Vestibular Implant Imaging.

Analogous to hearing restoration via cochlear implants, vestibular function could be restored via vestibular implants that electrically stimulate vestibular nerve branches to encode head motion. This study presents the technical feasibility and first imaging results of CT for vestibular implants in 8 participants of the first-in-human Multichannel Vestibular Implant Early Feasibility Study. Imaging characteristics of 8 participants (3 men, 5 women; median age, 59.5 years; range, 51-66 years) implanted with a Multichannel Vestibular Implant System who underwent a postimplantation multislice CT (n = 2) or flat panel CT (n = 6) are reported. The device comprises 9 platinum electrodes inserted into the ampullae of the 3 semicircular canals and 1 reference electrode inserted in the common crus. Electrode insertion site, positions, length and angle of insertion, and number of artifacts were assessed. Individual electrode contacts were barely discernible in the 2 participants imaged using multislice CT. Electrode and osseous structures were detectable but blurred so that only 12 of the 18 stimulating electrode contacts could be individually identified. Flat panel CT could identify all 10 electrode contacts in all 6 participants. The median reference electrode insertion depth angle was 9° (range, -57.5° to 45°), and the median reference electrode insertion length was 42 mm (range, -21-66 mm). Flat panel CT of vestibular implants produces higher-resolution images with fewer artifacts than multidetector row CT, allowing visualization of individual electrode contacts and quantification of their locations relative to vestibular semicircular canals and ampullae. As multichannel vestibular implant imaging improves, so will our understanding of the relationship between electrode placement and vestibular performance.

Surgineering: curriculum concept for experiential learning in upper-level biomedical engineering.

PURPOSE: A strong foundation in the fundamental principles of medical intervention combined with genuine exposure to real clinical systems and procedures will improve engineering students' capability for informed innovation on clinical problems. To help build such a foundation, a new course (dubbed Surgineering) was developed to convey fundamental principles of surgery, interventional radiology (IR), and radiation therapy, with an emphasis on experiential learning, hands-on with real clinical systems, exposure to clinicians, and visits to real operating theaters. The concept, structure, and outcomes of the course of the first run of the first semester of the course are described. METHOD: The course included six segments spanning fundamental concepts and cutting-edge approaches in a spectrum of surgical specialties, body and neurological IR, and radiation therapy. Each class involved a minimum of didactic content and an emphasis on hands-on experience with instrumentation, equipment, surgical approaches, anatomical models, dissection, and visits to clinical theaters. Outcomes on the quality of the course and areas for continuing improvement were assessed by student surveys (5-point Likert scores and word-cloud representations of free response) as well as feedback from clinical collaborators. RESULT: Surveys assessed four key areas of feedback on the course and were analyzed quantitatively and in word-cloud representations of: (1) best aspects (hands-on experience with surgeons); (2) worst aspects (quizzes and reading materials); (3) areas for improvement (projects, quizzes, and background on anatomy); and (4) what prospective students should know (a lot background reading for every class). Five-point Likert scores from survey respondents (16/19 students) indicated: overall quality of the course 4.63 ± 0.72 (median 5.00); instructor teaching effectiveness 4.06 ± 1.06 (median 4.00); intellectual challenge 4.19 ± 0.40 (median 4.00); and workload somewhat heavier (62.5%) compared to other courses. Novel elements of the course included the opportunity to engage with clinical faculty and participate in realistic laboratory exercises, work with clinical instruments and equipment, and visit real operating theaters. An additional measure of the success of the course was evidenced by surveys and a strong escalation in enrollment in the following year. CONCLUSIONS: The Surgineering course presents an important addition to upper-level engineering curricula and a valuable opportunity for engineering students to gain hands-on experience and interaction with clinical experts. Close partnership with clinical faculty was essential to the schedule and logistics of the course as well as to the continuity of concepts delivered over the semester. The knowledge and experience gained provides stronger foundation for identification of un-met clinical needs and ideation of new engineering approaches in medicine. The course also provides a valuable prerequisite to higher-level coursework in systems engineering, human factors, and data science applied to medicine.

A comparative finite element analysis of maxillary expansion with and without midpalatal suture viscoelasticity using a representative skeletal geometry.

