State of the Art &&&&&&&&&&&&&& Neuroimaging and the Timing of Fetal and Neonatal Brain Injury Patrick D. Barnes, MD modalities provide spatial resolution based upon physiologic or metabolic data. Some modalities may actually be considered to provide both structural and functional information. Ultrasonography (US) Current and advanced structural and functional neuroimaging techniques is primarily a structural imaging modality with some functional 1±11 are presented along with guidelines for utilization and principles of imaging capabilities (e.g., Doppler ÐFigure 1). It is readily accessible, diagnosis in fetal and neonatal central nervous system abnormalities. portable, fast, real time and multiplanar. It less expensive than other Pattern of injury, timing issues, and differential diagnosis are addressed with cross-sectional modalities and relatively noninvasive (nonionizing emphasis on neurovascular disease. Ultrasonography and computed radiation). It requires no contrast agent and infrequently needs tomography provide relatively rapid and important screening information patient sedation. The resolving power of US is based on variations in regarding gross macrostructural abnormalities. However, current and acoustic reflectance of tissues. Its diagnostic effectiveness, however, is advanced MRI techniques often provide more definitive macrostructural, primarily dependent upon the skill and experience of the operator and microstructural, and functional imaging information. interpreter. Also, US requires a window or path unimpeded by bone or Journal of Perinatology 2001; 21:44±60. air for cranial and spinal imaging. Probably the most important uses of US are (1) fetal and neonatal screening, (2) screening of the infant who cannot be examined in the radiology department (e.g., premature neonate with intracranial hemorrhage, ECMO, intrao- INTRODUCTION perative), (3) when important adjunctive information is quickly In this presentation, current and advanced neuroimaging needed (e.g., cystic versus solid, vascularity, vascular flow, e.g., technologies are discussed along with guidelines for utilization and Doppler Ðsee Figure 1, or increased intracranial pressure), and principles of imaging diagnosis in fetal, perinatal, and neonatal (3) for real-time guidance and monitoring of invasive diagnostic brain abnormalities. This includes pattern of injury and timing or therapeutic surgical and interventional procedures. issues with special emphasis on neurovascular diseases and In the last few years, advances in US techniques have continued to differential diagnosis. In the causative differentiation of static improve at a dramatic pace.1±11 The development of high-resolution encephalopathies (e.g., cerebral palsy ÐCP) from progressive transducers, improvements in color Doppler signal processing, and encephalopathies, specific disease categories and gestational timing new scanning techniques have significantly improved our ability to are addressed (Table 1). These include developmental abnormal- visualize structural and vascular abnormalities in the neonatal brain. ities, trauma, neurovascular disease, infections and inflammatory Examples are the mastoid view to better visualize the posterior fossa, processes, and metabolic disorders. Although a rare but important power Doppler and transcranial Doppler (TCD) to evaluate cause of progressive perinatal encephalopathy, neoplastic processes intracranial hemodynamics [e.g., resistive indices (RI) Ðsee are not considered in detail here. Figure 1], and the graded fontanelle compression Doppler technique to evaluate hydrocephalus. Another recent advance in US technology is the development of vascular US contrast agents to amplify reflected NEUROIMAGING TECHNOLOGIES AND GENERAL sound waves. Potential applications include the detection of slow flow UTILIZATION and the assessment of organ perfusion. Increased sensitivity and Imaging modalities may be classified as structural or functional.1±4 specificity also may soon be provided by advances in computerized Structural imaging modalities provide spatial resolution based analysis of textural features. primarily on anatomic or morphologic data. Functional imaging Computed tomography (CT) is also primarily a structural imaging modality that has some functional capabilities (e.g., CT angiography).1 ± 4,6 ± 8,12,13 Although using ionizing radiation, current- generation CT effectively collimates and restricts the X-ray exposure Lucile Salter Packard Children's Hospital, Stanford University Medical Center, 725 Welch Road, Palo Alto, CA 94304. to the immediate volume of interest. Direct imaging is usually restricted to the axial or coronal plane (Figures 2 and 3). Address correspondence and reprint requests to Patrick D. Barnes, MD, Lucile Salter Packard Children's Hospital, Stanford University Medical Center, 75 Welch Road, Palo Alto, CA 94304. Reformatting from thin axial sections to other planes (e.g., coronal Journal of Perinatology 2001; 21:44 ± 60 # 2001 Nature Publishing Group All rights reserved. 