Bilal H. Malik

Optical axial scanning in confocal microscopy using an electrically tunable lens

This paper presents the use and characterization of an electrically focus tunable lens to perform axial scanning in a confocal microscope. Lateral and axial resolution are characterized over a >250 µm axial scan range. Confocal microscopy using optical axial scanning is demonstrated in epithelial tissue and compared to traditional stage scanning. By enabling rapid axial scanning, minimizing motion artifacts, and reducing mechanical complexity, this technique has potential to enhance in vivo three-dimensional imaging in confocal endomicroscopy.

Real-time, closed-loop dual-wavelength optical polarimetry for glucose monitoring.

The development of a real-time, dual-wavelength optical polarimetric system to ultimately probe the aqueous humor glucose concentrations as a means of noninvasive diabetic glucose monitoring is the long-term goal of this research. The key impact of the work is the development of an approach for the reduction of the time-variant corneal birefringence due to motion artifact, which is still a limiting factor preventing the realization of such a device. Our dual-wavelength approach utilizes real-time, closed-loop feedback that employs a classical three-term feedback controller and efficiently reduces the effect of motion artifact that appears as a common noise source for both wavelengths. In vitro results are shown for the open-loop system, and although the dual-wavelength system helps to reduce the noise, it is shown that closed-loop control is necessary to bring the noise down to a sufficient level for physiological monitoring. Specifically, in vitro measurement results with the closed-loop dual-wavelength approach demonstrate a sensitivity of 12.8 mg/dl across the physiologic glucose range in the presence of time-variant test cell birefringence. Overall, it is shown that this polarimetric system has the potential to be used as a noninvasive measure of glucose for diabetes.

Double-Stage Taper for Coupling Between SOI Waveguides and Single-Mode Fiber

A low-loss polarization-independent and wavelength-insensitive mode converter is demonstrated for coupling between standard single-mode fiber (SMF) and 1.5-¿m-thick silicon waveguides. This mode converter consists of a double-stage taper fabricated using planar processing. Optical testing results show facet loss of approximately -1.5 dB/facet, for TE and TM polarizations across a wide wavelength range.

Modeling the corneal birefringence of the eye toward the development of a polarimetric glucose sensor

Optical polarimetry for monitoring glucose concentration in the aqueous humor of the eye as a potential noninvasive means of assessing blood glucose has promise, but the realization of such an approach has been limited by noise from time-varying corneal birefringence due to motion artifact. Modeling the corneal birefringence of the eye is critically important toward understanding the overall effect of this noise source compared to other changes in the signal, and can aid in design of the polarimetric system. To this end, an eye model is introduced in this work that includes spatially varying birefringence properties of the cornea. The degree of birefringence and the fast axis orientation is calculated as a function of beam position on the anterior chamber. It is shown that the minimum change in polarization vector orientation occurs for beam position near the midpoint between the corneal apex and limbus. In addition, the relative wavelength independence of motion artifact is shown in the same region. The direct consequence of these findings are that a multiwavelength polarimetric system can potentially be utilized to eliminate the effect of time-varying corneal birefringence, and that eye coupling is optimal at the midpoint between the apex and limbus.

Fluorescence lifetime imaging and reflectance confocal microscopy for multiscale imaging of oral precancer

Abstract. Optical imaging techniques using a variety of contrast mechanisms are under evaluation for early detection of epithelial precancer; however, tradeoffs in field of view (FOV) and resolution may limit their application. Therefore, we present a multiscale multimodal optical imaging system combining macroscopic biochemical imaging of fluorescence lifetime imaging (FLIM) with subcellular morphologic imaging of reflectance confocal microscopy (RCM). The FLIM module images a 16×16  mm2 tissue area with 62.5 μm lateral and 320 ps temporal resolution to guide cellular imaging of suspicious regions. Subsequently, coregistered RCM images are acquired at 7 Hz with 400 μm diameter FOV, <1  μm lateral and 3.5 μm axial resolution. FLIM-RCM imaging was performed on a tissue phantom, normal porcine buccal mucosa, and a hamster cheek pouch model of oral carcinogenesis. While FLIM is sensitive to biochemical and macroscopic architectural changes in tissue, RCM provides images of cell nuclear morphology, all key indicators of precancer progression.

