The Oghalai lab has two major thrusts. Our basic science/translational research efforts are designed to better understand the mechanisms of hearing loss and our clinical research approaches are targeted to directly and rapidly improve the care of patients with hearing loss.
A common clinical scenario is that a child is initially identified with a partial hearing loss, which then progresses to profound hearing loss over a period of months to years. Genetic defects are responsible for over half of these cases, however the specific mechanisms of how many of these mutations cause progressive sensorineural hearing loss is unclear. Right now, all we can tell a patient with hearing loss is that we know they have hearing loss, and that it is because of a problem in the cochlea. There are no more detailed tests available.
Because of the difficulty in performing auditory research in humans, we study normal and transgenic mice that have hearing loss. We strive to perform comprehensive evaluation of the pathophysiology that creates the hearing loss. For example, cochlear function is monitored with measurements of the compound action potential, the auditory evoked brainstem response, distortion product otoacoustic emissions, the cochlear microphonic, and the olivocochlear reflex. Basilar membrane motion is measured using laser doppler vibrometry. Histological study of the inner ear is performed using immunohistochemistry. We also use the patch-clamp technique with to study hair cell physiology. Recently, we have begun using fluorescent-activated cell sorting (FACS) to isolate outer hair cells from the adult cochlea after noise or blast exposure to study the regulation of genes after cellular injury.
We are also working to develop techniques that will allow us to perform research in humans. For example, we are in the process of developing novel optical techniques for in vivo imaging using optical coherence tomography (OCT). The level of detail within the cochlea that we can now image is roughly two orders of magnitude better than what is currently available with the latest MRI or CT techniques. Our goal is to be able to identify why any given patient that comes to clinic has hearing loss, and use this information to guide management using regenerative strategies that are in active development. Here is a mouse cochlea imaged using OCT:
Below is a 3-D reconstruction of the hair cell epithelium imaged using a two-photon microscope. Green labels prestin within the lateral wall of the outer hair cells and red labels actin within the stereocilary bundles at the top of the hair cells.
Recently, we have been using acousto-optical deflectors (AODs) to control a laser in the near-infrared range (680-950 nm). Unlike conventional mirror setups, AODs allow near-instantaneous, random access across a sample, power control, and dwell time in the microsecond range. The following two videos demonstrate the capabilities we have for controlling the laser with an AOD. The images were obtained by recording the reflected image of a 680 nm laser with a CCD camera.
Our clinical research is focused on improving what we are currently doing to help children with deafness. Cochlear implants (CI) are the most common treatment for deafness. While many factors influence the ability of a deaf child who is hearing through a CI to develop speech and language skills, an important factor is to properly program the CI. However, implementing the optimal CI program is a challenging, individualized, and iterative process with variable success.
One difficulty in CI programming is obtaining behavioral measurements from the young children in which CIs are usually implanted. Therefore, we are developing the technique of near-infrared spectroscopy (NIRS) to functionally image activity within the auditory cortex of children hearing through a cochlear implant. The photo to the left shows a collaborator, Heather Bortfeld, Ph.D. wearing the NIRS headset as she views her brain’s response to hearing bells. Below are images demonstrating activty within a subject’s auditory cortex while he/she was listening to different types of speech.
As well, we are running a multi-site, prospective randomized clinical trial of deaf children with special needs. The goal of the study is to determine the best treatment options for children that require such complex and individualized care. This trial is actively enrolling participants at Lucile Packard Children’s Hospital in Palo Alto, CA and at Texas Children’s Hospital in Houston, TX.
For more information about this clinical trial, click here.