The basal ganglia (basal nuclei) are symmetrical subcortical gray nuclei embryologically assigned to the prosencephalon, the most rostral of the three vesicles dividing into telencephalon and diencephalon at Carnegie stage 14 (GW 6 + 5, CRL 5-7mm). Ganglionic eminence is one of the most important transient brain structures, cell proliferation and migration causing the development of the basal ganglia as well as the thin neocortical cerebral wall. In particular, the basal ganglia arise from two outpouchings of the ventral telencephalon, the medial ganglionic eminence (mGE), which gives rise to the globus pallidus, and the lateral ganglionic eminence (lGE), which gives rise to the caudate and putamen[1, 11]. The ganglionic eminences are further the major source of interneurons that migrate along the pallium into the cerebral cortex [12]. In 2002 caudal ganglionic eminence (cGE) was scientifically confirmed as an independent precursor region for the caudal migratory stream into the caudal cerebral cortex and hippocampus [13].
As development continues, the hemispheres grow around the diencephalon followed by a pronounced growth in size of ganglionic eminence and basal nuclei resulting in a marked widening of the hemispheric peduncle, now allowing the passage of nerve fibers that connect the hemispheres to other regions of the nervous system. The new afferent and efferent fibers developing in this embryologic period squeeze through the striated body and appear as the capsula interna. Medial to this thick medullary sheet of white matter lie the thalamus and caudate nucleus, lateral to it nucleus lentiformis consisting of the putamen and globus pallidus.
Apart from some publications on fetal cerebral midline structures GW 12–14 most researchers in recent years have focused on measurements of the lateral ventricles and the choroid plexus for the diagnosis of ventriculomegaly, genetic disorders, and spina bifida [14–16].
Only one study was presented in 2017 by Dan Boitor-Borza, which confirmed the possibility to visualize GE by transvaginal 3D sonography in multiplanar and in particular in render mode in 18 fetuses at 9–13 SSW[17]. This study demonstrates the possibility to analyze GE in detail embryologically and quantified with standard values (Fig. 2a,b Fig. 3a,c,d). Attempts to measure GE in the region extending laterally into the mantle have failed due to the impossibility of defining the lateral boundary accurately, resulting in unacceptable values for interobserver and intraobserver variability. Similarly, isolated thickness measurement of GE was rejected because of the fuzzy transition from GE to BG.
In 1987, a study of 90 fetuses transabdominally examined in the "standard neuroanatomic plane" in GW 15–35 first established normative values for the basal ganglia measuring the distance between the edges of the thalamus and the Sylvian fissure. The measurement method (Basal Ganglia - Insula) was argued to be based on the fact that only a small portion of the insula could be allocated [18]. The parameter GE - Insula presented and measured in this work demonstrates in contrast to the existing measurements the direct distance from GE to the outer margin of the insula and not the distance from thalamus to insula (Fig. 3a). Furthermore, measured values demonstrating the direct extension of GE and BG in axial (ap and lat) and coronary (cc) sections were generated (Fig. 3b,c; Fig. 2b,c). In addition, capsula interna could be visualized especially in the coronary but also in several cases in the axial section, demonstrating the subdivision of BG into its parts nucleus caudatus and lentiformis (Fig. 2a,c; Fig. 3). The clear presentation of the Sylvian fissure in the axial plane must also be mentioned in this context (Fig. 3a,b).
An early study in 1989 described the measurements of the thalamus (max ap and transverse diameter) using transvaginal evaluation (B image) in 50 fetuses in GW 12–14 [19]. While more current scientific data reproducibly measure thalamic diameter (TD) in the transcerebellar plane at week 18–22 [20], a volume measurement of the thalamus presented in 2011 was not shown to be useful due to its limited reproducibility [21]. Our study presents the clearly defined structures of thalamus in coronary transthalamic plane dorsal to the hemispheric peduncle ending caudally with hypothalamus laterally well delineated by choroid plexus. The exact definition of the measurement plane as well as the clear separation from the surrounding structures allows unambiguous measurements of Th lat and Th/HyT cc (Fig. 4).
Using a transabdominal approach Sari in 2005 published a work describing size and configuration of the third ventricle providing normal values for fetuses from 12 to 40 weeks of gestation, 35 fetuses in GW 12–14 [22]while Loureiro in 2012 published a work on 410 fetuses transvaginally examined presenting normative data of the roof of the third ventricle [14]. Implementing the knowledge of our last publication on the third ventricle and its roof developing from the cavum velum interpositum [23] it was the intention of this work to develop a current normal value of the 3rd ventricle (Fig. 4) measured below CVI transvaginally with high resolution in addition to the already existing normal value of the roof (CVI) by Loureiro.
The latest paper to be discussed is a review by Volpe 2021 [4], summarizing all previous work, highlighting in particular the study planes that we specified in the first part of the study fixing the already known planes to clear anatomical/embryological points in order to ensure the reproducibility of our measurement points and to create a coordinate system that can reproducibly represent the planes in GW 12–14.
The first part of our study proves the possibility of detailed visualization of GE, BG, Th/HyT and the 3rd.V in ultrasound and their correlation to histological images. For the first time, the fibers of the internal capsule, caudate (nucleus caudatus) putamen (nucleus lentiformis), hemispheric peduncle, and caudal GE are described in detail, including a detailed description of the 3.v. in coronal section. It can be stated that the relevant structures can be clearly visualized sonomorphologically in the described levels using targeted brain sonography.
In addition we present scatter plots with prediction intervals for the described structures; regression analyses showed for axGE ap, axGE/I, axGE/BG, coGE/BG, coTh lat., coTh/HyT p < 0.001, co3.V showed p = 0.024.
Intraobserver variability showed almost perfect agreement for axGE ap, axGE/I, axGE/BG, coGE/BG, coTh lat, coTh/HyT - and co3.V lat showed a substantial agreement.
Interobserver variability showed almost perfect agreement according to the parameters axGE ap, axGE/I, axGE/BG lat, coTh lat and coTH/HyT lat, the remaining parameters coGE/BG and co3.V showed a substantial agreement.
As a limitation has to be mentioned that the imageability of the presented structures was sufficient in 71% of the high-resolution 3D volumes, in 57% of the fetuses the structures could be measured at least on one side. When creating the normal values, we had to face a long learning curve for identifying the limits of GE, so we now mainly recommend using the parameters GE/BG and GE/I.
This study should be seen as a basis for clarifying the diagnostic criteria of pathologic changes in the presented structures, pathologies of migration (lissencephaly, polymicrogyria, early severe CMV infections[24]), dysplasia of the thalamus (mild forms of holoprosencephaly[2]) and dysplasia of the basal ganglia (polymicrogyria). After primary detection of abnormalities in transabdominal ultrasound experienced sonographers could in a second step by targeted transvaginal 3D ultrasound analyze the details of the prosencephalic structures to evaluate different pathologic entities.
Beyond all the data presented here for targeted transvaginal 3D ultrasound examination in GW 11 + 3 to 13 + 6, all experienced investigators should be encouraged to address embryologic development of GE, BG Th/HyT on ultrasound. Imaging is successful in a high percentage of cases. A warning must be given against using the standard values for decisions in clinical routine; further studies, especially including pathological changes, are necessary for this purpose.