The goal of this investigation was to adapt and incorporate a nonlinear viscoelastic material model representative of the midpalatal suture's viscoelastic nature into finite element analysis simulations of maxillary expansion treatment. Step-wise displacements were applied to a partial skull geometry to simulate treatment using an expansion screw appliance. Four simulation cases were considered for the midpalatal and intermaxillary sutures: 1. Neglecting suture tissue; 2. Linear elastic properties; 3. Viscoelastic properties; 4. A fused intermaxillary and viscoelastic midpalatal suture. Results from simulations indicated that removal of suture tissue and inclusion of viscoelastic properties resulted in the same maxillary displacement following 29 activations of 0.125 mm applied directly to the maxilla; however, assuming a fused intermaxillary suture significantly changed maxillary displacement patterns. Initial stress results within the suture complex were significantly influenced by the inclusion of suture viscoelasticity as compared to linear elastic properties. The presented study demonstrates successful incorporation of suture viscoelasticity into finite element analysis simulations of maxillary expansion treatment, and elucidates the appropriateness of various suture material property assumptions depending desired research outcomes.

Sound abnormally stimulates the vestibular system in canal dehiscence syndrome by generating pathological fluid-mechanical waves.

Individuals suffering from Tullio phenomena experience dizziness, vertigo, and reflexive eye movements (nystagmus) when exposed to seemingly benign acoustic stimuli. The most common cause is a defect in the bone enclosing the vestibular semicircular canals of the inner ear. Surgical repair often corrects the problem, but the precise mechanisms underlying Tullio phenomenon are not known. In the present work we quantified the phenomenon in an animal model of the condition by recording fluid motion in the semicircular canals and neural activity evoked by auditory-frequency stimulation. Results demonstrate short-latency phase-locked afferent neural responses, slowly developing sustained changes in neural discharge rate, and nonlinear fluid pumping in the affected semicircular canal. Experimental data compare favorably to predictions of a nonlinear computational model. Results identify the biophysical origin of Tullio phenomenon in pathological sound-evoked fluid-mechanical waves in the inner ear. Sound energy entering the inner ear at the oval window excites fluid motion at the location of the defect, giving rise to traveling waves that subsequently excite mechano-electrical transduction in the vestibular sensory organs by vibration and nonlinear fluid pumping.

PKCiota promotes ovarian tumor progression through deregulation of cyclin E.

The high frequency of relapse of epithelial ovarian tumors treated with standard chemotherapy has highlighted the necessity to identify targeted therapies that can improve patient outcomes. The dynamic relationship between cyclin E and PKCiota frequent overexpression in high-grade ovarian tumors poses a novel pathway for therapeutic investigation. We hypothesized that a phosphoinositide 3-kinase (PI3K)-dependent signaling pathway activating PKCiota perpetuates cyclin E deregulation during ovarian tumorigenesis. We observed a positive correlation between PKCiota and cyclin E in a panel of 19 ovarian cancer cell lines. Modulation of cyclin E had no effect on PKCiota knockdown/overexpression; however, PKCiota differentially regulated cyclin E expression. In the serous ovarian cancer cells (IGROV and OVCAR-3), shPKCiota decreased proliferation, caused a G1 arrest and significantly prolonged overall survival in xenograft mouse models. In vitro, shPKCiota decreased the ability of IGROV cells to grow under anchorage-independent conditions and form aberrant acini, which was dependent on Ad-cyclin E or Ad-LMW-E expression. Reverse-phase protein array analysis of PKCiota wild-type, catalytic active, dominant-negative protein isoforms strengthened the association between phospho-PKCiota levels and PI3K pathway activation. Inhibitors of PI3K coordinately decreased phospho-PKCiota and cyclin E protein levels. In conclusion, we have identified a PI3K/PKCiota/cyclin E signaling pathway as a therapeutic target during ovarian tumorigenesis.

Viscoelastic response of the midpalatal suture during maxillary expansion treatment.

