We are developing a method to visualize functional hair cells and other cellular elements of the inner ear within the intact mammalian cochlea using fluorescence microendoscopy. Our laboratory has begun work on this minimally invasive in vivo imaging technique to provide high-resolution images of deep tissues previously inaccessible in live subjects. Using microendoscopes as small as 0.3 mm in diameter, we have successfully imaged individual red blood cells flowing within capillaries inside the mammalian cochlea. We are extending this work by labeling functional neural elements with fluorescent dyes to concurrently reveal mechanotransduction as well as microanatomy.
Current work includes microendoscopy using a styryl dye (FM-143) in the guinea pig. It is anticipated t hat this will allow us to accurately map hair cell injury following ototoxin exposure, and to observe the recovery of hair cells from temporary threshold shift noise damage. The use of microendoscopes should provide an opportunity to observe specific hair cell populations over time -- information previously unavailable through conventional techniques.
An imaging technology to observe functional hair cells and dendrites within live mammalian subjects will provide considerable benefit, and enable progress in a broad range of previously intractable hearing science questions. The success of inner ear microendoscopy will provide a basis on which inner ear surgery can be established. The inner ear is one of the last areas of the human body to remain largely inaccessible to direct examination and surgical intervention. This is because of the combination of its small size and its extraordinary fragility to mechanical manipulation. The development of non-destructive imaging techniques will enable diagnostic and therapeutic manipulations, including the optimal placement of cochlear implant arrays, or the specific delivery of stem cells or growth factors to enable hearing restoration.
Inner Ear Surgery and Robotics
Collaborators: Nikolas Blevins, MD, Kenneth Salisbury PhD, , David Camarillo MS, Byongho Park PhD, Fritz Prinz PhD
Because of its size, location and considerable fragility, the inner ear has long been inaccessible to direct, non-destructive surgical manipulation. We are in the process of designing scalable robotic surgical instruments designed to allow inner ear surgery. These devices are intended to allow the surgeon the ability to see and feel inner ear structures, and afford the dexterity required for manipulation of tissues at this small scale. The use of robotic control technology will scale down motions of the human hand, to allow navigation and dissection to proceed at the small scale necessary. The successful achievement of this goal will open a new frontier in otology. It will allow the development of more effective inner ear prostheses and regenerative techniques, and will enable new therapeutic opportunities for a host of common otologic disorders. This work is the result of a collaboration between Otolaryngology, Mechanical Engineering, and Computer Science.
Mathematical Modeling of Cochlear Biomechanics
Collaborators: Nikolas Blevins, MD, Sunil Puria PhD, Charles Steele PhD
We are designing a computational model of inner ear mechanics to understand the mechanisms that support the highly sensitivity, dynamic, and non-linear properties of normal hearing. This understanding will allow the functional characterization of alterations arising from a variety of cochlear disorders and from therapeutic interventions. We will develop an anatomically based three-dimensional computational model for the cochlea that incorporates the details of the micro-mechanics of the hair cells, neurons, supporting structures, membranes, and surrounding fluid environment. The model will be based on previous work by Dr. Steele in our group.
A systematic and comprehensive computational model of inner ear mechanics will provide the basis for addressing a number of clinically important issues. For example, we will be able to predict the mechanical effect of cochlear implant array placement, and how it may influence residual acoustic hearing in the implanted ear. Such data may help us to develop more effective acoustic-electric hybrid prostheses for individuals with high frequency hearing loss. Similarly, we will explore the mechanical sequellae of endolymphatic hydrops, and the degree to which this could contribute to hearing loss in Meniere’s disease. With the anticipated advent of micro-robotics, otologists will develop technology to manipulate the organ of Corti in an attempt to improve hearing. The benefit of this exciting future technology can only be fully realized if therapy is grounded a clear understanding of cochlear mechanics as will be provided by our project. Another important future technology for hearing restoration is the regeneration of cochlear sub structures through the introduction and differentiation of stem cells. The yet unknown mechanical consequences on hearing of these regenerative efforts can be explored in the proposed biomechanical framework.
Otology & Neurotology
About Nikolas Blevins, MD and Robert K. Jackler, MD
Stanford is conducting active clinical research into novel surgical treatments for ear and skull base disorders. An Otologic Research Laboratory exists at the Palo Alto VA Medical Center under the direction of Richard L. Goode, MD and Sunil Puria, PhD. The laboratory focuses on applied human middle ear research with emphasis on development and testing of improved middle ear ossicular replacement prostheses, and other middle and external ear prostheses designed to improve hearing thresholds.
Planned Subtotal Resection and Stereotactic Radiotherapy for Acoustic Neuroma
The advent of stereotactic radiosurgery has provided the clinician with a non-surgical option to control the growth of acoustic tumors. With the development of the Cyberknife linear accelerator system, Stanford has long been a pioneer in the non-surgical management of skull base disease. Despite considerable experience with small acoustic tumors, the role of radiosurgery into the treatment of large tumors remains to be fully defined. The potentially synergistic effect of combined microsurgical resection and stereotactic radiotherapy could offer effective new options to individuals who remain at most risk given conventional treatment.
