Sleep Magnetic Resonance Imaging: Dynamic Characteristics of the Airway During Sleep in Obstructive Sleep Apnea Syndrome

Transcription

1 The Laryngoscope VC 2011 The American Laryngological, Rhinological and Otological Society, Inc. TRIOLOGICAL SOCIETY CANDIDATE THESIS Sleep Magnetic Resonance Imaging: Dynamic Characteristics of the Airway During Sleep in Obstructive Sleep Apnea Syndrome Jose E. Barrera, MD Objectives/Hypothesis: To determine the dynamic characteristics of airway obstruction in subjects with obstructive sleep apnea (OSA) syndrome. Study Design: A prospective cohort study of 20 OSA patients and 19 control subjects who underwent real-time magnetic resonance imaging (MRI) evaluation between 2006 and Methods: The dynamics of the upper airway were visualized using real-time MRI (RTHawk system, Stanford, CA) during natural sleep. Respiratory and desaturation events were correlated to polysomnogram results, and anatomic site of obstruction was determined from the real-time MRI sequences. The relation between visually observed airway obstructions and autonomic system changes was quantified and reliability calculated (Cronbach a, Aabel 2009; Gigawiz, Ltd., Tulsa, OK). An automated analysis tool was developed to determine which respiratory event is associated with the longest duration and location of obstruction in the posterior airway space (Matlab 2009; Mathworks, Inc., Natick, MA). Results: Airway obstructions visualized on Sleep MRI during natural sleep included retropalatal, retroglossal, and combined obstruction. Respiratory events (mean rate of 31.9 per hour per subject) and desaturations (mean rate of 19.4 per hour per subject) temporally coincided with airway obstructive events. Intrarater reliability coefficients ranged from a low of 0.95 to a high of 1.0 for each rater. Inter-rater reliability coefficients ranged from a low of 0.85 to a high of 1.0. Conclusions: Sleep MRI is a novel and reliable approach to simultaneously evaluate airway obstructions and respiratory events in real time during natural sleep. Sleep MRI can define the dynamic characteristics of airway obstruction in both surgically naive and postsurgical OSA patients. Key Words: Real time magnetic resonance imaging, obstructive sleep apnea, surgery, palate, hypopharynx. Level of Evidence: 1b. Laryngoscope, 121: , 2011 INTRODUCTION The diagnosis of obstructive sleep apnea (OSA) syndrome (OSAS) is most often confirmed by attended overnight polysomnography (PSG). PSG is conducted under as natural sleeping conditions as possible and allows simultaneous quantification of sleep state and certain related physiologic measures. The physiologic measures include blood oxygen saturation and indirect information about respiratory events (RE) such as changes in the airflow from apneic and hypopneic events. However, PSG does not provide any direct information concerning what structures specifically caused Additional Supporting Information may be found in the online version of this article. From the Division of Sleep Surgery, Department of Otolaryngology, Wilford Hall Medical Center, Lackland Air Force Base, Texas; and Division of Sleep Surgery, Stanford University School of Medicine, Stanford, California, U.S.A. Editor s Note: This Manuscript was accepted for publication March 9, The author has a financial interest as the patent holder for Sleep MRI, as a member of an advisory board for Ethicon, Inc., and as the owner of Endormir Sleep Solutions, LLC. The author has no other funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Jose E. Barrera, MD, Division of Sleep Surgery, 2200 Bergquist Drive, Ste 1, Lackland AFB, TX jose.barrera@us.af.mil DOI: /lary the REs. This is a significant limitation because of the fact that multiple structures in the airway can cause an RE, each structure can be involved to different degrees, and surgical intervention will differ substantially if the specific site and nature of the obstruction are known. Other approaches such as drug-induced sleep endoscopy (DISE) do provide direct airway information but do not employ measures of sleep state (i.e., specific sleep stages versus awake and arousals) and are conducted under less-than-natural sleeping conditions including sedation, presence of endoscopic instruments, and an artificial surgical environment. The test-retest reliability of DISE has been recently published. Rodriguez-Bruno et al. 1 noted that with DISE it is difficult to simplify the relationships between two separate anatomic regions such as the palate and hypopharynx because of the dynamic interactions that are not understood completely. Previous work in sleep magnetic resonance imaging (MRI) 2 describes the technology to evaluate these two independent but yet dynamic events with the hope of better understanding the locations and dynamics of airway obstructions in OSAS patients. This work presents a regional and site-specific method to better characterize the airway obstruction under dynamic conditions, identify its location, and improve knowledge to guide surgical treatment and advancements. 1327

