The Laryngoscope C 2015 The American Laryngological, V
Rhinological and Otological Society, Inc.
Volumetric MRI Analysis Pre- and Post-Transoral Robotic Surgery for Obstructive Sleep Apnea Rebecca C. Chiffer, MD; Richard J. Schwab, MD; Brendan T. Keenan, MS; Ryan C. Borek, MD; Erica R. Thaler, MD Objectives/Hypothesis: To quantitatively measure volumetric changes in upper airway soft tissue structures using magnetic resonance imaging (MRI) pre- and post transoral robotic surgery for obstructive sleep apnea (OSA-TORS). Study Design: Prospective, nonrandomized, institutional board-approved study. Methods: Apneics undergoing OSA-TORS, which included bilateral posterior hemiglossectomy with limited pharyngectomy and uvulopalatopharyngoplasty, had upper airway MRIs pre- and postoperatively. Changes (percent and absolute values) in upper airway and surrounding soft tissue volumes were calculated. We assessed whether there were significant volumetric changes and if changes correlated with apnea-hypopnea index (AHI) changes. Results: Nineteen MRIs and 18 polysomnograms were analyzed pre- and postoperation. Total airway volume increased by 19.4% (P 5 0.030). Soft palate and tongue volumes decreased by 18.3% (P 5 0.002) and 5.8% (P 5 0.013), respectively. Retropalatal and total lateral wall volumes decreased by 49.8% (P 5 0.0001) and 17.9% (P 5 0.008), respectively. Changes in other structures were not significant. Eleven patients had surgical success, with a mean AHI decrease of 52.9; six were nonsuccesses with a mean AHI decrease of 4.5 (P 50.006). Decreased retropalatal lateral wall volume correlated with decreased AHI. Conclusion: Airway, tongue, soft palate, and lateral wall volumes change significantly after OSA-TORS. Changes in the volume of the lateral walls correlated with changes in AHI. Volumetric upper airway MRI may be a helpful tool to better understand reasons for surgical success. Key Words: Transoral robotic surgery, volumetric MRI analysis, obstructive sleep apnea, uvulopalatopharyngoplasty. Level of Evidence: 4. Laryngoscope, 125:1988–1995, 2015
INTRODUCTION Obstructive sleep apnea (OSA) is a growing epidemiological problem affecting a significant portion of the population.1 Recent estimates state that up to 20% of adults have mild OSA and 6-7% have moderate to severe OSA.2 Obstructive sleep apnea affects multiple organ
Additional Supporting Information may be found in the online version of this article. From the Department of Otorhinolaryngology–Head and Neck Surgery, Hospital of the University of Pennsylvania (R.C.C., R.C.B.); the Department of Otorhinolaryngology–Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania (E.R.T.); the Department of Medicine, Division of Sleep Medicine, Pulmonary, Allergy and Critical Care Division, Penn Sleep Center (R.J.S.); and Perelman School of Medicine at the University of Pennsylvania, Division of Sleep Medicine, Center for Sleep and Circadian Neurobiology (B.T.K.), University of Pennsylvania Medical Center; Philadelphia, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication February 25, 2015. Presented at the Annual Meeting of the Broncho-Esophagological Association at the Combined Otolaryngology Society Meeting, Las Vegas, Nevada, U.S.A., May 14, 2014. The imaging portion of this research was funded by an Intuitive grant awarded to E.R.T. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Rebecca C. Chiffer, MD, Department of Otorhinolaryngology–Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104. E-mail: [email protected] DOI: 10.1002/lary.25270
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systems and can lead to serious medical complications. Obstructive sleep apnea has been associated with hypertension, stroke, coronary artery disease, congestive heart failure, insulin resistance, and neurocognitive dysfunction.1,2 For these reasons, it is important to study not only the risk factors associated with developing this disease, but also the optimal treatment modalities. Because many patients have difficulty tolerating continuous positive airway pressure, which is the first line treatment for OSA, 3 these patients often seek surgical evaluation. Surgical treatment for OSA, however, has considerable variability with a wide range of results.3–7 Transoral robotic surgery (TORS) has recently become a new area of research for the treatment of OSA because it allows for direct visualization of, and better access to, the base of tongue, compared to open procedures.5–7 Investigators have reported a surgical cure rate of 66.7% with transoral robotic glossectomy.6 Another group reported a cure rate of 70% with TORS based on apnea-hypopnea index (AHI) parameters.5 Although these data are promising, the question remains as to why some patients respond and other patients do not respond to TORS. It may be possible to answer this question by examining the soft tissue and bony structures that are most likely to be causing the patient’s upper airway (UA) collapse and obstruction, and are directly within the surgical field. Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
normal subjects.9,10 Furthermore, it has been shown that UA soft tissue enlargement is a significant risk factor for developing OSA.10 Volumetric magnetic resonance imaging (MRI) can also be used to examine how the upper airway soft tissue volumes change, or do not change, following surgical intervention. In our study, we used T1-weighted MRI to measure the changes in upper airway soft tissue volumes in patients with OSA before and after undergoing transoral robotic surgery, or OSA-TORS. We hypothesized that the volumes of the airway and soft tissue structures within the surgical field would change significantly, and that these changes would correlate to changes in postoperative AHI.
MATERIALS AND METHODS
Fig. 1. Magnetic resonance imaging segmentation shown in one example patient pre- and postoperatively at comparable crosssectional regions. (A) Increase in airway volume at the retropalatal airway level. (B) Increase in airway volume at the retroglossal airway level (defined as airway between the caudal margin of the soft palate and the rostral margin of the epiglottis.) (C) Increase in airway volume at the retroepiglottal airway level. Color Key: white 5 mandible; light green 5 retropalatal airway; light blue 5 retroglossal airway; dark blue 5 retroepiglottal airway; light purple 5 epiglottis; pink 5 soft palate; red 5 genioglossus tongue; brown 5 other tongue muscles; yellow 5 parapharyngeal fat pads; neon green 5 pterygoid muscles; orange 5 retropalatal lateral walls; dark purple 5 retroglossal lateral walls.
Previous studies have shown that the soft tissues of the upper airway differ between apneics and normal subjects.8–11 More specifically, airway caliber is significantly smaller and the volume of UA soft tissue structures is significantly larger in apneics compared to Laryngoscope 125: August 2015
Study subjects were selected as part of a prospective, nonrandomized, institutional board-approved (University of Pennsylvania) study. All patients were at least 18 years of age at the time of treatment, had documented OSA with an AHI > 5, as defined by a preoperative polysomnography (PSG), and signed a written informed consent. Exclusionary criteria included age < 18 years, unexplained fever and/or untreated active infection, pregnancy, previous head and neck surgery precluding transoral/robotic procedures, and the presence of a medical condition that contraindicated general anesthesia or a transoral surgical approach. In addition to a preoperative PSG, all patients underwent a preoperative upper airway MRI and drug-induced sleep endoscopy (DISE). All DISEs were performed by one coinvestigator (E.R.T.) according to the previously described technique by Lee et al.4 and Borek et al.12 Patients found to have significant obstruction at the retroglossal region, as demonstrated by a significant percentage change in cross-sectional area during DISE, were given the option of undergoing OSA-TORS. Many patients also demonstrated retropalatal obstruction on DISE; however, the decision to offer the OSA-TORS procedure was based upon retroglossal obstruction. All patients were informed of the risks, benefits, and alternatives to surgical treatment, and written informed consent was obtained prior to the procedure. The OSA-TORS procedure was performed by one coinvestigator (E.R.T.) with the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) according to the previously described technique by Lee et al.4 The procedure consisted of a bilateral robotic posterior hemiglossectomy with limited pharyngectomy followed by a uvulopalatopharyngoplasty (UPPP), which was a modification of the expansion sphincteroplasty technique. This part of the procedure was also performed by one coinvestigator (E.R.T.). Of note, all patients underwent bilateral limited pharyngectomy with modified UPPP, regardless of degree of retropalatal obstruction seen on preoperative DISE. Each patient who underwent surgery was scheduled for a follow-up PSG to determine the outcome of the procedure and a repeat upper airway MRI at least 3 months (range 6–24 months) after surgery. The criteria for surgical success included both a reduction in preoperative AHI of at least 50% and a postoperative AHI of less than 20 events per hour. A surgical response was defined as a reduction from the preoperative AHI of at least 50%. Preoperative and postoperative upper airway MRI scans were analyzed by one coinvestigator (R.C.C.) with an overall review and consensus from the entire team. Preoperative MRIs were performed at varying institutions; all postoperative MRIs were performed at the University of Pennsylvania Medical
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TABLE I. Summary of Clinical and Treatment Data. Subject
Gender
Age
Pre-BMI
Post-BMI
Pre-AHI
Post-AHI
Surgical Success
Surgical Response
1
M
24
26.6
24.6
2 3
M M
59 45
34.5 38
34.5 37.6
22.9
14.3
N
N
66 66
11.6 10
Y Y
Y Y
4
M
44
31
5 6
M M
32 37
27.9 29.6
n/a
36
n/a
n/a
n/a
27.2 29.6
112 56
2 30.7
Y N
Y N
7
M
58
32.1
8 9
M M
47 49
29.99 31.2
30.7
45.4
49.4
N
N
26.5 22.6
52.2 44.6
3.7 15
Y Y
Y Y
10
M
43
37.2
11 12
F M
45 57
55 36.8
34.9
50
13.8
Y
Y
55.7 36.8
44.7 34
26.5 11
N Y
N Y
13
F
53
31.4
29.9
17
15.4
N
N
14 15
M M
43 41
33.3 30.7
32.6 29.3
92.6 25.3
6.1 9.6
Y Y
Y Y
16
M
48
45.5
32.9
88
7.7
Y
Y
17 18
M F
59 52
35.4 30
35.4 28.4
33.1 48
95.2 6.9
N Y
N Y
19
M
53
30
30
72
28
N
Y
AHI 5 apnea-hypopnea index; BMI 5 body mass index; F 5 female; M 5 male; N 5 no; Y 5 yes.
