Jamie Perry, Ph.D. - US grants

DESCRIPTION (provided by applicant): It is likely that there are specific dimensions for the musculature of the velopharynx that are required in order for a child to develop normal sounding speech. If a child has a primary repair of the levator muscle that does not conform to that of normal anatomy, it is likely that they will develop hypernasal speech and would require secondary palate surgery. Data has not demonstrated what constitutes "normal" levator muscle anatomy or how race and sex impact those normative measures. We will elucidate what constitutes normative muscle dimension range based on sex, race, craniometric dimensions, and/or velopharyngeal closure patterns. These results can be directly utilized to guide primary surgery. Such patient specific surgical planning will decrease the incidence of hypernasality during speech development and thus reduce the need for secondary surgical management later in life. The aims of this R03 proposal are to address unresolved issues concerning the interaction of race and sex on the structure and function of the velopharynx. The study will also assess the interaction of craniometric measurements and velopharyngeal closure patterns as it relates to levator dimensions found in different racial/ethnic groups and/or gender groups. Analyses of the relationship of these variables will enable us to identify whether racial differences in oral clefts are a result of morphological differences at the skeleto- muscular level. More applicably, data obtained here will have a direct impact on surgical practices in the treatment of children born with cleft palate. Thus, the long term goal of this study is to improve the diagnostic and surgical planning care for children born with cleft palate. The information gathered from these investigations will lead to improved speech outcome measures as well as a reduced need for subsequent secondary palatal surgeries. The following specific aims are proposed: (a) to identify morphologic differences in the levator muscle at rest and during speech production as a function of race (b) to determine whether sex differences exist in the morphology of the levator muscle at rest or during speech production. A total of 84 subjects will be recruited for participation in the study. Magnetic resonance images will be obtained while the velum is at rest (non-speech) and during speech. MR images will be used to measure craniometric measures and levator muscle morphology. Nasoendoscoy will be performed to determine velopharyngeal closure patterns. The data will be imported into a 3D software system to create a computer model in three dimensions of space for improved measurements and visualization of the internal craniofacial and velopharyngeal structures. PUBLIC HEALTH RELEVANCE: Hardin-Jones and Jones (2005) found 68% of preschoolers with repaired cleft palate were enrolled in speech therapy. More interestingly, 37% had moderate to severe hypernasality or had received secondary surgical management due to an incompetent velopharyngeal mechanism. Primary surgical repair (initial surgery) that is patient specific (based on race, sex, and levator muscle dimensions) would reduce the incidence of aberrant speech found among many children with cleft palate and reduce the need for subsequent surgeries (secondary surgical management).

? DESCRIPTION (provided by applicant): It is expected that 25-35% of children with repaired cleft palate will have VPD as evidenced by hypernasal speech. If a child has a primary repair of the levator veli palatini (levator) muscle (i.e., primary muscle for velar elevation during speech) that does not conform to that of normal anatomy, it is likely that the child will develop hypernasa speech and will require secondary palate surgery. The primary cause of VPD is due to what we term disadvantageous biomechanics. Specifically, the anatomy and mechanics of the velopharyngeal (VP) mechanism post-surgically are not adequate for proper VP function. Our research team has demonstrated that surgical planning in which pre-surgical muscle arrangement and function are used to determine post-surgical structure is critical to a successful speech outcome. The goal of this proposal will be to develop subject-specific models based on magnetic resonance imaging data to determine how and why certain children have VPD following surgery. Our vision is to ultimately improve outcomes of cleft palate repair by providing a framework in which pre-surgical muscle arrangement and function are used to inform surgical plans to optimize post-surgical structure. Our goals are in this project are to: (i) determine whic anatomical features lead to disadvantageous biomechanics in children who have VPD, and (ii) reveal the ways in which the anatomy could be changed to restore normal VP function. We intend to achieve these goals through the following specific aims: (Aim 1) Create computational models of children with and without VPD who have had cleft palate repair; and (Aim 2) Use the subject-specific models to determine the cause of VPD in each child. After successful completion of this R21 project, we will have demonstrated that the subject-specific models are predictive of function in children post-cleft palate repair. These results will empower us to move towards modeling patients pre-repair and determining if patient-specific models can be used as a guide for making patient-specific surgical decisions. This and follow-on studies will address long-standing questions of speech outcomes following surgery and the effect of growth and maturation of the VP structures on VP function.