OBJECTIVES: The viscoelastic response of the midpalatal suture during maxillary expansion treatment has been sparsely studied. The aim of our study was to use viscoelastic models to investigate the effect of appliance mechanics on sutural tissue. MATERIALS AND METHODS: Four creep-strain models were utilized in predicting the midpalatal suture's response to a constant-force application during expansion treatment. The functional forms included a three-term separable, three-term inseparable, two-term inseparable, and single-term arrangement. The functions were then transformed into subsequent stress-relaxation representations to predict suture response as a result of 0.25, 0.20, 0.15, and 0.10 mm displacements. Finally, the single-term creep-strain representation was altered to simulate treatment decaying force during treatment. A force that decays 30 and 10% of an initially applied 0.98 N was considered for decaying functions over a 6-week period, and compared to strain resulting from a constant-force application. RESULTS: This analysis illustrated that the decay in suture strain closely followed decay in force and that the path of decay had minimal impact on overall results. Also, it was found that a single screw activation would likely not cause suture soft tissue failure, even for a 0.25 mm displacement, and that suture stress rapidly decayed within minutes of activation. CONCLUSION: Results from this study support the notion of maintaining a low-magnitude constant traction on the suture during treatment to avoid soft tissue failure and promote tissue remodeling.

Numerical model for intraosseous infusion of the human calvarium for hydrocephalus shunting.

Hydrocephaly is the defective absorption of cerebrospinal fluid (CSF) into the blood stream. This work is an experimental and computational fluid dynamic modelling study to determine the permeability of the diploë as a potential receptor for CSF. Human calvariae were studied by micro-CT to measure their porosity, the area of flow and develop model geometry. Pressure-flow measurements were conducted on specimens to determine their permeability in the physiological and transverse flow directions to compare with numerical results. The overall porosity and permeability of the calvaria were spatially variable. Results suggest an order of magnitude increase in permeability for a 14% increase in overall porosity based on a small number of samples. Numerical results fell within the experimental infusion tests results. Due to the difficulty and ethical considerations in obtaining adolescent skull samples to perform large-scale testing, the developed model will be invaluable.

The validity, reliability, and time requirement of study model analysis using cone-beam computed tomography-generated virtual study models.

OBJECTIVES: To investigate the validity, reliability, and time spent to perform a full orthodontic study model analysis (SMA) on cone-beam computed tomography (CBCT)-generated dental models (Anatomodels) compared with conventional plaster models and a subset of extracted premolars. SETTING AND SAMPLE POPULATION: A retrospective sample of 30 consecutive patient records with fully erupted permanent dentition, good-quality plaster study models, and CBCT scans. Twenty-two extracted premolars were available from eleven of these patients. MATERIALS AND METHODS: Five evaluators participated in the inter-rater reliability study and one evaluator for the intrarater reliability and validity studies. Agreement was assessed by ICC and cross-tabulations, while mean differences were investigated using paired-sample t-tests and repeated-measures anova. RESULTS: For all three modalities studied, intrarater reliability was excellent, inter-rater reliability was moderate to excellent, validity was poor to moderate, and performing SMA on Anatomodels took twice as long as on plaster. CONCLUSIONS: Study model analysis using CBCT-generated study models was reliable but not always valid and required more time to perform when compared with plaster models.

Towards a viscoelastic model for the unfused midpalatal suture: development and validation using the midsagittal suture in New Zealand white rabbits.

Maxillary expansion treatment is a commonly used procedure by orthodontists to widen a patient's upper jaw. As this is typically performed in adolescent patients, the midpalatal suture, connective tissue adjoining the two maxilla halves, remains unfused. Studies that have investigated patient response to expansion treatment, generally through finite element analysis, have considered this suture to behave in a linear elastic manner or it was left vacant. The purpose of the study presented here was to develop a model that could represent the midpalatal suture's viscoelastic behavior. Quasilinear viscoelastic, modified superposition, Schapery's, and Burgers modeling approaches were all considered. Raw data from a previously published study using New Zealand White Rabbits was utilized for model parameter estimation and validation. In this study, Sentalloy(®) coil springs at load levels of 0.49N (50g), 0.98N (100g), and 1.96N (200g) were used to widen the midsagittal suture of live rabbits over a period of 6 weeks. Evaluation was based on a models ability to represent experimental data well over all three load sets. Ideally, a single set of model constants could be used to represent data over all loads tested. Upon completion of the analysis it was found that the modified superposition method was able to replicate experimental data within one standard deviation of the means using a single set of constants for all loads. Future work should focus on model improvement as well as prediction of treatment outcomes.

