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1 Center for Sleep and Respiratory Neurobiology
3 Biomedical Statistical Consulting, University of Pennsylvania, 991 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA
2 Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
4 Department of Medicine, University of Pennsylvania and Pulmonary, Critical Care and Sleep Section, Philadelphia Veterans Administration Medical Center (111P), University and Woodland Avenue, Philadelphia, PA 19104, USA
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Abstract |
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(Received 7 August 2004;
accepted after revision 1 October 2004;
first published online 7 October 2004)
Corresponding author M. J. Brennick: Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 991 Maloney Building, 3600 Spruce Street, Philadelphia, PA 19104, USA. Email: brennick{at}mail.med.upenn.edu
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Introduction |
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To address these limitations, we have adopted MRI in combination with spatial modulation of magnetization (SPAMM, developed at the University of Pennsylvania) to track tissue motion in the pharyngeal wall during muscle stimulation (Axel & Dougherty, 1989). The SPAMM technique uses a series of radio frequency (RF) and magnetic field gradient pulses to generate an evenly spaced grid of dark lines in the target tissues. These lines track with the tissues as they move during muscle stimulation. Acquisition of images before and during muscle contraction using a spoiled gradient recalled imaging (SPGR) MRI protocol results in a series of images in which the grid pattern is distorted due to the tissue motion. Analysis of the images using the distorted grid lines as fiducial markers yields detailed information about tissue motion in the pharyngeal walls. MRI with SPAMM tagging has been used extensively to study cardiac mechanics (Axel et al. 1992; Marcus et al. 1997; Gotte et al. 1999; Scott et al. 1999; Yuan et al. 2000) and there have been several reports using MRI and SPAMM to investigate tongue movements in relation to speech (Niitsu et al. 1994; Napadow et al. 1999; Stone et al. 2001). However, this is the first application of MRI with SPAMM to examine pharyngeal mechanics during selective muscle stimulation. Specifically, we examined how stimulation of the medial branch of the hypoglossus nerve, supplying motor output to the genioglossus, geniohyoid and intrinsic tongue muscles, affects the displacement and strain of tissues surrounding the pharyngeal airway and how this pharyngeal wall tissue motion relates to changes in airway size and shape.
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Methods |
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All studies were conducted with the approval of the University of Pennsylvania Institutional Animal Care and Use Committee. The surgical and MRI protocols were carried out in 11 male Sprague-Dawley rats, mean weight 386 ± 9.5 g (S.E.M. given throughout), under urethane anaesthesia (1.8 g kg–1, I.P., supplemented with 0.2 g kg–1, I.P., as needed). Following the experiments, the anaesthetized rats were killed by intracardiac injection of KCl-saturated aqueous solution. Arterial oxygen saturation, heart rate and temperature were continuously monitored (VetOx 4700, Sensor Devices, Inc. Waukesha, WI, USA). Core temperature was maintained at 35–36°C using a heated water pad (T-Pump, Gaymar Ind., Orchard Park). An adequate depth of anaesthesia was determined by the absence of any response to strong pressure on the paw. With the rat supine, a ventral mid-line incision from the genu of the mandible to the sternum allowed for the placement of a tracheal cannula and exposure of the medial hypoglossal nerve bilaterally. The rat breathed spontaneously from a 100% oxygen flow-by connected to the tracheal cannula. The hypoglossal nerve was separated from surrounding tissues and cut at a point approximately 1.0–1.5 cm proximal to the bifurcation of its medial and lateral branches. The lateral branch was cut away from the nerve trunk, leaving the medial branch intact. The distal cut end of the nerve trunk was installed into a cuffed bipolar electrode that utilized 0.127 mm diameter Teflon-coated platinum wires with 1.0 mm exposure on the tips. These cuffed electrodes were used to stimulate the medial hypoglossal nerve (Brennick et al. 2001).
The bipolar platinum leads (15 cm long) from each cuff electrode were connected to 26 G PVC-insulated and shielded copper wires that extended to a constant current photo-isolated stimulus unit (Grass PSIU 8, Astro-Medical, Warwick) and stimulator (Grass S44, Astro-Medical). Two stimulators were connected in tandem to provide a single stimulation train pattern with independent adjustment of current levels for each bipolar electrode. All pulsed nerve stimulations were delivered at 90 Hz, 0.1 ms pulse duration. This frequency achieves fused contraction in upper airway muscles (Brennick et al. 2001). Following electrode placement, we determined initial current settings for each electrode as the minimum current that visually produced maximum tongue protrusion. Final settings were determined using an iterative process during imaging, as described below.
