Which Videofluoroscopy Parameters Are Susceptible to the Influence of Differences in Barium Product and Concentration?

Abstract

Purpose:

Prior studies suggest there may be differences in videofluoroscopic measures of swallowing across different barium concentrations. Whether different barium products of identical concentration result in similar swallowing physiology remains unknown. This is important, as barium intended for videofluoroscopy (i.e., Bracco Varibar) is not available globally. Our aim was to identify differences in healthy swallowing across five different barium stimuli.

Method:

Twenty healthy adults (10 women), aged 22–54 years, underwent videofluoroscopy including comfortable sips of thin liquid barium: two sips of 20% weight-to-volume (w/v) barium prepared with E-Z-HD powder, and two sips each of 20%w/v and 40%w/v barium prepared with Liquid Polibar Plus and E-Z-Paque powder. Recordings were analyzed according to the Analysis of Swallowing Physiology: Events, Kinematics and Timing Method. Measures of timing, kinematics and residue were obtained. Chi-square, Friedman's, and Wilcoxon signed-ranks test were used to identify differences across stimuli.

Results:

Significant differences were seen across barium stimuli for upper esophageal sphincter (UES) opening duration, UES diameter, pharyngeal area at maximum constriction, and residue. In all cases, smaller values were seen with the 20%w/v E-Z-HD stimulus; however, this stimulus had questionable opacity for visualization. Patterns of residue severity were not explained by barium concentration.

Conclusions:

This study confirms that some measures of swallowing are influenced by barium product and/or concentration. Measures are not necessarily similar across different barium products at the same concentration. This study illustrates the importance of using standard and appropriate stimuli in videofluoroscopy, and for clinicians to report not only the product but also the concentration of stimuli used.

Supplemental Material:

https://doi.org/10.23641/asha.20669712

Videofluoroscopic swallowing studies (VFSS) are commonly used to evaluate swallowing safety and efficiency. Contrast media used in these studies are radiopaque and attenuate the X-rays. The two most common ingredients used in contrast media are barium sulfate and iodine. Barium sulfate is the most commonly used contrast agent for VFSS in North America. Barium products come in the form of powders for reconstitution and liquid suspensions. It is now common for imaging of the oropharynx to be performed using low concentration products between 20% and 40% weight-to-volume (%w/v; Martin-Harris et al., 2021; Peladeau-Pigeon & Steele, 2013; Steele et al., 2021). Standardized barium preparations designed specifically for oropharyngeal swallowing examinations, such as Bracco Imaging's Varibar (40%w/v), are not available globally. When Varibar is not available, it is common practice for clinicians to use other barium products that are intended for gastrointestinal imaging, but to mix these barium products in ways that differ from the manufacturer instructions. For example, Bracco's E-Z-HD powder is a widely used product for double-contrast radiographic examinations of the esophagus, stomach, and duodenum, for which the manufacturer instructions prescribe mixing with water to produce a 238%w/v suspension. Similarly, Bracco's E-Z-Paque powder is a 96%w/w barium product intended for single contrast radiographic examinations of the esophagus, stomach, duodenum, and small bowel, for which the manufacturer instructions indicate that water should be added to the 169 g of barium sulfate in the single-dose bottle; fill-lines are marked on the bottle to guide reconstitution of this product to concentrations ranging from 60% to 115%w/v. When products like E-Z-HD or E-Z-Paque are used in VFSS, clinicians frequently add more water to achieve a thinner bolus. In doing so, however, the barium concentration is lowered, reducing the visibility of the barium during VFSS. Additionally, when clinicians are unable to access standardized barium preparations in different consistencies (e.g., Varibar Nectar or Thin Honey suspensions), it is common practice to mix barium powders into prethickened liquids or to add commercial thickeners to a thin liquid suspension. These practices also extend into the preparation of pureed and solid consistency stimuli for use in videofluoroscopy, such as the mixing of barium powder into applesauce, or the smearing of a paste consistency barium product onto a cookie or cracker. Although widespread, nonstandard barium preparation practices are strictly off-label and result in poorly controlled barium concentration and consistency (Steele et al., 2013), which may impact both the diagnostic accuracy and comparability of VFSS examinations.

Existing literature describing the expected physiological differences across barium concentration is limited. Early work by Dantas et al. (1989) suggested that differences were present in some swallow timing measures in healthy young men between a “thin barium preparation” using a diluted liquid barium suspension (Liquid E-Z) with a 140%w/v concentration and a “thick barium preparation” of E-Z-HD described to have a 250%w/v concentration. Using simultaneous videofluoroscopy and manometry, they showed that oral transit time, pharyngeal transit time, pharyngeal clearance time, upper esophageal sphincter (UES) opening duration, and sagittal measures of UES opening diameter were all greater with the higher concentration barium stimulus, while laryngeal vestibule closure (LVC) duration and superior hyoid movement remained unchanged. One issue that is challenging to tease apart from this article, is whether the observed differences are attributable to the concentration of the barium (referred to as density in the paper) or to the associated difference in flow properties (e.g., viscosity). The higher concentration barium was reported to have a viscosity of 300 mPas, compared to 200 mPas for the lower concentration. Based on these reported viscosities, both of these products are likely to have been considerably thicker than water; however, important details regarding measurement were not provided, such as the shear rate at which viscosity was tested. Furthermore, it should be noted that both of the products in this study were used at much higher concentrations of barium than the products that are typically used in VFSS today.