2 Several researchers 3 10 have investigated the site of airway obstruction dynamically, but the measures were in patients who were either awake or under sedation during MRI. One study did evaluate pharyngeal airway status dynamically with MRI along with simultaneous electroencephalography without use of sedatives; that study suggested complete pharyngeal obstruction during apneic episodes in sleeping patients with OSAS. A multisite obstructive pattern of the naso-, oro-, and hypopharyngeal space was detailed with complete widening of the pharyngeal space with arousal. 11 However, this technique induced signal image artifacts from the electroencephalogram electrodes and leads, making image analysis difficult and imprecise. In general, these previous studies have had significant shortcomings in their ability to characterize relevant airway conditions and have provided very limited specific information that could be used to direct corrective surgical intervention or to measure intervention outcome. The ideal diagnostic tool would allow natural sleep without sedation and dynamically characterize location, type, magnitude, and duration of upper airway obstructions and narrowing coincident with REs. The thesis presented herein describes a new tool, Sleep MRI, an MRI movie that characterizes the upper airway such that the specific anatomic site, magnitude, and duration of airway obstruction is determined simultaneously with the MRI-compatible physiologic measures of pulse arterial tone (PAT), hemoglobin oxygen saturation, and pulse rate in OSAS patients. The goal of the study is not to determine whether Sleep MRI can replace PSG but to describe a new technique that provides new and additional information concerning precise dynamic airway characteristics during sleep that has the potential to guide surgical management and to measure effectiveness of surgical intervention. MATERIALS AND METHODS Study Design The study design was a prospective, single clinical site, nonrandomized, open enrollment descriptive cohort of 20 adult OSAS subjects and 19 controls who were recruited from, evaluated, and followed by the Department of Otolaryngology Head and Neck Surgery at Stanford University in California. The study protocol was approved by the institutional review board, and written informed consent was obtained. Human Subjects All subjects were evaluated and followed by one physician (J.B.) in his academic-based sleep practice. Inclusion criteria were 1) mild to severe OSAS as diagnosed with comprehensive in-laboratory conventional overnight PSG that included an apneahypopnea index (AHI), a measure of the lowest oxyhemoglobin saturation level (LSAT), the results of the functional outcomes of sleep questionnaire (FOSQ), and an Epworth Sleepiness Scale (ESS); and 2) age of 18 to 70 years. Exclusion criteria were 1) pregnancy, 2) a body mass index (BMI) greater than 40 kg/m 2, and 3) any evidence of the usual contraindications to MRI (pacemaker or other electronic or metallic implant, excessive dental metal in oral cavity, claustrophobia, etc.). All subjects also underwent conventional site of obstruction testing while sitting upright and awake by head and neck examination with flexible 1328 Fig. 1. System embodiment of the present invention for diagnosing sleep apnea experienced by a subject (A). The system shows a magnetic resonance imaging device (B) and a pulse arterial tone device (C) for imaging obstructions and collecting pulse arterial tone measurements, respectively. nasopharyngoscopy to determine Fujita classification, defined in the following ways: type I: palate only obstruction or narrowing; type II: palate and tongue; and type III: tongue only. In addition, cephalometric analysis and visual determination of tongue/palate relationships were used to verify clinical Fujita classification. Control subjects were randomly chosen from volunteers who responded to flyers advertised throughout the institution. Control subjects underwent overnight sleep study with the Watch- PAT 100 (Itamar Medical, Caesarea, Israel), and OSA subjects received a standard overnight PSG. All subjects enrolled completed an ESS and FOSQ. A volumetric MRI was performed in both controls and OSA subjects. Sleep MRI Protocol The Sleep MRI technique has been described previously. 