This is a pre-publication version of this manuscript. Please DO NOT distribute without permission.
Acknowledgments: The authors would like to acknowledge Dr. Stratos Achlatis for assistance in study planning and Jane Kelly for assistance with reliability analysis.
Age-related changes in pharyngeal lumen size: A retrospective MRI analysis
Age-related loss of muscle bulk and strength (sarcopenia) is often cited as a potential mechanism underlying age-related changes in swallowing. Our goal was to explore this phenomenon in the pharynx, specifically, by measuring pharyngeal wall thickness and pharyngeal lumen area in a sample of young vs older women. MRI scans of the neck were retrospectively reviewed from 60 women equally stratefied into three age groups (20s, 60s, 70+). Four deidentified slices were extracted per scan for randomized, blinded analysis: one midsagittal and three axial slices were selected at the anterior inferior border of C2 and C3, and at the pit of the vallecula. Pixel-based measures of pharyngeal wall thickness and pharyngeal lumen area were completed using ImageJ and then converted to metric units. Measures of pharyngeal wall thickness and pharyngeal lumen area were compared between age groups with one-way ANOVAs using Sidak adjustments for post-hoc pairwise comparisons. A significant main effect for age was observed across all variables whereby pharyngeal wall thickness decreased and pharyngeal lumen area increased with advancing age. Pairwise comparisons revealed significant differences between 20s vs 70+ for all variables and 20s vs 60s for all variables except C2. Effect sizes ranged from 0.54 to 1.34. Consistent with exisiting sacropenia literature, the pharyngeal muscles appear to atrophy with age and consquently, the size of the pharyngeal lumen increases.
A vital mechanism for safe and efficient bolus propulsion through the pharynx during swallowing is through the action of the pharyngeal muscles. The pharyngeal constrictors successively contract and relax behind the bolus in a peristaltic action, propelling it toward and through the esophagus, while the longitudinal muscles of the pharynx facilitate simultaneous pharyngeal shortening, decreasing the distance the bolus must travel [1,2]. Deficits in pharyngeal muscle contraction can result in post-swallow residue [3-8] with increased aspiration risk once the pharynx reverts to a post-swallow breathing configuration [9,10].
Sarcopenia, the age-related reduction of muscle mass and associated strength , is thought to play a role in presbyphagic changes to swallow function. Although research in sarcopenia of swallowing musculature has been primarily focused on the tongue [12-16], there is emerging evidence for similar changes in the pharynx. In 2001, Kendall and Leonard  employed two-dimensional lateral view videofluoroscopy to demonstrate delayed and incomplete pharyngeal constriction in elderly patients compared to both younger and age-matched non-dysphagic controls. In 2004  they demonstrated that the elderly (non-dysphagic) had greater unobliterated pharyngeal space during maximal constriction in swallowing (e.g., poorer pharyngeal constriction) compared to healthy young controls. In the same study, using an anterior-posterior videofluoroscopic view, they found that the maximal width of the pharynx during swallowing was greater in elderly participants compared to younger controls. They suggest that this finding could be explained by tissue changes to the pharyngeal musculature common in aging. Most recently, Aminpour, Leonard, Fuller and Belafsky  found reduced pharyngeal wall thickness both at rest and during swallowing in older subjects as measured on lateral view videofluoroscopy. No differences were observed between men and women in either age category.
Taken together, the existing literature supports the notion that pharyngeal muscles are prone to atrophy with aging. These changes are also likely associated with increased pharyngeal lumen size at rest. In the current study, we sought to examine pharyngeal lumen size from axial MRI slices in young and older women. We hypothesized that a) pharyngeal muscle thickness would decrease with advancing age and b) pharyngeal lumen size would increase with advancing age. To address this issue, sagittal and axial MRI slices of the neck were examined from 60 women across three age groups (20s, 60s and 70+).
Participants: The current study was approved by the Institutional Review Board. Electronic medical charts from women who underwent MRI of the neck at our local institution between June 2011 and July 2014 were reviewed Exclusion criteria included past history of dysphagia, obstructive sleep apnea, progressive neurological disease, neurological injury, cervical spine surgery and/or head and neck malignancy treated with radiation ±chemotherapy. Twenty participants were consecutively enrolled into each of three age categories (20s, 60s and 70+) resulting in a total sample of 60 patients stratified by age. All studies were conducted in the supine position. In the analysis phase, scans from two participants in the oldest category were excluded secondary to poor image quality (n=1) and mid-swallow capture (n=1). Details regarding the age distribution of our sample is as follows: 20s (n = 20, mean = 25.4 years, SD = 2.8), 60s (n = 20, mean = 63.8 years, SD = 2.5) and 70+ (n = 18, mean = 76.6 years, SD = 5.4).