Fink and Ross (2009) investigated the difference between two much lower concentration preparations of Varibar Thin Liquid barium: (a) undiluted 40%w/v and (b) an approximately 20%w/v concentration, prepared by mixing the 40%w/v product in equal proportion with water, and labelled “ultrathin” in the article. These stimuli were used to study aspiration frequency in a patient cohort referred for VFSS. The protocol began with the 40%w/v concentration stimulus, and if aspiration was not seen, the protocol continued on to the lower concentration. The authors reported that 50% of the patients who did not aspirate on the 40%w/v “thin” barium showed aspiration on at least one trial of the 20%w/v “ultrathin” barium, across the four different volumes presented. For this reason, the authors argued that the 20%w/v “ultrathin” concentration was more representative of a true thin liquid, such as water. As with the Dantas et al. study (Dantas et al., 1989), the Fink and Ross study (Fink & Ross, 2009) conflates barium concentration with viscosity using labels that imply presumed flow properties (“thin,” “ultrathin”). Additionally, the order of bolus presentation was not randomized in the study (i.e., 40%w/v was always tested first, followed by 20%w/v). We know from recent literature that patients who aspirate may not do so on every trial (Steele et al., 2019). Thus, the finding of an increased frequency of aspiration on the later trials of the 20%w/v concentration barium cannot necessarily be attributed to the difference in barium concentration alone.

Stokely et al. (2014) also used the terms “ultrathin” and “thin” in a study exploring the impact of barium concentration on swallowing physiology in 20 healthy young individuals. Stimuli consisted of 22%w/v (“ultrathin”) and 40%w/v (“thin”) prepared by diluting Bracco Liquid Polibar suspension with water. In addition, 5-ml boluses of each product were presented 3 times, with the order of barium concentration randomized. The authors reported significantly longer stage transition duration (small effect size), pharyngeal transit time (large effect size), and UES opening duration (large effect size) with the higher concentration stimuli. In a related publication using the same data set, Nagy et al. (2015) found no differences in measures of hyoid velocity between the ultrathin and thin stimuli. A limitation in both of these studies is the fact that sip volume was fixed at 5 ml, which is now known to underrepresent the typical sip size of 11–14 ml in healthy adults (Steele et al., 2019).

A further potential consequence of differences in barium concentration is the impact on pharyngeal residue ratings (Steele et al., 2013). Barium sulfate formulations that are manufactured for gastrointestinal imaging (also known as “double contrast” products) often involve thickeners that are intended to promote mucosal coating along the gastrointestinal tract (Sireci, 2021). The common practice of using diluted versions of these products for oropharyngeal imaging raises the possibility that mucosal coating may occur, but may be mistaken for residue by clinicians, leading to faulty interpretations regarding the presence of swallowing impairment (Steele et al., 2013). When selecting barium products and determining ideal concentration for oropharyngeal imaging, it is important for clinicians to understand issues of opacity and mucosal coating.

The collective results of these prior studies suggest that the concentration of barium may influence a variety of findings on videofluoroscopy, including the likelihood of penetration–aspiration in people with dysphagia, the duration of timing measures, and the likelihood that residue will be identified as a concern. However, it remains unclear whether these findings are attributable to barium concentration and associated differences in opacity, methodological limitations of prior studies, bolus flow characteristics, and/or to differences across brands of barium, given that these products frequently contain other ingredients such as suspension agents, or ingredients intended to minimize foaming. Hyoid kinematics appear less likely to vary at low concentrations, and, to our knowledge, there is no available evidence regarding concentration-dependent variations in UES opening diameter or pharyngeal constriction. The aim of this study was to determine whether measures of swallowing timing, kinematics, and residue in healthy young adults differed as a function of barium product and/or concentration using five different thin liquid barium stimuli, all manufactured by Bracco Imaging, a 20%w/v concentration prepared with E-Z-HD powder, 20%w/v and 40%w/v concentrations prepared with Liquid Polibar Plus suspension, and 20%w/v and 40%w/v concentrations prepared with E-Z-Paque powder. Based on prior literature, we hypothesized that significantly longer timing measures and significantly greater residue would be identified with the 40%w/v stimuli compared to 20%w/v stimuli, but that no differences would be seen in measures of swallowing kinematics, or for any measures across barium products at the same concentration. Given the focus on healthy participants, we did not expect to see penetration–aspiration or incomplete LVC, and did not expect any differences in these parameters or in the number of swallows per bolus across barium stimuli.

Method

Stimuli

All five barium stimuli were prepared using bottled water (Nestlé Pure Life). Consistency was tested in triplicate using the International Dysphagia Diet Standardisation Initiative (IDDSI) Flow Test (Hanson et al., 2019) at room temperature. This test measures amount of liquid remaining in a standard BD 303134 slip tip syringe after 10 s of flow. Liquids with less than 1 ml remaining are classified as thin (Hanson et al., 2019). For comparison, water is reported to typically exit completely from the syringe in 7 s (IDDSI, 2019).

Participants

The study protocol received human subjects approval from the local institutional ethics review board at the University Health Network (CAPCR ID 15–9431). Adults were eligible for the study if they had no prior history of swallowing, motor speech, gastroesophageal or neurological difficulties, chronic sinusitis, taste disturbance, surgery to the speech or swallowing apparatus (other than routine tonsillectomy or adenoidectomy), Type I diabetes, known allergies to the ingredients of the products used, or X-ray to the neck in the past 6 months. Pregnant women were also excluded. Written informed consent was obtained from participants prior to enrollment.

Data Collection

A nonradiographic intake session was completed to collect data regarding race and ethnicity (as required by the funding agency), dentition, saliva production, chewing, and tongue strength. Detailed information regarding the nonradiographic data are not included in this article, as these parameters are not pertinent to the specific research questions in this report. Videofluoroscopy was performed using a Toshiba Ultimax fluoroscope (Toshiba America Medical Systems Inc.). The VFSS was conducted in lateral view at 30 pulses per second and recorded at 30 frames per second on the TIMS 2000-SP system (software version 3.3.4000). Participants were seated comfortably inside the fluoroscope and positioning was adjusted to ensure that structures of interest were visible (vertically from the nasopharynx down to the lower margin of the UES and horizontally from the oral cavity to the back of the cervical vertebrae). The liquid barium stimuli for the current analysis were included as part of a larger VFSS protocol. Each stimulus was presented twice and participants were randomly assigned to one of two orders of presentation (see Supplemental Material S1). Stimuli were presented in 120-ml capacity Styrofoam cups filled with 40 mL of liquid and participants were asked to take comfortable discrete sips and swallow without a cue. Participants were blinded to barium product and concentration. Sip volumes were calculated based on pre- and post-sip cup weights using a digital balance.

