Neonatal Neuroimaging: CUS and Brain MRI

An “early” CUS at 4 to 14 days of age and a “late” CUS at 35 to 42 weeks’ postmenstrual age (PMA) were obtained for NEURO study participants. CUS imaging was obtained per local center clinical protocol and did not specify views. Central reader interpretations were used for all study analyses. Two masked central readers (D.B. and Thomas L. Slovis, MD [see acknowledgments]) reviewed all study CUS independently by using a modified central reading form used in previous NICHD NRN studies.¹⁸ A composite adverse finding on early CUS was defined as the presence of grade III or IV intracranial hemorrhage (ICH)¹⁹ or cystic periventricular leukomalacia (cPVL) on either or both sides. A composite adverse finding on late CUS was defined as having cPVL or porencephalic cyst, moderate-to-severe ventricular enlargement (VE) on either or both sides, or a shunt. For all CUS, assessment of interobserver reliability between central readers revealed κ = 0.75 for the early CUS composite adverse finding and a κ = 0.88 for the late CUS composite adverse finding. Mastoid views were included in only 48.2% of early CUS and 46.1% of late CUS.¹⁵

A conventional brain MRI was obtained at 35 to 42 weeks’ PMA and within 2 weeks of late CUS. Minimum requirements have been previously described,¹⁵ and it was advised that neonatal brain MRIs be obtained without the use of sedation. Central reader interpretations were used for study analyses. Copies of MRIs were sent to RTI International by sites in digital or film format. A masked central reader (P.D.B.) reviewed all brain MRIs by using a central reader form that included WMA scoring according to a widely used classification system used to evaluate 5 areas of white matter assessment.^6,20 Interrater agreement for moderate or severe WMA by using this classification system has been reported to be >95%.²⁰ Significant cerebellar lesions were defined as lesions that were bilateral, cystic, and/or ≥4 mm in size. Adverse findings on brain MRI were defined as moderate or severe WMA or significant cerebellar lesions.