2 All OSA patients underwent a 90-minute Sleep MRI nap conducted in an open-magnet MRI system (0.5T Signa SP; General Electric, Waukesha, WI) after their volumetric MRI. A small, oval receive coil was placed encircling the face of the subject to optimize images of the upper airway. Acoustic scanner noise was attenuated with head-worn noise protectors and earplugs during the Sleep MRI. The subjects were allowed to sleep in their preferred position, whether supine or lateral. However, movement inside the bore of the open MRI was limited (Fig. 1). Images were acquired with an imaging system (RTHawk) 12 that used a real-time two-dimensional spiral sequence with six interleaves, acquiring a midline sagittal view with a resolution of mm over a 20-cm field of view. Constrained by the gradient hardware (12 mt/m gradient amplitude, 16 T/m/second slew rate), the system was able to acquire images at an actual frame rate of 5.5 frames per second. This rate was fast enough to accurately capture the REs that occurred at much slower rates. A sliding window algorithm was used to reconstruct the images at 33 frames per second providing a smooth transition between frames resulting in a Sleep MRI movie. The real-time imaging system also provided interactive control of the scan plane to compensate for the unrestrained subject s movements and to allow dynamic adjustment of scan parameters such as field of view, flip angle, and frame rate to optimize contrast and image quality. Subject position was based on the subject s preferred position to facilitate sleep, which was supine for 19 of 20 subjects. Although it is recognized that position affects the severity of obstruction in PSG and multiple sleep latency tests, 13 our goal was to get the subjects to sleep within the MRI machine. No

3 Fig. 2. Left: An airway obstruction caused by both retropalatal (upper arrow) and retroglossal (lower arrow) obstruction on sleep magnetic resonance imaging. Right: Same subject with retropalatal narrowing and patent retroglossal area. sedation was used. The mean total sleep time was 63 minutes during the 90-minute period for this group of subjects. Physiology Protocol Image degradation associated with conventional MRI-incompatible electroencephalogram electrodes was avoided with the alternative approach for measuring sleep state. A small, battery-operated physiology monitoring system (Watch-PAT WP100) 14 was placed on the left arm with a small probe clipped onto the left index finger. The monitoring system continuously recorded wrist actigraphy, PAT, pulse rate, and pulse oximetry. Automatic analysis of PAT has been found to accurately detect arousals from sleep and already has been incorporated into the PSG, having been validated in detecting arousals from sleep as determined by the American Academy of Sleep Medicine. 15 Although this portable device was not specifically designed to be MRI compatible, separate experiments of the device alone in the scanner and with three separate subjects before subject trials proved its accuracy, efficacy, and safety in the MRI environment and did not cause image artifacts. The Watch-PAT (WP) was positioned adjacent to the subject s torso so as to minimize interference with sleep. Presumably this approach allowed accurate estimates of simultaneous measures of peripheral arterial tone, pulse oximetry, and pulse rate and an appropriate environment for sleep without sedation. Given that we can measure sleep versus wake state with the WP without the image artifact, we believe this approach is a reasonable and acceptable alternative indicator of airway obstruction using Sleep MRI. The internal clock of the WP was synchronized with the MRI time clock. Both Sleep MRI and physiologic data were then recorded simultaneously and continuously for 90 minutes. The WP sampled and stored physiologic data at a rate of one measure per second throughout the sleep study. Sleep versus wake and arousals were defined through actigraphy and automatically scored based on an algorithm (WP, zzzpat algorithm) that scored an arousal if the PAT signal amplitude (vasoconstriction) dropped 40% and was associated with a pulse rate increase or a drop in blood oxygen saturation greater than 4%. 