Center, Philadelphia, Pennsylvania. All MRIs were performed with the patients awake and breathing comfortably. The images were obtained contiguously over a several-minutes-long sequence in order to average any airway volume changes that occurred during inspiration or exhalation.10 Only T1-weighted images were analyzed. All images were analyzed using the image analysis program Amira 4.2.1 (Visage Imaging; Richmond, Victoria, Australia). Volume of the upper airway soft tissue structures were measured within an anatomically defined region of interest, as performed in our previous studies.10 Examples of MRI segmentation using Amira (Visage Imaging) can be seen in Figure 1. The volumes of the following upper airway structures were measured: mandible, including mandibular teeth; airway, which was divided into three parts including retropalatal (from the hard palate to the distal margin of the soft palate), retroglossal (between the caudal margin of the soft palate and the rostral margin of the epiglottis), and retroepiglottal (from the rostral to caudal margins of the epiglottis); epiglottis; soft palate; tongue, which was defined as the genioglossus muscle; other tongue, which included all tongue musculature excluding the genioglossus; fat pads, which included the parapharyngeal fat between the lateral walls of the airway and the pterygoid muscles; pterygoid muscles; and lateral pharyngeal muscular walls, which were divided into retropalatal lateral walls (defined as posterior to the soft palate) and retroglossal lateral walls (measured from the disappearance of the soft palate until the disappearance of the tongue). Of note, palatine tonsil tissue was included in the segmentation of the lateral walls. Once all upper airway structures were segmented within the anatomical boundaries of interest, Amira (Visage Imaging) was used to calculate volumes of each anatomical structure. Patient-specific percent and absolute changes from baseline were calculated for the volume of each upper airway structure (based on pre- and postoperative MRI) and for the apneahypopnea index (based on pre- and postoperative PSG). Contin-
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uous variables were summarized using means 6 standard deviations (SDs) and medians (ranges). We assessed whether changes in UA volumes pre- and postoperation were significantly different from zero using Wilcoxon signed-rank tests and compared changes between groups using nonparametric Wilcoxon rank sum tests. Associations between changes in upper airway structures and change in AHI were assessed using Spearman rank correlations. Upper airway structures were grouped into three distinct domains: 1) mandible (n 5 1); 2) airway measures (n 5 7): retropalatal (RP) area and volume, retroglossal (RG) area and volume, retroepiglottal (RE) area and volume, and total airway volume; and 3) soft tissue volumes (n 5 9): epiglottis, soft palate, genioglossus, other tongue, parapharyngeal fat pads, pterygoid, RP lateral walls, RG lateral walls, and total lateral walls (RP 1 RG). Within each domain, we used a Bonferroni corrected level of significance (P < 0.05/ [no. of measures]), resulting in thresholds for significance of P 5 0.05 for the mandible, P 5 0.0071 for airway measures, and P 5 0.0056 for soft tissue structures. A P < 0.05 was considered suggestive for all analyses. Analyses were performed by one biostatistician (B.T.K.) using Stata Version 12, StataCorp (College Station, Texas) or SAS Software, version 9.3 (SAS Institute, Cary, NC).
RESULTS Overall, 19 preoperative and postoperative upper airway MRI scans were analyzed, and 18 preoperative and postoperative polysomnograms were analyzed (Table I). Sixteen patients (84.2%) were male and three patients (15.8%) were female. The ages of the patients ranged from 24 to 59 years, with a mean age of 46.8 years. The preoperative body mass index (BMI) ranged from 26.6 to 55.0 with a mean preoperative BMI of Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
TABLE II. Examining Changes in AHI, BMI, and MRI Structures Between Successes and Nonsuccesses.* Change From Baseline Measure
AHI (events/hour) BMI (kg/m2)
Non-Success (n 5 7)
24.51 6 33.45 20.60 6 1.01
Success (n 5 11)
252.85 6 29.00 22.89 6 4.05
Percent Change From Baseline P†
Non-Success (n 5 7)
Success (n 5 11)
P†
0.0057 0.1194
0.35 6 85.84 22.20 6 3.32
281.56 6 12.48 28.06 6 10.23
0.0005 0.1310
Mandible (mm3)
22,687 6 5,564
2395 6 4,058
0.6256
24.71 6 9.34
20.92 6 6.87
0.4350
RP airway volume (mm3) RP airway area (mm2)
21,166 6 2,097 212.49 6 62.39
21,127 6 855 216.02 6 31.63
0.6836 0.8738
222.95 6 43.02 24.99 6 32.53
232.89 6 24.20 212.85 6 27.42
0.9639 0.6338
RG airway volume (mm3)
2,166 6 3,029
2,424 6 2,008
0.8209
123.23 6 189.25
91.13 6 94.74
0.8209
RG airway area (mm2) RE airway volume (mm3)
16.89 6 91.96 290.3 6 1,526.7
9.30 6 76.89 101.4 6 1,467.5
0.5604 0.7513
16.84 6 42.72 35.74 6 83.03
5.43 6 27.96 7.44 6 42.09
0.4914 0.5561
26.59 6 88.01
0.5604
42.81 6 112.48
5.09 6 44.57
0.3683
1,398 6 2,856 25.29 6 368.63
0.9639 0.4414
20.24 6 43.10 5.75 6 31.63
14.01 6 27.32 2.92 6 29.72
0.8919 0.8209
RE airway area (mm2) Total airway volume (mm3) Epiglottis (mm3)
4.25 6 196.95 1,291 6 3,623 45.55 6 273.48
Soft palate (mm3)
21,422 6 1,875
22,347 6 1,704
0.2215
215.83 6 22.62
220.95 6 15.70
0.3416
Tongue (mm3) Other tongue (mm3)
25,238 6 8,223 23,722 6 4,966
26,572 6 8,126 299.1 6 3,069.2
0.6184 0.0971
26.46 6 9.21 210.23 6 22.15
25.85 6 6.76 3.72 6 22.79
0.8209 0.0971
Fat pads (mm3)
270.62 6 1,275.20
2693.8 6 1,052.4
0.5152
2.73 6 24.05
29.76 6 14.58
0.3290
Pterygoid (mm3) RP lateral walls (mm3)
2274.7 6 1,870.0 23,659 6 3,749
21,353 6 2,419 26,876 6 4,700
0.4273 0.1351
20.85 6 8.94 243.11 6 22.18
24.61 6 11.22 252.58 6 21.28
0.3683 0.4414
RG lateral walls (mm3) Lateral walls (mm3)
864.9 6 1,239.4 22,754 6 4,398
1,685 6 1,343
0.4094
21.10 6 30.49
22.10 6 18.13
0.7237
24,427 6 4,305
0.3458
210.70 6 21.07
220.85 6 19.37
0.3458
*Surgical success defined as AHI reduction by at least 50% and final AHI < 20. † P value from nonparametric Wilcoxon rank sum test comparing changes in successes and nonsuccesses. AHI 5 apnea-hypopnea index; BMI 5 body mass index; MRI 5 magnetic resonance imaging; RE 5 retroepiglottal; RG 5 retroglossal; RP 5 retropalatal.
