Anatomical variations of the frontal sinus: A computed tomography-based study

Background: The pneumatization of the frontal sinus is variable between individuals, including monozygotic twins. The volumetric anatomic variants of the frontal sinus are classified into aplasia, hypoplasia, medium-sized, and hyperplasia. We aimed to study the frontal sinus morphology in Omani patients using computed tomography (CT) evaluations. Methods: Retrospectively, 1220 frontal sinus CT scans from 610 patients investigated at Sultan Qaboos University Hospital, Oman, from January 2019 to December 2020 were reviewed. The frontal sinus morphology was classified according to the classification proposed by Guerram et al. The Chi-square test was used to determine the influence of sex. Results: With regard to the unilateral occurrence, the most prevalent frontal sinus category observed was medium-sized (13.3%), followed by hyperplasia (7.9%), hypoplasia (5.4%), and aplasia (2%) categories. Similarly, in bilateral occurrence, the most common frontal sinus category observed was medium-sized (53%), followed by hyperplasia (13.1%), hypoplasia (3.4%) and aplasia (2%) categories. Right and left frontal sinus aplasia were observed in 2.1% and 1.8% of cases, respectively. In terms of sex influence, the left unilateral ( p<0.01) and the bilateral hypoplasia ( p<0.05) were significantly higher in females. On the other hand, the left unilateral ( p<0.01) and the bilateral hyperplasia ( p<0.05) were higher in males. Conclusions: The baseline data of frontal sinus category frequencies reported in the present study is helpful in the diagnostic evaluation of sinusitis in the clinical setting. The preoperative recognition of frontal sinus types, particularly frontal sinus aplasia in multiplanar CT scans, is crucial to avoid unexpected complications while performing endoscopic sinus surgery.


Introduction
Frontal sinuses are a pair of funnel-shaped pneumatic cavities situated in the squamous part of the temporal bone.Two frontal sinuses are separated by a bony septum, which is rarely located in the midline. 1 Frontal sinuses emerge as an outgrowth in the region of the frontal recess of the nose in the fourth month of intrauterine life.At birth, they are rudimentary or absent.They begin to develop and become evident only after the second year of life.They grow at the age of seven or eight and mature after puberty. 2,3After 20 years of age, the size of the sinuses remains unchanged until the atrophic changes begin to appear due to advancing age. 4 Frontal sinuses drain into the anterior part of the middle meatus of the nose through an ethmoid infundibulum or a frontonasal duct.The volume of the frontal sinus is highly variable between the two individuals.In adults, the mean size of the sinus is around ten cc and it may reach a maximum of 37 cc. 5 Frontal sinuses are rarely symmetrical as both sinuses develop individually. 5The pneumatization of the frontal sinus is known to be highly variable.The frontal sinus morphology varies from aplasia to hyperplasia within the same individual and even between monozygotic twins. 6][9][10][11][12] These studies have confirmed that climate and geography influence the frontal sinus morphology differences between the populations.7][18][19][20] Furthermore, these variations and the unique morphology of the frontal sinus are helpful in the identification of subjects for forensics. 14,21Previously, few studies have proposed classifications for frontal sinus morphology based on two-dimensional and three-dimensional evaluations.Despite tremendous clinical significance, few recent papers have dealt with frontal sinus morphology, particularly in Middle Eastern populations.Hence, the objective of the present study was to assess the frontal sinus morphology in Omani patients using computed tomography (CT) according to the classification by Guerram et al. 10

Patient population
The present study is a retrospective review of the electronic medical records database (TrakCare Unified Health Information System) at the Department of Radiology and Molecular Imaging, Sultan Qaboos University Hospital, Oman.All Omani patients aged ≥18 years referred for CT scan of the paranasal sinuses from January 2019 to December 2020 were included in the study.Patients with anterior skull base trauma, fibro-osseous lesions or significant motion artifacts that impaired the visualization of the frontal sinuses were excluded from the study.The present study obtained institutional ethical approval from the Medical Research Ethics Committee, Sultan Qaboos University.

CT acquisition protocol
All the scans were performed using a 64 multidetector CT scanner (Siemens Sensation 64) with the following parameters: 120 kVp, tube current modulation with reference mAs of 130 and 0.75-mm slice thickness.The Picture Archiving and Communication System (PACS) (Synapse PACS, FUJIFILM Worldwide, version 5.7.102) was used for screening the scans.

