Optical coherence tomography (OCT) of the human cochlea has potential to reveal pathophysiological details of hearing disorders and cochlear function via vibrometry and angiography. However, the ability of 1.3μm OCT to image the detailed microanatomy inside the cochlea is limited by light scattering in the tympanic membrane and otic capsule. Since light scattering in biological tissues is reduced at longer wavelengths, we investigated the use of a 1.7μm swept-source laser for OCT imaging of an ex-vivo human cochlea to compare with 1.3μm OCT imaging. We found that 1.7μm OCT could provide sharper details and greater contrast inside the cochlea compared to 1.3μm OCT due to reduced multiple scattering from the bony otic capsule. These results support the continued development of 1.7μm OCT for cochlear imaging.
Magnetic Resonance Imaging and x-ray Computed Tomography have limitations when applied to diseases of the human inner ear due to insufficient resolution. Key morphological features of the inner ear are below the resolving power of both modalities; thus, they are unable to measure functional aspects of the microstructures in the cochlea. Furthermore, general access to the cochlea is a challenge due to its location in the inner ear and its bony encapsulation. These limitations cause clinicians to rely on clinical history when diagnosing and managing hearing loss in patients, which is not ideal. This paper explores the application of Optical Coherence Tomography (OCT) as a diagnostic tool for inner ear diseases. OCT’s high spatial and temporal resolution allows for detailed imaging of inner ear structures and their function. To address the challenge of accessing the cochlea in humans, a hand-held endoscopic OCT device has been developed that can image through the round window membrane. The technology has been tested in cadaver temporal bone, enabling functional and morphological imaging of the cochlea when navigated to the round window. Alongside the device, we are developing an algorithm to perform subsequent stitching of volumes to overcome limitations with a small field of view. Applying this algorithm on cadaver tissue serves as a preliminary step before advancing to live human cochlear imaging. By utilizing our hand-held OCT endoscope, clinicians will have the ability to record changes in morphological and functional information, thereby improving the approach to diagnosing and treating patients with inner ear diseases.
We describe the optimization and application of a multi-window approach for improved resolution, side-lobe suppression, and phase sensitivity. Using the Hann window as a reference, we show that 10 windows are sufficient to achieve 42% resolution improvement, -31 dB side-lobe intensity, and a 20% improvement in phase sensitivity. We explored the benefits of this windowing technique for OCT imaging using a prototype narrow-band laser, OCT vibrometry, and Doppler OCT for angiography. Experimental data are in good agreement with simulation. We believe it will be possible using this optimized approach to achieve real-time processing and display, despite the added computational load.
We have engineered nano-sized constructs from erythrocytes doped with the FDA-approved near infrared (NIR) chromophore, indocyanine green (ICG). Herein, we present results that demonstrate membrane cholesterol enrichment is associated with reduced uptake of these nanoparticles by macrophages in vitro, and greater accumulation of the nanoparticles in intraperitoneal implants in immunodeficient mice. These preliminary findings suggest that cholesterol-enrichment of erythrocyte-derived optical nanoparticles can provide a potential capability for enhanced NIR imaging of tumors.
We have engineered nano-vesicles, derived from erythrocytes, which can be doped with various near infrared (NIR) organic chromophores, including the FDA-approved indocyanine green (ICG). We refer to these vesicles as NIR erythrocyte-mimicking transducers (NETS) since in response to NIR photo-excitation they can generate heat or emit fluorescent light. Using biochemical methods based on reduction amination, we have functionalized the surface of NET with antibodies to target specific biomolecules. We present results that demonstrate the effectiveness of NETs in targeted imaging of cancer cells that over-express the human epidermal growth factor receptor-2 (HER2).
Erythrocyte-based nanoparticle platforms can offer long circulation times not offered by traditional drug delivery methods. We have developed a novel erythrocyte-based nanoparticle doped with indocyanine green (ICG), the only FDA-approved near-infrared chromophore. Here, we report on the absorption and fluorescence emission characteristics of these nanoparticles fabricated using ICG concentrations in the range of 161-323 μM. These nanoparticles may serve as biocompatible optical materials for various clinical imaging and phototherapeutic applications.
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