34.0 kg/m2. The postoperative BMI ranged from 22.6 to 55.7, with a mean postoperative BMI of 32.2 kg/m2. Preoperative and postoperative AHI was determined for each patient. Of note, patient 17 completed the postoperative PSG at a different sleep center from the preoperative PSG; this exam was scored differently, and therefore the patient’s postoperative AHI may not be equivalent to the rest of the values. Of the 18 patients who completed their postoperative PSG, 11 (61%) patients were surgical successes and 12 (67%) patients were surgical responders, based on the criteria described above (Table I). The patients with surgical success had a mean 6 SD AHI decrease of 52.9 6 29.0 events/hour, and the nonsuccesses had an AHI decrease of 4.5 6 33.5 events/hour (P 5 0.006), as seen in Table II. The patients with surgical response had a mean AHI decrease of 52.1 6 27.8 events/hour, and the nonresponders had a mean AHI increase of 2.1 6 31.3 events/hour (P 5 0.002), as seen in Table III. Tables II and III also show changes in BMI, upper airway and soft tissue volumes between successes/nonsuccesses, and responders/nonresponders, respectively. There were no statistically significant differences seen in these measurements. Changes in upper airway structures based on preoperative and postoperative volumetric upper airway MRI analysis are presented in Table IV and Supporting Table SI. Not surprisingly, we saw no significant change in mandibular volume following surgery. For our airway Laryngoscope 125: August 2015
measures, the RP airway volume decreased by a mean of 28.8 6 31.1% (P 5 0.004), and the RG airway volume increased by a mean of 110.4 6134.3% (P 5 0.0005). These significant regional changes were reflected in a nominally significant increase in total airway volume (19.4 6 34.8%; P 50.030). There was no statistically significant change in RE airway volume (mean change 19.9 6 59.3%, P 5 0.398, Table IV). Similar results were seen when examining absolute changes (Supp. Table SI). Figure 1 A–C shows an example MRI segmentation of a patient whose airway increased in volume postoperatively at the RP, RG, and RE levels. When examining the upper airway soft tissue volumes, we observed significant decreases in the volume of the soft palate (218.3 6 18.0%, P 5 0.0015) and retropalatal lateral walls (249.8 6 21.3%, P 50.0001), and a significant increase in the retroglossal lateral wall volume (20.2 6 22.9%; P 5 0.002). These regional changes in the RP and RG lateral walls are reflected in a nominally significant decrease in the total lateral walls (217.9 6 19.8%, P 5 0.0084) (Table IV). Figure 1A demonstrates an example of a patient with a decrease in postoperative RP lateral wall volume. We also saw a suggestive decrease in genioglossus tongue volume (25.8 6 7.5%, P 5 0.013), which is demonstrated in Figure 1C, most notably at the base of the tongue region. Pre- and postoperative volumetric changes in the other structures analyzed, including the epiglottis, other tongue musculature, parapharyngeal fat pads, and Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
1991
TABLE III. Examining Changes in AHI, BMI, and MRI Structures Between Responders and Nonresponders.* Change From Baseline Measure
AHI (events/hour) BMI (kg/m2)
Nonresponse (n 5 6)
2.07 6 31.29 20.70 6 1.07
Mandible (mm3)
22,055 6 5,814
RP airway volume (mm3) RP airway area (mm2)
2483.3 6 1,165.4 3.92 6 49.06
RG airway volume (mm3)
2,355 6 3,273
RG airway area (mm2) RE airway volume (mm3)
22.98 6 99.18 271.1 6 1,304.0
Response (n 5 12)
252.11 6 27.77 22.65 6 3.95
Percent Change From Baseline P†
Nonresponse (n 5 6)
Response (n 5 12)
P†
0.0020 0.2759
10.59 6 89.22 22.56 6 3.48
279.86 6 13.28 27.39 6 10.03
0.0007 0.2979
2948 6 4,264
0.8407
23.57 6 9.69
21.88 6 7.26
0.9199
21,472 6 1,446 225.52 6 42.33
0.2234 0.329
216.17 6 42.83 2.01 6 29.31
235.45 6 24.73 216.26 6 28.01
0.4537 0.2328
2,308 6 1,956
0.9254
139.00 6 202.21
85.92 6 92.11
1.0000
6.41 6 73.07 297.8 6 1,555.8
0.329 0.7079
21.00 6 45.21 31.49 6 90.11
4.07 6 26.71 11.93 6 43.03
0.2781 1.0000
RE airway area (mm2)
210.38 6 211.54
3.27 6 88.64
>0.999
44.21 6 123.14
8.02 6 43.03
0.6644
Total airway volume (mm3) Epiglottis (mm3)
1,800 6 3,683 213.29 6 246.32
1,134 6 2,872 56.39 6 367.62
0.6396 0.7787
25.46 6 44.72 20.17 6 30.11
11.91 6 27.04 6.12 6 30.42
0.5121 0.7079
Soft palate (mm3)
21,054 6 1,755
22,454 6 1,666
0.0752
213.69 6 23.99
221.60 6 15.14
0.1340
Tongue (mm3) Other tongue (mm3)
23,919 6 8,157 23,940 6 5,403
27,120 6 7,978 52 6 3,024
0.3490 0.1594
25.26 6 9.47 210.16 6 24.26
26.50 6 6.82 2.41 6 22.05
0.5121 0.1317
Fat pads (mm3) Pterygoid (mm3) RP lateral walls (mm3) RG lateral walls (mm3) Lateral walls (mm3)
44.6 6 1,390.4 322 6 1,096 23,149 6 3,831
2689.5 6 998.5
0.4615
5.14 6 26.07
29.72 6 13.83
0.3356
21,603 6 2,414 26,863 6 4,481
0.1585 0.0610
1.48 6 7.09 240.13 6 22.70
25.63 6 11.06 253.29 6 20.44
0.1289 0.3029
1,090 6 1,241
1,491 6 1,408
0.9025
25.88 6 31.47
19.61 6 18.82
0.7133
21910 6 4,338
24,682 6 4,138
0.1416
25.97 6 19.69
222.19 6 18.75
0.1416
*Surgical response defined as AHI reduction by at least 50%. † P value from nonparametric Wilcoxon rank sum test comparing changes in responders and nonresponders. AHI 5 apnea-hypopnea index; BMI 5 body mass index; MRI 5 magnetic resonance imaging; RE 5 retroepiglottal; RG 5 retroglossal; RP 5 retropalatal.
TABLE IV. Percentage Change From Preoperation in MRI Upper Airway Structures. Domain
Measure
N
Mean 6 SD
Median (Range)
P*
Mandible
Volume (%)
18
22.1 6 7.9
23.7 (218.8, 13.1)
Airway Measures†
RP airway volume (%)
19
228.8 6 31.1
233.1 (266.6, 51.4)
0.0038
RP airway area (%) RG airway volume (%)
17 19
28.4 6 28.4 110.4 6 134.3
29.2 (253.6, 51.4) 41.8 (234.3, 485.1)
0.1930 0.0005
Soft Tissue Volumes‡
0.2485
RG airway area (%)
17
13.7 6 35.9
11.5 (250.2, 91.7)
0.1239
RE airway volume (%) RE airway area (%)
19 17
19.9 6 59.3 25.9 6 80
22.5 (260.4, 206.3) 10.7 (260.1, 282.9)
0.3981 0.4074
Total airway volume (%)
19
19.4 6 34.8
7.3 (229.0, 101.7)
0.0298
Epiglottis (%) Soft palate (%)
19 19
4.0 6 28.7 218.3 6 18.0
25.9 (225.3, 72.7) 219.5 (259.9, 20.0)
0.7782 0.0015
Genioglossus (%)
19
25.8 6 7.4
23.9 (218.2, 4.3)
0.0126
Other tongue (%) Fat pads (%)
18 17
20.8 6 22.8 24.0 6 18.9
23.7 (231.6, 57.5) 29.3 (234.7, 42.9)
0.5566 0.2868
Pterygoid (%)
17
22.3 6 10.2
0.1 (225.0, 9.0)
0.6192
RP lateral walls (%) RG lateral walls (%)
19 16
249.8 6 21.3 20.2 6 22.9
255.2 (286.1, 25.8) 10.6 (25.4, 73.9)
0.0001 0.0019
Total lateral walls (%)
16
217.9 6 19.8
220.1 (246.7, 16.9)
0.0084
*P value from Wilcoxon signed rank test assessing whether observed change is significantly different from zero. † Bonferroni corrected level of significance: P < 0.0071. ‡ Bonferroni level of significance: P < 0.0056. MRI 5 magnetic resonance imaging; RE 5 retroepiglottal; RG 5 retroglossal; RP 5 retropalatal; SD 5 standard deviation.