Data collection and definitions
We evaluated right and left frontal sinuses from 610 patients' CT scans, based on the standard method described by Guerram et al., to determine the prevalence of frontal sinus size categories. 10Using this method, frontal sinus size was categorized into four types, including aplasia, hypoplasia, medium-sized, and hyperplasia.To evaluate the frontal sinus categories, supraorbital and mid-orbital lines were generated on CT sections.The supraorbital line was a horizontal tangent connecting the superior margins of both orbits, while the mid-orbital line was a vertical line drawn at the midpoint of the distance between the medial and lateral borders of the orbit parallel to the mid-sagittal plane.Based on these lines, frontal sinus size categories were classified as follows: Aplasia: no pneumatization; Hypoplasia: minimal pneumatization under the supraorbital line; Medium-sized: pneumatization over the supraorbital line but medial to the mid-orbital line; Hyperplasia: lateral to the mid-orbital line (Figure 1).All the scans were reviewed by a single observer who is a boardcertified radiologist.After screening, the data from each patient was recorded in the Microsoft Excel spreadsheet.

REVISED Amendments from Version 1
The following information was added to the new version of the manuscript: The title of the study was modified.The importance of this study was highlighted in the discussion section.Table 3, summarizing the prevalence of frontal sinus variations from different studies, was added to the discussion.The role of the frontal sinus in forensic investigation was added to the discussion and conclusion.
Any further responses from the reviewers can be found at the end of the article

Statistical analysis
The statistical analysis was performed using SPSS software package (v.23) for Windows v24.0 (IBM Corp., Armonk, N.Y., USA).Descriptive statistics (e.g., frequency and percentage) were used to present the data.The sex difference was determined using the Chi-square test.A p-value <0.05 was considered statistically significant.

Results
In the present study, the morphometry of 1220 frontal sinuses from 610 patients was recorded concerning the frequency of each type of frontal sinus.Among the study group, 314 were males (51.5%), and 296 (48.5%) were females, with a mean age of 43.1 AE 15.5 (SD) years.The unilateral and bilateral occurrence of each type of frontal sinus frequency was summarized in Tables 1 and 2. With regard to the unilateral occurrence, the most common frontal sinus category observed  was medium-sized (13.3%), followed by hyperplasia (7.9%), hypoplasia (5.4%), and aplasia (2%).Similarly, in bilateral occurrence, the most common frontal sinus category observed was medium-sized (53%), followed by hyperplasia (13.1%), hypoplasia (3.4%) and aplasia (2%) categories, respectively.Right and left frontal sinus aplasia were observed in 2.1% and 1.8% of cases, respectively.The sex-wise distribution of frontal sinus categories was presented in Tables 1  and 2. There was a significant sex difference in the frequencies of left frontal sinus hypoplasia and hyperplasia categories (Table 1).Regarding the bilateral occurrence, a statistically significant sex difference was observed in the frequencies of hypoplasia and hyperplasia categories.The left unilateral (p<0.01) and the bilateral hypoplasia (p<0.05) were significantly higher in females than in males (Tables 1 and 2).On the other hand, the left unilateral (p<0.01) and the bilateral hyperplasia (p<0.05) were higher in males than in females (Tables 1 and 2).The representative images of CT scans showing frontal sinus categories are provided in Figure 2.

