PROJECT SUMMARY
Despite advances in neonatal and neurosurgical care, post-hemorrhagic hydrocephalus remains among the
most frequent, severe neurological complications of very preterm birth (gestational age at birth =32 weeks) and
now represents the most common cause of pediatric hydrocephalus in North America. It also carries a heavy
neurodevelopmental toll, with cognitive deficits and/or cerebral palsy diagnosed in greater than 75% of affected
children. After the failure of medical approaches to impact its neurological sequelae, recent research has
centered on optimizing neurosurgical treatment of post-hemorrhagic hydrocephalus, with a focus on mitigating
ongoing injury due to progressive ventricular distension, a long-recognized risk factor for poor outcomes. The
objectives of this proposal are to define the pathophysiological effects of post-hemorrhagic hydrocephalus on
cerebral connectivity and neurological outcomes and, more specifically, to determine how ventricular volume
modifies these relationships. Our Central Hypotheses are that 1) impaired structural and functional connectivity
across key white matter tracts (e.g., corticospinal tracts, optic radiations, corpus callosum) and related functional
networks (e.g., somatomotor, visual, default mode networks) are associated with neurological disability in post-
hemorrhagic hydrocephalus, 2) ventricular distension contributes to post-hemorrhagic hydrocephalus-related
connectivity deficits, and 3) these alterations in connectivity improve with neurosurgical ventricular
decompression. Recent advances in MRI now enable characterization of functional and structural connectivity
in the developing brain with unparalleled spatial and temporal resolution. Analysis of these data using the highly
innovative diffusion basis spectrum imaging approach affords unique capabilities to characterize the complex
neuropathological changes underlying these differences in cerebral connectivity. Here, our multidisciplinary team
will employ these state-of-the-art MRI techniques in combination with detailed neurodevelopmental assessments
to study a large cohort (N=180) that includes very preterm infants with and without post-hemorrhagic
hydrocephalus prospectively recruited and followed longitudinally after discharge from the Neonatal Intensive
Care Unit. In addition, infants with post-hemorrhagic hydrocephalus will undergo neuroimaging studies both
before and after cerebrospinal fluid shunt surgery, characterizing the reversible effects on cerebral connectivity
while also defining the role of ventricle size in its pathology. Application of these cutting-edge MRI acquisition
and analysis approaches enables unprecedented characterization of the effects of post-hemorrhagic
hydrocephalus on the developing brain. Further, we will extend these methods to delineate relationships between
imaging measures and neurodevelopmental outcomes, improving our understanding of the modifiable effects of
this devastating disease. Critically, these results will address long-standing, clinically important questions related
to the care of infants with post-hemorrhagic hydrocephalus and inform development of innovative assessment
tools to support clinical trials seeking to thwart the developmental disability observed in this high-risk population.