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Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
TABLE V. Spearman Correlations Between Changes in MRI Structures and Changes in AHI.* Percent Change Domain
Mandible Airway Measures†
Soft Tissue Volumes‡
Measure
Volume (mm3) RP airway volume (mm3)
Absolute Change
N
rho
P
rho
P
17 18
20.29 0.23
0.2602 0.3627
20.33 0.31
0.1911 0.2096
RP airway area (mm2)
16
0.36
0.1723
0.40
0.1217
RG airway volume (mm3) RG airway area (mm2)
18 16
20.15 0.15
0.5645 0.5717
20.17 0.10
0.4941 0.7125
RE airway volume (mm3)
18
20.07
0.7726
20.15
0.5590
RE airway area (mm2) Total airway volume (mm3)
16 18
0.01 20.06
0.9828 0.8103
20.18 20.13
0.4991 0.6099
Epiglottis (mm3)
18
0.02
0.9514
0.16
0.5153
Soft palate (mm3) Tongue (mm3)
18 18
0.32 20.05
0.1971 0.8421
0.31 20.09
0.2033 0.7354
Other tongue (mm3)
17
20.47
0.0581
20.39
0.1246
Fat pads (mm3) Pterygoid (mm3)
16 16
20.01 0.19
0.9569 0.4921
20.11 0.07
0.6963 0.7867
RP lateral walls (mm3)
18
0.53
0.0232
0.69
0.0014
RG lateral walls (mm3) Lateral walls (mm3)
15 18
0.15 0.56
0.5848 0.0284
0.17 0.63
0.5327 0.0121
*Measures of absolute change from baseline are correlated with AHI change from baseline, and MRI percent change are correlated with percent change in AHI. † Bonferroni corrected level of significance: P < 0.0071. ‡ Bonferroni level of significance: P < 0.0056. MRI 5 magnetic resonance imaging, AHI 5 apnea-hypopnea index, RP 5 retropalatal, RG 5 retroglossal, RE 5 retroepiglottal.
pterygoid muscles, were not statistically significant (Table IV). As with airway measures, similar results were seen when examining absolute changes (Supp. Table SI). Results of analyses examining the correlation between changes in upper airway structures and changes in AHI are presented in Table V. Although no result met our Bonferroni-corrected level of significance, we found suggestive correlations with change in AHI and both RP (rho 5 0.53, P 5 0.023) and total (rho 5 0.56, P 5 0.028) lateral walls. In both instances, greater decreases in lateral wall volume correlated with greater decreases in AHI. When examining absolute changes rather than percent change, we observed a statistically significant correlation between RP lateral walls and AHI (rho 5 0.69, P 5 0.0014) and nominally significant correlations between total lateral walls and AHI (rho 5 0.63, P 5 0.0121). Volumetric changes in other structures did not correlate with a change in AHI, as shown in Table V.
DISCUSSION Obstructive sleep apnea is a significant problem in our population that can lead to serious medical complications.1,2 Surgical treatment for OSA has been an area of debate for many years, primarily due to the variable success rate.3 Transoral robotic surgery is a new technique in the field of sleep surgery and has shown promising results4–7; however, the question of why some patients respond and some do not respond to surgery remains. Laryngoscope 125: August 2015
Volumetric MRI analysis is a validated tool to measure UA soft tissue structures in patients with OSA.10 Most previous MRI studies on patients with sleep apnea, however, have been done only in the preoperative or nonoperative setting in order to make comparisons either with normal subjects8,10,11 or between the same subjects during periods of wakefulness or sleep.13 One group has used pre- and postoperative MRI to measure the vallecular line as a method of evaluating for the transoral resectability of exophytic base of tongue tumors14; however, our study is the first describing the volumetric changes in upper airway structures after undergoing transoral robotic surgery for OSA. Our results show that the airway, tongue, soft palate, and lateral wall volumes change significantly after OSATORS. It was expected that the soft palate, tongue, and RP lateral wall volumes would decrease after surgery; and it was expected that the retroglossal, retroepiglottal, and total airway volumes would increase after surgery. It was also expected that the volumes of structures not involved in the surgical resection, such as the mandible, parapharyngeal fat pads, and pterygoid muscles, would not change significantly postoperatively. Our results confirmed these expectations. The overall decrease in size of the retropalatal airway and increase in retroglossal lateral wall volumes after surgery were related to a postoperative reduction (retropalatal) or increase (retroglossal) in the measured length of these structures on MRI, which was necessary in order to keep the anatomical boundaries of segmentation constant Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
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between pre- and postoperative imaging. For example, the soft palate was shortened postoperatively, resulting in fewer retropalatal airway slices and effectively reducing the airway in the retropalatal region. Similarly, the volume of retropalatal lateral walls, which was based on the size of the soft palate, was reduced postoperatively. The volume of the retroglossal lateral walls, however, increased postoperatively. By reducing the length of the soft palate, there were more slices measured in the retroglossal region, thus increasing the retroglossal lateral wall volume. Our data also show that a decrease in retropalatal and total lateral wall volume correlates with a decrease in postoperative AHI. This may be explained by several factors. First, the transoral robotic bilateral posterior hemiglossectomy procedure was accompanied by a bilateral limited pharyngectomy in the retroglossal region, effectively expanding the airway in a lateral direction. Additionally, this data could also be explained by the fact that the palatine tonsils are within the retropalatal lateral wall tissue, and the tonsils are removed during the UPPP/modified expansion sphincteroplasty. It is well known that in apneic patients with large tonsils, removing the tonsils can improve sleep apnea.15 Of note, our study did not correlate preoperative tonsil size with changes in retropalatal lateral wall volume or surgical outcome; however, this may represent an interesting area of future study. Furthermore, during the modified expansion sphincteroplasty, the posterior tonsillar pillar and a portion of the retropalatal lateral wall within the superior aspect of the tonsillar fossa is retracted and secured out laterally, thus decreasing the overall volume of the retropalatal lateral pharyngeal walls. These results suggest that decreases in the volume of the lateral walls are an important indicator of patient response to surgery. In addition to a small sample size, other limitations of this study include one patient failing to complete the postoperative PSG and changes in length of several segmented and measured structures (as explained above) in order to keep the anatomic boundaries constant between pre- and postoperative analysis. Although all postoperative MRI scans were performed at one institution (University of Pennsylvania Medical Center), the preoperative MRIs were performed at different institutions, making it difficult to control the MRI protocols. Furthermore, pre- and postoperative polysomnograms were completed at varying institutions for ease on the patient, but this increased variability in the AHI measurement. It is notable that several patients in our study had substantial decreases in BMI postoperatively, specifically patients 9 and 16, and this may have contributed to their individual surgical success or response. Although BMI changes were not controlled for in this study, Tables II and III show that, within the group, changes in BMI were not statistically significant between successes and nonsuccesses and responders and nonresponders. Another weakness of this study is that the MRI analysis was not blinded to surgical outcome, thus creatLaryngoscope 125: August 2015
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ing potential bias. If the MRI scans had been scored independently and the scorer had been blinded to outcome, this potential bias would have been removed. Further research will include additional pre- and postoperative MRIs and PSGs in the data analysis. We will also use T2-weighted MR imaging to measure strictly base of tongue and lingual tonsil volumetric changes separately from the entire tongue. The current MRI protocol did not capture T2-weighted images. Additional studies within independent populations are an important next step in order to replicate results and increase generalizability.
CONCLUSION This is the first study to examine the effect of transoral robotic surgery (OSA-TORS) on the soft tissues of the upper airway in patients with obstructive sleep apnea. As expected, the total airway volume increased postoperatively, whereas the volumes of the soft palate, tongue, and total and retropalatal lateral pharyngeal walls decreased. Larger decreases in the total and retropalatal lateral pharyngeal wall volumes correlated with greater decreases in postoperative AHI. These results are an important step toward further understanding the postsurgical anatomical changes following sleep surgery.
Acknowledgments This research was performed at the Hospital of the University of Pennsylvania, Department of Otorhinolaryngology– Head and Neck Surgery (R.C.C., R.C.B., E.R.T.) and Department of Medicine, Division of Sleep Medicine (R.J.S., B.T.K.), Philadelphia, Pennsylvania. Many thanks to Sarika Shinde for her help with this project. Our thanks to Intuitive for funding the imaging portion of this project.
BIBLIOGRAPHY 1. Lee W, Nagubadi S, Kryger MH, Mokhlesi B. Epidemiology of obstructive sleep apnea: a population-based perspective. Expert Rev Respir Med 2008;2:349–364. 2. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med 2002;165:1217–1239. 3. Camacho M, Certal V, Capasso R. Comprehensive review of surgeries for obstructive sleep apnea syndrome. Braz J Otorhinolaryngol 2013;79: 780–788. 4. Lee JM, Weinstein GS, O’Malley BW, Thaler ER. Transoral roboticassisted lingual tonsillectomy and uvulopalatopharyngoplasty for obstructive sleep apnea. Ann Otol Rhinol Laryngol 2012;121:635– 639. 5. Vicini C, Dallan I, Canzi P, et al. Transoral robotic surgery of the tongue base in obstructive sleep apnea-hypopnea syndrome: anatomic considerations and clinical experience. Head Neck 2012;34:15–22. 6. Friedman M, Hamilton C, Samuelson CG, et al. Transoral robotic glossectomy for the treatment of obstructive sleep apnea-hypopnea syndrome. Otolaryngol Head Neck Surg 2012;146:854–862. 7. Lin HS, Rowley JA, Badr MS, et al. Transoral robotic surgery for treatment of obstructive sleep apnea-hypopnea syndrome. Laryngoscope 2013;123:1811–1816. 8. Schwab RJ, Gupta KB, Gefter WB, Metzger LJ, Hoffman EA, Pack AI. Upper airway and soft tissue anatomy in normal subjects and patients with sleep-disordered breathing. Am J Respir Crit Care Med 1995;152: 1673–1689. 9. Schwab RJ, Gefter WB, Hoffman EA, Gupta KB, Pack AI. Dynamic upper airway imaging during awake respiration in normal subjects and patients with sleep disordered breathing. Am Rev Respir Dis 1993;148: 1385–1400. 10. Schwab RJ, Pasirstein M, Pierson R, et al. Identification of upper airway anatomic risk factors for obstructive sleep apnea with volumetric
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magnetic resonance imaging. Am J Respir Crit Care Med 2003;168: 522–530. 11. Whittle AT, Marshall I, Mortimore IL, Wraith PK, Sellar RJ, Douglas NJ. Neck soft tissue and fat distribution: comparison between normal men and women by magnetic resonance imaging. Thorax 1999;54: 323–328. 12. Borek RC, Thaler ER, Kim C, Jackson N, Mandel JF, Schwab RJ. Quantitative airway analysis during drug-induced sleep endoscopy for evaluation of sleep apnea. Laryngoscope 2012;122:2592–2599.