Videofluoroscopy Analysis

The VFSS lateral view recordings were spliced to bolus level clips and assigned randomly in batches of n = 100 clips for post hoc duplicate analysis by trained raters, blind to participant, task, and order of bolus presentation in the VFSS. The rating procedure was performed using ImageJ software (Research Services Branch, National Institute of Mental Health) and followed the Analysis of Swallowing Physiology: Events, Kinematics and Timing (ASPEKT) Method (Steele, Peladeau-Pigeon, et al., 2019), beginning with annotation of the number of swallows per bolus, any observations of penetration–aspiration, and the identification of frame number for a series of key events (see Table 1). The standard procedure in the lab is to monitor interrater agreement across paired ratings for each rating batch (i.e., 100 bolus clips). Whenever rating discrepancies exceed prespecified thresholds, the associated clip and measures are sent to a consensus meeting for review and resolution. Each consensus meeting involves at least three trained raters from the lab; the original raters may or may not be part of this consensus review group.

Table 1.

Definitions of timing events and parameters.

Event/parameter	Description
Bolus passing mandible (BPM)	The first frame where the leading edge of the bolus touches or crosses the shadow of the ramus of the mandible
Onset of the hyoid burst (HYB)	The first anterior and/or superior “jump” of the hyoid that is associated with a swallow
Laryngeal vestibule closure (LVC)	The first frame of most-complete closure, where there is maximum approximation of the arytenoids to the laryngeal surface of the epiglottis
Offset of laryngeal vestibule closure (LVC Off)	The first frame where there is a visible opening (white space) in the laryngeal vestibule after LVC
Upper esophageal sphincter opening (UESO)	The first frame where the leading edge of the bolus (or in rare cases, air) passes through the upper esophageal sphincter (UES)
Maximum UES opening (UESMax)	The first frame where distension of the UES has the widest width (i.e., widest lumen width and/or bolus column)
Upper esophageal sphincter closure (UESC)	The first frame where the UES achieves closure behind the bolus tail
Maximum pharyngeal constriction (MPC)	The first frame showing maximum constriction of the pharynx (i.e., least amount of bolus flow and/or airspace in the pharynx). This frame occurs between UESO and LVC Off.
Swallow rest	The first frame showing the pyriform sinuses at their lowest position, relative to the spine, prior to any hyoid burst or laryngeal elevation for a subsequent swallow
Swallow reaction time (SRT)	Time from BPM to HYB
Hyoid-burst-to-UES-opening interval (HYB-UESO)	Time from HYB to UESO
UES opening duration (UESDur)	Time from UESO to UESC
Time-to-laryngeal-vestibule-closure (TTLVC)	Time from HYB to LVC
LVCDur	Time from LVC to LVC Off

For event identification review, one rater takes control of the mouse and advances the clip frame by frame in the consensus meeting; each rater present documents and then declares the frame number that they believe corresponds to the event of interest. Discussion ensues, and the clip may be further reviewed until consensus is achieved. Our practice has traditionally involved routine review of frame identification discrepancies > 5 frames (Steele, Peladeau-Pigeon, et al., 2019). In cases where disagreements fall below this threshold, rules are applied for selecting the rating of record, as described in the original ASPEKT Method supplement (Steele, Peladeau-Pigeon, et al., 2019). However, the magnitude of discrepancies across raters in the lab is monitored quarterly and on a per-batch basis, in case the characteristics of a given study cohort or a change in composition of the rating team may have led to smaller or greater spread in preconsensus ratings, requiring additional scrutiny and the adjustment of thresholds. Our goal is to ensure review of at least the top 10% of the discrepancy distribution for each parameter. Accordingly, the event identification review thresholds used for this particular project were > 3 frames for bolus passing mandible, hyoid burst onset, LVC, UES opening, maximum UES opening and maximum pharyngeal constriction, and at ≥ 5 frames for UES closure and the terminal “swallow rest” event. After resolution of frame identification, timing measures were derived, as listed in Table 1.

The frames of maximum UES opening, maximum pharyngeal constriction, and swallow rest for the initial swallow of each bolus were then extracted for pixel-based measurements of length or area (Steele, Peladeau-Pigeon, et al., 2019). Line measures of lateral UES diameter on the frame of maximum UES opening were normalized to a cervical spine scalar defined by the length between the anterior inferior corners of the second and fourth cervical vertebrae, henceforth annotated as (C2–4), and expressed in %(C2–4) units. Pharyngeal area at maximum constriction was measured and normalized to the (C2–4) anatomical scalar and expressed in %(C2–4)² units. Residue area was measured in the valleculae, the pyriform sinuses and elsewhere in the pharynx, and expressed in %(C2–4)² units, normalized to the (C2–4) anatomical scalar. These area-specific measures were then summed for a total pharyngeal residue measure. Residue ratings were made on any visible barium without prior qualitative classification of the amount as trace or more-than-trace. The discrepancy review process for pixel-based measures was similar to that used for event identification. Thresholds for consensus review of pixel-based measures from this dataset were as follows: UES diameter: > 7% (C2–4); pharyngeal area at maximum constriction: > 3.5% (C2–4)²; vallecular residue: > 2% (C2–4)²; residue in other locations: > 2.4% (C2–4)². In cases where disagreements in these pixel-based measures fell below these thresholds, the smaller rating was taken as the rating of record (Steele, Peladeau-Pigeon, et al., 2019).

