Early Ultrasound Detection of Brain Anomalies and Neural Tube Defects

A comprehensive understanding of fetal development in the first trimester is fundamental for early NTD detection. During these initial 11 weeks, the fetus undergoes rapid and complex development, and while major brain abnormalities typically emerge later, valuable early indicators can still be detected. Key structures assessed by ultrasound during this period include the cranial bones, midline falx, choroid plexus, thalami, and brainstem. These structures offer critical insights into the fetal neurological system's development⁵. Recognizing anomalies in these areas can provide early diagnostic clues, opening avenues for timely intervention and care management strategies.

Key points about early fetal brain ultrasound landmarks:

1. Fourth ventricle/Intracranial translucency (IT)

The fourth ventricle/IT is seen as a translucent clear area within the skull (Figure 1), located between two reflective borders: the back edge of the brain stem at the front and the choroid plexus of the fourth ventricle at the back. To measure this area, calipers are placed on the front and back reflective borders of the fourth ventricle during the later part of the first trimester, specifically between 11.4 and 13.6 weeks⁶. Sonographic studies of the developing human brain have shown that the fourth ventricle can be easily identified from 8 weeks onward as a structure that appears less reflective.

Figure 1

2. Midline falx

The midline falx (Figure 2), a hyperechoic line, is an anatomical structure that separates the two cerebral hemispheres². This distinct line should appear straight and uninterrupted, dividing the brain into two symmetrical halves. Any disruption or discontinuity in the midline echo may indicate the presence of alobar holoprosencephaly⁶, a condition characterized by the fusion of the brain hemispheres.

Figure 2

3. Choroid Plexus

The lateral ventricles exhibit highly echogenic structures, which become more pronounced around the 9th week of gestation. The choroid plexus, responsible for production of cerebrospinal fluid, can be evaluated in conjunction with the lateral ventricles. The two choroid plexuses are expected to be similar in size and symmetrical in terms of shape and position², creating an overall appearance akin to a butterfly(Figure 2). Abnormal enlargement or asymmetry of these structures may indicate the presence of neural tube defects, such as hydrocephalus, which often accompany conditions like spina bifida⁶.

4. Thalami

Figure 2b, (3) planes of the fetal head, the transventricular plane(TV), transthalamic plane(TT), and transcerebellar plane(TC)

The diencephalon is a component of the forebrain located above the brainstem, containing structures that can be visualized in the transthalamic plane, which is instrumental in understanding the midline anatomy of the brain¹. A caudal sweep with the transducer allows for the acquisition of the transthalamic view, which is characterized by a slightly oblique section of the head (Figure 2b). This view displays the thalamus, cavum, and aqueduct of Sylvius³. In this orientation, only the anterior third of the midline falx is visible, while the posterior segment is obscured by the third ventricle⁵. The third ventricle is represented as a slender, anechoic space located between the two thalami, which are seen as symmetrical, anechoic ovoid forms. The aqueduct of Sylvius is identified as a rectangular anechoic cavity, bordered by the anechoic tectum on either side². (Figure 3)

Figure 3

One of the key conditions that can be identified as early as 8 weeks is alobar holoprosencephaly (Figure 4). This severe brain malformation is characterized by a single large fluid-filled cavity, instead of the normal two lateral ventricles. This indicates the absence of divided cerebral hemispheres. Additionally, the thalamus, which normally separates, appears fused at the cavity's floor⁶.

Figure 4
Key Ultrasound Indicators:
1. Large Single Cavity: Look for a large fluid-filled cavity instead of distinct left and right ventricles.
2. Absence of Hemispheric Division: The cerebral hemispheres are not separated, a hallmark of this condition.
3. Fused Thalami: A critical indicator is the thalami appearing fused at the cavity's base.

5. Cranium Integrity

In the realm of prenatal care, assessing fetal cranial bones is pivotal, especially before 11 weeks of gestation. This early evaluation can provide valuable insights into fetal developmental health and forewarn medical professionals about potential abnormalities (Figure 5).

Figure 5, Acrania is characterized by the absence of skull bones enclosing the brain. By examining the cranial bones through ultrasound, this condition can be recognized when the cranial vault is absent.

Here's what to keep in mind during these assessments:

Skull Shape²:
- Pay close attention to the contours and symmetry of the fetal skull.
- Identifying unusual shapes or asymmetries early on can be indicative of issues concerning skull or brain formation.