Discussion
1][12] These studies have used different parameters for classification with a small sample size.Moreover, these studies used dry skulls for the evaluation of variants (Table 3).To the best of our knowledge, for the first time, the present study evaluated the frontal sinus volumetric anatomic variants in a large sample of patients in the Middle Eastern population and analyzed the gender and laterality differences in these variants.The present study followed Guerram et al.'s classification to determine the morphology of the frontal sinuses. 10Similar to previous studies, in the present study, the mediumsized category of frontal sinus was the most common type of frontal sinus morphology. 10,12,22The values of mediumsized frontal sinus frequency observed in the present study are comparable with the frequency of 65.84% reported in a recent study by Ozdemir et al. 22 In contrast, in a study by Yüksel Aslier et al., hyperplasia (44.5%) was the most common type, followed by medium-sized (37.2%), hypoplasia (14.2%) and aplasia (4.1%) categories. 11Similarly, in a study by Buller et al., following Guerram et al.'s morphologic classification, hyperplasia was found to be the most frequent sinus category (66%), followed by medium-sized (30.2%) and hypoplasia (3.8%) categories. 23However, no cases of aplasia were observed in this study. 23The study's small sample size and inclusion criteria could possibly be the reason for these contrasting results.After aplasia, hypoplasia of the frontal sinuses is a rare morphology of the frontal sinuses.In studies by Yuksel Aslier et al. and Guerram et al., hypoplasia was observed in 14.2% and 9.5%, respectively. 10,11The frequency of hypoplasic frontal sinuses observed in the present study (8.7%) is comparable with Guerram et al. study findings. 10egarding sex influence on frontal sinus categories, our study findings are comparable with the previous study by Guerram et al. 10 In their study, hypoplasia was higher in females (13.7%) than males (5%).On the other hand, hyperplasia was higher in males (16.3%) than in females (7.5%). 10ong different frontal sinus morphology variations, the frontal aplasia type is well documented in different populations worldwide.In the existing literature, the reported frequency of bilateral frontal sinus aplasia greatly varies among populations worldwide.In a recent study on Saudi individuals, bilateral frontal sinus aplasia was found to be 3.3%. 24n Jordanian 25 and Iranian 26 individuals, prevalences of 4.2% and 8.3% were reported, respectively.A study from Turkey reported a low prevalence of 0.73%. 7Similarly, two studies on Indian subjects reported low frequencies of 2.05% and 2.5%, respectively. 15,27Contrary to these studies, high frequencies were reported in Northern Irish (10%) and Chinese individuals (16.6%). 28,29Surprisingly, unusually high frequencies of 43% and 40%, respectively, in Canadian Inuit males and females, and 25% and 36%, respectively, in Native Alaskans males and females, were observed. 30,31These highest frequencies were thought to be due to the influence of extremely cold climatic conditions. 25In our study, the frequency of bilateral frontal sinus aplasia was noted in 2% of cases.This frequency is close to that reported in the Indian population. 15Similar or comparable frequencies of frontal sinus aplasia in relative populations could be attributed to the ontogenic development of the frontal sinus. 23In most studies, bilateral frontal sinus aplasia is found to be more frequent in females than in males. 1,7,32,33In contrast, in Jordanian subjects, the frequency is higher in males than females. 25Similar to most of the studies, bilateral frontal aplasia is found to be more common in females than in males though it was not statistically significant.
The reported frequency of unilateral frontal sinus aplasia among different populations has varied between 0.8% and 12.7%.Higher frequencies of 12.7%, 10%, 6.5%, and 6.6% unilateral aplasia were reported in Chinese, 29 Indian, 15 Saudi, 24 and Jordanian subjects, 25 respectively.In contrast, low frequencies of 1.2%, 2%, and 2.5% were reported in Turkish, 7 Northern Irish, 28 and upper Rhine subjects, 10 respectively.In Iranian subjects, unilateral aplasia was identified in 5.6% of cases. 26In Omani subjects, the recorded unilateral aplasia frequency was low and similar to Turkish subjects.Concerning the sex differences, in Indian, 33 Saudi, 24 and Turkish subjects, 1 unilateral aplasia was more common in females.On the other hand, in Jordanian, 25 Japanese 13 and Iranian subjects, 26 unilateral aplasia was more frequent in males.In the present study, unilateral aplasia was more frequent in females than in males though it was not statistically significant.With regard to laterality differences, most of the studies from Saudi Arabia, 24 Japan, 13 Turkey, 7 Iran, 26 and India 33 have reported aplasia more frequently on the right side.In contrast, no laterality difference was observed in the present study.
The anatomy of the frontal sinus is the most complex compared to other paranasal sinuses.Due to its close relationship with the anterior cranial fossa and orbits, frontal sinusitis is considered a main source of orbital and cranial complications. 34,357][18][19][20] Another recent study reported a significant association between the frontal sinus type and frontal sinusitis frequency. 22In the same study, the prevalence of sinusitis in mediumsized and large sinuses was significantly higher than in small sinuses. 22Hence, the baseline data of frontal sinus types reported in the present study is helpful in the diagnostic evaluation of sinusitis in the clinical setting.The preoperative recognition of frontal sinus types, particularly frontal sinus aplasia in multiplanar CT scans, is crucial to avoid unexpected complications while performing endoscopic sinus surgery.For example, in endoscopic sinus surgery, opening a nonexistent frontal sinus is a disastrous step. 25Furthermore, frontal sinus aplasia is known to increase the risk of having traumatic brain injuries. 36Hence, the frontal sinus morphology reported in the present study alert surgeons to rely on the preoperative radiological evaluation of the frontal sinus.The frontal sinus is well recognized for individual identification in forensic investigations. 37The unique morphological characteristics of the frontal sinus, particularly the low prevalence of frontal sinus aplasia, are helpful in individual identification by comparing antemortem and postmortem radiographs. 38Furthermore, the stability of the frontal sinus throughout life and its unique pattern, even between monozygotic twins, increased its importance in the forensic field. 39,40

