Bilateral Continuous Automated Distraction Osteogenesis: Proof of Principle.

The purpose of this study was to demonstrate that automated, continuous, curvilinear distraction osteogenesis (DO) in a minipig model is effective when performed bilaterally, at rates up to 3 mm/day, to achieve clinically relevant lengthening. A Yucatan minipig in the mixed dentition phase underwent bilaterally, at a continuous DO at a rate of 2 mm/day at the center of rotation; 1.0 and 3.0 mm/day at the superior and inferior regions, respectively. The distraction period was 13 days with no latency period. Vector and rate of distraction were remotely monitored without radiographs, using the device sensor. After fixation and euthanasia, the mandible and digastric muscles were harvested. The ex vivo appearance, stability, and radiodensity of the regenerate were evaluated using a semiquantitative scale. Percent surface area (PSA) occupied by bone, fibrous tissue, cartilage, and hematoma were calculated using histomorphometrics. The effects of DO on the digastric muscles and mandibular condyles were assessed via microscopy, and degenerative changes were quantified. The animal was distracted to 21 mm and 24 mm on the right and left sides, respectively. Clinical appearance, stability, and radiodensity were scored as "3" bilaterally indicating osseous union. The total PSA occupied by bone (right = 75.53 ±â€Š2.19%; left PSA = 73.11 ±â€Š2.18%) approached that of an unoperated mandible (84.67 ±â€Š0.86%). Digastric muscles and condyles showed negligible degenerative or abnormal histologic changes. This proof of principle study is the first report of osseous healing with no ill-effect on associated soft tissue and the mandibular condyle using bilateral, automated, continuous, and curvilinear DO at rates up to 3 mm/day. The model approximates potential human application of continuous automated distraction with a semiburied device.

Assessment of the OsteoMark-Navigation System for Oral and Maxillofacial Surgery.

PURPOSE: To assess the accuracy of a novel navigation system for maxillofacial surgery using human cadavers and a live minipig model. MATERIALS AND METHODS: We tested an electromagnetic tracking system (OsteoMark-Navigation) that uses simple sensors to determine the position and orientation of a hand-held pencil-like marking device. The device can translate 3-dimensional computed tomographic data intraoperatively to allow the surgeon to localize and draw a proposed osteotomy or the resection margins of a tumor on bone. The accuracy of the OsteoMark-Navigation system in locating and marking osteotomies and screw positions in human cadaver heads was assessed. In group 1 (n = 3, 6 sides), OsteoMark-Navigation marked osteotomies and screw positions were compared to virtual treatment plans. In group 2 (n = 3, 6 sides), marked osteotomies and screw positions for distraction osteogenesis devices were compared with those performed using fabricated guide stents. Three metrics were used to document the precision and accuracy. In group 3 (n = 1), the system was tested in a standard operating room environment. RESULTS: For group 1, the mean error between the points was 0.7 mm (horizontal) and 1.7 mm (vertical). Compared with the posterior and inferior mandibular border, the mean error was 1.2 and 1.7 mm, respectively. For group 2, the mean discrepancy between the points marked using the OsteoMark-Navigation system and the surgical guides was 1.9 mm (range 0 to 4.1). The system maintained accuracy on a live minipig in a standard operating room environment. CONCLUSION: Based on this research OsteoMark-Navigation is a potentially powerful tool for clinical use in maxillofacial surgery. It has accuracy and precision comparable to that of existing clinical applications.

Skeletal and soft tissue response to automated, continuous, curvilinear distraction osteogenesis.

