Abstract
The cochlear aqueduct (CA) is a bony canal located at the base of the scala tympani of the cochlea. It connects the inner ear perilymph fluid to the cerebrospinal fluid of the posterior cerebral fossa. Its function is not well understood, as it seems to be patent in only a fraction of adult patients. Indirect observations argue in favor of the CA being more patent in children. To study the CA morphology in children, we performed a retrospective single-center study of 85 high-resolution temporal bone computed tomography (hrCT) scans of children with a mean age of 3.23 ± 3.07 years (13 days of life up to 18 years), and compared them with a group of 22 adult hrCT (mean age of 24.01 ± 3.58 years). The CA morphology measurements included its total length, its funnel (wider intracranial portion) length and width and its type (indicating its radiological patency), according to a previously published classification. The dimensions of the CA were significantly smaller in children compared with adults for the axial length (10.37 ± 2.58 versus 14.63 ± 2.40 mm, respectively, p < 0,001) and the funnel length (3.94 ± 1.59 versus 6.01 ± 1.77 mm, respectively, p < 0,001). The funnel width tended to be smaller but the difference was not significant: 3.49 ± 1,33 versus 3.89 ± 1.07 mm, p = 0,22. The repartition of types of CA was also statistically different. The CA appeared to be more identifiable in the children population. Type 1 (CA visible along its entire course) accounted for 42% (36/85) of children and only 5% (1/22) of adults, type 2 (visible in the medial two thirds) for 30% (25/85) versus 31% (7/22), type 3 (not visible completely along the medial two thirds) for 27% (23/85) versus 50% (11/22). Finally, type 4 (undetectable) was found in only 1% (1/85) of children and 14% (3/22) of adults (p < 0,001). Our study showed significant postnatal growth of the length of the CA, which was more rapid before the age of 2, and slowed after 6 years of age. Its width increased less, with children older than 2 years presenting a similar width to adults. The CA was more identifiable in hrCT in children, arguing for a more permeable tract. The number of completely ossified CA was significantly lower in the children population. These findings highlight the differences between the CA morphology in adults and children and raise the question of differences in function. Moreover, these differences may impact the pharmacodynamics of drugs or vectors delivered into the pediatric inner ear. Further studies are required, both on the anatomy of temporal bones and on the function of the CA in children.
Supplementary Information
The online version contains supplementary material available at 10.1007/s10162-024-00963-0.
Keywords: Cochlear aqueduct, Children, Computed tomography, Anatomy, Temporal bone
Introduction
The cochlear aqueduct (CA) is a slender conduit within the temporal bone that runs between the basal turn of the cochlea and the posterior cranial fossa. Its lateral opening is found at the base of the interior surface of the crista fenestrae near to the round window membrane, and its funnel shaped medial aperture opens on the inferior surface of the petrous pyramid in the posterior cranial fossa [1]. The function of the CA is not clearly defined. Significant fluid flow seems not to be possible due to its morphology in adults [2–4], but it may serve as a nonlinear pressure regulator between the inner ear and the cerebrospinal fluid space [5, 6].
The morphology of the CA has been studied in adults histopathologically [2, 4], by molding techniques [1, 7] and more recently by micro computed tomography [8] and high resolution computed tomography (hrCT) [1, 9–12]. The patency of the CA is variable in adults, only one third was found to be open in a temporal bone histological study [4]. Different clinical conditions argue in favor of a wider patency and a shorter length in children [10, 13], as passage for virus, bacteria, and erythrocytes are more common between the inner ear and the CSF in both directions in newborns. To date, comprehensive description of the progressive evolution of the CA structures during childhood in the literature is limited [13, 14].
This study endeavors to bridge this knowledge gap, employing hrCT to describe the dynamics of the CA growth and to describe its radiological patency, comparatively to adults, from birth to adulthood.
Materials and Methods
Study Population and Data Source
In this retrospective single-center study, we reviewed 107 temporal bone hrCT, obtained as part of the radiological assessments of patients at our tertiary hospital in Montpellier, France from January 2010 to June 2023. The scans were conducted to investigate disorders such as conductive hearing loss, cholesteatoma, facial paralysis, and as a component of the pre-operative assessment for cochlear implantation. A complete list of indications can be found in Supplementary Data Table 1. Patients with diagnosed inner ear or cranial malformation, congenital bone disease, osteitis or syndromic conditions, were excluded. Thus, the scans were not obtained from strictly asymptomatic patients. However, the indications for the scans were unlikely to be related to any developmental or postnatal growth issues of the temporal bone. Therefore, we consider these scans as close as possible to normal ear anatomy.