Conclusions
In our study, the most prevalent frontal sinus category was medium-sized, followed by hyperplasia, hypoplasia, and aplasia categories.The sex factor influenced the frequencies of hypoplasia and hyperplasia categories.The frequencies of unilateral and bilateral aplasia were low, and these values were comparable with values reported in Indian and Turkish populations.The baseline data of volumetric anatomic variations of frontal sinuses is crucial to minimize the complications associated with surgical procedures as well as for the forensic investigations.

Are the conclusions drawn adequately supported by the results? Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Neuroradiology, Head and neck Radiology I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.

Malaysia
This manuscript is accepted and ready for publication after the minor changes I stated below.Overall, this finding can help in clinical cases such as sinusitis and trauma and the forensic case for identification.I hope that more statistical analysis should be done in the future, for example, the traditional morphometric methods, such as measurement of length and the volume of the frontal sinus, and more advanced analysis of the shape, such as geometric morphometric methods and artificial intelligence research for the future.The parameter for the identification, for example, age determination, can also increase the manuscript's value.Please add the ethics approval number in the methodology part as you use the patient data for the research.
The comments for the manuscripts as below Title -Suggested topic Anatomical variations of the frontal sinus: A computed tomographybased study. 1.
Abstract -Please change the paranasal sinus to the frontal sinus.

2.
Introduction -The introduction is enough for introducing the paper.Initially, the authors explain the anatomy of the frontal sinus, link with the previous study, and relate with the clinical and forensic function of forensic sinuses.

3.
Result: Table 1 and Table 2 Gender association is significant on the left side for hypoplasia and hyperplasia.*p<0.01.*p<0.05Please change gender to sex, while *p<0.01 to **p<0.01 and maintain *p<0.05 4.
Discussion -"Two studies on Indian subjects reported low frequencies of 2.05 and 2.5%, respectively."Please add percentage 2.05%

5.
Discussion -Please add the forensic contribution for identification from the frontal sinus.6.
Conclusion -Please add also the forensic contribution for identification from frontal sinus.7.

Are sufficient details of methods and analysis provided to allow replication by others? Yes
If applicable, is the statistical analysis and its interpretation appropriate?Partly Are all the source data underlying the results available to ensure full reproducibility?Introduction -The introduction is enough for introducing the paper.Initially, the authors explain the anatomy of the frontal sinus, link with the previous study, and relate with the clinical and forensic function of forensic sinuses.Response: Thank you for your valuable comments

3.
Result: Table 1 and Table 2 Gender association is significant on the left side for hypoplasia and hyperplasia.*p<0.01.*p<0.05Please change gender to sex, while *p<0.01 to **p<0.01 and maintain *p<0.05Response: The suggested changes were made in the results section and highlighted with track changes.

4.
Discussion -"Two studies on Indian subjects reported low frequencies of 2.05 and 2.5%, respectively."Please add percentage 2.05% Response: The correction was made.

5.
Discussion -Please add the forensic contribution for identification from the frontal sinus.Response: The importance of frontal sinus for the forensic investigation was added in the discussion and highlighted with the track changes.

6.
Conclusion -Please add also the forensic contribution for identification from frontal sinus.Response: The importance of frontal sinus for the forensic investigation 7.

Figure 1 .
Figure 1.Schematic representation of morphological classification of frontal sinus size categories.SOL: supraorbital line.MOL: midorbital line.Image was prepared using biorender.com.

Figure 2 .
Figure 2. Reformatted coronal computed tomography images of the paranasal sinuses showing types of frontal sinus pneumatization: (a) bilateral aplasia of the frontal sinuses, (b) bilateral hypoplasia, (c) mediumsized pneumatization of the right frontal sinus and hyperplasia of the left frontal sinus, and (d) bilateral hyperplasia of the frontal sinuses.

Table 1 .
The frequency of unilateral-frontal sinus size categories.
Sex association is significant on the left side for hypoplasia and hyperplasia.**p<0.01.*p<0.05;Chi-square test.Values presented as number (%).

Table 2 .
The frequency of bilateral-frontal sinus size categories.

Table 3 .
The prevalence of frontal sinus categories in different studies.