Data Extraction: Using the mid-sagittal slice from each MRI, three additional axial T1 weighted 1mm thick slices were extracted for analysis– one from the anterior inferior border of C2, one from the anterior inferior border of C3, and one from the pit of the vallecula (Figure 1). These four images per participant, henceforth abbreviated as Sag, C2, C3, and Vpit, were de-identified, assigned unique alpha-numeric codes and randomized for blinded analysis.
INSERT FIGURE 1 HERE
Measurement: All analyses were conducted by the first author using ImageJ (National Institutes of Health, Bethesda, MD). First, using the line tool, the thickness (pixels) of the pharyngeal musculature was measured from midline of all three axial images (see Vpit example in Figure 2) and from the sagittal image at the level of the anterior inferior corner of C3. Using the wand (tracing) tool and the brush selection tool, the area (pixels) of the pharyngeal lumen was measured from the three axial images (see Vpit example in Figure 2). When the epiglottis was apparent in the lumen, the lumen measurement included the epiglottis. Similarly, Vpit images often included pyriform sinus space, which was also included in the lumen measurement. Next, using the line tool the length of the C2-4 vertebra (from the anterior inferior corner of C2 to the anterior inferior corner of C4) was measured (pixels) to provide an indicator of subject size [19,20]. Finally, the length a 1-centimeter (cm) calibration ruler segment was measured in pixels using the line tool so that all measurements could be transformed from pixels to cm or cm2. Fifteen percent of the data were re-rated for intra-rater reliability as well as rated by a second rater (trained research assistant) for inter-rater reliability. Reliability was tested on all pixel-based outcome variables using two-way mixed intraclass coefficients (ICC) for consistency. Reliability results appear in Table 1. All values fall within the good to excellent range .
INSERT FIGURE 2 HERE
INSERT TABLE 1 HERE
Data Analysis: All statistical analyses were conducted using IBM SPSS Statistics, version 21. Two-tailed p-values < 0.05 were considered statistically-significant. Pearson’s correlation coefficients were first used to examine the relationship between participant size (C2-4 length) and each dependent variable. Correlations of r>0.2 were a priori deemed as appropriate for inclusion of participant size in subsequent statistical models as a potential covariate. Dependent variables included pharyngeal lumen area (at C2, C3 and Vpit) and pharyngeal wall thickness (at C2, C3, Vpit and Sag). Incidentally, none of these variables were significantly correlated with C2-4 length and therefore no participant size covariates were included in subsequent analyses. One-way ANOVAs with a between-participant factor of age category (20s, 60s and 70+) were run to test the influence of age on pharyngeal muscle thickness and pharyngeal lumen size. When main effects were significant, post-hoc pairwise comparisons were conducted with Sidak adjustments for multiple comparisons and effect size was calculated using Cohen’s d.
Descriptive statistics and main effects for age appear in Table 2. All measures of pharyngeal muscle thickness and pharyngeal lumen area revealed a significant main effect for age. Detailed findings for each measure are discussed below.
INSERT TABLE 2 HERE
Pharyngeal Muscle Thickness: A significant main effect of age was found for all four measures of pharyngeal wall thickness whereby pharyngeal wall thickness decreased with advancing age (Figure 2). Significant pairwise comparisons were discovered for 20s vs 70+ at all four levels and for 20s vs 60s at all levels except C2. In addition, significant pairwise comparisons were found between the two older age groups at the level of C3 and Vpit. Effect sizes were found to be medium to large, ranging from 0.54 to 1.34 .
INSERT FIGURE 3 HERE
Pharyngeal Lumen Area: A significant main effect for age was found for all four measures of pharyngeal lumen area whereby pharyngeal lumen area increased with advancing age (Figure 3). Significant pairwise comparisons were observed for 20s vs 70+ at all four levels and for 20s vs 60s at all levels except C2. No significant pairwise comparisons for pharyngeal lumen size were observed between the two older age groups. Effect sizes were found to be medium to large, ranging from 0.72 to 1.09 .
INSERT FIGURE 4 HERE
This retrospective study investigating the thickness of the pharyngeal muscles and the size of the pharyngeal lumen on MRI in young and older women supports the hypothesis that swallowing musculature is prone to sarcopenic changes associated with aging. Significant differences between young and older women were observed for both pharyngeal muscle thickness and pharyngeal lumen size at all anatomical levels measured (C2, C3, Vpit and Sag). The pharyngeal wall thickness data from the sagittal MRI slices replicate previous work  from (lateral) view videofluoroscopy with comparable data despite different imaging modalities. The young women in Aminpour’s sample had a mean pharyngeal wall thickness of 0.376 cm (mean=0.367 cm in the current study) and their older women had a mean pharyngeal wall thickness of 0.292 cm (mean=0.283 cm in the current study, pooled across 60s and 70+).
