research.steinhardt.nyu.edu · Web viewmusculature 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

Age Related Changes in Pharyngeal Lumen Size: A Retrospective MRI Analysis

Manuscript submission to Dysphagia

Molfenter, S.M.1, Amin, M.R.2, Branski, R.C. 2, Brumm, J.D. 2, Hagiwara, M.3, Roof, S.A.2 & Lazarus, C.L.4

1. Communicative Sciences & Disorders, Steinhardt, New York University, New York, NY2. Otolaryngology-Head and Neck Surgery, New York University Langone Medical Center,

New York, NY3. Radiology, New York University Langone Medical Center, New York, NY4. Otolaryngology-Head & Neck Surgery, Mount Sinai Beth Israel, New York, NY

Corresponding Author:

Sonja M Molfenter, Ph.D. Communicative Sciences & DisordersNew York University665 Broadway, Room 934 New York, NY 10012Tel: (212) 992 7694E-mail: [email protected]

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 2

Age-related changes in pharyngeal lumen size: A retrospective MRI analysis

Abstract

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.

Keywords

Swallowing, Deglutition, Aging, Pharynx, Sarcopenia


Introduction

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 [11], 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 [17]

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 [2] 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 [18] 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+).

Methods

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 [21].


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.

Results

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 [22].


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 [22].



Discussion

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 [18]

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 [1]. Previous work has confirmed that elderly people have delayed onset of

pharyngeal contraction and poorer pharyngeal constriction during swallowing compared with

their younger counterparts [17]. 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 [26]. 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).

Limitations

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 [27]. However, it is worth pointing out that in their large sample of 178

normal adults, Aminpour and colleagues [18] 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 [28]. The impact of

these changes on swallowing function also warrants careful prospective study.

Conclusion

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)Intra-rater Inter-rater

Pharyngeal Wall

Thickness (cm)

C2 0.91 (0.59-0.98) 0.93 (0.73-0.98)C3 0.99 (0.96-0.99) 0.89 (0.58-0.97)Vpit 0.96 (0.84-0.99) 0.81 (0.37-0.96)

Sag (at C3) 0.94 (0.73-0.99) 0.86 (0.69-0.98)

Pharyngeal Lumen Area

(cm2)

C2 0.94 (0.74-0.99) 0.99 (0.96-0.99)C3 0.98 (0.91-0.99) 0.97 (0.86-0.99)Vpit 0.99 (0.94-0.99) 0.96 (0.84-0.99)

Table 1 Reliability Analyses using Intraclass Coefficients (ICC) and 95% Confidence Intervals (CI).


Age Categorymean (SD) Main Effect of Age

20s 60s 70+ F statistic p

Pharyngeal Muscle

Thickness (cm)

C2 0.25 (0.05) 0.22 (0.08) 0.19 (0.07) 4.2 0.020

C3 0.29 (0.07) 0.25 (0.06) 0.19 (0.05) 11.7 0.000

Vpit 0.32 (0.08) 0.26 (0.09) 0.21 (0.06) 10.9 0.000

Sag 0.37 (0.09) 0.30 (0.09) 0.27 (0.08) 6.5 0.003

Pharyngeal Lumen Area

(cm2)

C2 1.55 (0.63) 2.02 (0.57) 2.44 (1.43) 4.2 0.019

C3 1.90 (0.88) 2.89 (1.06) 3.29 (1.46) 7.5 0.001

Vpit 1.95 (0.99) 2.81 (0.94) 3.22 (1.27) 7.0 0.002

Table 2 Descriptive statistics and main effects of age for all dependent variables.


Figure 1 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 2 Example of pharyngeal lumen area and pharyngeal muscle thickness measures from a representative Vpit slice.


Figure 3 Results of pharyngeal muscle thickness by age analysis. Significance of p <0.05 is indicated by *. d = effect sizes for significant pairwise comparisons.


Figure 4 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.


Works Cited

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 2003 46: 689-701.

Documents

research.steinhardt.nyu.edu · Web viewmusculature 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