PROJECT SUMMARY Cleft lip and palate is the most prevalent birth defect in the United States affecting one out of every 577 births. Despite advances in surgery, it is estimated that 25-38% of children with a repaired cleft palate will continue to have hypernasal speech due to insufficient velopharyngeal closure, requiring additional surgeries. Although nasal endoscopy is frequently used to determine the type of surgery, it provides only limited views of the movements of speech. Insufficient information is available from current diagnostic technologies to visualize the location of muscles and their quantitative functional arrangement in the child. Magnetic resonance imaging (MRI) provides excellent visualization of soft tissue structures, such as muscles, but has traditionally been too slow to capture speech dynamics where complete contractions may occur in 100 ms. The current proposal develops a dynamic MRI imaging method that can image the full vocal tract in 3D+time with high spatial and high temporal resolution, achieving 166 frames per second (FPS) for the entire volume. Specifically, a dynamic speech imaging technique will be developed that is suitable for application in children aged 5-8 years old, a critical age range for re-repair of cleft palate in secondary surgical management. The technique integrates a spatiotemporal atlas that describes the mean motions across a population of healthy children for particular speech samples. The imaging technique leverages the atlas to: improve the quality of the reconstructed images, automatically label edges for quantitative analysis, and focuses the analysis on variances in motion from one subject compared to the healthy atlas. In order to examine the dependency of the population mean atlas on sex, race, and dialect, spatiotemporal atlases will be developed at three different geographical sites, with 40 healthy children ages 5-8 years old at each site, with equal numbers of both sexes and equal numbers of two races. Additionally, we will recruit 45 cleft palate patients ages 5-8 years old following cleft palate repair with and without velopharyngeal insufficiency with resulting hypernasality. We will apply our imaging technique to examine temporal characteristics of velopharyngeal muscle function, determining movement differences related to hypernasality.

PROJECT SUMMARY Cleft lip and palate is the most prevalent birth defect in the United States affecting one out of every 577 births. Despite advances in surgery, it is estimated that 25-38% of children with a repaired cleft palate will continue to have hypernasal speech due to insufficient velopharyngeal closure, requiring additional surgeries. Although nasal endoscopy is frequently used to determine the type of surgery, it provides only limited views of the movements of speech. Insufficient information is available from current diagnostic technologies to visualize the location of muscles and their quantitative functional arrangement in the child. Magnetic resonance imaging (MRI) provides excellent visualization of soft tissue structures, such as muscles, but has traditionally been too slow to capture speech dynamics where complete contractions may occur in 100 ms. The current proposal develops a dynamic MRI imaging method that can image the full vocal tract in 3D+time with high spatial and high temporal resolution, achieving 166 frames per second (FPS) for the entire volume. Specifically, a dynamic speech imaging technique will be developed that is suitable for application in children aged 5-8 years old, a critical age range for re-repair of cleft palate in secondary surgical management. The technique integrates a spatiotemporal atlas that describes the mean motions across a population of healthy children for particular speech samples. The imaging technique leverages the atlas to: improve the quality of the reconstructed images, automatically label edges for quantitative analysis, and focuses the analysis on variances in motion from one subject compared to the healthy atlas. In order to examine the dependency of the population mean atlas on sex, race, and dialect, spatiotemporal atlases will be developed at three different geographical sites, with 40 healthy children ages 5-8 years old at each site, with equal numbers of both sexes and equal numbers of two races. Additionally, we will recruit 45 cleft palate patients ages 5-8 years old following cleft palate repair with and without velopharyngeal insufficiency with resulting hypernasality. We will apply our imaging technique to examine temporal characteristics of velopharyngeal muscle function, determining movement differences related to hypernasality.