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 CMRO
2 identified as a key parameter for clinical evaluation.
3–6 Jain, et al.
5 demonstrated correlations between MRI and NIRS measures of CMRO
2 pre-surgically when measured simultaneously in anesthetized neonates. We present MRI and NIRS measures of cerebral hemodynamics (OEF,CBF and CMRO
2) 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 SvO
2 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. SvO
2 measurements in our study are significantly correlated between modalities, but CBF, and therefore CMRO
2, 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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