PURPOSE: To document the bone formation and soft tissue changes in response to automated, continuous, curvilinear distraction osteogenesis (DO) at rates greater than 1 mm/day in a minipig model. MATERIALS AND METHODS: Two groups of Yucatan minipigs underwent automated, continuous, curvilinear DO of the right mandible: group A, 1.5 mm/day (n = 5); and group B, 3.0 mm/day (n = 5). Each minipig underwent 12 mm of distraction followed by 24 days of fixation. The distracted and contralateral mandibles were harvested at the end of fixation. The percentage of surface area (PSA) of the regenerate occupied by bone, fibrous tissue, cartilage, and hematoma was determined using computerized histomorphometric analysis. The control groups consisted of DO wounds distracted discontinuously at 1 mm/day and the nonoperated contralateral mandible. The ipsilateral and contralateral digastric muscles were harvested and stained for proliferating cell nuclear antigen (PCNA), myogenic differentiation-1 (MyoD), and paired Box 7 protein (PAX7). RESULTS: All 10 minipigs completed the distraction and fixation period. The PSA occupied by bone was similar for groups A (PSA 64.36% ± 5.87%) and B (PSA 63.83% ± 3.37%) and the control group (1 mm/day; PSA 64.89% ± 0.56%) but was less than that on the nonoperated side (PSA 84.67% ± 0.86%). The PSA occupied by cartilage and hematoma in all groups was minimal (<1.1%). The digastric muscles had no abnormal tissue or inflammation, and PAX7, MyoD, and PCNA expression had returned to the baseline levels. CONCLUSIONS: The results of the present study indicate that bone formation in response to automated, continuous, and curvilinear DO at a rate of 1.5 and 3.0 mm/day is nearly identical to that with discontinuous DO at 1 mm/day. In addition, no deleterious effects were found on the digastric muscles.

A mathematical model of pulse-coded hormone signal responses in pituitary gonadotroph cells.

Cells in the pituitary that synthesize luteinizing and follicle-stimulating hormones regulate the relative production of these two key reproductive hormones in response to signals from the hypothalamus. These signals are encoded in the frequency of gonadotrophin-releasing-hormone pulses. In vitro experiments with a murine-derived cell line have identified key elements of the processes that decode the signal to regulate transcription of the subunits encoding these hormones. The mathematical model described in this paper is based on the results of those experiments and advances quantitative understanding of the biochemical decoder. The model consists of non-linear differential equations for each of six processes that lead to the synthesis of follicle-stimulating hormone. Simulations of the model exhibit key characteristics found in the experiments, including a preference for follicle-stimulating hormone synthesis at low pulse frequencies and a loss of this characteristic when a mutation is introduced.

Automated continuous distraction osteogenesis may allow faster distraction rates: a preliminary study.

PURPOSE: To determine if automated continuous distraction osteogenesis (DO) at rates faster than 1 mm/day results in bone formation by clinical and radiographic criteria, in a minipig model. MATERIALS AND METHODS: An automated, continuous, curvilinear distraction device was placed across a mandibular osteotomy in 10 minipigs. After 12 mm of distraction and 24 days of fixation, the animals were sacrificed and bone healing was evaluated. The continuous distraction rates were 1.5 mm/day (n = 5) and 3 mm/day (n = 5). A semiquantitative scale was used to assess the ex vivo clinical appearance of the distraction gap (3 = osteotomy not visible; 2 = <50% visible; 1 = >50% visible; 0 = 100% visible), stability (3 = no mobility; 2 and 1 = mobility in 1 plane or 2 planes, respectively; 0 = mobility in 3 planes), and radiographic density (4 = 100% of gap opaque; 3 = >75%; 2 = 50% to 75%; 1 = <50%; 0 = radiolucent). Groups of 4 minipigs distracted discontinuously at 1, 2, and 4 mm/day served as controls. RESULTS: Automated, continuous DO at 1.5-mm/day and 3-mm/day had similar bone formation compared to discontinuous DO at 1-mm/day. The continuous DO 1.5-mm/day group had significantly higher scores for appearance and radiographic density compared with the discontinuous 4-mm/day group. The continuous DO 3-mm/day group had significantly higher scores for appearance and radiographic density compared with the discontinuous 4-mm/day group and greater stability compared with the discontinuous 2- and 4-mm/day groups. CONCLUSIONS: Results of this preliminary study indicate that continuous DO at rates of 1.5 and 3.0 mm/day produces better bone formation compared with discontinuous DO at rates faster than 1 mm/day.

A novel actuator for simulation of epidural anesthesia and other needle insertion procedures.