Imaging protocol
MRI was performed in a 40 cm bore, 4.7 T magnet (Magnex, Concord) with a Varian INOVA Console (Varian, Palo Alto) using a 12 cm shielded gradient insert capable of generating gradients up to 25 g cm–1. A 65 mm inside diameter Litz coil (Doty, Columbia) was used for transmission and reception. The supine rat rested on a Plexiglas platen that inserted into the RF probe so that the junction of the hard and soft palate of the rat (centre of the region of interest) was at the mid-point of the probe's 52 mm RF window, at the isocentre of the gradient coil. A sagittal scout image was used to position the rat and probe in the magnet.
The gated SPGR with SPAMM protocol proceeded as follows: (1) a trigger signal from the stimulator initiated the cycle followed by a delay (250–350 ms); (2) SPAMM pre-conditioning pulses (9.8 ms) were followed by the first multislice SPGR image acquisition (87 ms); (3) bilateral stimulation of the medial hypoglossal nerve was initiated and no images were acquired during the following 100 ms; and (4) the second multislice image series was acquired (87 ms) during nerve stimulation. Each SPGR axial image was a square matrix, 128 pixels x 128 pixels, field of view (FOV) 35 mm, slice thickness 1 mm, interslice gap 1 mm, repetition time (TR) 87 ms, echo time (TE) 2.2 ms, with four averages so that 512 cycles were required for image data acquisition.
We used an iterative method to determine the stimulus intensity level for right and left electrodes. Previous studies (Brennick et al. 2001) revealed that medial hypoglossal stimulation dilated both the oropharyngeal and velopharyngeal airways. Therefore, a preliminary series of axial images (with two instead of four averages) were acquired using the initial stimulus intensity settings (determined on the bench level from direct observation, as described above) and these images were carefully inspected on the console for two criteria: (1) stimulation causing oropharyngeal and velopharyngeal dilatation throughout the airway; and (2) left to right symmetry in axial slices during stimulation. The stimulator constant-current output to each electrode was adjusted to achieve these two criteria usually in one or two trials. In order to determine whether the desired stimulation intensity was obtained, another SPGR iteration was performed at twice the operating level. The lower stimulation level was considered optimal if stimulation with the greater current caused no further appreciable airway dilatation. If additional significant dilatation was observed, then the current was again doubled and compared to the previous level until no further increases in airway size were observed. It should be noted that, in order to preserve the electrode–nerve interface, the upward iterations of current were not tested when relatively small increases in airway size were observed with the higher current. The mean current for a single electrode (when averaged over all electrodes) for all rats was 0.29 ± 0.09 mA.
We monitored the stimulator outputs (trigger signal and stimulator currents) with a digital oscilloscope (Agilent, Model 5461B, Palo Alto). The stimulus train duration averaged 184 ± 7 ms. The time for a single pass of the gated MRI protocol was 430 ± 20 ms for the first three experiments and was increased to 610 ± 20 ms for the later eight experiments. After it was discovered in the first three experiments that the SPAMM lines would persist for a longer period, the imaging cycle time was increased to (1) reduce the possibility of muscle fatigue by reducing muscle duty cycle (stimulus on/stimulus off) from approximately 45% to 25.6%, and (2) improve the overall image quality by increasing repetition time (TR; see discussion on MRI protocol considerations).
Following the determination of stimulus intensity levels, a complete set of axial images was acquired in two offset (11 slice) series with 1.0 mm interslice gap that were then merged to form a contiguous (22 slice) axial series. Post-acquisition interleaving of the two axial series improved the signal to noise ratio by limiting signal loss that would occur if the series were initially acquired as one contiguous acquisition. The image data were interpolated to a 256 pixel x 256 pixel matrix and transferred to a Silicon Graphics Octane workstation (SGI, Mountain View) for analysis using the SPAMM visualization software package (SPAMMVU, University of Pennsylvania). Sagittal images, using the same MRI protocol with FOV of 80 mm on a 128 by 128 square matrix, were also obtained to determine tissue displacement orthogonal to the axial plane images.