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13. Wang Y, Mcdonald JP, Liu Y, Pan K, Zhang X, Hu R. Dynamic alterations of the tongue in obstructive sleep apnea-hypopnea syndrome during sleep: analysis using ultrafast MRI. Genet Mol Res 2014;4552–4563. 14. Hai N, Taheri MR, Sadeghi N. The vallecular line: an objective measure in evaluating the base of the tongue and vallecular cancers for transoral robotic surgery. J Comput Assist Tomogr 2013;37:686–693. 15. Verse T, Kroker BA, Pirsig W, Brosch S. Tonsillectomy as a treatment of obstructive sleep apnea in adults with tonsillar hypertrophy. Laryngoscope 2000;110:1556–59.
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Rhinological and Otological Society, Inc.
Volumetric MRI Analysis Pre- and Post-Transoral Robotic Surgery for Obstructive Sleep Apnea Rebecca C. Chiffer, MD; Richard J. Schwab, MD; Brendan T. Keenan, MS; Ryan C. Borek, MD; Erica R. Thaler, MD Objectives/Hypothesis: To quantitatively measure volumetric changes in upper airway soft tissue structures using magnetic resonance imaging (MRI) pre- and post transoral robotic surgery for obstructive sleep apnea (OSA-TORS). Study Design: Prospective, nonrandomized, institutional board-approved study. Methods: Apneics undergoing OSA-TORS, which included bilateral posterior hemiglossectomy with limited pharyngectomy and uvulopalatopharyngoplasty, had upper airway MRIs pre- and postoperatively. Changes (percent and absolute values) in upper airway and surrounding soft tissue volumes were calculated. We assessed whether there were significant volumetric changes and if changes correlated with apnea-hypopnea index (AHI) changes. Results: Nineteen MRIs and 18 polysomnograms were analyzed pre- and postoperation. Total airway volume increased by 19.4% (P 5 0.030). Soft palate and tongue volumes decreased by 18.3% (P 5 0.002) and 5.8% (P 5 0.013), respectively. Retropalatal and total lateral wall volumes decreased by 49.8% (P 5 0.0001) and 17.9% (P 5 0.008), respectively. Changes in other structures were not significant. Eleven patients had surgical success, with a mean AHI decrease of 52.9; six were nonsuccesses with a mean AHI decrease of 4.5 (P 50.006). Decreased retropalatal lateral wall volume correlated with decreased AHI. Conclusion: Airway, tongue, soft palate, and lateral wall volumes change significantly after OSA-TORS. Changes in the volume of the lateral walls correlated with changes in AHI. Volumetric upper airway MRI may be a helpful tool to better understand reasons for surgical success. Key Words: Transoral robotic surgery, volumetric MRI analysis, obstructive sleep apnea, uvulopalatopharyngoplasty. Level of Evidence: 4. Laryngoscope, 125:1988–1995, 2015
INTRODUCTION Obstructive sleep apnea (OSA) is a growing epidemiological problem affecting a significant portion of the population.1 Recent estimates state that up to 20% of adults have mild OSA and 6-7% have moderate to severe OSA.2 Obstructive sleep apnea affects multiple organ
Additional Supporting Information may be found in the online version of this article. From the Department of Otorhinolaryngology–Head and Neck Surgery, Hospital of the University of Pennsylvania (R.C.C., R.C.B.); the Department of Otorhinolaryngology–Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania (E.R.T.); the Department of Medicine, Division of Sleep Medicine, Pulmonary, Allergy and Critical Care Division, Penn Sleep Center (R.J.S.); and Perelman School of Medicine at the University of Pennsylvania, Division of Sleep Medicine, Center for Sleep and Circadian Neurobiology (B.T.K.), University of Pennsylvania Medical Center; Philadelphia, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication February 25, 2015. Presented at the Annual Meeting of the Broncho-Esophagological Association at the Combined Otolaryngology Society Meeting, Las Vegas, Nevada, U.S.A., May 14, 2014. The imaging portion of this research was funded by an Intuitive grant awarded to E.R.T. The authors have no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Rebecca C. Chiffer, MD, Department of Otorhinolaryngology–Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104. E-mail: [email protected] DOI: 10.1002/lary.25270
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systems and can lead to serious medical complications. Obstructive sleep apnea has been associated with hypertension, stroke, coronary artery disease, congestive heart failure, insulin resistance, and neurocognitive dysfunction.1,2 For these reasons, it is important to study not only the risk factors associated with developing this disease, but also the optimal treatment modalities. Because many patients have difficulty tolerating continuous positive airway pressure, which is the first line treatment for OSA, 3 these patients often seek surgical evaluation. Surgical treatment for OSA, however, has considerable variability with a wide range of results.3–7 Transoral robotic surgery (TORS) has recently become a new area of research for the treatment of OSA because it allows for direct visualization of, and better access to, the base of tongue, compared to open procedures.5–7 Investigators have reported a surgical cure rate of 66.7% with transoral robotic glossectomy.6 Another group reported a cure rate of 70% with TORS based on apnea-hypopnea index (AHI) parameters.5 Although these data are promising, the question remains as to why some patients respond and other patients do not respond to TORS. It may be possible to answer this question by examining the soft tissue and bony structures that are most likely to be causing the patient’s upper airway (UA) collapse and obstruction, and are directly within the surgical field. Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
normal subjects.9,10 Furthermore, it has been shown that UA soft tissue enlargement is a significant risk factor for developing OSA.10 Volumetric magnetic resonance imaging (MRI) can also be used to examine how the upper airway soft tissue volumes change, or do not change, following surgical intervention. In our study, we used T1-weighted MRI to measure the changes in upper airway soft tissue volumes in patients with OSA before and after undergoing transoral robotic surgery, or OSA-TORS. We hypothesized that the volumes of the airway and soft tissue structures within the surgical field would change significantly, and that these changes would correlate to changes in postoperative AHI.
MATERIALS AND METHODS
Fig. 1. Magnetic resonance imaging segmentation shown in one example patient pre- and postoperatively at comparable crosssectional regions. (A) Increase in airway volume at the retropalatal airway level. (B) Increase in airway volume at the retroglossal airway level (defined as airway between the caudal margin of the soft palate and the rostral margin of the epiglottis.) (C) Increase in airway volume at the retroepiglottal airway level. Color Key: white 5 mandible; light green 5 retropalatal airway; light blue 5 retroglossal airway; dark blue 5 retroepiglottal airway; light purple 5 epiglottis; pink 5 soft palate; red 5 genioglossus tongue; brown 5 other tongue muscles; yellow 5 parapharyngeal fat pads; neon green 5 pterygoid muscles; orange 5 retropalatal lateral walls; dark purple 5 retroglossal lateral walls.