The Stanford Department of Otolaryngology in collaboration with the departments of Neurosurgery and Radiation Oncology, is leading a prospective multicenter trial to assess the efficacy of managing large acoustic neuromas (over 3 cm) with a combination of planned subtotal resection followed by stereotactic radiosurgery. Patients enrolled in the protocol will undergo planned subtotal resection avoiding potentially injurious dissection of the facial nerve from the tumor capsule. Patients will be followed with serial MRI scans, and will receive stereotactic radiation to the tumor remnant if growth is detected.
The prospective nature of this study will provide valuable data towards establishing optimal treatment of advanced disease, while minimizing the risk of postoperative facial nerve dysfunction.
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1. Planned subtotal resection of an acoustic neuroma
2. The Stanford Cyberknife.
The Use of Stacked ABR for the Assessment of Hearing Preservation in Acoustic Neuroma Resection
Patients with small acoustic neuromas and good hearing are faced with a choice of treatment options. Whether they choose to undergo microsurgical resection or stereotactic radiotherapy (such as with Cyberknife) can be largely influenced by the likelihood of hearing preservation. The short-term rates of hearing preservation with stereotactic radiation are excellent, but given the persistence of tumor and possible long-term neurovascular changes, hearing levels may deteriorate with time. Microsurgery in contrast, often places additional risks to hearing in the short term. However, the expectation for maintaining hearing that is present post-operatively is quite favorable. Unfortunately, there is a current lack of preoperative predictors of which patients are more likely to retain hearing through a surgical procedure.
The Stanford Departments of Otolaryngology and Audiology are engaged in a prospective clinical trial to assess innovative of electrophysiologic testing to predict the success of hearing-preservation attempts. The study applies highly sensitive auditory brainstem response techniques (“stacked ABR”) that may be an accurate predictor of the potential for an involved cochlear nerve to withstand surgical manipulation and tumor extraction.
The development of such non-invasive preoperative predictors will substantively assist with patient counseling and treatment planning in patients with acoustic neuromas. Given this additional information, patients and their clinicians may make better-informed decisions about the pursuit of treatment options.
Non-invasive Diagnosis of Cholesteatoma using High-Resolution Diffusion-Weighted MRI Sequences
The Department of Otolaryngology, in conjunction with the Department of Radiology, is engaged in a prospective study to establish the efficacy of innovative MRI techniques in the diagnosis of cholesteatoma. Standard diffusion-weighted MRI is capable of detecting intratemporal squamous epithelium. However, it is subotipmal in its anatomic resolution and is subject to significant artifacts, both of which limit its clinical utility.
Our protocol involves the use of new signal processing techniques (SENSE-DWI). The resulting improved images have the potential to make MRI clinically useful in treatment planning for patients with possible occult cholesteatoma. Patients in whom a second-look procedure is contemplated may benefit greatly from this non-invasive imaging modality.
Innovations in Cochlear Implant Technology
In 1964, the first human multichannel cochlear implant was placed at Stanford. The Department of Otolaryngology continues this long history of innovation in the development and application of inner ear prostheses. Related basic science projects include the application of stem-cells for inner ear regeneration, computational modeling of inner ear function, and inner ear microendoscopy for therapeutics and inner ear microrobotics.
The LPCH/Stanford Cochlear Implant Center is actively involved in clinical trials for cochlear implants. We are a center for the clinical trial of the Nucleus Electrical-Acoustic Hybrid implant. These devices offer the potential benefits of cochlear implantation to the vast number of individuals who suffer from high frequency hearing loss, since residual acoustic hearing in the lower frequencies can be maintained.
Surgical Simulation
Collaborators: Nikolas Blevins, MD, Kenneth Salisbury PhD, Federico Barbagli PhD, Christopher Sewell MS, Daniel Morris MS
In order to be safe and effective, the otologic surgeon must have a complete understanding of the intricate anatomy of the ear and skull base. Such an understanding is difficult to acquire from traditional two-dimensional media. Similarly, the surgical technique of working within this confined space in close proximity to vital neurovascular structures is difficult to convey within the setting of actual surgery. For these reasons, the application of an immersive computer simulation environment is a natural fit for providing education in this surgical subspecialty.
We are developing a surgical simulator for ear and temporal bone surgery. In collaboration with the Biorobotics group, a working system for skull base dissection has been created incorporating anatomically accurate stereoscopic models, and a touch-feedback (haptic) interface.
The Stanford Temporal Bone Surgical Simulator has incorporated innovative simulation techniques to maximize its realism and educational utility. Such innovative features include a hybrid volumetric and surface representation of anatomy for haptic and graphic rendering, a custom-developed simulation environment and user interface, and the potential for networked haptics – allowing multiple user s to manipulate and “feel” the same anatomic simulation. The system also incorporates a scripting language through which an instructor can establish the expected flow of the surgical procedure. Through the application of these rules, and more generalized metrics defining safe and effective surgery, the user can receive timely feedback regarding performance. Future plans include the incorporation of patient-specific data from preoperative imaging studies to allow for rehearsal of scheduled procedures.