We included 43 children, aged between 13 days up to 18 years, with a mean age of 3.23 ± 3.07 years, and each temporal bone was treated as an individual sample. One hrCT was excluded because of severe osteitis. We thus analyzed 85 single hrCT of children. The children group was subsequently stratified into four age-specific subgroups: Group 1 (less than 1 year, n = 22 hrCT), Group 2 (1 to 2 years, n = 31 hrCT), Group 3 (3 to 6 years, n = 18 hrCT) and Group 4 (7 to 18 years, n = 14 hrCT).
Additionally, a control group of adults, aged over 18 years (mean age of 24.01 ± 3.58 years, n = 22 hrCT) was included in the analysis who underwent hrCT scans with similar indications to those in the children group. The sex ratio in males versus females was not different between the children and adult population: 20/23 (86%) and 4/7 (57%), respectively, p = 0.6531. The study was conducted in accordance with the local review board (number 2024–04-049).
Cochlear Aqueduct Morphology
The CA was identified in accordance to that described by Jackler and Hwang [10]. Axial cuts exported from our picture archiving and communication system (General Electric, Universal Viewer 7) were used for measuring the CA. Images were exported in a consecutive mode with a slice thickness of 625 µm without overlap between sequential slices. The CA total length was measured, as well as its funnel (larger portion of its cranial opening) length and width (Fig. 1). The CA was not always visible in its entire course in a single axial slice; instead, it necessitated calculation over several slices using the Pythagorean theorem. This method was used and described in a previously published study [15]. Briefly, treating the length of the CA as the hypotenuse of a right triangle, one leg of the triangle was determined as the distance between the cochlear aperture and the projection of the cranial opening of the CA in the axial slice where the cochlear aperture was visible. The second leg involved the height between the cranial and the cochlear apertures, computed by multiplying the number of slices between the visible apertures and the slice thickness. We did not attempt to measure the CA diameter because the histological measures (0.14 mm [4]) indicated a dimension far below the resolution of the hrCT.
Fig. 1.
The cochlear aqueduct morphological evaluations. Left panel: 3D reconstruction of the inner ear, the internal auditory canal (IAC, in green) and the CA (in red). According to Migirov and Kronenberg [16]: Type 1 CAs are visualized as a line, along their entire course. Type 2 CAs are visible in the medial two thirds of their course but are not completely visualized entirely in the lateral third. Type 3 CAs are not visualized completely along the medial two thirds of their course. Type 4 CAs are undetectable or unidentifiable. CA: cochlear aqueduct (in red), IAC: internal auditory canal (in green), A apex of the cochlea, B base of the cochlea,, LSCC: left semicircular canal, ASCC = Anterior semicircular canal, PSCC = Posterior semicircular canal, L: total length of the CA, FL: CA funnel length, FW: CA funnel width. *: medial opening region of the CA, not identifiable in Type 4 CAs. Cranium shows the orientation of the head from this viewpoint
To estimate the radiological patency of the CA, we used a classification in accordance with the previously established outline by Migirov and Kronenberg [16] (Fig. 1). This classification was the following: Type 1 CAs were visualized as a line, along their entire course. Type 2 CAs were visible in the medial two thirds of their course but are not completely visualized entirely in the lateral third. Type 3 CAs were not visualized completely along the medial two thirds of their course. Type 4 CAs were undetectable or unidentifiable.
Analysis
Prism 9.0.2 (GraphPad Software LLC) was used for the statistical analysis. Wilcoxon rank-sum test and chi-squared test were used to compare the dimensions and types in the different groups, respectively (the data failed the Shapiro–Wilk normality test). Statistical differences in the dimensions of the subgroups were compared using one-way ANOVA (Kruskal–Wallis test by ranks); once the significance of the group differences (p ≤ 0.05) was established, Dunn’s tests were used for post-hoc comparisons between pairs of groups. p-values are indicated in the legends of each figure.