Previous studies have shown that the soft tissues of the upper airway differ between apneics and normal subjects.8–11 More specifically, airway caliber is significantly smaller and the volume of UA soft tissue structures is significantly larger in apneics compared to Laryngoscope 125: August 2015
Study subjects were selected as part of a prospective, nonrandomized, institutional board-approved (University of Pennsylvania) study. All patients were at least 18 years of age at the time of treatment, had documented OSA with an AHI > 5, as defined by a preoperative polysomnography (PSG), and signed a written informed consent. Exclusionary criteria included age < 18 years, unexplained fever and/or untreated active infection, pregnancy, previous head and neck surgery precluding transoral/robotic procedures, and the presence of a medical condition that contraindicated general anesthesia or a transoral surgical approach. In addition to a preoperative PSG, all patients underwent a preoperative upper airway MRI and drug-induced sleep endoscopy (DISE). All DISEs were performed by one coinvestigator (E.R.T.) according to the previously described technique by Lee et al.4 and Borek et al.12 Patients found to have significant obstruction at the retroglossal region, as demonstrated by a significant percentage change in cross-sectional area during DISE, were given the option of undergoing OSA-TORS. Many patients also demonstrated retropalatal obstruction on DISE; however, the decision to offer the OSA-TORS procedure was based upon retroglossal obstruction. All patients were informed of the risks, benefits, and alternatives to surgical treatment, and written informed consent was obtained prior to the procedure. The OSA-TORS procedure was performed by one coinvestigator (E.R.T.) with the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA) according to the previously described technique by Lee et al.4 The procedure consisted of a bilateral robotic posterior hemiglossectomy with limited pharyngectomy followed by a uvulopalatopharyngoplasty (UPPP), which was a modification of the expansion sphincteroplasty technique. This part of the procedure was also performed by one coinvestigator (E.R.T.). Of note, all patients underwent bilateral limited pharyngectomy with modified UPPP, regardless of degree of retropalatal obstruction seen on preoperative DISE. Each patient who underwent surgery was scheduled for a follow-up PSG to determine the outcome of the procedure and a repeat upper airway MRI at least 3 months (range 6–24 months) after surgery. The criteria for surgical success included both a reduction in preoperative AHI of at least 50% and a postoperative AHI of less than 20 events per hour. A surgical response was defined as a reduction from the preoperative AHI of at least 50%. Preoperative and postoperative upper airway MRI scans were analyzed by one coinvestigator (R.C.C.) with an overall review and consensus from the entire team. Preoperative MRIs were performed at varying institutions; all postoperative MRIs were performed at the University of Pennsylvania Medical
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TABLE I. Summary of Clinical and Treatment Data. Subject
Gender
Age
Pre-BMI
Post-BMI
Pre-AHI
Post-AHI
Surgical Success
Surgical Response
1
M
24
26.6
24.6
2 3
M M
59 45
34.5 38
34.5 37.6
22.9
14.3
N
N
66 66
11.6 10
Y Y
Y Y
4
M
44
31
5 6
M M
32 37
27.9 29.6
n/a
36
n/a
n/a
n/a
27.2 29.6
112 56
2 30.7
Y N
Y N
7
M
58
32.1
8 9
M M
47 49
29.99 31.2
30.7
45.4
49.4
N
N
26.5 22.6
52.2 44.6
3.7 15
Y Y
Y Y
10
M
43
37.2
11 12
F M
45 57
55 36.8
34.9
50
13.8
Y
Y
55.7 36.8
44.7 34
26.5 11
N Y
N Y
13
F
53
31.4
29.9
17
15.4
N
N
14 15
M M
43 41
33.3 30.7
32.6 29.3
92.6 25.3
6.1 9.6
Y Y
Y Y
16
M
48
45.5
32.9
88
7.7
Y
Y
17 18
M F
59 52
35.4 30
35.4 28.4
33.1 48
95.2 6.9
N Y
N Y
19
M
53
30
30
72
28
N
Y
AHI 5 apnea-hypopnea index; BMI 5 body mass index; F 5 female; M 5 male; N 5 no; Y 5 yes.
Center, Philadelphia, Pennsylvania. All MRIs were performed with the patients awake and breathing comfortably. The images were obtained contiguously over a several-minutes-long sequence in order to average any airway volume changes that occurred during inspiration or exhalation.10 Only T1-weighted images were analyzed. All images were analyzed using the image analysis program Amira 4.2.1 (Visage Imaging; Richmond, Victoria, Australia). Volume of the upper airway soft tissue structures were measured within an anatomically defined region of interest, as performed in our previous studies.10 Examples of MRI segmentation using Amira (Visage Imaging) can be seen in Figure 1. The volumes of the following upper airway structures were measured: mandible, including mandibular teeth; airway, which was divided into three parts including retropalatal (from the hard palate to the distal margin of the soft palate), retroglossal (between the caudal margin of the soft palate and the rostral margin of the epiglottis), and retroepiglottal (from the rostral to caudal margins of the epiglottis); epiglottis; soft palate; tongue, which was defined as the genioglossus muscle; other tongue, which included all tongue musculature excluding the genioglossus; fat pads, which included the parapharyngeal fat between the lateral walls of the airway and the pterygoid muscles; pterygoid muscles; and lateral pharyngeal muscular walls, which were divided into retropalatal lateral walls (defined as posterior to the soft palate) and retroglossal lateral walls (measured from the disappearance of the soft palate until the disappearance of the tongue). Of note, palatine tonsil tissue was included in the segmentation of the lateral walls. Once all upper airway structures were segmented within the anatomical boundaries of interest, Amira (Visage Imaging) was used to calculate volumes of each anatomical structure. Patient-specific percent and absolute changes from baseline were calculated for the volume of each upper airway structure (based on pre- and postoperative MRI) and for the apneahypopnea index (based on pre- and postoperative PSG). Contin-
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uous variables were summarized using means 6 standard deviations (SDs) and medians (ranges). We assessed whether changes in UA volumes pre- and postoperation were significantly different from zero using Wilcoxon signed-rank tests and compared changes between groups using nonparametric Wilcoxon rank sum tests. Associations between changes in upper airway structures and change in AHI were assessed using Spearman rank correlations. Upper airway structures were grouped into three distinct domains: 1) mandible (n 5 1); 2) airway measures (n 5 7): retropalatal (RP) area and volume, retroglossal (RG) area and volume, retroepiglottal (RE) area and volume, and total airway volume; and 3) soft tissue volumes (n 5 9): epiglottis, soft palate, genioglossus, other tongue, parapharyngeal fat pads, pterygoid, RP lateral walls, RG lateral walls, and total lateral walls (RP 1 RG). Within each domain, we used a Bonferroni corrected level of significance (P < 0.05/ [no. of measures]), resulting in thresholds for significance of P 5 0.05 for the mandible, P 5 0.0071 for airway measures, and P 5 0.0056 for soft tissue structures. A P < 0.05 was considered suggestive for all analyses. Analyses were performed by one biostatistician (B.T.K.) using Stata Version 12, StataCorp (College Station, Texas) or SAS Software, version 9.3 (SAS Institute, Cary, NC).
RESULTS Overall, 19 preoperative and postoperative upper airway MRI scans were analyzed, and 18 preoperative and postoperative polysomnograms were analyzed (Table I). Sixteen patients (84.2%) were male and three patients (15.8%) were female. The ages of the patients ranged from 24 to 59 years, with a mean age of 46.8 years. The preoperative body mass index (BMI) ranged from 26.6 to 55.0 with a mean preoperative BMI of Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
TABLE II. Examining Changes in AHI, BMI, and MRI Structures Between Successes and Nonsuccesses.* Change From Baseline Measure
AHI (events/hour) BMI (kg/m2)
Non-Success (n 5 7)
24.51 6 33.45 20.60 6 1.01
Success (n 5 11)
252.85 6 29.00 22.89 6 4.05
Percent Change From Baseline P†
Non-Success (n 5 7)
Success (n 5 11)
P†
0.0057 0.1194
0.35 6 85.84 22.20 6 3.32
281.56 6 12.48 28.06 6 10.23
0.0005 0.1310
Mandible (mm3)
22,687 6 5,564
2395 6 4,058
0.6256
24.71 6 9.34
20.92 6 6.87
0.4350
RP airway volume (mm3) RP airway area (mm2)
21,166 6 2,097 212.49 6 62.39
21,127 6 855 216.02 6 31.63
0.6836 0.8738
222.95 6 43.02 24.99 6 32.53
232.89 6 24.20 212.85 6 27.42
0.9639 0.6338
RG airway volume (mm3)
2,166 6 3,029
2,424 6 2,008
0.8209
123.23 6 189.25
91.13 6 94.74
0.8209
RG airway area (mm2) RE airway volume (mm3)
16.89 6 91.96 290.3 6 1,526.7
9.30 6 76.89 101.4 6 1,467.5
0.5604 0.7513
16.84 6 42.72 35.74 6 83.03
5.43 6 27.96 7.44 6 42.09
0.4914 0.5561
26.59 6 88.01
0.5604
42.81 6 112.48
5.09 6 44.57
0.3683
1,398 6 2,856 25.29 6 368.63
0.9639 0.4414
20.24 6 43.10 5.75 6 31.63
14.01 6 27.32 2.92 6 29.72
0.8919 0.8209
RE airway area (mm2) Total airway volume (mm3) Epiglottis (mm3)
4.25 6 196.95 1,291 6 3,623 45.55 6 273.48
Soft palate (mm3)
21,422 6 1,875
22,347 6 1,704
0.2215
215.83 6 22.62
220.95 6 15.70
0.3416
Tongue (mm3) Other tongue (mm3)
25,238 6 8,223 23,722 6 4,966
26,572 6 8,126 299.1 6 3,069.2
0.6184 0.0971
26.46 6 9.21 210.23 6 22.15
25.85 6 6.76 3.72 6 22.79
0.8209 0.0971
Fat pads (mm3)
270.62 6 1,275.20
2693.8 6 1,052.4
0.5152
2.73 6 24.05
29.76 6 14.58
0.3290
Pterygoid (mm3) RP lateral walls (mm3)
2274.7 6 1,870.0 23,659 6 3,749
21,353 6 2,419 26,876 6 4,700
0.4273 0.1351
20.85 6 8.94 243.11 6 22.18
24.61 6 11.22 252.58 6 21.28
0.3683 0.4414
RG lateral walls (mm3) Lateral walls (mm3)
864.9 6 1,239.4 22,754 6 4,398
1,685 6 1,343
0.4094
21.10 6 30.49
22.10 6 18.13
0.7237
24,427 6 4,305
0.3458
210.70 6 21.07
220.85 6 19.37
0.3458
*Surgical success defined as AHI reduction by at least 50% and final AHI < 20. † P value from nonparametric Wilcoxon rank sum test comparing changes in successes and nonsuccesses. AHI 5 apnea-hypopnea index; BMI 5 body mass index; MRI 5 magnetic resonance imaging; RE 5 retroepiglottal; RG 5 retroglossal; RP 5 retropalatal.