15 An RE was defined as a PAT attenuation associated with pulse rate elevation and/or drop in blood oxygen saturation greater than 4% as defined by the WP algorithm occurring during an anatomic event as evidenced on real-time MRI. We then correlated the REs with the BMI, PSG, and WP data from subjects using the Pearson correlation coefficient (Excel 2007; Microsoft Inc., Redmond, WA). An airway obstruction was defined as a narrowing greater than 50% of the airway diameter for either one of two airway sites (retropalatal or retroglossal) (Fig. 2). To validate the site of obstruction, two experienced sleep surgeons rated the Sleep MRI movies, and inter- and intrarater evaluations were made. 16 Five dimensions were assessed. The first dimension was a determination of the presence or absence of any obstruction. For the second and third dimensions, the location of obstruction was rated as occurring at the retropalatal area (due to palate or lateral/posterior pharyngeal wall movement) or at the retroglossal area (secondary to hypopharyngeal obstruction from the tongue, epiglottis, or lateral pharyngeal wall). The fourth dimension was the presence or absence of a false obstruction due to a swallow (a short obstruction lasting less than 3 seconds) compared to a true obstruction (a site-specific obstruction lasting greater than 10 seconds). A swallow was distinguished from an airway obstruction by the presence of a bolus, in contrast to an airway obstruction, which did not incorporate a bolus but demonstrated dynamic site-specific and repeatable obstruction. Moreover, during Sleep MRI, a swallow is characterized by the combination of a rise of the soft palate and the elevation and anterior movement of the larynx and hyoid bone. The ratings for obstructions between these two time periods were not obtained during this study. The fifth dimension was a determination of the duration of an obstructive event as measured from the time indicator in the image sequence in seconds. The presence versus absence data were analyzed by comparing the ratings for various conditions using a reliability statistic (Cronbach a, Aabel 2009; Gigawiz, Ltd., Tulsa, OK). The duration estimation data were analyzed using a correlation coefficient (Pearson product moment correlation coefficient, Aabel 2009; Gigawiz, Ltd., Tulsa, OK). An automated analysis tool was developed to determine which RE is associated with the longest duration and location of obstruction in the posterior airway space (Matlab 2009; Mathworks, Inc., Natick, MA). This tool allows for comparative evaluation of the PAT, pulse rate, and oxyhemoglobin saturation occurring precisely with anatomic events visualized on Sleep MRI. A sample Sleep MRI movie is available online. RESULTS OSA Subject Demographics Twenty OSA patients and 19 control subjects who underwent MRI evaluation between 2006 and 2008 were prospectively enrolled. All patients were diagnosed by sleep study, the OSA patients by conventional PSG and the control group by the WP. The mean OSA patient age was (range, 21 53) years, and 33% were female (5 of 15). The mean BMI was kg/m

4 TABLE I. Subject Demographics. Controls OSA P Value No Age (yr) BMI ( kg/m 2 ) ESS FOSQ AHI (events/hr) LSAT (%) P value is based on a 2-tailed Student t test. OSA ¼ obstructive sleep apnea; BMI ¼ body mass index; ESS ¼ Epworth sleepiness scale; FOSQ ¼ functional outcomes sleep questionnaire; AHI ¼ apnea-hypopnea index; LSAT ¼ lowest oxyhemoglobin saturation. The control group mean age was (range, 24 52) years, and 20% were female (4 of 20). The mean BMI was kg/m 2. The ESS score for OSA subjects was compared to for controls. The composite FOSQ score for OSA subjects was compared to for controls. The control AHI was events per hour with LSAT of 93.3% 6 2.4%. Control subjects clearly did not have OSA (Table I). Eight OSA subjects were surgery naive; 12 OSA subjects had previously undergone surgery but demonstrated persistent OSA by PSG. Physiologic measures from the prior PSG data revealed a mean (standard deviation) PSG AHI of 36.8 (26.9) REs per hour with a range between 9.2 and and a mean PSG LSAT of 86.6% (6.5) with a range of 76% to 97%. The results from the WP during Sleep MRI included total sleep time, AHI, LSAT, RE, and percent of desaturations. The average total sleep time during the 90-minute measurement period was 63 minutes with a range between 34 and 74 minutes. The mean WP AHI was 35.1 (26.0) events per hour with a range between 1.6 and 81.3 events per hour. In comparison, the PSG AHI was 36.8 (29.1). The mean WP LSAT was 90.9% (3.25) with a range between 85% and 95%, and the PSG LSAT was 86.6% (6.51). A large number of REs were identified in every subject. Mean REs during sleep was 31.9 (27.5) events per hour, and the mean rate of desaturations was 19.4 (22.7) events per hour. The mean duration of desaturation events was 25.6 (6.4) seconds (Table II). As previously discussed, the WP has been validated as an ambulatory monitoring device for OSAS. 15 A very strong association between the WP AHI during Sleep MRI evaluation and REs was also found (Pearson correlation coefficient ¼ 0.98). 