Image analysis
For each rat, a series of 22 contiguous axial slices were obtained. These data sets were aligned using a method previously described (Brennick et al. 2001). Briefly, a single axial slice in the forebrain just caudal to the olfactory bulb was identified as having a brain cross-section that was significantly smaller than the previous caudal slice. This unique and identifiable alignment slice was approximately 3 mm rostral to the junction of the hard to soft palate. Once this slice was identified in the axial series of each rat, a one-to-one correspondence among axial slices among all rats was easily obtained and verified by matching anatomical landmarks in aligned slices. Three single slices from levels that were 4, 7 and 10 mm caudal to the alignment slice were selected for detailed analysis of velopharyngeal and oropharyngeal airway dimensions and pharyngeal wall tissue displacement and strain. These levels were defined for this study as the rostral, mid- and caudal pharyngeal levels. The velopharynx was defined as the airway dorsal to the soft palate, and the oropharynx, as the airway ventral to the soft palate.
We used NIH-Image (v. 1.61/ppc, US National Institutes of Health http://rsb.info.gov/nih-image/) to measure velopharyngeal and oropharyngeal cross-sectional area (CSA) in axial slices at each pharyngeal level (rostral, mid- and caudal). Lateral and anteroposterior (AP) dimensions were calculated as the major and minor axes of the best fitting ellipse for the airway inscribed from the NIH-Image CSA measurements. The term AP dimension will be used in this report to identify the airway dimension in the ventro-dorsal direction, i.e. perpendicular to the lateral dimension.
Analysis of tissue motion (displacement and strain) in axial slices was performed using the SPAMMVU analysis program. First, an optical flow subprogram was used to estimate pixel displacements between images obtained before and during stimulation (Dougherty et al. 1999). The optical flow method, originally developed for military use for the extraction of motion information from image sequences, was adapted to track the local deformation in tagged pharyngeal airway images and makes use of the SPAMM lines that serve as fiducial markers. The optical flow method is a coarse-to-fine model-based motion-estimation technique for estimating first, a global parametric transformation, and then local deformations (Dougherty et al. 2003). Thus, it computes the flow field that describes the warping of an image of one phase (before stimulation) into alignment with the next (during stimulation). This optical flow software has been adapted to overcome the requirement of constant pixel intensity in standard optical flow methods by pre-processing the input images to reduce any intensity bias which results from the reduction in stripe contrast due to the relaxation of the magnetization of the spins within the tagged area throughout the imaging cycle (Dougherty et al. 1999).
The analysis was performed on a selected rectangular region of interest (1.4 cm x 1.2 cm) surrounding the airways. Once the pixel displacements were determined using the optical flow method, two-dimensional strain analysis using SPAMMVU was performed. While the optical flow method computes the displacement of every pixel in the region of interest, the SPAMMVU program utilizes only a subset of these data (two points per 2.0 mm SPAMM line width) to perform the finite element analysis.
Figure 1 shows a representative caudal axial slice before stimulation (left panel) and during stimulation (middle panel). The third panel (right) shows the before stimulation image (as in left panel) with the displacement data represented as arrows overlaid on the image. These arrows represent the displacement vectors determined from the optical flow analysis. The base of each arrow is located at the initial point of the pixel (i.e. pixel locus before stimulation), and the arrowhead indicates the locus where that pixel was displaced during stimulation. The length and direction of the arrows are equal to the tissue displacements during stimulation. In a few cases there were errors due to aliasing (caused by tissue movements that were greater than a single SPAMM line width) so the displacements were determined manually, using identifiable local tissue landmarks.
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1 and 2, respectively. These values are the orthogonal eigenvectors of the strain tensor and represent the fractional change in length (1 ± (
L/Lo) where L is positive for stretch (1) and negative for compression (2)) of the axes of the unit circle of triangle A that is transformed to an ellipse in triangle B after stimulation (see Fig. 2). SPAMMVU software calculates: the principal major (1) and minor (2) strains, the direction angle (ß) of 1 relative to the origin, and the angle of rigid body rotation (
) that represents the pure rotation of the triangle excluding shape-related changes ( shown in C inset in Fig. 2).