Overcoming Nonlinear Partial Volume Effects in Known-Component Reconstruction of Cochlear Implants.

Nonlinear partial volume (NLPV) effects can be significant for objects with large attenuation differences and fine detail structures near the spatial resolution limits of a tomographic system. This is particularly true for small metal devices like cochlear implants. While traditional model-based approaches might alleviate these artifacts through very fine sampling of the image volume and subsampling of rays to each detector element, such solutions can be extremely burdensome in terms of memory and computational requirements. The work presented in this paper leverages the model-based approach called "known-component reconstruction" (KCR) where prior knowledge of a surgical device is integrated into the estimation. In KCR, the parameterization of the object separates the volume into an unknown background anatomy and a known component with unknown registration. Thus, one can model projections of an implant at very high spatial resolution while limiting the spatial resolution of the anatomy - in effect, modeling NLPV effects where they are most significant. We present modifications of the KCR approach that can be used to largely eliminate NLPV artifacts, and demonstrate the efficacy of the modified technique (with improved image quality and accurate implant position estimates) for the cochlear implant imaging scenario.

Technical assessment of a cone-beam CT scanner for otolaryngology imaging: image quality, dose, and technique protocols.

PURPOSE: As cone-beam CT (CBCT) systems dedicated to various imaging specialties proliferate, technical assessment grounded in imaging physics is important to ensuring that image quality and radiation dose are quantified, understood, and justified. This paper involves technical assessment of a new CBCT scanner (CS 9300, Carestream Health, Rochester, NY) dedicated to imaging of the ear and sinuses for applications in otolaryngology-head and neck surgery (OHNS). The results guided evaluation of technique protocols to minimize radiation dose in a manner sufficient for OHNS imaging tasks. METHODS: The technical assessment focused on the imaging performance and radiation dose for each of seven technique protocols recommended by the manufacturer: three sinus protocols and four ear (temporal bone) protocols. Absolute dose was measured using techniques adapted from AAPM Task Group Report No. 111, involving three stacked 16 cm diameter acrylic cylinders (CTDI phantoms) and a 0.6 cm(3) Farmer ionization chamber to measure central and peripheral dose. The central dose (D(o)) was also measured as a function of longitudinal position (z) within and beyond the primary radiation field to assess, for example, out-of-field dose to the neck. Signal-difference-to-noise ratio (SDNR) and Hounsfield unit (HU) accuracy were assessed in a commercially available quality assurance phantom (CATPHAN module CTP404, The Phantom Laboratory, Greenwich, NY) and a custom phantom with soft-tissue-simulating plastic inserts (Gammex RMI, Madison, WI). Spatial resolution was assessed both qualitatively (a line-pair pattern, CATPHAN module CTP528) and quantitatively (modulation transfer function, MTF, measured with a wire phantom). Imaging performance pertinent to various OHNS imaging tasks was qualitatively assessed using an anthropomorphic phantom as evaluated by two experienced OHNS specialists. RESULTS: The technical assessment motivated a variety of modifications to the manufacturer-specified protocols to provide reduced radiation dose without compromising pertinent task-based imaging performance. The revised protocols yielded D(o) ranging 2.9-5.7 mGy, representing a ∼30% reduction in dose from the original technique chart. Out-of-field dose was ∼10% of D(o) at a distance of ∼8 cm from the field edge. Soft-tissue contrast resolution was fairly limited (water-brain SDNR ∼0.4-0.7) while high-contrast performance was reasonably good (SDNR ∼2-4 for a polystyrene insert in the CATPHAN). The scanner does not demonstrate (or claim to provide) accurate HU and exhibits a systematic error in CT number that could potentially be addressed by further calibration. The spatial resolution is ∼10-16 lp∕cm as assessed in a line-pair phantom, with MTF exceeding 10% out to ∼20 lp∕cm. Qualitative assessment by expert readers suggested limited soft-tissue visibility but excellent high-contrast (bone) visualization with isotropic spatial resolution suitable to a broad spectrum of pertinent sinus and temporal bone imaging tasks. CONCLUSIONS: The CBCT scanner provided spatial and contrast resolution suitable to visualization of high-contrast morphology in sinus, maxillofacial, and otologic imaging applications. Rigorous technical assessment guided revision of technique protocols to reduce radiation dose while maintaining image quality sufficient for pertinent imaging tasks. The scanner appears well suited to high-contrast sinus and temporal bone imaging at doses comparable to or less than that reported for conventional diagnostic CT of the head.