Flexible endoscope for continuous in vivo multispectral fluorescence lifetime imaging

Fluorescence lifetime imaging (FLIM) offers a noninvasive approach for characterizing the biochemical composition of biological tissue. There has been an increasing interest in the application of multispectral FLIM for medical diagnosis. Central to the clinical translation of FLIM technology is the development of compact and high-speed endoscopy systems. Unfortunately, the predominant multispectral FLIM approaches suffer from limitations that impede the development of endoscopy systems that are suitable for in vivo tissue imaging. We present a compact wide-field time-gated FLIM flexible endoscope capable of continuous lifetime imaging of up to three fluorescence emission bands simultaneously. This endoscope design will facilitate the evaluation of FLIM for in vivo applications.

Handheld multispectral fluorescence lifetime imaging system for in vivo applications

There is an increasing interest in the application of fluorescence lifetime imaging (FLIM) for medical diagnosis. Central to the clinical translation of FLIM technology is the development of compact and high-speed clinically compatible systems. We present a handheld probe design consisting of a small maneuverable box fitted with a rigid endoscope, capable of continuous lifetime imaging at multiple emission bands simultaneously. The system was characterized using standard fluorescent dyes. The performance was then further demonstrated by imaging a hamster cheek pouch in vivo, and oral mucosa tissue both ex vivo and in vivo, all using safe and permissible exposure levels. Such a design can greatly facilitate the evaluation of FLIM for oral cancer imaging in vivo.

Characterizing dual wavelength polarimetry through the eye for monitoring glucose

Diabetes is an insidious disease that afflicts millions of people worldwide and typically requires the person with the disease to monitor their blood sugar level via finger or forearm sticks multiple times daily. Therefore, the ability to noninvasively measure glucose would be a significant advancement for the diabetic community. The use of optically polarized light passed through the anterior chamber of the eye is one proposed noninvasive approach for glucose monitoring. However, the birefringence of the cornea and the difficulty in coupling the light across the eye have been major drawbacks toward realizing this approach. A dual wavelength optical polarimetric approach has been proposed as a means to potentially overcome the birefringence noise but has never been fully characterized. Therefore, in this paper an optical model has been developed along with experiments performed on New Zealand White rabbit eyes for characterizing the light path and corneal birefringence at two different wavelengths as they are passed through the anterior chamber of the eye. The results show that, without index matching, it is possible to couple the light in and out of the eye but only across a very limited range otherwise the light does not come back out of the eye. It was also shown that there is potential to use a dual wavelength approach to accommodate the birefringence noise of the cornea in the presence of eye motion. These results will be used to help guide the final design of the polarimetric system for use in noninvasive monitoring of glucose in vivo.

Efficient Mode Converter for Coupling between Fiber and Micrometer Size Silicon Waveguides

A low-loss polarization independent mode converter for coupling standard single mode fiber to a silicon chip is presented. For a micrometer size silicon waveguide, we demonstrate a coupling loss of 1-1.5 dB/facet.

In Vivo Glucose Monitoring Using Dual-Wavelength Polarimetry to Overcome Corneal Birefringence in the Presence of Motion

OBJECTIVE Over the past 35 years considerable research has been performed toward the investigation of noninvasive and minimally invasive glucose monitoring techniques. Optical polarimetry is one noninvasive technique that has shown promise as a means to ascertain blood glucose levels through measuring the glucose concentrations in the anterior chamber of the eye. However, one of the key limitations to the use of optical polarimetry as a means to noninvasively measure glucose levels is the presence of sample noise caused by motion-induced time-varying corneal birefringence. RESEARCH DESIGN AND METHODS In this article our group presents, for the first time, results that show dual-wavelength polarimetry can be used to accurately detect glucose concentrations in the presence of motion-induced birefringence in vivo using New Zealand White rabbits. RESULTS In total, nine animal studies (three New Zealand White rabbits across three separate days) were conducted. Using the dual-wavelength optical polarimetric approach, in vivo, an overall mean average relative difference of 4.49% (11.66 mg/dL) was achieved with 100% Zone A+B hits on a Clarke error grid, including 100% falling in Zone A. CONCLUSIONS The results indicate that dual-wavelength polarimetry can effectively be used to significantly reduce the noise due to time-varying corneal birefringence in vivo, allowing the accurate measurement of glucose concentration in the aqueous humor of the eye and correlating that with blood glucose.