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To assess tissue motion in specific regions of the pharyngeal wall in the axial images, we selected bilateral square sectors in the lateral and ventral pharyngeal walls. Each sector consisted of eight triangles formed from the points determined by the optical flow methods. The right and left lateral wall sectors contained the points closest to the lateral edges of the oropharyngeal airway. The right and left ventral sectors were adjacent to the mid-sagittal line and included the points nearest to the ventral edge of the oropharyngeal airway. A fifth sector, located in the brain tissue, was selected to serve as a control that theoretically would not show any tissue motion due to stimulation of the pharyngeal muscles. Displacement and strain were measured in the control sectors and these values were used for statistical comparisons with the lateral and ventral pharyngeal wall sectors. Use of an image plane control sector (as opposed to a zero effect unstimulated control value) reduced the chance of over-estimating positive results as noise, errant motion in the images, or optical flow analysis errors would be common to both target and control sectors, thus limiting any bias.
The sectors were readily identified in a repeatable manner (by a trained operator) in the images after triangulation analysis. The sectors in a representative axial image of the caudal pharynx are highlighted in Fig. 3. The averaged strain and displacement data for the eight triangles of each sector were computed. Given the overall symmetry of the measured values, we reduced the sector comparisons from five to three by combining and averaging the data from the two lateral sectors and the two ventral sectors. Medial–lateral displacement results for both the lateral and ventral sectors were combined by multiplying the left sided medial–lateral displacement data by –1, and averaging these with the results on the contralateral side. The ventral–dorsal displacements did not need transformation before averaging. Lateral and ventral sector ß and angles on the left side were converted to right-sided values by the formula: right sided angle = 180 deg – left sided angle. Simple averaging and analysis of the angles was facilitated using angles in radians that were later converted to degrees. The values did not require any mirror image conversion before averaging.
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Statistical analysis
We used a mixed model two-way ANOVA on repeated measures (SAS Institute, Cary) (n
= 11 rats) to test the effect of stimulation (no stimulation versus stimulation) and pharyngeal level (rostral, mid- and caudal) on airway dimension variables (CSA, AP and lateral dimensions) in both the oropharynx and velopharynx (Littell et al. 1996; Singer, 1998). The ANOVA model was used to test the effect of different levels of pharyngeal region (rostral, mid- and caudal) and pharyngeal wall sectors (ventral, lateral and control) on the tissue displacement and strain variables (ventral–dorsal displacement, medial–lateral displacement, 1, 2, 1 direction angle (ß) and ‘rigid-body’ rotation angle ()). Examination of second-order interactions tested whether pharyngeal level and sector had combined or independent effects on: the tissue displacement (ventral–dorsal or medial–lateral), strain and strain angle variables (1, 2, ß and ). Significance for post hoc pair-wise comparisons were evaluated using Tukey-Kramer adjusted P values where significance was assumed for P < 0.05. Post hoc comparisons for subset of specific dimensional parameters were evaluated assuming a limited number of planned contrasts, i.e. stimulated versus non-stimulated in each of three individual regions. In these cases, a Bonferroni adjustment (P < 0.05/3 or 0.017) was used to compare the differences of the least squared means for that contrast or comparison (Winer et al. 1991).
The effect of stimulation on airway shape was analysed by examining the change in elliptical ratio defined as lateral dimension/AP dimension. An elliptical ratio of unity denotes a perfect circle whereas, a ratio smaller than unity represents a prolate ellipsoid (long axis in AP dimension) and a ratio greater than unity represents an oblate ellipsoid (long axes in lateral dimension). If, for example, an airway with elliptical ratio greater than unity becomes more circular during stimulation, then the resulting elliptical ratio would be smaller, i.e. closer to unity. Two-way ANOVA was used to test the effect of stimulation and pharyngeal level on elliptical ratio in the velopharynx and oropharynx. Post hoc analysis of the elliptical ratio was similar to that for the other dimensions.
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Results |
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Figure 6 shows 1 and 2 values compared by sector and pharyngeal region. 1 (tissue stretch) in the lateral sector was significantly greater than that in the control sector in both the mid- and caudal regions (lateral versus control: mid-, P < 0.05; lateral versus control: caudal, P < 0.0001). Tissue stretch in lateral sectors was 24 and 30% greater than the initial length (Lo) in the mid- and caudal regions, respectively. 2 (tissue compression) values were significantly different in the order: ventral < lateral < control (Tukey-Kramer, P < 0.05) in all regions, and there were significant differences when comparing the average 2 values across regions (mid- > caudal, Tukey-Kramer, P < 0.013). For 2 values there were no significant interactions between sector (ventral, lateral and control) and pharyngeal region (rostral, mid- and caudal). Stimulation therefore was associated with significant stretch of tissues in the lateral pharyngeal wall sectors in the mid- and caudal pharyngeal regions and significant compression in both the ventral and lateral pharyngeal wall sectors in all regions.