Results
The dimensions of the CA were significantly smaller in children compared with adults for the axial length (10.37 ± 2.58 versus 14.63 ± 2.40 mm, respectively, p < 0,001) and the funnel length (3.94 ± 1.59 versus 6.01 ± 1.77 mm, respectively, p < 0,001). The funnel width tended to be smaller but the difference was not significant: 3.49 ± 1,33 versus 3.89 ± 1.07 mm, p = 0,22. The repartition of types of CA as described by Migirov and Kronenberg [16] was also statistically different. The CA was more patent in the children population. Type 1 (CA visible along its entire course) accounted for 42% (36/85) of children and only 5% (1/22) of adults, type 2 for 30% (25/85) versus 31% (7/22), type 3 for 27% (23/85) versus 50% (11/22). Finally, type 4 (undetectable) was found in only 1% (1/85) of children and 14% (3/22) of adults (p < 0,001). When comparing the left and right temporal bone for each patient, the CA types were not significantly different (Wilcoxon matched-pairs test, p = 0.17). We observed the same CA type on both sides in 49% (26/53) of patients (Supplementary Data Fig. 1).
The cochlear aqueduct (CA) exhibited a rapid linear increase in its total length and in the length and width of its funnel, during the initial years of life until 6 years, followed by a shift toward a plateau into adulthood (Fig. 2).
Fig. 2.
Post-natal growth of the cochlear aqueduct dimensions. Dimensions of the total length (in red), the funnel length (in cyan) and width (in black) of the cochlear aqueduct at different age. The dimensions exhibited a rapid linear increase during the first years of life until 6 years, followed by a shift toward a plateau into adulthood. Dotted line: ages defining different subgroups. Non-linear regression, respectively: R2 = 0.72; R2 = 0.29; R2 = 0.36. The 95% confidence interval are represented
We found that the total length was significantly different between group 1 (less than 1 year), 2 (1 to 2 years) and 3 (3 to 6 years) and the adult group (7.32 ± 1.02, 9.22 ± 0.98, 11.53 ± 1.54, 14.36 ± 2.35 mm, respectively, p < 0.001). However, the length of the group 4 (7 to 18 years, 13.60 ± 1.64 mm) was similar to the adult group (p = 0.54) (Fig. 3A).
Fig. 3.
Subgroup analysis of the cochlear aqueduct dimensions and types. A The total length of the cochlear aqueduct, and its funnel (enlarged medial portion) length and width are shown. B The classification of cochlear aqueduct types according to Migirov and Kronenberg gives an estimation of the ossification of the cochlear aqueduct, (type one is visualized along their entire course, type 4 is undetectable and completely ossified). Kruskal–Wallis test by ranks, p < 0.05 (*), p < 0.001 (**), p < 0.001 (***), p < 0.0001 (****)
The funnel length statistically increased in size between group 1 and 2 (2.62 ± 0.61 and 4.40 ± 1.42 mm, respectively, p < 0.03). No difference was found between group 2, group 3 (4.44 ± 1.45 mm) and group 4. However, a statistical difference was observed between group 4 and the adults (4.65 ± 1.41 versus 6.01 ± 1.77 mm, respectively, p = 0.049) (Fig. 3A).
The funnel width was not different between group 1 and group 2 (2.34 ± 0.46 versus 3.12 ± 0.81 mm, respectively, p = 0,44), but became significant between group 1 and group 3 (4.44 ± 1.46 mm, p = 0.0001). The funnel width was similar between group 3 (4.11 ± 1.46 mm) and group 4 (4.23 ± 1.05 mm) and adults (3.89 ± 1.07 mm) (Fig. 3A).
Regarding the types of CA, the repartition was statistically different between the groups (Fig. 3B). The proportion of type 1 and type 2 CAs showed an increase in younger age groups, whereas there was a corresponding increase in the proportion of type 3 and type 4 with advancing age (chi-square test for trend, 13.26, 1, p < 0.0001).
Discussion
In this hrCT study, we described the postnatal growth of the CA in normal temporal bones. We showed that the total length of the CA greatly increased. The funnel of the CA (i.e. the largest part at its medial opening) increased in length significantly between the first and second year of age, and then plateaued until teenagerhood. Its width increased less; children older than 2 years presenting similar width than adults. The CA was more identifiable in hrCT in children, arguing for a more permeable tract. The number of completely ossified CA was significantly lower in the children population.