0743-8346/01 $17 44 www.nature.com/jp Neuroimaging of Fetal and Neonatal Brain Injury Barnes Table 1 Continued Table 1 Classification of CNS Abnormalities by Gestational Timing Modified from van der Knaap and Valk,34 and Wolpert and Barnes75 I. Disorders of dorsal neural tube development (3-4 wk) *Often require MRI for definitive diagnosis. Anencephaly Cephaloceles or sagittal) is the alternative. Projection scout images may provide Chiari malformations information similar to plain films but with less spatial resolution. CT Spinal dysraphism* of the pediatric CNS is usually done using either the conventional or Hydrosyringomyelia the helical/spiral technique. CT requires sedation in infants and II. Disorders of ventral neural tube development (5-10 wk) young children more often than does US but less often than MRI. The Holoprosencephalies neonate or very young infant, however, may be examined while Agenesis septum pellucidum asleep after a feeding or during a nap. CT occasionally needs Optic and olfactory hypoplasia/aplasia* intravenous iodinated contrast enhancement, and sometimes Pituitary-hypothalamic hypoplasia/aplasia* cerebrospinal (CSF) contrast opacification. High-resolution bone Cerebellar hypoplasia/aplasia and soft-tissue algorithms are important for demonstrating fine Dandy Walker spectrum anatomy (e.g., skull base). Advances in computer-display Craniosynostosis technology include image fusion, two-dimensional reformatting, three-dimensional volumetric and reconstruction methods, seg- III. Disorders of migration and cortical organization (2±5 mo) mentation, and surface-rendering techniques. These high-resolution Schizencephaly* display techniques are used for CT angiography and venography, Neuronal heterotopia* craniofacial and spinal imaging for surgical planning, and for Agyria/pachygyria* Lissencephaly stereotactic image guidance of radiotherapy, interventional, and Polymicrogyria* neurosurgical procedures. Agenesis corpus callosum The role of CT has been redefined in the context of accessible and reliable US and MRI.2±4 US is the procedure of choice for IV. Disorders of neuronal, glial, and mesenchymal proliferation, primary imaging or screening of the brain and spinal neuraxis in differentiation, and histiogenesis (2±6 mo) the neonate and young infant. When US does not satisfy the clinical Micrencephaly inquiry, or an acoustic window is not available, then CT becomes Megalencephaly the primary modality for brain imaging in children, especially in Hemimegalencephaly acute or emergent presentations. This is especially important for Aqueductal anomalies* Colpocephaly acute neurologic presentations. In these situations, CT is primarily Cortical dysplasias* used to screen for acute or subacute hemorrhage (see Figure 2), Neurocutaneous syndromes* edema (see Figure 3), herniation, fractures, hypoxic±ischemic Vascular anomalies injury, focal infarction, hydrocephalus, tumor mass, or abnormal Malformative tumors collection (e.g., pneumocephalus, abscess, empyema). Other Arachnoid primary indications for CT include the evaluation of bony or air- space abnormalities of the skull base, cranial vault, orbit, paranasal V. Encephaloclastic processes ( >5±6 mo) sinuses, facial bones, and the temporal bone. Additionally, CT is the Hydranencephaly definitive procedure for detection and confirmation of calcification. Porencephaly It is also important in the bony evaluation of a localized spinal Multicystic encephalopathy column abnormality (e.g., trauma). Contraindications to CT in Encephalomalacia childhood are unusual, particularly with the proper application of Leukomalacia Hemiatrophy radiation protection, the appropriate use of nonionic contrast Hydrocephalus agents, the proper administration of sedation or anesthesia, and the Hemorrhage use of vital monitoring. Infarction When CT is used, intravenous enhancement for blood pool effect (e.g., CT angiography) or blood±brain barrier disruption is VI. Disorders of maturation (7 mo±2 yr) additionally recommended for the evaluation of suspected or known Hypomyelination* vascular malformation, infarction, neoplasm, abscess, or empye- Delayed myelination* ma.2±4 Enhanced CT may help evaluate a mass or hemorrhage of Dysmyelination* unknown etiology and identify the membrane of a chronic subdural Demyelination* collection (e.g., child abuse). By identifying the cortical veins, Cortical dysmaturity enhanced CT may distinguish prominent low-density subarachnoid Journal of Perinatology 2001; 21:44 ± 60 45 Barnes