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1 and 2) in the control sectors was only minimally different from unity, (i.e. negligible strain; see Fig. 6), we compared the ß angles between lateral and ventral sectors across pharyngeal levels by two-way ANOVA. Thus, in the mid- and caudal regions, where 1 was significantly greater than control, the ß angles in the ventral sectors were nearly perpendicular to the airway in a ventral direction (73.0 ± 5.4 deg 
ß
84.2 ± 6.2 deg). In the lateral sectors for the mid- and caudal regions, the ß angles were directed in a more ventral–lateral direction (43.1 ± 7.4 deg
ß
53.4 ± 7.4 deg). The direction of maximum tissue compression is by definition perpendicular to the ß angle. The angle results in Table 2B indicate that, compared to control, there was no significant tissue rotation with stimulation in either ventral or lateral sectors in all regions. The mean absolute maximum rotation in any sector was not greater than 1.67 ± 1.27 deg.
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Discussion |
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1) in the lateral pharyngeal wall sectors the in the mid- and caudal pharyngeal regions was significantly greater than control sectors. In addition, there was in all regions, a significant compression (2) of both ventral and lateral pharyngeal wall tissues. The strain analysis implies that there was some resultant force (stress) that was pulling the lateral tissues in a ventral–lateral direction causing a significant degree of stretch in those tissues. Significant compression of the both the lateral and ventral tissues may indicate either active contraction in those tissues or compression that resulted from other active contractile tissues being stimulated by the medial hypoglossal nerve. Overall, the results reveal that the increase in airway size and change in shape from oblate ellipsoid to a more circular shape, resulting from stimulation of the medial branch of the hypoglossal nerve, is predominantly due to ventral motion of the ventral and lateral pharyngeal walls. In response to stimulation, the lateral pharyngeal wall sector was displaced in a ventral or ventral–medial direction but stretched in a ventral–lateral direction. This lateral pharyngeal wall tissue motion was associated with a significant increase in lateral oropharyngeal airway dimension. Lateral displacement of the lateral pharyngeal walls with stimulation was never observed. Therefore, changes in airway size (AP or lateral) with hypoglossal nerve stimulation cannot be explained simply on that basis of radial traction (i.e. a dilating force perpendicular to the tangent of the airway circumference). Instead, airway dilatation caused by stimulation of the medial branch of the hypoglossus appears to involve complex mechanical relationships, whereby ventral displacement and ventral–lateral stretch of the pharyngeal wall tissues causes significant increases in both the anteroposterior and lateral airway dimension.
Given the importance of state-related changes in pharyngeal muscle activity in the pathogenesis of obstructive sleep apnoea, numerous previous studies have examined the mechanical effects of pharyngeal muscle activation on airway function using a variety of techniques (Brouillette & Thach, 1980; Strohl et al. 1987; Hida et al. 1995; Eisele et al. 1997; Ilomaki et al. 1997; Fuller et al. 1998; Isono et al. 1999). Physiological studies have determined the effects of pharyngeal muscle activation on airway collapsibility by measuring pressure–volume (area) relationships in an isolated sealed upper airway under static conditions and critical airway pressure under dynamic conditions (Strohl et al. 1987; Schwartz et al. 1993, 1998; Hida et al. 1995; Fuller et al. 1999). These studies demonstrate that activation of the tongue protrudor muscles dilates and stiffens the pharyngeal airway. The techniques employed provide a global assessment of pharyngeal airway mechanics, but are limited in their ability to localize the effects to a particular region of the airway. Imaging of the pharyngeal airway with fibre optics, CT or MRI can localize effects to specific regions of the airway (Suratt et al. 1983; Shepard & Thawley, 1990; Ryan & Love, 1996). For example, recent fibre optic studies from this laboratory in animals have shown that selective stimulation of pharyngeal airway muscles has very different effects on different regions of the pharyngeal airway (Kuna, 2001, Kuna, 2004; Kuna & Brennick, 2002). Although fibre optic imaging can evaluate changes in airway size and shape, this technique provides no information about pharyngeal wall tissues. CT and MRI have been used to evaluate the pharyngeal airway and its surrounding soft tissue volumes in humans, and investigators report that patients with obstructive sleep apnoea have a reduced pharyngeal airway volume and increased volume of soft tissue structures in the airway wall (Horner et al. 1989a, 1989b; Shelton et al. 1993; Schwab et al. 1996, 2003). However, like fibre optic imaging, conventional CT and MRI are unable to directly evaluate pharyngeal wall tissue motion. The use of MRI with SPAMM allows, for the first time, the ability to track tissue motion in the pharyngeal wall and explore how this motion translates into changes in airway size and shape.