Pharyngeal constriction and shortening are crucial in the execution of an efficient pharyngeal swallow . Previous work has confirmed that elderly people have delayed onset of pharyngeal contraction and poorer pharyngeal constriction during swallowing compared with their younger counterparts . Elderly individuals are also more likely to have post-swallow residue [23-25] which has been associated with reduced amplitude of pharyngeal contraction on pharyngeal manometry . These impairments are all thought to be associated with age-related reductions in pharyngeal muscle function. The present study adds to the existing literature by confirming that the size of the pharyngeal lumen increases with aging. What remains unknown at present, is what impact this increase has on swallowing function. As pharyngeal lumen size increases, one can imagine that greater contractile forces over larger distances may be required to achieve adequate pharyngeal constriction. The pharyngeal lumen is not only comprised of pharyngeal muscles. The base of the tongue forms the anterior border of the hypopharynx. Constriction of the pharynx is achieved by approximation of the base of tongue to the posterior-lateral pharyngeal walls. The current data illustrate the need for careful prospective study of the relationship between muscle atrophy (pharynx and base of tongue), pharyngeal lumen size, and functional swallowing outcomes. This work should elucidate whether there is a threshold for the degree of muscle loss (or lumen size) that interferes with functional swallowing and whether that threshold is specific to certain etiological conditions (i.e. myopathy). Future work should also attempt to prospectively separate age-related muscle loss (sarcopenia) from disease-related muscle loss (disuse atrophy).
This study sample was limited to women, and replication in men is warranted especially in light of theories that muscle mass loss in women may be impacted by post-menopausal decline in estrogen . However, it is worth pointing out that in their large sample of 178 normal adults, Aminpour and colleagues  found no significant difference in pharyngeal wall thickness from lateral videofluoroscopy between men and women in either the young or old age categories. However, we acknowledge that because this data was collected in a supine position and subject to different gravitational forces, comparisons to seated, upright data are limited. Finally, we acknowledge that there are other dimensional characteristics of the pharynx prone to changing with advancing age such as pharyngeal length and total volume . The impact of these changes on swallowing function also warrants careful prospective study.
The current study contributes to a growing body of literature regarding age-related changes to swallowing musculature. Specifically, we replicated previous findings that pharyngeal muscle thickness decreases with advancing age. Further, we provided quantitative evidence that size of the pharyngeal lumen at rest appears to increase with age. Future work should focus on the functional implications for these changes.
Reliability- ICC (95% CI)
Pharyngeal Wall Thickness (cm)
Sag (at C3)
Pharyngeal Lumen Area (cm2)
Table Reliability Analyses using Intraclass Coefficients (ICC) and 95% Confidence Intervals (CI).
Table Descriptive statistics and main effects of age for all dependent variables.
Figure Four MRI slices extracted for analysis: Sagittal (Sag), anterior inferior C2 (C2), anterior inferior C3 (C3), pit of the vallecula (Vpit). Measures of pharyngeal wall thickness (in midline on axial images and at anterior inferior C3 on Sag) and pharyngeal lumen area (from axial images only) were extracted.
Figure Example of pharyngeal lumen area and pharyngeal muscle thickness measures from a representative Vpit slice.
Figure Results of pharyngeal muscle thickness by age analysis. Significance of p <0.05 is indicated by *. d = effect sizes for significant pairwise comparisons.
Figure Results of pharyngeal lumen area by age analysis. Significance of p <0.05 is indicated by *. d = effect sizes for significant pairwise comparisons.
Conflicts of Interest
This work has been accepted for oral presentation at the 2015 Dysphagia Research Society Meeting. No conflicts of interest to disclose.
1. Kahrilas PJ, Logemann JA, Lin S, Ergun GA. Pharyngeal clearance during swallowing: A combined manometric and videofluoroscopic study. Gastroenterology 1992;103(1):128-136.
2. Leonard R, Kendall KA, McKenzie S. Structural displacements affecting pharyngeal constriction in nondysphagic elderly and nonelderly adults. Dysphagia 2004;19(2):133-141.
3. Logemann JA. Evaluation and treatment of swallowing disorders. 2nd ed. Austin, TX: Pro-Ed; 1998.
4. Leonard R, Rees CJ, Belafsky P, Allen J. Fluoroscopic Surrogate for Pharyngeal Strength: The Pharyngeal Constriction Ratio (PCR). Dysphagia 2011;26(1):13-17.
5. Palmer JB, Tanaka E, Ensrud E. Motions of the posterior pharyngeal wall in human swallowing: A quantitative videofluorographic study. Arch Phys Med Rehabil 2000;81(11):1520-1526.
