IVH can be caused by several factors, but its fundamental aetiology lies in the weakness of the immature germinal matrix. It is theorised to result from CBF instability caused by increased arterial flow, increased venous pressure, and/or impaired cerebral autoregulation [4]. In the presence of symptomatic PDA, ACA velocity reduces as systolic flow pumps out via the opening, decreasing EDV and consequently increasing RI. RI of ≥ 0.8 has been reported as an especially strong predictor of severe IVH [16]. Fluctuating ACA velocity in the presence of symptomatic PDA is hypothesised to provoke IVH when pressure spikes cause germinal matrix capillaries to rupture [17]. Therefore, patients with symptomatic arterial complications which could affect ACA velocity were excluded from our investigation of potential associations between it and CBV as measured by NIRS. However, we did not find CBV to significantly correlate with any ACA flow-related variable examined (i.e., PSV, EDV, or RI; Table 3a). Before our study, ACA flow velocity had not been tested for associations with CBV, but one group comparing it with cerebral saturation as measured by NIRS did report a significant correlation between cerebral saturation and RI (i.e., of the ACA) [6]. In the tNIRS-1 system that we used, cerebral saturation corresponds to “StO2”; however, StO2 did not correlate with either PSV, EDV, or RI in our analysis (Table 4a). One potential limitation was our inability to eliminate the effects of outlier values; namely, the HHb concentration of Case 20 (26.3 µmol/L). However, the HHb concentration of Case 20 was higher than those of other cases. Since HHb (i.e., deoxyhaemoglobin) reflects oxygen consumption, we speculate that oxygen consumption increased in her brain tissue; however, the reason for this elevated value remains unclear as she did not develop IVH.
ICV flow in new-born infants is typically continuous, i.e., non-pulsatile [18]. However, ICV fluctuations have been documented in ELBWIs who later develop IVH [7]. While the mechanism underlying these fluctuations is unclear, the junction of the ICV with the upstream subependymal vein (SEV), which receives venous blood from the germinal matrix before it, may be involved. This junction is highly vulnerable to hemodynamic changes, so IVH may be easily provoked by venous congestion in this region [4, 19]. Our examination of potential associations between ICV haemodynamics and CBV as measured by NIRS—a topic never investigated in prior research—found CBV to significantly correlate with ICV velocity in ELBWIs in whom ICV flow was confirmed to be continuous (Table 3b; Fig. 4). One potential limitation was our inability to eliminate possible interaction effects because birth weight, corrected gestational age at measurement, and weight at measurement were well correlated with CBV, whereas these variables were not correlated with ICV.
Finally, CBF can be destabilised by dysfunctional cerebral autoregulation. Previous NIRS studies of preterm infants have found that impaired autoregulation likely to precede severe IVH can manifest as a correlation between CBF and mean arterial pressure (MAP) [20, 21]. Differences in the NIRS devices used their measurement principles and the fact that our blood pressure-monitoring technique was non-invasive preclude a straightforward comparison with our results; however, we did not observe CBV correlate with mean blood pressure in a manner suggestive of impaired autoregulation (Table 4). Our CBV observations were obtained simultaneously with ACA velocity (mean: 2.14 ± 0.33 mL/100 g) and ICV velocity (2.15 ± 0.34 mL/100 g); they do not deviate greatly from the figures reported by previous studies of preterm infants (1.7 ± 0.8 mL/100 g [22]) and neonates using TRS (2.3 ± 0.6 mL/100 g [23]).
CBV was not found to correlate with ACA velocity by our analysis but did significantly correlate with ICV velocity. The germinal matrix—a vasculari bounding zone between cerebral arterial and cerebral venous beds—is highly susceptible to IVH. Blood entering this region via arteries ultimately empties into the internal cerebral veins. When its flow becomes congested or impeded, the resulting increase in intravenous pressure can lead to matrix rupture [4]. The correlation observed does not constitute a causal relationship. However, as blood supply to the germinal matrix by the ACA exits via the ICV, NIRS-based CBV monitoring could identify warning signs of increased venous pressure by proxy, with lower ICV velocity corresponding to decreased CBV perfusion upstream.
Besides the potential effects of outliers mentioned above, other limitations of this study include small sample size, the possibility that the brain tissue measured by tNIRS-1 extended beyond the germinal matrix, and the fact that the presence of a correlation does not prove causation.
In conclusion, a significant correlation between ICV flow and CBV was confirmed in this investigation. Continuous monitoring using the tNIRS-1 system for IVH prevention could hold even greater utility if similar relationships with CBV were confirmed than cases with symptomatic PDA (associated with ACA velocity), cases with non-continuous ICV flow, and cases of severe IVH.