2 BMI correlated fairly highly with REs (Pearson correlation coefficient ¼ 0.71). As BMI increased, the number of REs also increased. WP lowest oxygen hemoglobin saturation (WP LSAT) correlated fairly highly with PSG LSAT (Pearson correlation coefficient ¼ 0.73). A lack of correlation was found between PSG AHI and WP AHI (Pearson correlation coefficient ¼ 0.41), as expected, because the Sleep MRI evaluation was performed during a nap study (Table III). Analysis was performed only on 30-second portions of the 90-minute Sleep MRI recordings for several reasons. First, the temporal relations between the physiologic measures and the airway conditions are completely unknown. For example, it is unknown whether a drop in oxyhemoglobin saturation occurs at the onset of, for the duration of, or after an apnea. In a seminal study describing the use of PAT for OSA, Schnall et al. 17 defined a significant arousal as a 33% decrease of PAT from baseline for 3 to 30 seconds or a 15% increase in heart rate. This concept was carried over to Sleep MRI analysis, where we analyzed only the MRI recordings temporally surrounding PAT attenuation to identify an RE (Fig. 3). In addition, it has been previously determined that the precise site of airway obstruction as measured by Sleep MRI is associated with REs in OSAS patients. 2 An attempt to characterize and validate each obstruction was performed to determine the location of obstruction at both the retropalatal and retroglossal locations. Retropalatal obstruction was evaluated for the presence of palatal and posterior pharyngeal wall displacement. Retroglossal obstruction was evaluated for the presence of tongue base, posterior pharyngeal wall, or epiglottic displacements. Every RE evaluated was associated with an obvious airway obstruction affecting airflow. Nasopharyngoscopy results varied with subjects showing palate only (type I), palate and tongue (type II), and tongue base obstruction (type III). Of the eight surgery-naive subjects, seven were type II and one was type III. Sleep MRI demonstrated that the one type III subject was really a type II and that one of the type II subjects was actually type I. In the 12 subjects who were evaluated due to previous surgery failure, two subjects TABLE II. Physiologic Measures From Sleep Magnetic Resonance Imaging and Polysomnography. PSG Sleep MRI AHI (events/hr) LSAT (%) Respiratory events (no.) Desaturations (no.) Mean duration of desaturation (s) PSG ¼ polysomnography; MRI ¼ magnetic resonance imaging; AHI ¼ apnea-hypopnea index; LSAT ¼ lowest oxyhemoglobin saturation. TABLE III. Correlation Among Physiologic Events. Pearson Correlation Coefficient AHI and respiratory events 0.98 WP LSAT and PSG LSAT 0.73 BMI and respiratory events 0.71 PSG AHI and WP AHI 0.41 AHI ¼ apnea-hypopnea index; WP ¼ Watch-PAT 100; LSAT ¼ lowest oxyhemoglobin saturation; PSG ¼ polysomnography; BMI ¼ body mass index. 1330

5 obstruction, presence or absence of a retroglossal obstruction, and duration of obstruction from real-time Sleep MRI sequences are also very high. This is true despite multiple points of overlap associated with the categories measured (Table IV). Fig. 3. Sleep magnetic resonance imaging palate obstruction coincides with respiratory event. Pulse arterial tone (PAT) signal attenuation and amplitude reduction, pulse rate acceleration in beats per minute (bpm), and desaturation event are shown. SaO 2 ¼ oxygen saturation. were type II and one was type III on clinical evaluation, but all showed isolated persistent palate obstruction on Sleep MRI (type I). Overall, airway obstructions visualized on the Sleep MRI were predictive of the Fujita class. However, the Sleep MRI characterized more complex obstructions than Fujita class, thus augmenting this clinical classification. The Cronbach a coefficient was used to assess reliability of observer ratings that range from 0 (no reliability) to 1.00 (perfect reliability). For all dimensions, intrarater reliability coefficients ranged from a low of 0.95 to a high of 1.00 for each rater. Inter-rater reliability coefficients ranged from a low of 0.85 to a high of Analyses of Sleep MRI have high testretest reliability for determination of both retropalatal and retroglossal airway obstructions. The specific location of obstruction in the airway was reproducible during continuous MRI