Multimodal image analysis of clinical influences on preterm brain development

Abstract

ObjectivePremature birth is associated with numerous complex abnormalities of white and gray matter and a high incidence of long‐term neurocognitive impairment. An integrated understanding of these abnormalities and their association with clinical events is lacking. The aim of this study was to identify specific patterns of abnormal cerebral development and their antenatal and postnatal antecedents.MethodsIn a prospective cohort of 449 infants (226 male), we performed a multivariate and data‐driven analysis combining multiple imaging modalities. Using canonical correlation analysis, we sought separable multimodal imaging markers associated with specific clinical and environmental factors and correlated to neurodevelopmental outcome at 2 years.ResultsWe found five independent patterns of neuroanatomical variation that related to clinical factors including age, prematurity, sex, intrauterine complications, and postnatal adversity. We also confirmed the association between imaging markers of neuroanatomical abnormality and poor cognitive and motor outcomes at 2 years.InterpretationThis data‐driven approach defined novel and clinically relevant imaging markers of cerebral maldevelopment, which offer new insights into the nature of preterm brain injury. Ann Neurol 2017;82:233–246

The developing human connectome project: A minimal processing pipeline for neonatal cortical surface reconstruction

“…Numerous works have been published in the literature that have improved our understanding of the perinatal brain (Ball et al, 2013b(Ball et al, , 2017Counsell et al, 2013;Doria et al, 2010;Kapellou et al, 2006;Keunen et al, 2017;Krishnan et al, 2017;Xue et al, 2007;Dubois et al, 2008a,b;Pienaar et al, 2008;RodriguezCarranza et al, 2008;Awate et al, 2010;Hill et al, 2010;Rathbone et al, 2011;Moeskops et al, 2013;Li et al, 2014b,a;Meng et al, 2014;Nie et al, 2014;Wang et al, 2014;Engelhardt et al, 2015;Lefevre et al, 2015;Li et al, 2015b;Moeskops et al, 2015;Li et al, 2016;Hazlett et al, 2017). Study- ing the developing connectome will open up many opportunities in future, not least because neonatal brain imaging data is changing rapidly, at scales that can be clearly resolved using current MRI technology.…”

“…Whilst invaluable, it is known that early exposure to the extra-uterine environment has longterm implications (Ball et al, 2012(Ball et al, , 2013a(Ball et al, , 2017Counsell et al, 2014;Hintz et al, 2015;Ullman et al, 2015). For this reason, the Developing Humanadvocation of surface-based processing and analysis of brain MR images.…”

Sex differences in brain connectivity and male vulnerability in very preterm children

“…A number of neuroimaging studies aimed to clarify the underlying mechanism of male disadvantage, investigating sex differences in brain structure in the preterm population. The most consistent finding was a larger intracranial volume in preterm boys compared to girls (Ball et al, ; Benavides et al, ; Kersbergen et al, ; Liu et al, ; Skiöld et al, ; Thompson et al, ; Urben et al, ; Vasileiadis, Thompson, Han, & Gelman, ). However, bigger brain volume in boys is also observed in the full‐term population and was not shown to be related to preterm birth or long‐term outcome.…”

Lipopolysaccharide‐induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo

“…We used a well‐characterized paradigm of systemic inflammation driven neuroinflammation (Favrais et al, ; Krishnan et al, ; Van Steenwinckel et al, ), which is known to have effects on brain development and behavior consistent with those reported in infants and children born preterm (Ball et al, ; Raju, Buist, Blaisdell, Moxey‐Mims, & Saigal, ). Experimental protocols were approved by the institutional guidelines of the Institute National de la Santé et de la Recherche Scientifique (Inserm) France.…”