The changes in airway CSA with medial hypoglossal stimulation in the current study support results from a previous MRI study in rats (Brennick et al. 2001). In agreement with those previous findings, the current study found that medial hypoglossal branch stimulation caused significant oropharyngeal and velopharyngeal dilatation. The previous study did not include AP or lateral dimensional analysis and the analysis of soft tissue motion was limited to a single linear measurement of tongue displacement in the ventral direction. The current study extends these findings by showing that increases in AP and lateral airway dimensions with stimulation are associated with displacement and strain in discrete sectors of the pharyngeal walls. The ability to quantify tissue motion in the pharyngeal wall represents a powerful new technique to assess pharyngeal mechanics.
Although MRI with SPAMM has been thoroughly tested and detailed in previous studies of cardiac and tongue motion (Axel et al. 1992; Young et al. 1993; Niitsu et al. 1994; Marcus et al. 1997; Napadow et al. 1999; Scott et al. 1999; Yuan et al. 2000; Stone et al. 2001; Yeon et al. 2001), we will address some important technical aspects of this study as they relate to our novel application of gated MRI with SPAMM using nerve stimulation to study pharyngeal airway mechanics. The degree of spatial and temporal resolution in MRI is subject to the limits of the equipment. We controlled temporal resolution to a large degree by using a stimulus-gated protocol. By this method, nerve stimulation was initiated at a precise time between acquisition of the two images. This stimulus-gated protocol is based on standard MRI gated imaging techniques and offers the advantage of being able to adjust the cycle time with an external stimulator. This contrasts with cardiac gated imaging where heart rate, although fairly constant, is not under direct experimental control (Yuan et al. 2000). Control of cycle time allowed us to increase spatial resolution because, in the protocol used in this study, longer cycle time increases TR and this improves the image quality for SPGR imaging. Overall, spatial resolution is a result of many factors in MRI including magnet field strength, gradient capabilities, technical specifics of the RF imaging coil and the MRI protocol design. Whenever possible, we optimized variables to obtain the best possible image quality.
We chose to employ a SPGR echo sequence as this would allow two or more images to be acquired following the deposition of SPAMM lines. Although spin echo has been used with SPAMM applications (Crespigny et al. 1991), the drawback is that the total imaging process is much longer as the TR needed for spin echo sequence is of the order of 1 s or more compared to the 200 ms or less needed for the SPGR sequence. Thus, we tried to maximize the spatial resolution in the SPGR imaging by maximizing TR and minimizing TE (we used 0.2 ms, which was approximately the limit of our equipment). We also found that it was preferable to extend the cycle time from 480 ms to 630 ms. There was no loss of SPAMM line contrast with this adjustment, and the longer cycle time reduced the stimulated muscle duty cycle.
SPAMMVU software was designed for 2-dimensional (2D) motion and strain analysis in the heart, and the significant structural differences between the heart and pharynx potentially could affect the analysis and interpretation of the results in pharyngeal tissue. In general, cardiac tissue is relatively homogeneous with alignment of muscle fibres in an overlaying pattern in order to produce a single repetitive function (Noordegraaf, 1978). During systole, cardiac ventricular muscle contracts in a unified manner or as a syncytium and thus, when viewed in transverse short axis slices, the cardiac wall stretches in the radial direction and compresses tissue in the circumferential direction (Axel et al. 1992; Scott et al. 1999). In addition, the ventricles have clearly defined inner and outer surfaces. In contrast, the pharynx is a much more heterogeneous structure. The pharyngeal skeletal muscles are anatomically arranged in complex and varied patterns, and they are not generally activated in unison (Bartlett, 1986). The pharyngeal walls are not clearly bounded on the non-airway side and can be quite thick in some regions especially the ventral part that is primarily composed of the tongue. To compensate for these anatomical differences between the heart and pharynx, we developed a method utilizing the SPAMMVU software to examine tissue movements in discrete, selected regions of the pharyngeal wall. In addition, while the geometry of the heart lends itself to a cylindrical coordinate system, we used a Cartesian coordinate system to represent pharyngeal tissue displacement and strain. These changes did not affect the theoretical basis for strain calculations (Axel et al. 1992). However, they did allow us to extend the SPAMMVU software to the unique anatomical characteristics of the pharynx. Thus, we were able to adapt the 2D tissue analysis software SPAMMVU to the pharynx and develope a method that quantifies local deformation and displacement of pharyngeal tissues in any region of interest.