6. Olsson R, Castell J, Johnston B, Ekberg O, Castell DO. Combined videomanometric identification of abnormalities related to pharyngeal retention. Acad Radiol 1997 5;4(5):349-354.
7. Pauloski BR, Logemann JA, Fox JC, Colangelo LA. Biomechanical analysis of the pharyngeal swallow in postsurgical patients with anterior tongue and floor of mouth resection and distal flap reconstruction. J Speech Hear Res 1995;38(1):110-123.
8. Ekberg O, Nylander G. Pharyngeal constrictor paresis in patients with dysphagia: a cineradiographic study. Clin Radiol 1982;33(3):253-258.
9. Dejaeger E, Pelemans W, Ponette E, Joosten E. Mechanisms involved in postdeglutition retention in the elderly. Dysphagia 1997;12(2):63-67.
10. Perlman AL, Booth BM, Grayhack JP. Videofluoroscopic predictors of aspiration in patients with oropharyngeal dysphagia. Dysphagia 1994;9(2):90-95.
11. Berger MJ, Doherty TJ. Sarcopenia: Prevalence, mechanisms, and functional consequences. Interdisciplinary Topics in Gerontology 2010;37:94-114.
12. Robbins J, Kays SA, Gangnon RE, Hind JA, Hewitt AL, Gentry LR, et al. The Effects of Lingual Exercise in Stroke Patients With Dysphagia. Arch Phys Med Rehabil 2007;88(2):150-158.
13. Robbins J, Gangnon RE, Theis SM, Kays SA, Hewitt AL, Hind JA. The effects of lingual exercise on swallowing in older adults. J Am Geriatr Soc 2005;53(9):1483-1489.
14. Ota F, Connor NP, Konopacki R. Alterations in contractile properties of tongue muscles in old rats. Annals of Otology, Rhinology and Laryngology 2005;114(10):799-803.
15. Nagai H, Russell JA, Jackson MA, Connor NP. Effect of aging on tongue protrusion forces in rats. Dysphagia 2008;23(2):116-121.
16. Feng X, Todd T, Lintzenich CR, Ding J, Carr JJ, Ge Y, et al. Aging-related geniohyoid muscle atrophy is related to aspiration status in healthy older adults. Journals of Gerontology - Series A Biological Sciences and Medical Sciences 2013;68(7):853-860.
17. Kendall KA, Leonard RJ. Pharyngeal constriction in elderly dysphagic patients compared with young and elderly nondysphagic controls. Dysphagia 2001;16(4):272-278.
18. Aminpour S, Leonard R, Fuller SC, Belafsky PC. Pharyngeal wall differences between normal younger and older adults. ENT: Ear, Nose & Throat Journal 2011;90(4).
19. Molfenter SM, Steele CM. Use of an anatomical scalar to control for sex-based size differences in measures of hyoid excursion during swallowing. Journal of Speech, Language, and Hearing Research 2014:1-11.
20. Chitose S, Haraguchi M, Nagata S, Katayama R, Sato K, Fukahori M, et al. Analysis of Passive Motion of Para-and Retropharyngeal Structures During Swallowing Using Dynamic Magnetic Resonance Imaging. Dysphagia 2014:1-9.
21. Fleiss JL. The design and analysis of clinical experiments. New York: Wiley; 1986.
22. Kotrlik J, Williams H. The Incorporation of Effect Size in Information Technology, Learning, and Performance Research. Inform Technol Learn Perform 2003;21:1.
23. Yoshikawa M, Yoshida M, Nagasaki T, Tanimoto K, Tsuga K, Akagawa Y, et al. Aspects of swallowing in healthy dentate elderly persons older than 80 years. J Gerontol A Biol Sci Med Sci 2005 Apr;60(4):506-509.
24. Cook I, Weltman M, Wallace K, Shaw D, McKay E, Smart R, et al. Influence of aging on oral-pharyngeal bolus transit and clearance during swallowing: scintigraphic study. American Journal of Physiology-Gastrointestinal and Liver Physiology 1994;29(6):G972.
25. Ekberg O, Feinberg MJ. Altered swallowing function in elderly patients without dysphagia: Radiologic findings in 56 cases. Am J Roentgenol 1991;156(6):1181-1184.
26. Dejaeger E, Pelemans W, Bibau G, Ponette E. Manofluorographic analysis of swallowing in the elderly. Dysphagia 1994;9(3):156-161.
27. Messier V, Rabasa-Lhoret R, Barbat-Artigas S, Elisha B, Karelis AD, Aubertin-Leheudre M. Menopause and sarcopenia: a potential role for sex hormones. Maturitas 2011;68(4):331-336.
28. Xue, SA and Hao, GJ. Changes in the human vocal tract due to aging and the acoustic correlates of speech production: A pilot study. Journal of Speech, Language, and Hearing Research 200346: 689-701.