Review of maxillary expansion appliance activation methods: engineering and clinical perspectives.

Objective. Review the reported activation methods of maxillary expansion devices for midpalatal suture separation from an engineering perspective and suggest areas of improvement. Materials and Methods. A literature search of Scopus and PubMed was used to determine current expansion methods. A U.S. and Canadian patent database search was also conducted using patent classification and keywords. Any paper presenting a new method of expansion was included. Results. Expansion methods in use, or patented, can be classified as either a screw- or spring-type, magnetic, or shape memory alloy expansion appliance. Conclusions. Each activation method presented unique advantages and disadvantages from both clinical and engineering perspectives. Areas for improvement still remain and are identified in the paper.

Surface analysis of etched molar enamel by gas adsorption.

Much research has been devoted to the study of etched enamel, since it is critical to bonding. Currently, there are no precise data regarding the etched-enamel specific surface area. The aim of this study was to characterize, by two different methods, the surface of human dental enamel in vitro after being etched. It was hypothesized that differences would be observed between specimens in terms of specific surface area and grade of etching. Sixteen third molar enamel samples were etched for 30 sec with 37% phosphoric acid prior to being viewed by SEM. Etched enamel surfaces were graded according to the Galil and Wright classification. The total surface area of etched samples was determined by the BET gas absorption method. A substantial variability in total surface area was observed between and among samples. A Pearson's Correlation Coefficient showed a lack of relationship between etch pattern and total surface area.

Maxillary expansion treatment using bone anchors: development and validation of a 3D finite element model.

OBJECTIVE: Develop a finite element (FE) model of a skull to perform biomechanical studies of maxillary expansion using bone anchors (BA). MATERIALS AND METHODS: A skull model was developed and assigned material properties based on Hounsfield unit (HU) values of cone-beam computerized tomography (CBCT) images. A 3 mm diameter cylindrical BA was modelled and inserted in the palatal bone. A 4 mm transverse displacement was applied on the anchor. An evaluation on the effect on local stresses of BA implantation inclination angle was performed. RESULTS: Proper displacement results and strain-stress trends for the expansion process were present. Stress distribution patterns were similar as reported in the literature. No significant difference between BA inclination angles was found. CONCLUSION: This work leads to a better understanding and prediction of craniofacial and maxillary bone remodelling during ME with BA treatments and is a first step towards the development of patient specific treatments.

Ototoxicity of carboplatin delivered locally in a monkey brainstem.

Ototoxicity is a common side effect of platinum-based chemotherapy. Intratumoral drug delivery theoretically could reduce the ototoxic effects of systemic drug infusions. However, local delivery to central nervous system (CNS) tumors might promote ototoxicity through drug release into cerebrospinal fluid (CSF). This report describes an examination of the cytoarchitecture of vestibular cells of cynomolgus monkeys that had chronic brainstem infusions with the maximum tolerated dose (MTD) of carboplatin. The brainstems of adult monkeys were infused for 30 days at 0.42 mu l/h with 0.025 to 0.25 mg/kg (MTD) of carboplatin. The vestibular sensory epithelia of eight drug-treated animals were isolated for microscopic examination of vestibular hair cells and support cells. Local infusions produced chronic elevated CSF levels of platinum, neurological symptoms, and radiographic evidence of pontine injury. Histology revealed significant cell damage at the infusion sites. Microscopic examinations of vestibular support cells and hair cells demonstrate a small reduction in cell counts in the drug-treated monkeys compared to a noninfused control animal. Parametric and nonparametric tests show no effect of dose in predicting the vestibular cell counts. In this single study of eight monkeys, a dose-dependent reduction of vestibular hair cells or support cells was not observed in animals infused with brainstem infusions of 0.025 to 0.25 mg/kg of carboplatin.