Development and evaluation of diffuse correlation spectroscopy to monitor cerebral blood flow and detect intraventricular hemorrhage in extremely premature infants

PROJECT SUMMARY/ABSTRACT
Every year in the United States about 30% of the 60,000 infants born extremely premature (andlt;30 weeks
gestational age and andlt;1000 g birth-weight [ELGA]) develop intraventricular hemorrhage (IVH). IVH is associated
with high risk for cerebral palsy and significant intellectual disability, causing lifelong implications for affected
children and their families and considerable economic burden. IVH is caused by the rupture of the fragile
capillaries in the germinal matrix which cannot withstand fluctuations in cerebral blood flow (CBF). In andgt;90% of
cases, these injuries occur during the first three postnatal days during a period of cardiorespiratory instability
that has a direct effect on CBF, which results in periods of cerebral hypo- and hyper-perfusion. Current
management strategies, such as changes in ventilation or inotrope support, are blind to the impact on CBF.
Improved bedside technologies to continuously monitor CBF are urgently needed to allow the clinician to make
informed decisions, to optimize current strategies and foster the development of new interventions to reduce the
incidence of IVH in ELGA infants and to improve developmental outcomes. Building on 149 Medical founding
team’s ten years of success measuring infants with non-invasive bedside optical methods, we propose to design
and build a novel fast multi-distance diffuse correlation spectroscopy (DCS) system, optimized for continuous
monitoring of CBFi in ELGA infants. DCS directly quantifies an index of cerebral blood flow (CBFi) by measuring
the temporal fluctuations of light generated by the dynamic scattering of moving red blood cells. To be of use in
the ELGA infant, this bedside monitor needs to be safe, continuous, precise, reliable, quantitative and gently
wearable. These pre-requisites will be met by designing an optical sensor which can be gently applied to the
ELGA infant. The novel DCS system will be initially tested by the 149 Medical’s team in phantoms to verify
performance and demonstrate precision and accuracy of flow estimates. The system will then be tested in more
mature, stable premature infants at the Brigham and Womenandapos;s Hospital (BWH) NICU to evaluate feasibility of
long measurements, compatibility with the NICU environment, skin integrity after long monitoring periods, and
in-vivo algorithm validation. Finally, the device will be used in 50 ELGA infants during the first 72 hours of life to
test our hypothesis that DCS-measured CBFi fluctuations and pressure-passive events correlate with incidence
and severity of IVH. Our goal is to provide a much-needed cerebral blood flow monitor to guide individualized
treatment with the goal of reducing the risk of IVH and improving long term neurodevelopmental outcomes among
ELGA infants. This study in 50 ELGA infants will set the stage for a larger trial alongside commercialization.PROJECT NARRATIVE
There is a great need for a bedside, non-invasive and continuous neuromonitoring tool to provide a robust
measure of cerebral blood flow in premature infants. We propose to develop a novel near-infrared diffuse
correlation spectroscopy (DCS) system optimized for monitoring of the cerebral blood flow index in extremely
premature infants. The successful development, validation and demonstration of clinical feasibility and
effectiveness of our proposed technology will lead to new patient management approaches for reducing
neurological injury, protecting neurocognitive function, and reducing the overall morbidity and mortality
associated with prematurity.