34.0 kg/m2. The postoperative BMI ranged from 22.6 to 55.7, with a mean postoperative BMI of 32.2 kg/m2. Preoperative and postoperative AHI was determined for each patient. Of note, patient 17 completed the postoperative PSG at a different sleep center from the preoperative PSG; this exam was scored differently, and therefore the patient’s postoperative AHI may not be equivalent to the rest of the values. Of the 18 patients who completed their postoperative PSG, 11 (61%) patients were surgical successes and 12 (67%) patients were surgical responders, based on the criteria described above (Table I). The patients with surgical success had a mean 6 SD AHI decrease of 52.9 6 29.0 events/hour, and the nonsuccesses had an AHI decrease of 4.5 6 33.5 events/hour (P 5 0.006), as seen in Table II. The patients with surgical response had a mean AHI decrease of 52.1 6 27.8 events/hour, and the nonresponders had a mean AHI increase of 2.1 6 31.3 events/hour (P 5 0.002), as seen in Table III. Tables II and III also show changes in BMI, upper airway and soft tissue volumes between successes/nonsuccesses, and responders/nonresponders, respectively. There were no statistically significant differences seen in these measurements. Changes in upper airway structures based on preoperative and postoperative volumetric upper airway MRI analysis are presented in Table IV and Supporting Table SI. Not surprisingly, we saw no significant change in mandibular volume following surgery. For our airway Laryngoscope 125: August 2015
measures, the RP airway volume decreased by a mean of 28.8 6 31.1% (P 5 0.004), and the RG airway volume increased by a mean of 110.4 6134.3% (P 5 0.0005). These significant regional changes were reflected in a nominally significant increase in total airway volume (19.4 6 34.8%; P 50.030). There was no statistically significant change in RE airway volume (mean change 19.9 6 59.3%, P 5 0.398, Table IV). Similar results were seen when examining absolute changes (Supp. Table SI). Figure 1 A–C shows an example MRI segmentation of a patient whose airway increased in volume postoperatively at the RP, RG, and RE levels. When examining the upper airway soft tissue volumes, we observed significant decreases in the volume of the soft palate (218.3 6 18.0%, P 5 0.0015) and retropalatal lateral walls (249.8 6 21.3%, P 50.0001), and a significant increase in the retroglossal lateral wall volume (20.2 6 22.9%; P 5 0.002). These regional changes in the RP and RG lateral walls are reflected in a nominally significant decrease in the total lateral walls (217.9 6 19.8%, P 5 0.0084) (Table IV). Figure 1A demonstrates an example of a patient with a decrease in postoperative RP lateral wall volume. We also saw a suggestive decrease in genioglossus tongue volume (25.8 6 7.5%, P 5 0.013), which is demonstrated in Figure 1C, most notably at the base of the tongue region. Pre- and postoperative volumetric changes in the other structures analyzed, including the epiglottis, other tongue musculature, parapharyngeal fat pads, and Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
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TABLE III. Examining Changes in AHI, BMI, and MRI Structures Between Responders and Nonresponders.* Change From Baseline Measure
AHI (events/hour) BMI (kg/m2)
Nonresponse (n 5 6)
2.07 6 31.29 20.70 6 1.07
Mandible (mm3)
22,055 6 5,814
RP airway volume (mm3) RP airway area (mm2)
2483.3 6 1,165.4 3.92 6 49.06
RG airway volume (mm3)
2,355 6 3,273
RG airway area (mm2) RE airway volume (mm3)
22.98 6 99.18 271.1 6 1,304.0
Response (n 5 12)
252.11 6 27.77 22.65 6 3.95
Percent Change From Baseline P†
Nonresponse (n 5 6)
Response (n 5 12)
P†
0.0020 0.2759
10.59 6 89.22 22.56 6 3.48
279.86 6 13.28 27.39 6 10.03
0.0007 0.2979
2948 6 4,264
0.8407
23.57 6 9.69
21.88 6 7.26
0.9199
21,472 6 1,446 225.52 6 42.33
0.2234 0.329
216.17 6 42.83 2.01 6 29.31
235.45 6 24.73 216.26 6 28.01
0.4537 0.2328
2,308 6 1,956
0.9254
139.00 6 202.21
85.92 6 92.11
1.0000
6.41 6 73.07 297.8 6 1,555.8
0.329 0.7079
21.00 6 45.21 31.49 6 90.11
4.07 6 26.71 11.93 6 43.03
0.2781 1.0000
RE airway area (mm2)
210.38 6 211.54
3.27 6 88.64
>0.999
44.21 6 123.14
8.02 6 43.03
0.6644
Total airway volume (mm3) Epiglottis (mm3)
1,800 6 3,683 213.29 6 246.32
1,134 6 2,872 56.39 6 367.62
0.6396 0.7787
25.46 6 44.72 20.17 6 30.11
11.91 6 27.04 6.12 6 30.42
0.5121 0.7079
Soft palate (mm3)
21,054 6 1,755
22,454 6 1,666
0.0752
213.69 6 23.99
221.60 6 15.14
0.1340
Tongue (mm3) Other tongue (mm3)
23,919 6 8,157 23,940 6 5,403
27,120 6 7,978 52 6 3,024
0.3490 0.1594
25.26 6 9.47 210.16 6 24.26
26.50 6 6.82 2.41 6 22.05
0.5121 0.1317
Fat pads (mm3) Pterygoid (mm3) RP lateral walls (mm3) RG lateral walls (mm3) Lateral walls (mm3)
44.6 6 1,390.4 322 6 1,096 23,149 6 3,831
2689.5 6 998.5
0.4615
5.14 6 26.07
29.72 6 13.83
0.3356
21,603 6 2,414 26,863 6 4,481
0.1585 0.0610
1.48 6 7.09 240.13 6 22.70
25.63 6 11.06 253.29 6 20.44
0.1289 0.3029
1,090 6 1,241
1,491 6 1,408
0.9025
25.88 6 31.47
19.61 6 18.82
0.7133
21910 6 4,338
24,682 6 4,138
0.1416
25.97 6 19.69
222.19 6 18.75
0.1416
*Surgical response defined as AHI reduction by at least 50%. † P value from nonparametric Wilcoxon rank sum test comparing changes in responders and nonresponders. AHI 5 apnea-hypopnea index; BMI 5 body mass index; MRI 5 magnetic resonance imaging; RE 5 retroepiglottal; RG 5 retroglossal; RP 5 retropalatal.
TABLE IV. Percentage Change From Preoperation in MRI Upper Airway Structures. Domain
Measure
N
Mean 6 SD
Median (Range)
P*
Mandible
Volume (%)
18
22.1 6 7.9
23.7 (218.8, 13.1)
Airway Measures†
RP airway volume (%)
19
228.8 6 31.1
233.1 (266.6, 51.4)
0.0038
RP airway area (%) RG airway volume (%)
17 19
28.4 6 28.4 110.4 6 134.3
29.2 (253.6, 51.4) 41.8 (234.3, 485.1)
0.1930 0.0005
Soft Tissue Volumes‡
0.2485
RG airway area (%)
17
13.7 6 35.9
11.5 (250.2, 91.7)
0.1239
RE airway volume (%) RE airway area (%)
19 17
19.9 6 59.3 25.9 6 80
22.5 (260.4, 206.3) 10.7 (260.1, 282.9)
0.3981 0.4074
Total airway volume (%)
19
19.4 6 34.8
7.3 (229.0, 101.7)
0.0298
Epiglottis (%) Soft palate (%)
19 19
4.0 6 28.7 218.3 6 18.0
25.9 (225.3, 72.7) 219.5 (259.9, 20.0)
0.7782 0.0015
Genioglossus (%)
19
25.8 6 7.4
23.9 (218.2, 4.3)
0.0126
Other tongue (%) Fat pads (%)
18 17
20.8 6 22.8 24.0 6 18.9
23.7 (231.6, 57.5) 29.3 (234.7, 42.9)
0.5566 0.2868
Pterygoid (%)
17
22.3 6 10.2
0.1 (225.0, 9.0)
0.6192
RP lateral walls (%) RG lateral walls (%)
19 16
249.8 6 21.3 20.2 6 22.9
255.2 (286.1, 25.8) 10.6 (25.4, 73.9)
0.0001 0.0019
Total lateral walls (%)
16
217.9 6 19.8
220.1 (246.7, 16.9)
0.0084
*P value from Wilcoxon signed rank test assessing whether observed change is significantly different from zero. † Bonferroni corrected level of significance: P < 0.0071. ‡ Bonferroni level of significance: P < 0.0056. MRI 5 magnetic resonance imaging; RE 5 retroepiglottal; RG 5 retroglossal; RP 5 retropalatal; SD 5 standard deviation.
