My research focuses on developing non-invasive neuroimaging and genomic technologies to assess human fetal brain development and its clinical implications. Dr. Tarui's study goal is to translate those technologies to the clinical care of fetuses and infants with various neurological disorders (brain/spinal malformation, Down syndrome, twin-twin transfusion syndrome, and maternal obesity). Clinical translation: Prenatal diagnosis, neurodevelopmental prognosis, understanding disease mechanisms in living fetuses and neonates. Development of therapeutic interventions when neuroplasticity is the richest in early life.

Development of novel fetal neuroimaging technology to develop neurodevelopmental prognosis markers in prenatally diagnosed brain malformations and genetic syndrome

I contributed to the development of novel fetal neuroimaging technologies and the discovery of novel neuropathology such as alterations in global and regional brain growth, cerebral sulcal development, and their correlation with future neurodevelopmental outcomes after birth. Our technologies provide new research opportunities to study fetal brain development. It enables to detect subtle global and regional developmental aberrations in fetal brain growth, cerebral folding patterns, regional cerebral volume, and sulcal development specific to isolated ventriculomegaly, agenesis of corpus callosum, or Down syndrome (DS). Our approach detected altered sulcal positional development in the second trimester fetal brains of isolated agenesis of corpus callosum (Tarui et al. 2018) and isolated ventriculomegaly (Tarui et al. 2023). We have also developed novel automated cortical sulcal labeling technology to study spatio-temporal gyral development in living human fetuses (Yun et al. 2019). Our group conducted one of the first fetal brain MRI studies to analyze fetal brain anatomy in DS quantitatively. We successfully measured subtle reductions in cortical, subcortical, and cerebellar volume growth in the second- and third-trimester fetuses with DS. In the same fetuses with DS, our novel regional cortical folding pattern analysis found, for the first time, altered sulcal folding depth in the regions associated with language processing, fine motor, and executive functions, characteristically affected in children with Down syndrome (Yun, 2020).

 

Determination of the longitudinal neurodevelopmental impact of aberrant fetal brain development

Long-term neurodevelopmental follow-up studies are critical to know how aberrant fetal brain development impacts postnatal developmental outcomes. Isolated inferior vermian hypoplasia is one of the most common fetal cerebellar anomalies, which is used to associate with controversial postnatal neurodevelopmental outcomes. Our study contributed to changing the prenatal counseling of fetuses with inferior vermian hypoplasia by determining favorable outcomes using the comprehensive developmental testing battery (cognitive, language, social, and behavioral domains) (Tarui et al., 2014). No prior studies determined such favorable school-age outcomes. The co-I, Dr. O’Tierney-Ginn, and I contributed to publish a review article (Tarui, O’Tierney-Ginn, 2022) to comprehensively review the available evidence on how maternal obesity and aberrant maternal-neonatal lipid metabolism impact neurodevelopmental outcomes of offspring children and proposed nutritional intervention that could potentially mitigate offspring’s attention deficit hyperactivity disorder or autism spectrum disorder symptoms.

 

Discovery of novel disease mechanisms of human fetal neurological disorders using genome-wide transcriptomic analysis of fetal biofluid

Brain and spinal cord malformations have heterogeneous etiologies and disease mechanisms. Cell-free RNA in amniotic fluid supernatant reflects developmental changes in gene expression in the living fetus, including genes specific to the central nervous system. We identified novel molecular disease mechanisms in the second-trimester fetuses with myelomeningocele by analyzing amniotic fluid cell-free RNA expressions using human genome microarrays. Transcriptomic analysis of amniotic fluid cell-free RNA revealed dysregulated spinal cord development and neuronal inflammatory pathways. They are novel disease mechanisms identified in human fetuses with myelomeningocele (Tarui et al. 2017).

 

Identifying regulatory role of neuroprogenitor cell cycle on murine neocortical development

Neocortical neurons in mammals including rodents and human are derived from neuroprogenitor cells in germinal matrix lining on to the ventricular margin of developing fetal brain. Proliferation and differentiation of neuroprogenitor cells are finely regulated to formulate appropriate amount of neurons in neocortex. Our research team at Developmental Neurobiology Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, developed doxycycline induced p27Kip1 overexpression mice (tetOp27Kip1/-- and PnestinrtTA/-- double transgenic mice), in which G1- to S-phase transition inhibitor p27Kip1 can be overexpressed selectively and electively in the neuroepithelium of the embryonic brain. We found (1) that overexpression of p27Kip1 in the neuroepithelium from embryonic day 12 to 14 increases cells exit from proliferative cell cycle in neuroepithelium and (2) such increase in cell cycle exit is also associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. Our study concluded that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mechanisms that regulate exit from proliferative cell cycle. Moreover, they operate prior to post-proliferative mechanisms necessary to neocortical laminar assembly.

Ongoing projects

Double-blind Placebo-controlled Multicenter Randomized Trial of Intravenous versus Oral Iron for Treating Iron-Deficiency Anemia in Pregnancy

   Bill and Melinda Gates Foundation    2023 -2025 (just announced)     ROLE: Co-Investigator

 

Measuring cortical plate and subplate thickness in the human fetal brain from magnetic resonance images

    NIH, R01EB031170    09/24/2021 – 06/30/2025     ROLE: Co-investigator

 

 Completed projects (last three years)

Fetal neuroimaging predictors of childhood neurodevelopmental outcomes in fetuses with isolated ventriculomegaly

Tufts Clinical Translational Science Institute, National Center for Advancing Translational Sciences 05/01/2020 – 04/30/2021   ROLE: Principal Investigator

 

Prenatal diagnosis of brain malformations

    NICHD K23HD079605           04/01/2015 – 01/31/2020    ROLE: Principal Investigator

2018-2022 Top Doctors, Boston Magazine

2017 Abbott Nutrition Young Researcher Award, Perinatal Research Society

2016 Top five abstracts, International Society for Prenatal Diagnosis

2014 The Sydney S. Gellis, MD. Young Physician’s Award, Floating Hospital for Children, Tufts Medical Center

2013 Susan Saltonsall Award, Floating Hospital for Children, Tufts Medical Center

2013 Jerome Lejeune Foundation

2012 Young Scientist Award, International Society for Prenatal Diagnosis

2011 Clinical Research Training Fellowship Award, American Academy of Neurology

Associate Professor of Pediatrics and Neurology, The Warren Alpert Medical School of Brown University.

Director, Fetal Neonatal Neurology, Pediatric Neurology, Hasbro Children's Hospital

Director, Fetal Neonatal Neurology, Pediatrics, Women & Infants Hospital of Rhode Island

Neuro NICU Round (biweekly teaching sessions at Neonatal Intensive Care Unit at Women & Infants Hospital): Education to medical students, residents, fellows, and faculties on topics and case reviews in the field of neonatal neurocritical care.