Finally, an ImageJ pixel tracing macro was used to track hyoid position, relative to the anterior inferior corner of C4, in a coordinate system with the vertical (Y) axis defined by the C2-C4 cervical spine, on every frame, beginning five frames prior to the frame of hyoid burst onset, until five frames after UES closure. This process yields X (anterior), Y (superior), and XY (hypotenuse) coordinates for hyoid position on every frame, with these coordinates stored in an Excel spreadsheet. In the event that the hyoid moves outside the field of view on a given frame, or where the shoulder or other structures obstruct the view of the cervical spine, a missing data point is recorded. Once hyoid tracking for a given bolus clip is complete, A MATLAB algorithm is then used to search through the series of hyoid position measures to confirm the frames of peak position in each plane (X, Y, and XY). In the case of a plateau in hyoid movement at its peak position, the first frame at peak position is used. Measures of hyoid speed are also derived (i.e., the rate of change in position along the XY axis between the frames of hyoid burst onset and peak position). For this study, the data set was divided into two portions for hyoid tracking; both raters had previously completed training according to a standard operating procedure. Accuracy in identifying and marking hyoid location on a training set of single images is reviewed by a supervising trainer; feedback and further practice are provided until the trainee is deemed by the trainer to demonstrate sufficient competency.

Analysis

Interrater Agreement

All statistical analyses were performed in SPSS Version 28.0 using a p value of .05. Interrater agreement was calculated for frame identification based on the absolute difference (in frames) across each pair of ratings, prior to consensus resolution. Chi-square tests were then used to compare the frequency of (dis)agreement (greater than)/≤ 3 frames by barium stimulus. For pixel-based measures of kinematics and residue, descriptive statistics for absolute difference between raters were calculated across paired measures prior to consensus resolution. Intraclass correlation coefficients (ICCs) were performed based on a mean rating (k = 2) two-way mixed-effects model for consistency (Koo & Li, 2016).

Bolus Size

Linear mixed model repeated-measures analyses of variance (ANOVAs) with a compound symmetry structure, a random effect for participant, and an alpha criterion of .05 were used to identify the effects of task, sex, and age on measures of sip weight and sip volume. Post hoc Šidák tests were run to identify significant pairwise comparisons.

Stimulus Effects

Participant mean values for each videofluoroscopy parameter were calculated across task repetitions and used for the analysis of stimulus effects. Three parameters were treated as categorical: the number of swallows per bolus (1, 2, more than 2), Penetration–Aspiration Scale (PAS) scores (Rosenbek et al., 1996), and LVC integrity (complete vs. incomplete closure). For these, chi-square tests were used to identify differences in the frequencies of scores by barium stimulus. For the remaining continuous parameters of timing, kinematics, and residue, the preceding analysis of variations in sip size informed the decision that a factor of sex and covariates of age and sip volume did not need to be included in the statistical models. Inspection of the data showed that the majority of parameters displayed skewed distributions without normally distributed residuals; therefore, nonparametric Friedman's tests were used to look for within-participant differences across the five barium stimuli, with an alpha criterion of 0.05. Where significant stimulus differences were found, post hoc pairwise comparisons were performed using Wilcoxon signed-ranks tests.

Results

Stimuli

Table 2 provides descriptive information regarding the barium products used in the study. There were no evident differences in consistency across the five barium products, based on the IDDSI Flow Test (Hanson et al., 2019). All five barium stimuli were classified as thin liquid, based on residual fluid volumes of 0 ml after 10 s of flow through the BD303134 syringe. In fact, all samples of all stimuli exited the syringe completely in 8 s or less.

Table 2.

Descriptive statistics for flow properties, density, and sip size of the different barium stimuli.

Stimulus property	Variable	20%w/v E-Z-HD	20%w/v Polibar Plus	20%w/v E-Z-Paque	40%w/v Polibar Plus	40%w/v E-Z-Paque
IDDSI Flow Test	Residual volume after 10 s of flow (ml)	0	0	0	0	0
	Time to completely exit syringe (s)	7	7	7	8	6
	IDDSI Level	0 Thin	0 Thin	0 Thin	0 Thin	0 Thin
Density (g/ml)		1.16	1.16	1.16	1.31	1.31
Sip weight (g)	M	17.0	15.8	16.5	18.7	18.6
	SD	5.3	5.1	5.1	6.9	6.2
	Minimum	6.4	4.9	4.4	4.9	6.4
	Maximum	28.1	25.1	25.0	34.0	31.6
Sip volume (ml)	M	14.7	13.6	14.3	14.2	14.2
	SD	4.5	4.4	4.4	5.3	4.7
	Minimum	5.5	4.2	3.8	3.7	4.9
	Maximum	23.2	21.6	21.6	25.9	24.1

Note. w/v = weight-to-volume; IDDSI = International Dysphagia Diet Standardisation Initiative.

Participants

Recruitment for this study began prior to the COVID-19 pandemic, was placed on hold for some time early in the pandemic, and resumed once allowed by the institution. Consent was obtained from 23 participants for this study. Two participants completed the nonradiographic session prior to pandemic-related suspension but declined to return for the videofluoroscopy when the study resumed. A third participant was withdrawn following completion of the nonradiographic session due to reported gastrointestinal symptoms suggesting possible intolerance to the stimuli. The study was left with 20 participants (10 men and 10 women) who completed all required sessions. These participants ranged in age from 22 to 54 years old (M = 27.5). Race was reported as White by 13 participants, Black/African American by three participants, and Asian by four participants. None of the participants reported Hispanic ethnicity.