Our study is the first description of the radiological normal growth of the CA in children. The assessment of cochlear aqueduct morphology has predominantly relied on histological methods in a few specimens of pediatric temporal bone, as elucidated by E. Bachor et al.[14]. Discrepancies in measurements arose during the comparison of their histological findings with our radiological results: the mean total length was 4.64 mm in their study, versus 10.37 mm in ours. Potential explanations for these variations include the singular two dimensions histological cut used for the measurements, whereas we recalculated the total length in three dimensions. Moreover, the age of their population was younger, which encompassed patients up to 9 years old, contrasting with our study that included individuals up to 18 years of age. Finally, histopathological techniques classically induce shrinkage of the observed tissue, while CT scans tend to overestimate slightly the size of the measured structures [17, 18]
Prenatal growth of the CA has been described by Mejdoubi and colleagues [19], in radiological study throughout gestation in 153 fetuses. This study found that the CA dimensions grew during the fetal period, except for the aperture, which remained smaller than in adults, indicating a postnatal growth. The dimensions of the CA of late gestational ages (average axial length of 5 mm) were in line with the dimensions of our group of children before 1 year of age (7.32 ± 1.02 mm). Additionally, the CA was frequently not permeable at early gestational ages but consistently became patent later on, pointing to a fetal widening process. This was concordant with our results showing a significant increase of the CA dimensions in the first 2 years of age, in terms of its total length and its funnel dimensions.
The classification of the different types of CA is based on the ability to follow a hypodense tract from the cranial opening to the cochlear aperture. As an example, type 1 represents a complete visible tract, and type 4 represents unidentifiable or completely ossified CA. This classification can give an estimation of the patency of the CA. Our results suggest a wider and more patent CA in young children, significantly before 2 years, even if this estimation, based on hrCT, does not necessarily correlate with a fully patent duct. Since its identification, doubts have arisen regarding the patency of the cochlear aqueduct. It is widely permeable in small mammals and in the macaque, allowing for example the passage of viral vectors between the cisternal space and the inner ear fluids in both direction [20–23]. In humans, it has been shown that it is obliterated by bone or soft tissues in 66% of the observed adult temporal bone [4], and its functional role is controversial. CA can be filled with loosely arranged connective tissues [4, 24] in close relation with the round window membrane [25] that can modulate the diffusion of fluid. Mathiesen et al. [21] have recently described these tissues as lymphatic-like in mice, and showed they may play a role of diffusion of viral vectors from the cisternal space to the inner ear fluids. Whether or not the CA of children is widely open, allowing free passage of fluid and particles, or filled with connective tissues is unknown. Understanding the developmental course of this communication between the cochlea and the cerebrospinal fluids holds interest for the understanding of the pharmacodynamics of drugs and viral vectors administered to the cochlea in children. Successful gene therapy studies in mouse models of human deafness [26, 27] have paved the way for developing treatments for congenital genetic deafness. The clinical trials involve inner ear injections of viral vectors in young children (NCT05821959, NCT05901480, NCT05788536, ChiCTR2200063181, Audiogene clinical trial). A key question will be the pharmacodynamics of the infused solution. Our results suggest an increased patency based on hrCT, that could facilitate the permeability into the cerebral fossa, especially in children under 2 years of age. A precise description of the barriers and routes of communication of the temporal bone in the pediatric population is needed to clarify the efficacy and security of the future protocols. We previously showed that the passage of viral vectors was possible from the cisternal space to both cochleae in adult mice [20]. The findings of this hrCT study suggest that this route could be relevant in young children, with interest in defining new surgical access to the inner ear.
Finally, an increased patency of the CA the children population raises the question of shifts in inner ear pressure during childhood, as the CA becomes gradually longer and more obliterated. Understanding the postnatal trajectory of this anatomical conduit not only gives a perspective for investigating the functional adaptation of the inner ear, but also can explain various pathologies related to its role in the communication between the inner ear and the cerebrospinal fluid. These pathologies encompass complications associated with otitis, meningitis, as well as the post-lumbar puncture syndrome [4, 28].
Supplementary Information
Below is the link to the electronic supplementary material.
Author Contribution
Maha Abbas managed data curation, formal analysis, validation, investigation, visualization, methodology, and the review and editing process. Jing Wang has been pivotal in the methodology, supervision, and has been instrumental in drafting the original manuscript as well as in the subsequent administration and editorial processes. Nicolas Leboucq managed data curation and methodology. Michel Mondain has been pivotal in the conceptualization and methodology of the project. Fabian Blanc has led the project, contributing to the conceptual framework, visualization, methodology, supervision, and has been instrumental in drafting the original manuscript as well as in the subsequent administration and editorial processes.
Data Availability
All data generated or analyzed during this study are included in this published article and its Supplementary Information, and individual data are represented as single dots in the figures.
Declarations
Conflict of Interest
The authors declare no competing interests, financial or personal influences, related to this article.
Footnotes
Publisher's Note
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
All data generated or analyzed during this study are included in this published article and its Supplementary Information, and individual data are represented as single dots in the figures.