Optimizing unanesthetized cerebral oxygen consumption measures: comparison of MRI and near-infrared spectroscopy (NIRS) approaches in neonates with congenital heart disease
Jeffrey N Stout1, Silvina Ferradal2, Borjan Gagoski2, Lilla Zollei3, Divya S Bolar3,4, Alex Lin5, Henry H Cheng6, Elfar Adalsteinsson1,7,8, and Patricia Ellen Grant2

1Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States, 2Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children’s Hospital, Boston, MA, United States, 3Martinos Center for Biomedical Imaging, MGH/Harvard Medical School, Boston, MA, United States, 4Department of Radiology, Massachusetts General Hospital, Boston, MA, United States, 5Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States, 6Department of Cardiology, Boston Children’s Hospital, Boston, MA, United States, 7Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, United States, 8Institute for Medical Engineering and Science, Cambridge, MA, United States

Synopsis

Concern for cerebral perfusion in neonates with congenital heart disease (CHD) has driven investigations into cerebral hemodynamics. MRI in combination with bedside NIRS has the potential to provide complementary measures of hemodynamics to guide surgical timing and assess response to surgery. We compare MRI and NIRS measures of cerebral hemodynamics. Modality results compare well to literature studies, but intermodality correlation is limited. Before combining modalities additional studies are needed to better understand why cerebral blood flow and CMRO2 measures in MRI and NIRS differ.

Introduction

Moderate to severe CHD affects 6/1000 live births, with severe CHD resulting in adverse neurodevelopmental outcomes in over 50%.1,2 The etiology of neurodevelopmental disorders is unknown but evaluation of the hemodynamic state of CHD infants pre- and post-surgically has become a focus with CMRO2 identified as a key parameter for clinical evaluation.3–6 Jain, et al.5 demonstrated correlations between MRI and NIRS measures of CMRO2 pre-surgically when measured simultaneously in anesthetized neonates. We present MRI and NIRS measures of cerebral hemodynamics (OEF,CBF and CMRO2) in nine stable neonates with CHD. MRI measures were performed without anesthesia and NIRS measures were performed at the bedside within one day of MRI without anesthesia. MRI and NIRS measures are compared to literature values.

Methods

MRI and NIRS studies were performed at Boston Children’s Hospital with IRB approval and parental consent. MRI and NIRS studies (N=9, age=4.8±2.5 days, 8 male, 1 female) took place in the pre-operative period.

The MRI protocol included: (1) T1 structural imaging (volume navigated MEMPRAGE)7 (2) time of flight angiogram (MRA) positioned to include the circle of Willis and the neck, (3) velocity encoded phase contrast image positioned manually based on the MRA perpendicular to the basilar artery and interior carotid arteries8 (TE/TR=4.67/16.65ms, resolution=0.5x0.5x4.0mm, velocity encoding=100cm/s, Tacq=1:19), (4) T2-relaxation under spin tagging (TRUST)9,10 positioned 15 mm above the confluence of the sinuses perpendicular to the superior sagittal sinus (TE/TR=15/5000ms, resolution=2.3x2.3x5mm, inversion time=1025ms, tagging width=50mm, tagging gap=15mm, Tacq=1:19). Post-processing to estimate cerebral blood flow and venous T2 was performed in MATLAB. Venous oxygen saturation (SvO2) was calculated from T2 using a published calibration.11

The NIRS protocol included frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS).12 FD-NIRS provides regional measurements of oxygenated and deoxygenated hemoglobin, which was used to compute cerebral oxygen saturation. DCS provides a measure of microvascular perfusion by quantifying intensity fluctuations of multiply scattered light due to the movement of red blood cells (RBC) inside the sampled tissue. Regional CBF, measured as blood flow index (CBFi), has been extensively validated.13,14

Results

Table 1 gives the descriptive statistics for the MRI and NIRS studies and correlation statistics between modalities. Figures 1 and 2 show the comparisons between our results and the literature. Figure 3 shows the correlation between SvO2 measured by MRI and NIRS.

Discussion

Compared to other MRI studies, our MRI results show expected decreased mean CMRO2 compared to healthy neonates examined with a similar technique,9 and slightly higher CMRO2 than in anesthetized subjects with a similar technique (Figure 1).5,15 Similarly, compared to other NIRS studies our NIRS results show decreased CMRO2 in CHD compared to controls,16 but higher CMRO2 than anesthetized subjects (Figure 2).5 SvO2 measurements correlate across modalities suggesting that SvO2 measures capture similar information and/or are relatively stable in this cohort (Figure 3). However, there was no significant correlation between OEF, CBF and CMRO2 (Table 1).

There are three possibilities for the discrepancies between NIRS and MRI measurements of OEF, CBF and CMRO2: (1) Measurements were not performed simultaneously and subjects with CHD are unstable.16 (2) Sample size was limited as neonates needed to be stable and asleep to have a successful MRI scan. (3) MRI and NIRS rely on different models and assumptions that could lead to different measurement biases. We studied stable preoperative neonates without anesthesia and although the sample size was small the results compare well to other modality measures (Figures 1, 2). Thus, we suspect the discrepancy between modalities is due to different biases, particularly in CBF measures which have a direct effect on CMRO2. MRI CBF measurements are based on large cerebral artery blood volume inflow, whereas NIRS measurements are based on microvascular RBC flow.

Conclusion

MRI and NIRS provide complementary methods for quantification of cerebral hemodynamics, that if cross-validated would increase our confidence in both modalities and lead to more comprehensive clinical monitoring. However, before data between these two modalities can be compared or combined, additional studies are needed to better understand the relationship between large vessel bulk flow and microvascular RBC flow. SvO2 measurements in our study are significantly correlated between modalities, but CBF, and therefore CMRO2, are not in good agreement either due to differences in physiology or biases in these measurements.

Acknowledgements

This publication was made possible by NIBIB-NIH grants 5T32EB1680, R01EB017337, U01HD087211, and by NIH-NICHD grants R21HD072505.

References

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Figures

Figure 1: MRI based CMRO2 comparison between this study and literature. CMRO2 in this figure calculated with hematocrit, as in Liu 2014. (Dots are mean with standard deviation whiskers, except for Jain 2014 which is median and interquartile range)

Figure 2: NIRS based CMRO2i comparison between this study and literature. (Dots are median with interquartile range whiskers)

Figure 3: Significant correlations between MRI and NIRS measurements of SvO2, in the 9 subject sample with CBF measurements, and in a larger sample with only SvO2 measurements.

Table 1: Descriptive statistics and correlation coefficients for MRI and NIRS based measurements in neonates with CHD. CMRO2 calculated using concentration of hemoglobin for each modality.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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