Interrater Agreement

For frame identification, the mean difference between raters was two frames (SD = 7). Ratings fell ≤ 3 frames across raters in 85% of cases. Chi-square tests showed no significant differences in the frequency of agreement within three frames by event, across the five barium stimuli. Table 3 provides results for the evaluation of interrater agreement for pixel-based measure of kinematics and for residue in the valleculae, pyriform sinuses, elsewhere in the pharynx, and overall. These measures showed moderate preconsensus agreement for pharyngeal area at maximum constriction, and good preconsensus agreement across raters for all other pixel-based measures (Koo & Li, 2016). Post hoc exploration showed markedly poorer preconsensus interrater agreement for measures of pharyngeal area at maximum constriction on the 20%w/v E-Z-HD (ICC = .29, 95% confidence interval = 0 to .64). Preconsensus agreement for this parameter was also poor for the 40%w/v E-Z-Paque stimulus (ICC = .48, 95% confidence interval = .03 to .73). For the remaining three stimuli, preconsensus agreement for measures of pharyngeal area at maximum constriction was good with ICCs ≥ .75. As previously described, rating discrepancies were reviewed and resolved in consensus meetings.

Table 3.

Preconsensus interrater agreement for pixel-based measures.

Parameter	Absolute difference		Reliability
	M	SD	ICC c	Lower bound	Upper bound	Interpretation
Pharyngeal area at maximum constriction a	1.36	1.99	.73	.64	.79	Moderate
Maximum UES opening diameter b	3.19	2.88	.86	.82	.9	Good
Vallecular residue a	0.23	0.44	.77	.71	.83	Good
Pyriform sinus residue a	0.15	0.28	.86	.81	.89	Good
Other pharyngeal residue a	0.15	0.37	.82	.77	.86	Good
Total pharyngeal residue a	0.49	0.79	.83	.78	.87	Good

Note. ICC = intraclass correlation coefficient; UES = upper esophageal sphincter.

^a In %(C2–4)² units.

^b In %(C2–4) units.

^c Intraclass correlation based on a mean-rating (k = 2) two-way mixed-effects model for consistency.

Bolus Size

Descriptive statistics for sip weight and sip volume by stimulus can be found in Table 2 (above). The analysis showed no significant differences in sip weight across the five barium stimuli, with an overall mean of 17.3 g per bolus (SD = 5.8 g). There were no significant effects of participant sex or age on sip weight, and no significant interactions. The corresponding analysis of sip volume, which accounted for expected differences in stimulus density, showed an overall mean of 14.2 ml per bolus (SD = 4.6 ml) with no significant differences across stimuli, no significant sex or age effects, and no significant interactions.

Categorical Parameters

Across the 200 boluses in the data set, 136 (i.e., 68%) were swallowed in a single swallow. A further 61 (i.e., 30.5%) were swallowed with two swallows per bolus, whereas a third swallow was used for three boluses. There were no significant differences in the number of swallows per bolus by barium stimulus. With respect to penetration–aspiration, 173 (i.e., 86.5%) of the boluses were scored as showing no airway invasion (PAS = 1), whereas 27 (i.e., 13.5%) showed transient penetration (PAS = 2). There were no episodes of PAS scores of 3 or greater, and no significant differences in PAS scores by barium stimulus. LVC was rated as being complete for all 200 boluses.

Continuous Videofluoroscopy Parameters

Descriptive statistics for parameters measuring timing, kinematics, and residue can be found in Supplemental Material S2. Table 4 summarizes the results of the statistical analyses for these continuous quantitative videofluoroscopy parameters.

Table 4.

Results of the Friedman's tests and post hoc Wilcoxon signed-ranks tests for stimulus differences in quantitative videofluoroscopic parameters.

Parameter	Chi-square a (df 4)	p value	Stimulus	Statistic	20%w/v Polibar Plus	20%w/v E-Z-Paque	40%w/v PolibarPlus	40%w/v E-Z-Paque
Swallow Reaction time (ms)	6.23	.18
Hyoid burst to UES opening (ms)	5.11	.28
Time-to-LVC (ms)	1.23	.87
LVC Duration (ms)	3.55	.47
Hyoid peak position (X coordinate)	8.63	.07
Hyoid peak position (Y coordinate)	3.52	.48
Hyoid peak position (XY coordinate)	3.53	.47
Hyoid XY speed	6.80	.15
UES opening duration (ms)	50.01	< .001	20%w/v E-Z-HD	Z b	−3.83	−3.83	−3.93	−3.92
				p value	< .005*	< .005*	< .005*	< .005*
			20%w/v Polibar Plus	Z b		−0.71	−2.75	−3.09
				p value		0.48	.01*	.02*
			20%w/v E-Z-Paque	Z b			−2.21	−2.55
				p value			.03*	.01*
			40%w/v PolibarPlus	Z b				−0.49
				p value				.62
UES diameter [%(C2–4)2]	23.00	< .001	20%w/v E-Z-HD	Z b	−2.05	−2.95	−2.35	−3.70
				p value	.04*	< .005*	.02*	< .005*
			20%w/v Polibar Plus	Z b		−1.34	−1.20	−3.55
				p value		.18	.23	< .005*
			20%w/v E-Z-Paque	Z b			−0.49	−2.35
				p value			.63	.02*
			40%w/v PolibarPlus	Z b				−2.65
				p value				.01*
Pharyngeal area at maximum constriction [%(C2–4)2]	46.56	< .001	20%w/v E-Z-HD™	Z b	−3.92	−3.85	−3.92	−3.92
				p value	< .005*	< .005*	< .005*	< .005*
			20%w/v Polibar Plus	Z b		−0.60	−1.16	−3.21
				p value		.55	.25	< .005*
			20%w/v E-Z-Paque	Z b			−0.78	−2.58
				p value			.43	.01*
			40%w/v PolibarPlus	Z b				−1.83
				p value				.07*
Vallecular residue [%(C2–4)2]	36.11	< .001	20%w/v E-Z-HD	Z b	−2.76	−3.62	−3.68	−3.82
				p value	.01*	< .005*	< .005*	< .005*
			20%w/v Polibar Plus	Z b		−1.37	−3.16	−2.63
				p value		.17	< .005*	.01*
			20%w/v E-Z-Paque	Z b			−1.61	−1.29
				p value			.11	.20
			40%w/v PolibarPlus	Z b				−0.13
				p value				.90
Pyriform sinus residue [%(C2–4)2]	19.70	.001	20%w/v E-Z-HD	Z b	−2.60	−2.50	−2.83	−3.24
				p value	.01*	.01*	< .005*	< .005*
			20%w/v Polibar Plus	Z b		−1.78	−0.62	−2.97
				p value		.07*	.53	< .005*
			20%w/v E-Z-Paque	Z b			−0.31	−1.89
				p value			.75	.06*
			40%w/v PolibarPlus	Z b				−1.20
				p value				.23
Residue elsewhere in the pharynx [%(C2–4)2]	19.30	< .001	20%w/v E-Z-HD	Z b	−1.99	−2.94	−2.93	−2.93
				p value	.05*	< .005*	< .005*	< .005*
			20%w/v Polibar Plus	Z b		−1.71	−1.82	−2.43
				p value		.09*	.07*	.02*
			20%w/v E-Z-Paque	Z b			−0.26	−0.26
				p value			.80	.80
			40%w/v PolibarPlus	Z b				−1.31
				p value				.19
Total pharyngeal residue [%(C2–4)2]	45.04	< .001	20%w/v E-Z-HD	Z b	−3.17	−3.62	−3.82	−3.92
				p value	< .005*	< .005*	< .005*	< .005*
			20%w/v Polibar Plus	Z b		−2.32	−3.14	−3.17
				p value		.02*	< .005*	< .005*
			20%w/v E-Z-Paque	Z b			−1.13	−1.72
				p value			.26	.09*
			40%w/v PolibarPlus	Z b				−0.75
				p value				.46