Ossification Centers²:
- While not fully developed at this stage, observing the early ossification in frontal and parietal bones provides information about the fetus's skull development.

Important Considerations:
- Detection of irregular head shapes before 11 weeks is critical. Distortions might suggest the onset of the acrania-exencephaly-anencephaly sequence.
- Additionally, comparatives between the echogenicity of amniotic fluid and the extracelomic space play a role in accurate diagnosis⁵.

Brainstem

Shows up as a small, bright area in the posterior part of the skull, visible in the mid-sagittal view. It is clearly separate from the occipital bone, and its evaluation often involves calculating the ratio of the brainstem to the distance between it and the occipital bone (BS/BSOB ratio), ⁸which should be under 1.

Figure 6

Brain and Neural Tube Defects Summary

Normal Findings

Abnormal Findings

Cranium Integrity²:

Oval shape

Acrania/Anencephaly:

Irregular shape

Holoprosencephaly:

Round shape

Midline Falx²:

Hyperechoic midline line dividing brain into two even sides

Holoprosencephaly:

Absent midline falx

Encephalocele:

Deviated midline falx

Choroids²:

Echogenic/symmetrical plexuses seen on both sides of midline falx

Holoprosencephaly:

Fused choroids

Choroid Plexus Cysts:

Anechoic cyst(s) seen within choroid(s)

Thalami/cerebral peduncles/ Aqueduct of Sylvius³:

V-shape configuration

Aqueduct appears as an anechoic, box-shaped space located within the mid-brain

Spacing is observed between the occipital bone and the cerebral peduncles

Spina bifida:

Thalami and cerebral peduncles appear parallel

Aqueduct is compressed

Cerebral peduncles are shifted posteriorly, practically touching the occipital bones

4^th ventricle/Intracranial translucency:

Hypoechoic structure between brainstem and cerebellum

Spina Bifida:

Reduced fluid in the fourth ventricle

Dandy-Walker Malformation & Blake's Pouch Cyst:

Increased fluid in the fourth ventricle
Brainstem shifted towards the front

Brainstem:

Brain stem to brain stem-occipital bone distance ratio (BS/BSOB ratio) = <1

Spina Bifida/ Chiari Malformation⁸: (Figure 7)

Thickened brainstem

BS/BSOB ratio >1

Figure 7

MRI imaging has confirmed the presence of myelomeningocele and Chiari II malformation in the fetal posterior brain in this spina bifida case. There is a noticeable displacement and thickening of the brain stem, along with a reduced distance between the brain stem and the occipital bone (Figure 7), resulting in an increased BS/BSOB ratio⁸. Ultrasonography and magnetic resonance imaging (MRI) are extensively recognized as standard diagnostic techniques for detecting myelomeningocele and Chiari II malformation during both the antenatal and neonatal stages. While certain embryonic characteristics observable in first-trimester ultrasounds are noted for facilitating the early detection of open spina bifida⁵, the clarity of these features and the proficiency of the ultrasound practitioner are important factors that can affect the accurate identification of these anomalies.

In summary, the journey toward early detection of brain and neural tube defects (NTDs) remains a challenging frontier in maternal-fetal medicine. Yet, with advancements in ultrasound technology, clinicians are better equipped to identify pivotal brain anomalies at the earliest stages of pregnancy. By concentrating on specific fetal brain structures, we enhance our ability to detect significant conditions such as acrania and alobar holoprosencephaly⁵, even when these anomalies are subtle and difficult to pinpoint in the first trimester.

The routine visualization of these critical structures is indispensable in improving prenatal diagnosis, as this approach not only enhances the accuracy of findings but also ensures earlier intervention opportunities. As ultrasound and other imaging technologies continue to evolve, they promise to revolutionize prenatal care, offering families the reassurance and options needed when faced with potential complications.

Therefore, while the task of detecting NTDs before 11 weeks poses inherent challenges, embracing cutting-edge diagnostic tools and methodologies marks a pivotal step forward. This commitment to innovation highlights the immense potential for improving outcomes and reinforces the need for ongoing research and training in advanced imaging techniques⁸. By doing so, we can continue to make significant contributions to the health and well-being of both mothers and their developing babies, underscoring the critical role such technologies play in the broader landscape of prenatal care.

Advanced Fetal Ultrasound: Innovations & Insights for Early First Trimester Assessment

Chapter 2: Early Ultrasound Detection of Brain Anomalies and Neural Tube Defects