INTRODUCTION: When navigating a needle from skin to epidural space, a skilled clinician maintains a mental model of the anatomy and uses the various forms of haptic and visual feedback to track the location of the needle tip. Simulating the procedure requires an actuator that can produce the feel of tissue layers even as the needle direction changes from the ideal path. METHODS: A new actuator and algorithm architecture simulate forces associated with passing a needle through varying tissue layers. The actuator uses a set of cables to suspend a needle holder. The cables are wound onto spools controlled by brushless motors. An electromagnetic tracker is used to monitor the position of the needle tip. RESULTS: Novice and expert clinicians simulated epidural insertion with the simulator. Preliminary depth-time curves show that the user responds to changes in tissue properties as the needle is advanced. Some discrepancy in clinician response indicates that the feel of the simulator is sensitive to technique, thus perfect tissue property simulation has not been achieved. CONCLUSIONS: The new simulator is able to approximately reproduce properties of complex multilayer tissue structures, including fine-scale texture. Methods for improving fidelity of the simulation are identified.

Automating skeletal expansion: An implant for distraction osteogenesis of the mandible.

BACKGROUND: Distraction osteogenesis (DO) is a technique of bone lengthening that makes use of the body's natural healing capacity. An osteotomy is created and a rigid distraction device is attached to the bone. After a latency period, the device is activated 2-4 times per day for a total of 1 mm/day of bone lengthening. This technique is used to correct a variety of congenital and acquired deformities of the mandible, midface and long bones. To shorten the treatment period and to eliminate the complications of patient activation of the device, an automated continuous distraction device would be desirable. It has been reported that continuous distraction generates adequate bone with lengthening at a rate of 2 mm/day, thereby reducing the treatment time. METHOD OF APPROACH: The device we describe here uses miniature high-pressure hydraulics, position feedback, and a digital controller to achieve closed-loop control of the distraction process. The implanted actuator can produce up to 40N of distraction force on linear trajectories as well as curved distraction paths. In the paper we detail the spring-powered hydraulic reservoir, controller, and user interface. RESULTS: Experiments to test the new device design were performed in a porcine cadaver head and in live pigs. In the cadaver head, the device performed an 11-day/11 mm distraction with a root-mean-squared position error of 0.09 mm. The device functioned for periods of several days in each of five live animals, though some component failures occurred, leading to design revisions. CONCLUSIONS: The test series showed that the novel design of this system provides the capabilities necessary to automate distraction of the mandible. Further developments will focus on making the implanted position sensor more robust and then carrying out clinical trials.

Active retinal tracker for clinical optical coherence tomography systems.

An active, hardware-based retinal tracker is integrated with a clinical optical coherence tomography (OCT) system to investigate the effects of stabilization on acquisition of high-resolution retinal sections. The prototype retinal tracker locks onto common fundus features, detects transverse eye motion via changes in feature reflectance, and positions the OCT diagnostic beam to fixed coordinates on the retina with mirrors driven by a feedback control loop. The system is tested in a full clinical protocol on subjects with normal and glaucomatous eyes. Experimental analysis software is developed to coalign and coadd multiple fundus and OCT images and to extract quantitative information on the location of structures in the images. Tracking is highly accurate and reproducible on all but one subject, resulting in the ability to scan the same retinal location continually over long periods of time. The results show qualitative improvement in 97% of coadded OCT scans and a reduction in the variance of the position of the optic disc cup edge to less than 1 pixel (< 60 microm). The tracking system can be easily configured for use in research on ultra-high-resolution OCT systems for advanced image modalities. For example, tracking will enable very high density 3-D scans of the retina, which are susceptible to eye motion artifacts even for new high-speed systems.

Compact scanning laser ophthalmoscope with high-speed retinal tracker.

The effectiveness of image stabilization with a retinal tracker in a multifunction, compact scanning laser ophthalmoscope (TSLO) was demonstrated in initial human subject tests. The retinal tracking system uses a co confocal reflectometer with a closed-loop optical servo system to lock onto features in the fundus. The system is multifarious and modular to allow configuration for many research a clinical applications. Adult volunteers were tested without mydriasis to optimize the tracking instrumentation and to characterize imaging performance. The retinal tracking system achieves a bandwidth of greater than 1 kHz, which permits tracking at rates that greatly exceed the maximum rate of motion of the human eye. The TSLO system stabilized images to an accuracy of 0.05 deg in all test subjects during ordinary saccades with a velocity up to approximately 500 deg/s. Feature lock was maintained for minutes despite subject eye blinking. Even when nearly 1000 frames were coadded, image blur was minimal. Successful frame coaddition allowed image acquisition with decreased noise in low-light applications. The retinal tracking system significantly enhances the imaging capabilities of the scanning laser ophthalmoscope.