measures. Intrarater and interrater reliability for determination of presence or absence of any obstruction, presence or absence of a retropalatal Case Studies Three representative examples can illustrate some important advantages of this approach. Case 1 illustrates that Sleep MRI can provide additional information concerning airway conditions compared to that obtained by conventional PSG, even in mild OSAS. A representative sequence (Fig. 4) from a 32- year-old female with mild OSA (BMI 21, ESS 8, and FOSQ 3.86) is illustrated. Her PSG revealed an AHI of 11.5 events per hour and an LSAT of 97%. The WP data were similar, with an AHI of 7.1 events per hour and a LSAT of 95%. Standard clinical evaluation revealed that the subject had an omega-shaped epiglottis but no obvious airway obstruction. The Sleep MRI indicated a large epiglottis but no airway obstruction between REs, but during an RE her airway showed narrowing and obstruction at the palate, tongue, and epiglottis. Despite an image artifact due to dental work obscuring portions of the tongue, the obstructions of the airway were clearly visualized. Of note, the Sleep MRI was able to characterize the difference in airway patency during unimpeded breathing and obstructive episodes corresponding with autonomic changes during an RE. The clinical information and nasopharyngoscopy results were consistent with the Sleep MRI results between REs but did not provide the detail that Sleep MRI affords during an RE. Case 2 illustrates that Sleep MRI can also demonstrate a postsurgical burden that may remain after sleep surgery. Figure 5 demonstrates results from a 47-yearold male with moderate OSA (AHI 23.9, LSAT 88%, ESS 12, FOSQ 2.17) after uvulopalatopharyngoplasty, genioglossal advancement, septoplasty with repair of nasal valve stenosis, and turbinate reduction performed for severe OSA 2 years before Sleep MRI. On clinical examination, retropalatal narrowing without obstruction was seen on laryngoscopy, and an oblique position of the soft palate was seen on lateral cephalometry; on Sleep MRI, repeated obstruction with horizontal positioning of the soft palate against the posterior pharynx during REs was clearly seen. In this fashion, the Fujita class of this patient (type I) was confirmed by the Sleep MRI. In addition, a true horizontal posturing of the soft palate was demonstrated with each RE. The advantages of TABLE IV. Intrarater and Inter-rater Results for Rating 1 Versus Rating 2. Rater 1 Rater 2 Inter-rater Obstruction Retropalatal Retroglossal Swallow Duration(s)

6 the RE (lasting 20 seconds) was defined by PAT attenuation, pulse rate increase above threshold, and a desaturation. Palate, tongue, and epiglottic obstruction were demonstrated throughout the RE. Because the patients evaluated were asleep, the Muller maneuver was not used, but clear obstruction was evident. This study demonstrates that Sleep MRI can characterize airway changes in mild, moderate, and severe OSA and in both surgery-naive and postsurgical patients as seen in the case examples. In all cases, REs occurred coincident with obstructive phenomena. Automated Analysis: A Surgical Tool The presented cohort was further analyzed to determine what physiologic measure is the leading indicator Fig. 4. Comparison of unimpeded respiration in mild obstructive sleep apnea subject compared to obstructed airway in same subject at different nap times. Sleep magnetic resonance imaging (MRI) without associated respiratory event shows epiglottic enlargement. Sleep MRI associated with respiratory event shows combined palate, base of tongue, and epiglottic obstruction. The characteristic respiratory event occurred simultaneous with the airway obstruction. PAT ¼ pulse arterial tone; bpm ¼ beats per minute; SaO 2 ¼ oxygen saturation. characterizing the airway on Sleep MRI are clearly evident in this subject. Radiographic characteristics of the anatomic structures in the sequences, such as palatal length and shape of tongue, suggest the airway results of previous surgical treatment. Continued horizontal posturing of the palate demonstrates inadequate retropalatal treatment. A vertically oriented tongue after genioglossal advancement without retroglossal obstruction shows that the tongue base operation was successful at this level. Case 3 shows a severe OSA case in a 29-year-old male (AHI 108.3, LSAT 76%, ESS 11, and FOSQ of 2.57). The clinical examination was consistent with a Fujita type II classification. Palate, tongue base, and epiglottic obstruction were seen on Sleep MRI. The Fujita classification does not distinguish between different types of tongue base obstruction, but Sleep MRI demonstrated each level of narrowing and obstruction. Figure 6 notes 1332 Fig. 5. Comparison of sleep magnetic resonance imaging (MRI) midsagittal view of sleeping postsurgical subject with residual moderate obstructive sleep apnea compared to awake laryngoscopy view of airway. (A) Palate obstruction on Sleep MRI. (B) Palate narrowing on awake laryngoscopy. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

