Fetal and Maternal Medicine Review 2008; 19:1 1–31 C 2008 Cambridge University Press doi:10.1017/S0965539508002106 FETAL NEUROIMAGING 1R.K. POOH AND 2 K.H. POOH 1CRIFM Clinical Research Institute of Fetal Medicine PMC, Osaka, Japan. 2Department of Neurosurgery, Kagawa National Children’s Hospital, Kagawa, Japan. INTRODUCTION Imaging technologies have been remarkably improved and contribute to prenatal evaluation of fetal central nervous system (CNS) development and assessment of CNS abnormalities in utero. Conventional transabdominal ultrasonography, by which it is possible to observe fetuses through the maternal abdominal wall, uterine wall and sometimes placenta, has been most widely utilized for antenatal imaging. By the transabdominal approach, the whole CNS of the fetus can be well demonstrated, for instance, the brain in the axial section and the spine in the sagittal section. However, tissues between the ultrasound probe and the fetus, such as the maternal abdominal wall, placenta and fetal cranial bones, may at times pose significant obstacles to the ultrasound signals and therefore make it difficult to obtain clear and detailed images of the fetal CNS structure. The introduction of high-frequency transvaginal transducers have contributed to the development of “sonoembryology”1 and recent liberal use of transvaginal sonography in early pregnancy has enabled early diagnoses of major fetal anomalies.2 The brain is a three-dimensional structure, and should be assessed in sagittal, coronal and axial planes. Sonographic assessment of the fetal brain in the sagittal and coronal sections requires an approach through the anterior/posterior fontanelle and/or the sagittal suture. Transvaginal sonography of the fetal brain opened a new field in medicine, “neurosonography”.3 Application to the normal fetal brain during the second and third trimesters was introduced in the beginning of 1990s. It was the first practical application of three-dimensional central nervous system assessment by two-dimensional (2D) ultrasound.4 Transvaginal observation of the fetal brain offers sagittal and coronal views of the brain5–8 through the fontanelles and/or the sagittal suture as ultrasound windows. Serial oblique sections3 via the same ultrasound win- dow reveal the intracranial morphology in detail. This method has contributed to the prenatal assessment of congenital CNS anomalies and acquired brain damage in utero. Ritsuko K Pooh, MD, PhD, CRIFM Clinical Research Institute of Fetal Medicine PMC, 3–7, Uehommachi 7 Chome, Tennoji, Osaka #543–0001, Japan. 2 R.K. Pooh and K.H. Pooh Figure 1 Basic anatomy of the fetal brain. Axial (upper left), sagittal (upper right), anterior coronal (lower left) and posterior coronal (lower right) sections. BASIC ANATOMICAL KNOWLEDGE OF THE BRAIN The brain should be understood as a three-dimensional structure. It is generally believed that the brain anatomy is complicated. However, in order to demonstrate the brain structure and evaluate fetal CNS disorders, it is not necessary to remember all these detailed structures. Here, only essential anatomical structures are selected for neuroimaging and comprehension of fetal CNS diseases. Figure 1 shows the basic brain anatomy for fetal neuroimaging. TRANSVAGINAL 3D SONOGRAPHIC ASSESSMENT OF FETAL CNS Three-dimensional (3D) ultrasound is one of the most attractive modalities in the field of fetal ultrasound imaging. There are two scanning methods: free-hand scan and automatic scan. An automatic scan by a dedicated 3D transducer produces motor driven automatic sweeping (a fan scan). With this method, a shift and/or angle-change of the transducer are not required during scanning, and the scan duration takes only Fetal Neuroimaging 3 several seconds. After acquisition of the target organ, multiplanar imaging analysis and tomographic imaging analysis are possible. The combination of both transvaginal sonography and 3D ultrasound9–12 produces a great diagnostic tool for evaluation of three-dimensional structure of the fetal CNS. Recent advanced 3D ultrasound equipment has several useful functions: 1 Surface anatomy imaging 2 Bony structural imaging of the calvaria and vertebrae 3 Multiplanar imaging of the intracranial structures 4 Tomographic ultrasound imaging of the fetal brain in any section 5 Thick slice imaging of the intracranial structures 6 Simultaneous volume contrast imaging of the same section or vertical section of the fetal brain 7 Volume calculation of target organs such as intracranial cavity, ventricle, choroid plexus and intracranial lesions 8 Three-dimensional sono-angiography of the cerebral circulation (3D power Doppler or 3D colour Doppler) It is well known that 3D ultrasound demonstrates the surface anatomy beautifully. In cases of CNS