Note. w/v = weight-to-volume; UES = upper esophageal sphincter; LVC = laryngeal vestibule closure; (C2–4) = length between the anterior inferior corners of the second and fourth cervical vertebrae.

^a Friedman's test.

^b Wilcoxon signed-ranks test.

^*Statistically significant p value at an alpha level of p < .05.

Timing Measures

The Friedman's tests found no significant effects of barium stimulus on measures of swallow reaction time, the hyoid-burst-to-UES-opening interval, time-to-LVC, or LVC duration. However, significant stimulus differences were found for measures of UES opening duration, as shown in Figure 1. Post hoc Wilcoxon tests showed that UES opening duration was significantly shorter for the 20%w/v E-Z-HD stimulus compared to all other stimuli. UES opening durations for the 20%w/v Polibar Plus did not differ from the 20%w/v E-Z-Paque stimuli but were significantly shorter for each of these 20%w/v stimuli compared to both 40%w/v stimuli, suggesting an overall significant effect of concentration.

Figure 1.

Upper esophageal sphincter (UES) opening duration in milliseconds, by barium product and concentration. Significantly shorter UES opening durations were seen for (a) the 20%w/v E-Z-HD stimulus compared to all other stimuli and for (b) the 20%w/v Polibar Plus and E-Z-Paque stimuli compared to (c) the two 40%w/v stimuli. w/v = weight-to-volume.

Pixel-Based Measures

The Friedman's test showed significant stimulus differences in lateral measures of maximum UES opening diameter, as illustrated in Figure 2. Post hoc Wilcoxon tests confirmed significantly smaller UES opening diameter for the 20% E-Z-HD stimulus compared to all other stimuli, and significantly greater UES opening diameter for the 40% E-Z-Paque stimulus compared to all other stimuli.

Figure 2.

Measures of maximum lateral upper esophageal sphincter (UES) opening diameter in %(C2–4)² units, by barium product and concentration. Significantly smaller UES opening diameter was seen for (a) the 20% E-Z-HD product compared to all other stimuli and for (b) the 20%w/v Polibar Plus, 20%w/v E-Z-Paque, and the 40%w/v Polibar Plus stimuli compared to (c) the 40%w/v E-Z-Paque stimulus. w/v = weight-to-volume.

A similar pattern was seen for measures of pharyngeal area at maximum constriction, as illustrated in Figure 3. Post hoc Wilcoxon tests showed significantly smaller pharyngeal area with the 20%w/v E-Z-HD stimulus compared to all other stimuli, and significantly larger pharyngeal area for the 40%w/v E-Z-Paque stimulus compared to all other stimuli.

Figure 3.

Pharyngeal area at maximum constriction in %(C2–4)² units, by barium product and concentration. Significantly smaller area was seen for (a) the 20% E-Z-HD product compared to all other stimuli and for (b) the 20%w/v Polibar Plus, 20%w/v E-Z-Paque, and the 40%w/v Polibar Plus stimuli compared to (c) the 40%w/v E-Z-Paque stimulus. w/v = weight-to-volume.

With respect to measures of residue, the Friedman's tests showed a significant effect of stimulus for vallecular residue (see Figure 4a), with post hoc testing showing significantly less residue with the 20%w/v E-Z-HD stimulus compared to all other stimuli, and significantly greater residue with both 40%w/v stimuli compared to the 20%w/v Polibar Plus stimuli, but not the 20% w/v E-Z-Paque. A similar pattern was seen for pyriform sinus residue (see Figure 4b). Here, residue area measures were significantly smaller with the 20%w/v E-Z-HD stimulus compared to all other stimuli, and significantly larger for the 40%w/v E-Z-Paque stimulus compared to all of the 20%w/v stimuli. With respect to residue in other pharyngeal locations, the Friedman's tests again showed a significant effect of stimulus, with post hoc testing confirming significantly less residue with the 20%w/v E-Z-HD stimulus compared to all other stimuli, and significantly less residue with 20%w/v Polibar Plus compared to 40%w/v Polibar Plus and both concentrations of E-Z-Paque (see Figure 4c).

Figure 4a.

