Barks, 2008, Higgins and Shankaran, 2009, Higgins et al., 2006). It has been demonstrated that hyperperfusion may be present early on in these newborns, despite treatment with induced hypothermia (Wintermark et al., 2011), and was probably a manifestation of reperfusion injury. The measurement of brain perfusion is thus valuable for the early assessment and potentially the management of newborns with HIE, even if treated with hypothermia.
Many approaches have been applied to measure brain perfusion in newborns, and especially newborns with HIE. Most techniques provide only discrete, episodic data and are limited in assessing dynamic changes in cerebral circulation (Levene et al., 1989, Minhas et al., 2003). Arterial spin labeled perfusion magnetic resonance imaging (ASL-MRI) is currently the only method that provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values in multiple brain regions (Biagi et al., 2007, Huisman and Sorensen, 2004, Miranda et al., 2006, Wang and Licht, 2006, Wang et al., 2006, Wintermark et al., 2011). However, obtaining MRI scans in critically ill newborns is logistically challenging, expensive and not widely available. Near-infrared spectroscopy (NIRS) might prove to be an attractive alternative (Ancora et al., 2009, Ancora et al., 2013, Grant et al., 2009, Gucuyener et al., 2012, Toet and Lemmers, 2009, Toet et al., 2006, Wolfberg and du Plessis, 2006), as it permits continuous bedside monitoring of cerebral hemodynamics and oxygenation, by measuring changes in the concentration of oxygenated and deoxygenated hemoglobin (Marin and Moore, 2011, Meek et al., 1999, Pellicer and del Carmen Bravo, 2011, Soul and du Plessis, 1999, Wyatt, 1993). It thus does not provide direct measurement of CBF in different brain regions, but records regional mixed venous saturation (SctO2), which is representative of oxygen supply/demand ratio. NIRS monitoring is also much less expensive, and easily allows serial measures to be taken over time, which may be highly valuable in disorders such as HIE where brain perfusion and oxygen metabolism change over the course of the illness. NIRS monitoring is now becoming widely used in premature newborns (Greisen et al., 2011), as it provides valuable insights on the impact of intensive care on early brain development (Greisen et al., 2011, Roche-Labarbe et al., 2012). For example, SctO2 has been demonstrated to correlate with chronological age (Roche-Labarbe et al., 2012). NIRS has permitted to identify premature newborns with impaired cerebrovascular autoregulation, and thus with a high likelihood of severe brain injury (Tsuji et al., 2000). NIRS measurements were also showed to be highly influenced by routine caregiving procedures (Limperopoulos et al., 2008). Such extended use needs probably to be extended to the asphyxiated term newborns.
This study aimed to compare measurements of brain perfusion by NIRS and by MRI at specific time-points in term newborns with HIE treated with therapeutic hypothermia to determine whether NIRS provides a clinically useful measure of brain perfusion and oxygenation, as validated by ASL-MRI measures.
Section snippets
Patients
We conducted a prospective cohort study of term newborns with HIE admitted to the neonatal intensive care unit (NICU) within 6 h of life, who met criteria for therapeutic hypothermia: (1) gestational age ≥ 36 weeks and birth weight ≥ 2000 g; (2) evidence of fetal distress, e.g., history of acute perinatal event or cord pH ≤ 7.0; (3) evidence of neonatal distress, such as Apgar score ≤ 5 at 10 min, postnatal blood gas pH obtained within the first hour of life ≤ 7.0, or need for ventilation initiated at birth
Results
Twelve concomitant recordings were obtained in seven asphyxiated newborns treated with hypothermia. Five of these seven patients had brain MRIs on days 1 and 2; the remaining two had only one MRI during hypothermia on day 2. Mean CBF value averaged from both frontal lobes measured on each MRI was correlated with averaged SctO2 measured just before and just after the MRI (Table 1). For all patients for whom measurements were performed on both days 1 and 2, SctO2 and CBF values increased from day
Discussion
Lowering body temperature is thought to decrease brain perfusion uniformly (Laptook and Corbett, 2002, Polderman, 2008). In our five cases with measurements on both day 1 and day 2, SctO2 and CBF values increased over time during hypothermia treatment, even though body temperature remained the same, consistent with a previous study (Wintermark et al., 2011). These findings suggest that CBF (and likely oxygen supply) increases over time and extraction of oxygen (and likely oxygen demand or
Conclusion
In conclusion, both SctO2 and CBF increase from days 1 to 2 in all term newborns with HIE, despite treatment with hypothermia. SctO2 and CBF are highly correlated in newborns with severe encephalopathy. Newborns with severe encephalopathy have lower CBF than newborns with moderate encephalopathy. Newborns developing brain HI injury have higher SctO2 than newborns not developing brain injury. Correlating bedside monitoring measurements of SctO2 using NIRS and ASL-MRI measurements of CBF may thus
Funding
Pia Wintermark receives research grant funding from the Thrasher Research Fund Early Career Award Program and the William Randolph Hearst Fund Award. The work of Simon K. Warfield is supported by NIH grants R01 RR021885, R01 EB008015, and R01 LM010033. The Fore-sight™ cerebral oximeters (NIRS) were available for the study through in-kind support from Casmed.
Acknowledgments
The authors thank the families and their newborns for participating in this study. Special thanks are also due to the NICU nurses and MRI technicians who have made this study possible.
Conflict of interest
This manuscript has been contributed to, seen and approved by all the authors. There is no conflict of interest. All the authors fulfill the authorship credit requirements.
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