abnormalities, associated facial and limb abnormalities are often complicated. Therefore, surface reconstructed images could be helpful. Bony structural imaging of the calvaria and vertebrae (Figure 2) are useful in cases of craniosynostosis and spina bifida. The precise delineation of the level of involvement in spina bifida may provide important information to predict postnatal neurological deficits. In multiplanar imaging of the cerebral structure, it is possible to demonstrate not only the sagittal and coronal sections but also the axial section of the brain, which cannot be demonstrated by transfontanelle approach with a conventional 2D transvaginal sonography. Magnetic resonance imaging (MRI), like 3D ultrasound, provides a multiplanar cross-sectional analysis of fetal CNS structures. In general, transvaginal 3D ultrasound is the imaging modality of first choice during the first and early second trimesters. During this gestational period, 3D ultrasound usually enables a more detailed demonstration of the fetal brain structure than MRI. In the late second and third trimester, MRI is valuable because it can visualise structures which transvaginal 3D ultrasound cannot because of scan-angle limitations and acoustic shadowing due to ossification of the cranial bones.13 Parallel slicing of 3D volumes provides a tomographic visualization of internal morphology similar to MR imaging. Parallel slicing used to be displayed as a single image plane only. However, recent technology enables the display of tomographic ultrasound images as a series of parallel cutting slices on a single screen similar to MRI. (Figure 3) Images obtained by tomographic ultrasound imaging (TUI) are similar to those obtained with MRI. The advantage of TUI over MRI is that it is easy to change slice width, to rotate and magnify images. This function is extremely useful for detailed CNS assessment and also consultations with neurosurgeons and neurologists. 4 R.K. Pooh and K.H. Pooh Figure 2 3D maximum mode image of normal craniofacial structure at 13–14 weeks (upper) and vertebral structure at 16 weeks (lower). Upper left; Frontal oblique view. Upper right; Occipital view. Note the premature occipital bone appearance. Midline crack is demonstrated. Anterior fontanelle (AF), sphenoidal fontanelle (SF), frontal suture (FS), coro- nal suture (CS) are gradually formed according to cranial bony development. S; Sagittal suture, P; Parietal bone, PF; Posterior fontanelle, O; Occipital bone, Cla; Clavicula, Sca; Scapula, LS; Lambdoid suture. Lower figures show normal vertebral structure at 16 weeks, at the vertebral arch level (left) and vertebral body level (right). Intervertebral disc spaces are well demonstrated. Thick slice imaging of the intracranial structures and simultaneous volume contrast imaging (VCI) of the same plane are useful to observe the gyral formation and inside the lateral ventricles.14 Fetal Neuroimaging 5 Figure 3 Tomographic ultrasound imaging (TUI) of the fetal brain. Normal brain in the coronal section at 31 weeks of gestation. Intracranial structure including gyral formation are clearly demonstrated. Volume extracted images and volume calculation of the fetal brain in early pregnancy were first reported in the 1990s.15,16 The authors have used volume extraction and volume estimation of the brain structure.17–19 On three orthogonal images, the target organ can be traced automatically or manually with rotation of volume imaging data. After tracing, the volume extracted image is demonstrated and volume calculation data is shown. 3D fetal brain volume measurements have a good intraobserver and interobserver reliability20,21 and could be used for estimation of gestational age.20 Volume analysis by 3D ultrasound provides informative imaging data, an intelligible evaluation of the brain structure in total, and longitudinal and objective assessment of enlarged ventricles and intracranial space occupying lesions. Any intracranial structure can be chosen as a target for volumetry no matter how distorted its shape and appearance may be. The cerebral circulation demonstrated by transvaginal 2D power Doppler was first reported in 1996.22 Thereafter, transvaginal 3D power Doppler assessment of fetal brain vascularity was successful.18,23 Recently with the advanced technology of bidirectional power Doppler, 3D angiostructural imaging has become even more sophisticated. (Figure 4). Moreover it has been possible to demonstrate the fine medullary veins running from the cortex towards the subependymal area (Figure 4, lower). 6 R.K. Pooh and K.H. Pooh Figure 4 3D angiography of normal cerebral circulation at 28–31 weeks. Upper two figures show normal intracranial vasculature at 31 weeks. Anterior cerebral arteries and their branches are seen on the sagittal plane