We used an optical flow method to determine the estimated pixel displacements from the unstimulated to stimulated images (Dougherty et al. 1999). A validation study has shown that this optical flow method used with MRI of a mechanically rotated test phantom was within 4% of known values and within 6.7% of results obtained with a semiautomated, active contours model for SPAMM analysis (Dougherty et al. 1999). In some axial images there was a large movement from unstimulated image to stimulated image and this condition where the movement was greater than 1/2 SPAMM gridline separation, occurred in some instances and required manual validation or modification of points. Although the power requirements of the pulse sequence that produces the SPAMM lines limit the reduction of SPAMM line width and gridline separation, we were able to work within these requirements to obtain a SPAMM line width of approximately 0.27 mm or 2 pixels wide and a gridline separation of 2.0 mm or 14.6 pixels. We felt that this combination was optimal for imaging the pharynx of the rat.
We accounted for through plane motion using methods described by Marcus et al. (1997). In their MRI with SPAMM study of myocardial function, they used 2D strain analysis to quantify myocardial strain and accounted for through plane motion by acquiring complementary image series in orthogonal planes. They reasoned that where significant through plane motion was evident (approximately one slice thickness) then 2D results in one plane should be confirmed by analysis on the orthogonal plane. In the current study, we found that tissue displacement in the rostral–caudal direction was less than the slice thickness. In addition, we found that the mean ventral tissue displacements on the sagittal images were of the same magnitude as those in the axial slices from a comparable although more narrowly defined region, i.e. the ventral sectors adjacent to the oropharynx. Thus, although it is possible that through plane motion may have been a source of some measurement error, we believe that the overall 2D strain and displacements measurements accurately represent pharyngeal tissue movements.
In summary, we have introduced a new method to examine pharyngeal mechanics using MRI with SPAMM non-invasive tissue tagging in rats. In this study bilateral stimulation of the medial hypoglossal nerve caused a significant increase in oropharyngeal and velopharyngeal cross-sectional airway area in the rostral, mid- and caudal pharynx and increased the anteroposterior and lateral dimensions in all three levels of the oropharynx. This was associated with significant ventral displacement of tissues in the ventral and lateral walls. Although the increase in the oropharyngeal airway's lateral dimension was not associated with lateral displacement of the lateral pharyngeal wall tissues, there was significant stretch of lateral wall tissues in a ventral–lateral direction. Thus, the changes in airway size in a particular dimension reflect complex mechanical relationships. Overall, the significant increases in both the AP and lateral airway dimensions caused by stimulation of tongue protrudors involve ventral displacement of pharyngeal walls. The use of MRI with SPAMM to study pharyngeal tissue motion and the resulting changes in airway size may reveal new insights into pharyngeal mechanics and improve our understanding of the pathophysiology and treatment of obstructive sleep apnoea.
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) represent, respectively, oropharyngeal and velopharyngeal measurements without stimulation and open circles and triangles (
), lateral (
), and dorsal (
) sectors in the rostral, mid- and caudal pharynx. In each plot, displacement (ordinate) represents movement of a right-sided sector relative to the centroid of the velopharynx such that, positive medial–lateral displacements are directed laterally, and positive dorsal–ventral displacements are directed ventrally. Note in the left panel, the lateral sectors in the mid- and caudal regions showed significant displacement (less than control) in the medial direction (negative values) (P < 0.0001). Lateral sector movement was greater (in the negative diretion) than both ventral and control (*). Comparison of lateral sector displacement among regions showed that the caudal region (
) was significantly less that that in the mid- region (