Pixel-based measures of vallecular residue in %(C2–4)² units, by barium product and concentration. Significantly less vallecular residue was seen for (a) the 20% E-Z-HD product compared to all other stimuli and for (b) the 20%w/v Polibar Plus stimulus compared to (c) the two 40%w/v stimuli. The 20%w/v E-Z-Paque stimulus was not significantly different from either (b) the 20%w/v Polibar Plus stimulus or (c) the two 40%w/v stimuli. w/v = weight-to-volume.

Figure 4b.

Pixel-based measures of pyriform sinus residue in %(C2–4)² units, by barium product and concentration. Significantly less residue was seen for (a) the 20% E-Z-HD product compared to all other stimuli and for (b) the 20%w/v Polibar Plus stimulus compared to (c) the 20%w/v E-Z-Paque stimulus and (d) the 40%w/v E-Z-Paque stimulus. The 40%w/v Polibar Plus stimulus was not significantly different from either (b) the 20%w/v Polibar Plus stimulus or (c) the 20%. w/v E-Z-Paque stimulus.

Figure 4c.

Pixel-based measures of other pharyngeal residue in %(C2–4)² units, by barium product and concentration. Significantly less residue was seen for (a) the 20% E-Z-HD product compared to all other stimuli and for (b) the 20%w/v Polibar Plus compared to (c) the 20%w/v E-Z-Paque and the two 40%w/v stimuli. w/v = weight-to-volume.

When pharyngeal residue measures were summed across all locations, significantly less total pharyngeal residue was seen with the 20%w/v E-Z-HD stimulus compared to all other stimuli (see Figure 4d). Significantly less total pharyngeal residue was also seen with the 20%w/v Polibar Plus compared to the 40%w/v Polibar Plus stimuli and both concentrations of E-Z-Paque and significantly greater residue was seen with the 40%w/v compared to the 20%w/v concentration of E-Z-Paque. Finally, Friedman's tests for the X, Y, and XY coordinates of hyoid peak position and for hyoid XY speed failed to show any significant differences across the five barium stimuli.

Figure 4d.

Pixel-based measures of total pharyngeal residue in %(C2–4)² units, by barium product and concentration. Significantly less residue was seen for (a) the 20% E-Z-HD product compared to all other stimuli and (b) the 20%w/v Polibar Plus compared to (c) the 20%w/v E-Z-Paque, which, in turn, showed significantly less residue than (d) the 40%w/v E-Z-Paque stimulus. Residue on the 40%w/v Polibar Plus stimulus did not differ significantly from that seen with the two E-Z-Paque stimuli. w/v = weight-to-volume.

Discussion

The results of this study shed new light on the potential for measures of swallowing physiology to vary as a function of barium concentration, and, importantly, across different barium products at the same concentration. Prior studies have focused on barium concentration, and have attributed concentration-based differences in swallowing to a presumed correlation between barium concentration and viscosity. The current analysis shows that the story is not that simple. A recent review article describing the different components in barium formulations for imaging explains that emulsifiers, mucosal coating agents, noncoating thickeners, texturizers, laxatives, and solvents may all be included in barium products and may influence how the barium flows through or coats different regions of the gastrointestinal tract (Sireci, 2021).

Although it is true that barium products with higher density may also tend to be more viscous, this is not always the case, as seen in this study. Prior studies show that the rheological characteristics of barium should not be presumed. For example, Bracco's Varibar Thin product has been described to display constant Newtonian viscosity (Popa Nita et al., 2013), whereas other products show non-Newtonian shear thinning viscosity, which may further change dramatically with the addition of contrast agents (Steele et al., 2013). In this study, all five barium stimuli were confirmed to be thin liquids with flow properties very similar to water, based on the IDDSI Flow Test (Hanson et al., 2019). Furthermore, we found no significant differences in sip weight or sip volume across the five stimuli in this experiment.

Overall, the current results did not find evidence of significant differences in measures of swallow timing across the five barium stimuli studied. The hypothesis that longer timing measures would be seen with the 40%w/v concentration products was not supported. The only exception to these conclusions was UES opening duration, showing significantly shorter values for the 20%w/v E-Z-HD stimulus and both product and concentration differences seen across the remaining Polibar Plus and E-Z-Paque stimuli.

Our hypothesis that no differences would be seen in measures of swallowing kinematics across the five barium stimuli was confirmed for measures of hyoid peak position and speed, but not for measures of UES opening diameter and pharyngeal constriction. The pattern of results for UES opening diameter is similar to that seen for UES opening duration, with significantly narrower UES opening diameter for the 20% E-Z-HD stimulus and significantly wider diameter for the 40% E-Z-Paque stimulus compared to the other stimuli. UES opening diameter is known to vary as a function of bolus volume (Kahrilas et al., 1996); however, in this case, there were no significant differences in bolus volume and no significant differences in bolus weight across stimuli that might explain the observed differences in UES opening diameter.

The finding of significant differences in pharyngeal area at maximum constriction is important, because it suggests that the differences seen in related measures of residue are not simply attributable to the mucosal coating properties of different barium stimuli, but may arise in part from differences in swallowing physiology. In this study, significantly smaller pharyngeal area at maximum constriction was seen for the 20%w/v E-Z-HD product compared to the other stimuli, whereas significantly larger area was seen for the 40%w/v E-Z-Paque product. These patterns were also mirrored in the residue results, where measures of residue area were significantly smaller with the 20%w/v E-Z-HD product in all locations, whereas the greatest residue was consistently seen with the 40%w/v E-Z-Paque product. Importantly, however, residue measures did not show a consistent effect of barium concentration, such that within product comparisons of area-specific residue on the 20%w/v versus 40%w/v E-Z-Paque stimuli did not differ significantly. The recent review article by Sireci (2021) explains that differences in barium concentration should not be expected to influence residue, whereas differences in other ingredients, including mucosal coating agents and thickeners, may influence the amount of barium seen in the pharynx after the swallow.

