Diffuse correlation spectroscopy blood flow monitoring for intraventricular hemorrhage vulnerability in extremely low gestational age newborns

Abstract

In premature infants with an extremely low gestational age (ELGA, < 29 weeks GA), dysregulated changes in cerebral blood flow (CBF) are among the major pathogenic factors leading to germinal matrix/intraventricular hemorrhage (GM/IVH). Continuous monitoring of CBF can guide interventions to minimize the risk of brain injury, but there are no clinically standard techniques or tools for its measurement. We report the feasibility of the continuous monitoring of CBF, including measures of autoregulation, via diffuse correlation spectroscopy (DCS) in ELGA infants using CBF variability and correlation with scalp blood flow (SBF, served as a surrogate measure of systemic perturbations). In nineteen ELGA infants (with 9 cases of GM/IVH) monitored for 6-24 h between days 2-5 of life, we found a strong correlation between CBF and SBF in severe IVH (Grade III or IV) and IVH diagnosed within 72 h of life, while CBF variability alone was not associated with IVH. The proposed method is potentially useful at the bedside for the prompt assessment of cerebral autoregulation and early identification of infants vulnerable to GM/IVH.

Figure 1

The DCS optical sensor included 5 mm/short- and 20 mm/long-separation channels (A) and an accelerometer (B). The sensor was attached to the infant’s head with a hydrogel to ensure skin integrity during the long monitoring sessions and was covered by a continuous positive airway pressure (CPAP) hat (B). The DCS cart was equipped with a DCS device and a computer running the DCS graphical user interface (C). Arterial blood pressure measurements, when available, were co-recorded through an auxiliary port on the DCS device. (For B, the informed consent was obtained from the parent for publication of identifying images in an online open-access publication.)

Figure 2

High CBF fluctuation from a 25-week GA ELGA infant with grade IV IVH (Left) was indicated by large (based on the population range shown in Fig. 4b) values of the coefficient of variation (CV) calculated using 5-, 20-, and 40-min sliding windows. Right: In contrast, another ELGA infant with No-IVH (28 weeks GA) showed higher perfusion with low fluctuation, captured by the CV method.

Figure 3

Correlation-based indices of impaired (left) vs healthy (right) cerebral autoregulation showed a possible association with IVH. Left: A 24 week GA ELGA infant with grade IV IVH diagnosed on the same day of the DCS measurement (day 3 of life), showing strong and frequent pressure passive events as the correlation was 0.8–0.9, and the time lags were mostly at 0–5 s between CBF, SBF, and MAP. Right: In an infant with no IVH, CBF (red tracing) was out of phase compared to SBF (blue tracing with square markers) within the 3-min window, as well as in MAP (dotted green tracing) vs CBF (red tracing). On average, the correlation was lower (< 0.5) and with a longer lag (0–20 s) than in the IVH example. For both left and right: Visually, SBF (blue tracing with square markers) showed the signal peaks that were correlated with MAP (dotted green tracing); A 3-min, 50% overlapping sliding window was used to compute the best positive correlation between leading and following signals up to 20 s of time lag; Shown here is a segment of 10 min of data.

Figure 4

CBF_i fluctuation was not different between IVH groups, based on the coefficient of variation method (CV_CBFi). Each point was based on one day of measurement. Notable differences include a significantly lower scalp blood flow, while showing a higher mean arterial pressure, in the severe-IVH group (P values shown are based on Tukey post-hoc test. A linear mixed model was used to account for multiple measurements in each subject).

Figure 5

RiSC was higher in the severe-IVH group compared to other IVH groups after accounting for the effect of birthweight (Right panel; Tukey post-hoc test showed P = 0.04 in severe vs mild groups and P = 0.06 in severe vs no-IVH groups). Each point was based on one day of measurement. The plot on the left shows the original distribution before adjusting for body weight. The right panel shows the RiSC comparison after adjusting for the birthweight. Both the original RiSC and adjusted RiSC were marginally different in ELGA infants who were diagnosed with IVH within 72 h of life compared to controls (P = 0.07 and 0.07, respectively). (Red dot = diagnosed with IVH within 72 h of life; Blue open circle = no IVH within 72 h of life.)