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TABLE V. Spearman Correlations Between Changes in MRI Structures and Changes in AHI.* Percent Change Domain
Mandible Airway Measures†
Soft Tissue Volumes‡
Measure
Volume (mm3) RP airway volume (mm3)
Absolute Change
N
rho
P
rho
P
17 18
20.29 0.23
0.2602 0.3627
20.33 0.31
0.1911 0.2096
RP airway area (mm2)
16
0.36
0.1723
0.40
0.1217
RG airway volume (mm3) RG airway area (mm2)
18 16
20.15 0.15
0.5645 0.5717
20.17 0.10
0.4941 0.7125
RE airway volume (mm3)
18
20.07
0.7726
20.15
0.5590
RE airway area (mm2) Total airway volume (mm3)
16 18
0.01 20.06
0.9828 0.8103
20.18 20.13
0.4991 0.6099
Epiglottis (mm3)
18
0.02
0.9514
0.16
0.5153
Soft palate (mm3) Tongue (mm3)
18 18
0.32 20.05
0.1971 0.8421
0.31 20.09
0.2033 0.7354
Other tongue (mm3)
17
20.47
0.0581
20.39
0.1246
Fat pads (mm3) Pterygoid (mm3)
16 16
20.01 0.19
0.9569 0.4921
20.11 0.07
0.6963 0.7867
RP lateral walls (mm3)
18
0.53
0.0232
0.69
0.0014
RG lateral walls (mm3) Lateral walls (mm3)
15 18
0.15 0.56
0.5848 0.0284
0.17 0.63
0.5327 0.0121
*Measures of absolute change from baseline are correlated with AHI change from baseline, and MRI percent change are correlated with percent change in AHI. † Bonferroni corrected level of significance: P < 0.0071. ‡ Bonferroni level of significance: P < 0.0056. MRI 5 magnetic resonance imaging, AHI 5 apnea-hypopnea index, RP 5 retropalatal, RG 5 retroglossal, RE 5 retroepiglottal.
pterygoid muscles, were not statistically significant (Table IV). As with airway measures, similar results were seen when examining absolute changes (Supp. Table SI). Results of analyses examining the correlation between changes in upper airway structures and changes in AHI are presented in Table V. Although no result met our Bonferroni-corrected level of significance, we found suggestive correlations with change in AHI and both RP (rho 5 0.53, P 5 0.023) and total (rho 5 0.56, P 5 0.028) lateral walls. In both instances, greater decreases in lateral wall volume correlated with greater decreases in AHI. When examining absolute changes rather than percent change, we observed a statistically significant correlation between RP lateral walls and AHI (rho 5 0.69, P 5 0.0014) and nominally significant correlations between total lateral walls and AHI (rho 5 0.63, P 5 0.0121). Volumetric changes in other structures did not correlate with a change in AHI, as shown in Table V.
DISCUSSION Obstructive sleep apnea is a significant problem in our population that can lead to serious medical complications.1,2 Surgical treatment for OSA has been an area of debate for many years, primarily due to the variable success rate.3 Transoral robotic surgery is a new technique in the field of sleep surgery and has shown promising results4–7; however, the question of why some patients respond and some do not respond to surgery remains. Laryngoscope 125: August 2015
Volumetric MRI analysis is a validated tool to measure UA soft tissue structures in patients with OSA.10 Most previous MRI studies on patients with sleep apnea, however, have been done only in the preoperative or nonoperative setting in order to make comparisons either with normal subjects8,10,11 or between the same subjects during periods of wakefulness or sleep.13 One group has used pre- and postoperative MRI to measure the vallecular line as a method of evaluating for the transoral resectability of exophytic base of tongue tumors14; however, our study is the first describing the volumetric changes in upper airway structures after undergoing transoral robotic surgery for OSA. Our results show that the airway, tongue, soft palate, and lateral wall volumes change significantly after OSATORS. It was expected that the soft palate, tongue, and RP lateral wall volumes would decrease after surgery; and it was expected that the retroglossal, retroepiglottal, and total airway volumes would increase after surgery. It was also expected that the volumes of structures not involved in the surgical resection, such as the mandible, parapharyngeal fat pads, and pterygoid muscles, would not change significantly postoperatively. Our results confirmed these expectations. The overall decrease in size of the retropalatal airway and increase in retroglossal lateral wall volumes after surgery were related to a postoperative reduction (retropalatal) or increase (retroglossal) in the measured length of these structures on MRI, which was necessary in order to keep the anatomical boundaries of segmentation constant Chiffer et al.: MRI Analysis Pre- and Post-OSA-TORS
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between pre- and postoperative imaging. For example, the soft palate was shortened postoperatively, resulting in fewer retropalatal airway slices and effectively reducing the airway in the retropalatal region. Similarly, the volume of retropalatal lateral walls, which was based on the size of the soft palate, was reduced postoperatively. The volume of the retroglossal lateral walls, however, increased postoperatively. By reducing the length of the soft palate, there were more slices measured in the retroglossal region, thus increasing the retroglossal lateral wall volume. Our data also show that a decrease in retropalatal and total lateral wall volume correlates with a decrease in postoperative AHI. This may be explained by several factors. First, the transoral robotic bilateral posterior hemiglossectomy procedure was accompanied by a bilateral limited pharyngectomy in the retroglossal region, effectively expanding the airway in a lateral direction. Additionally, this data could also be explained by the fact that the palatine tonsils are within the retropalatal lateral wall tissue, and the tonsils are removed during the UPPP/modified expansion sphincteroplasty. It is well known that in apneic patients with large tonsils, removing the tonsils can improve sleep apnea.15 Of note, our study did not correlate preoperative tonsil size with changes in retropalatal lateral wall volume or surgical outcome; however, this may represent an interesting area of future study. Furthermore, during the modified expansion sphincteroplasty, the posterior tonsillar pillar and a portion of the retropalatal lateral wall within the superior aspect of the tonsillar fossa is retracted and secured out laterally, thus decreasing the overall volume of the retropalatal lateral pharyngeal walls. These results suggest that decreases in the volume of the lateral walls are an important indicator of patient response to surgery. In addition to a small sample size, other limitations of this study include one patient failing to complete the postoperative PSG and changes in length of several segmented and measured structures (as explained above) in order to keep the anatomic boundaries constant between pre- and postoperative analysis. Although all postoperative MRI scans were performed at one institution (University of Pennsylvania Medical Center), the preoperative MRIs were performed at different institutions, making it difficult to control the MRI protocols. Furthermore, pre- and postoperative polysomnograms were completed at varying institutions for ease on the patient, but this increased variability in the AHI measurement. It is notable that several patients in our study had substantial decreases in BMI postoperatively, specifically patients 9 and 16, and this may have contributed to their individual surgical success or response. Although BMI changes were not controlled for in this study, Tables II and III show that, within the group, changes in BMI were not statistically significant between successes and nonsuccesses and responders and nonresponders. Another weakness of this study is that the MRI analysis was not blinded to surgical outcome, thus creatLaryngoscope 125: August 2015
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ing potential bias. If the MRI scans had been scored independently and the scorer had been blinded to outcome, this potential bias would have been removed. Further research will include additional pre- and postoperative MRIs and PSGs in the data analysis. We will also use T2-weighted MR imaging to measure strictly base of tongue and lingual tonsil volumetric changes separately from the entire tongue. The current MRI protocol did not capture T2-weighted images. Additional studies within independent populations are an important next step in order to replicate results and increase generalizability.
CONCLUSION This is the first study to examine the effect of transoral robotic surgery (OSA-TORS) on the soft tissues of the upper airway in patients with obstructive sleep apnea. As expected, the total airway volume increased postoperatively, whereas the volumes of the soft palate, tongue, and total and retropalatal lateral pharyngeal walls decreased. Larger decreases in the total and retropalatal lateral pharyngeal wall volumes correlated with greater decreases in postoperative AHI. These results are an important step toward further understanding the postsurgical anatomical changes following sleep surgery.
Acknowledgments This research was performed at the Hospital of the University of Pennsylvania, Department of Otorhinolaryngology– Head and Neck Surgery (R.C.C., R.C.B., E.R.T.) and Department of Medicine, Division of Sleep Medicine (R.J.S., B.T.K.), Philadelphia, Pennsylvania. Many thanks to Sarika Shinde for her help with this project. Our thanks to Intuitive for funding the imaging portion of this project.
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13. Wang Y, Mcdonald JP, Liu Y, Pan K, Zhang X, Hu R. Dynamic alterations of the tongue in obstructive sleep apnea-hypopnea syndrome during sleep: analysis using ultrafast MRI. Genet Mol Res 2014;4552–4563. 14. Hai N, Taheri MR, Sadeghi N. The vallecular line: an objective measure in evaluating the base of the tongue and vallecular cancers for transoral robotic surgery. J Comput Assist Tomogr 2013;37:686–693. 15. Verse T, Kroker BA, Pirsig W, Brosch S. Tonsillectomy as a treatment of obstructive sleep apnea in adults with tonsillar hypertrophy. Laryngoscope 2000;110:1556–59.
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