7 for site-specific airway obstruction in order to trigger the scanner to produce short-duration movies rather than a very long 90-minute movie. Twenty-three consecutive Sleep MRI movies from eight subjects were analyzed at 5-minute intervals while synchronizing continuous PAT, oxyhemoglobin saturation, and pulse rate measurements. An automatic analysis tool was developed using Matlab 2009 (Mathworks Inc., Natick, MA). PAT attenuation was noted as the most significant indicator for worsening airway obstruction. Threshold changes as little as 58 absolute units were noted to show obstructive events; however, the greater the attenuation change, the worse the cause and site of obstruction to a maximal change of 1,305 absolute units. In respect to palate position, a vertical position was associated with a smaller PAT change, and greater PAT attenuation changes were associated with horizontal positioning of the velum (Fig. 7). More so, in subjects with retroglossal obstruction, the larger the PAT attenuation change, the more significant cause of retroglossal narrowing. In severe cases, tongue base, epiglottic narrowing, and lateral pharyngeal wall involvement were associated with the greatest PAT attenuation. A surgical diagnostic tool that determines cause and site of airway obstruction is warranted. Analyzing a 1-minute epoch demonstrates that the most significant site of airway obstruction occurs at the greatest PAT attenuation. Automated analysis of real-time REs encapsulated in a Sleep MRI movie is available online. Fig. 6. Sleep magnetic resonance imaging of a subject with severe obstructive sleep apnea. Autonomic measures depict a respiratory event that coincides with palate and tongue obstruction. PAT ¼ pulse arterial tone; bpm ¼ beats per minute; SaO 2 ¼ oxygen saturation. DISCUSSION This study demonstrated precise site of airway obstruction associated with REs in OSAS patients. PAT signal attenuation, PAT amplitude reduction, pulse rate acceleration, and desaturation events were coincident with airway obstructions during natural sleep. A realtime movie format allowed the characterization of diffuse and precise sites of obstruction throughout the recording period. Although the mid-sagital plane was used for evaluation, axial and coronal views are feasible. This approach details not only site but also cause of obstruction and lays the foundation to improve medical and surgical management of OSAS patients. The primary advantage of Sleep MRI lies in the noninvasive approach during natural sleep to determine site-specific obstruction and airway dynamics. In subjects with palatal obstruction, Sleep MRI can determine the degree of palatal deviation that occurs. Dynamic palatal movement was observed in every patient with obstruction at this level. Further study will need to be done to correlate this event with velar position. More so, patients with persistent OSA after uvulopalatopharyngoplasty can be assessed. In our study, palatal obstruction was evident in greater than 96% of the OSAS patients. This was true whether the patients were surgically naive or postuvulopalatopharyngoplasty and strongly suggests that palatal, rather than retroglossal, obstruction may be a more significant cause of surgical failure than previously believed. Moriwaki et al. determined the velopharynx to be the main obstructive site in 94% of cases evaluated using ultrafast dynamic MRI. 18 In cases of hypopharyngeal obstruction, Sleep MRI can demonstrate the location of obstruction whether tongue base, epiglottis, or lateral pharyngeal wall and can characterize the individual site-specific dynamic obstructions caused by these structures. Because soft tissues under dynamic conditions can be observed as well as tomographic sequences, volumetric determination of airway size can be measured showing the true efficacy associated with individual treatment protocols. Sleep MRI lends easily to tomographic measurements between surgical procedures. The WP AHI was highly correlated with REs. Therefore, REs may be used as an indicator for obstructive events. Further agreement was found between the LSAT during the Sleep MRI and the LSAT from the more definitive PSG, despite this being a nap study. A lack of association was found between the WP AHI during the 1333