Across all of the parameters evaluated in this study, it is clear that the 20%w/v E-Z-HD product is contributing to significantly shorter timing measures, smaller measures of pharyngeal constriction area and UES opening diameter, and residue area. One possible explanation for this phenomenon is that the 20%w/v concentration of this particular barium product has been diluted too far, beyond the boundary of reliable visibility on the X-ray. It is interesting to note that interrater agreement for pharyngeal area at maximum constriction was poorest on this stimulus, and that all parameters showing significant differences with this product are parameters requiring attention to the boundaries of the bolus, rather than a focus on anatomical structures. It seems possible that the boundaries of a 20%w/v E-Z-HD bolus might be difficult to distinguish from adjacent soft tissue boundaries. It must be acknowledged that the 20%w/v concentrations of all three barium products represent off-label recipes; in the case of E-Z-HD, this dilution represents a substantial reduction in density versus the 238%w/v concentration recommended on the product label for gastrointestinal imaging. For the Polibar Plus and E-Z-Paque products, the dilutions studied in this project are also lower than the 105% and 60%w/v formulations recommended on the manufacturer labels for gastrointestinal imaging. The current data illustrate the important take-home message that barium opacity is not, and should not be presumed to be uniform across different products at the same concentration.

The significant differences that are seen across barium stimuli in this study must be put into context. Currently, reference interval tables for ASPEKT Method measures of swallowing in healthy adults are available for 20%w/v concentration E-Z-Paque prepared in thin, slightly thick, mildly thick, moderately thick, and extremely thick consistencies using a xanthan-gum thickener, with these stimuli taken by natural sip and swallowed without a cue as in the current analysis (Steele, Peladeau-Pigeon, et al., 2019). The results of this analysis suggest that significantly higher values than those for 20%w/v E-Z-Paque should be expected on one or both of the 40%w/v products for several parameters, including UES opening duration, UES diameter, pharyngeal area at maximum constriction, pyriform sinus residue, and total pharyngeal residue. Higher values for UES opening duration and diameter are not likely to be interpreted as indicating impairment. However, variations in mucosal coating may lead to differences in clinician interpretation regarding the presence and severity of residue. As explained by Sireci (2021), mucosal coating may be expected as a normal finding with some barium products that are intended for gastrointestinal imaging. However, there is currently no clear consensus regarding the definition of expected or normal “trace” mucosal coating versus residue of concern. In this study, all visible barium in the pharynx after the swallow was traced and included in the residue measurement results. Scoring guidance for the MBSImP, by contrast, distinguishes “trace” or normal expected coating from either a “collection” of residue that is “sufficient to scoop or extract,” or a narrow column of barium between structures (Martin-Harris et al., 2008). It should also be noted that no mucosal coating is expected with the Varibar product line (Sireci, 2021). Together with the current data, these issues suggest that bespoke reference data may be needed to guide the clinical interpretation of residue severity with specific barium preparations.

Furthermore, this study highlights the potential pitfalls that exist when clinicians prepare off-label barium for use in videofluoroscopy. Such practice may not only alter the opacity and visibility of the barium, but the addition of extra water may alter the original formulas of the barium agents and associated properties. The thickeners in the manufacturers' preparation of the different types of barium agents, which were added to achieve specific goals of mucosal coating or barium particle suspension, may be reduced or rendered ineffective by with the addition of water in an attempt to achieve a thin liquid consistency.

Limitations

One limitation that must be acknowledged is the fact that this study did not include a 40%w/v concentration of the E-Z-HD product. This decision was related to the goal of limiting radiation exposure in the larger experimental protocol. We also did not explore differences across barium stimuli prepared in different consistencies, and did not include other contrast agents such as Bracco's Varibar product line or low-osmolar iodine-based contrast agents such as Omnipaque (Iohexol). Finally, the hyoid tracking procedure for this study was not performed in duplicate; consequently, interrater agreement statistics are not available for the derived measures of hyoid peak position and speed.

Conclusions

This study confirms and extends prior data, showing that some measures of swallowing physiology, and particularly the appearance of residue, may be influenced by differences in barium product and/or concentration. This is clear evidence of the need for, and importance of using standard and appropriate stimuli in videofluoroscopy, and for clinicians to report not only the product but also the concentration of stimuli that are used. In our opinion, this study shows that 20%w/v concentration of E-Z-HD is too dilute to afford reliable visualization and should not be used. However, the data for the other barium stimuli also show that clinicians need to be alert to the fact that measures of swallowing behavior on videofluoroscopy may differ across both product and concentration. This knowledge should particularly be kept in mind when using off-label preparations of barium products that are intended for gastrointestinal rather than oropharyngeal examinations. Just as it is critical to control for the influence of methodological factors on other medical tests (e.g., the impact of patient positioning on esophageal and gastric emptying during an esophagram), it is crucial to understand and control for the influences of barium stimuli on measures of swallowing. Transparent and rigorous reporting regarding the barium preparation used will enable comparison across serial examinations, and limit the risk that stimulus-related artifacts might lead to misleading interpretations. A thorough understanding of the expected physical–chemical effects of the additives in the original barium preparations, and how the modifications made by the user would affect them, will help to make it possible to properly evaluate other influences on swallowing, such as those seen across different bolus volumes, or when using compensatory maneuvers.

Author Contributions

Catriona M. Steele: Conceptualization (Lead), Data curation (Supporting), Formal analysis (Lead), Funding acquisition (Lead), Methodology (Lead), Project administration (Lead), Supervision (Lead), Writing – original draft (Lead), Writing – review & editing (Lead). Emily Barrett: Data curation (Supporting), Writing – original draft (Supporting), Writing – review & editing (Supporting). Melanie Peladeau-Pigeon: Conceptualization (Supporting), Data curation (Supporting), Formal analysis (Supporting), Methodology (Supporting), Project administration (Supporting), Supervision (Supporting), Writing – original draft (Supporting), Writing – review & editing (Supporting).

Data Availability

Additional data are available on request from the authors.

Funding Statement

Funding for this project was provided through an R01 Grant (DC011020) to the first author.