8 Fig. 7. Static capture of sleep magnetic resonance imaging movies of a surgically naive subject with obstructive sleep apnea depicting pulse arterial tone (PAT) threshold (absolute units), oxyhemoglobin saturation (Sat), and pulse rate. (A) PAT threshold attenuation change of 58 absolute units with a vertically oriented velum causing palatal narrowing. (B) PAT threshold change of 206 absolute units with a horizontally oriented velum causing palatal obstruction. sleep MRI and the AHI from the more definitive PSG, probably because of this being a nap study with a mean sleep time of only 63 minutes. A lack of correlation between PSG AHI and WP AHI exists even when evaluating non rapid eye movement (nrem) AHI; therefore, further investigation using longer sleep times equivalent to an overnight PSG is an area of further investigation and a potential problem with the technique. Other limitations include a small cohort size and the need to perform an overnight Sleep MRI. It is possible that resolving these limitations would resolve the lack of correlation between PSG AHI and WP AHI seen in this study. Sleep MRI has high test-retest intrarater and interrater reliability for both retropalatal (0.95 to 1.00) and retroglossal (0.85 to 1.00) airway obstructions. Intrarater and inter-rater reliability for determining the presence or absence of any obstruction, swallow, and duration of obstruction are also very high. In comparison, work on DISE has reported intraclass correlation coefficient analogs related to palatal obstruction ranging from 0.41 to 0.89 and hypopharyngeal airway estimates range from 0.57 to Clearly, the advantages of Sleep MRI include its reliability and accuracy in detecting site-specific airway obstructions during natural sleep. PAT attenuation was the leading indicator for airway obstruction. The greatest change in PAT also indicated worsening of the dynamic airway change in a given subject. Horizontal posturing of the velum was evident at greater PAT attenuation levels. In addition, greater involvement of the retroglossal area was associated with greater PAT attenuation levels in subjects with this level of obstruction. Automated analysis of real-time REs encapsulated in a Sleep MRI movie definitively described the airway events in surgically naive and postsurgical subjects. An additional limitation to this technique is cost. The use of the Sleep MRI approximated $1,000 for a 2- hour study. The cost may improve with an overnight study format because the MRI facility is kept operational continuously but has a decrease in usage during 1334 evening and early morning hours. At our research center, the cost of overnight testing is $100 per hour, a significant decrease. The cost for the PAT probe is $80, and it is designed for single use. As MRI technology becomes more affordable, stronger magnets may be more practical and result in higher quality imaging, although this would require specific shielding and isolation of the PAT device from the stronger magnetic fields. To further evaluate whether some of our parameters were independently associated with OSAS, a multivariate analysis would be required. Considering our small number of subjects, such an analysis was not valid at this time. The authors are investigating the utility of overnight Sleep MRI to improve the accuracy of diagnosing site of obstruction and documenting physiologic events during both nrem and REM sleep. This approach also can be used to instruct patients about their site of obstruction, which was clearly seen by them. CONCLUSION This study shows a novel, accurate, and reliable approach to simultaneously evaluate airway obstructions and respiratory and desaturation events in real time during sleep without sedation. Sleep MRI determined AHI, REs, and LSAT correlate with PSG determined LSAT and also BMI. Intrarater and inter-rater reliability coefficients from Sleep MRI sequences are very high. PAT attenuation is the leading indicator in identifying site of airway obstruction in Sleep MRI. By simultaneously observing site of obstruction dynamically as detailed by Sleep MRI and quantifying REs, this approach can feasibly characterize the actual site of dynamic obstruction and has the potential of improving predictions of successful surgical outcomes in OSAS patients. Sleep MRI is not meant to be an alternative to PSG; rather, it augments the diagnostic capability of PSG by showing what other studies cannot, dynamic

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