Introduction

I am interested in building new medical devices for early cancer detection. These devices are based on infrared optics. They work on the principle that when we shine light (laser or other types) on a tissue or a region in the human body, it interacts in predictable and quantitatively measurable ways. We analyze the light that goes through or comes back from tissue and from these measurements we create a picture of what is going on inside the tissue. We are able to see microscopic cellular structures and construct high resolution tissue images from which it is possible to determine if the tissue has a certain disease. More information about these techniques is presented below.

Optical Coherence Tomography

Optical Coherence tomography (OCT) is a technique that makes it possible to see deep inside an object using light without cutting the object. It is one of the most promising biomedical diagnostic tools available today. It is a non-invasive tomography technique that provides three dimensional images of tissue without sectioning or puncturing with a needle. We can use OCT for non-invasive disease diagnosis in a variety of diseases including glaucoma, Barrett's esophagus, Celiac Disease, etc.

In one of my projects as a post-doc, we are developing an optical device that is in the shape and size of a Tylenol pill or capsule. This tethered capsule is swallowed by a patient, then goes down the esophagus into the stomach. As it goes through the esophagus it performs video rate imaging of the entire esophagus at a high (~15μm) resolution. Unlike current endoscopies, it not only provides images of the surface of the esophagus, but also from deep inside the tissue. This is a central aspect of OCT. The entire procedure takes 2 to 3 minutes and does not require sedation or anesthesia. Data is processed in real time and can be seen by the doctor immediately. The doctor can examine the data and ask the patients relevant questions straightaway so as to narrow down the potential disease possibilities and arrive at more reliable conclusions.

In the diagnosis of celiac disease for example, the current standard of care is to sedate the patient, insert a needle-based device and collect small pieces of tissue from several points in the esophagus. The tissue is frozen, sliced, stained chemically and observed under a microscope. The diagnosis process takes several days to weeks. In contrast, OCT provides real time results without sedation and is significantly more reliable since we image the entire esophagus as opposed to taking samples at a small number of point (quasi "random" sampling). Such techniques are likely to improve patient care dramatically in the future.

Mid-Infrared Spectroscopic Imaging

Fundamental molecular vibrational modes of organic molecules occur in the mid-infrared region of the electromagnetic spectrum. These vibrational modes result in sharp (resonance) peaks in the mid-infrared and have been used to identify molecules in homogeneous bulk materials for more than four decades. The chemical significance of peaks in the "fingerprint region" of the mid-infrared spectrum has also been tabulated extensively in spectroscopy literature. The chemical composition of substances can be ascertained by analyzing their mid-infrared spectrum. Combining spectroscopy with microscopy has been a relatively recent development and this has resulted in spatially resolved spectroscopic information. With this innovation, it is possible to obtain an image of a chemically diverse sample and discover the chemical composition at every pixel in that image. This chemical information has been used in a variety of fields from forensics to art restoration to performing completely automated histopathology in tissue sections. In tissue, the molecular composition and chemical detail at every pixel can be mapped over the entire imaging area and tissue function can be studied.

Mid-infrared spectroscopic imaging is one of the most promising functional imaging tools available today. It is capable of chemical identification via pattern recognition and has been demonstrated to be successful in prostate, breast and colon cancer detection. Moreover, the biochemical basis for disease detection is also a byproduct of the analysis. Chemical or molecular changes often occur earlier than morphological changes detected by older microscopy techniques and can not only help understand disease, but can also provide an earlier detection. Reliable early detection is the key to solving several diseases including breast, colon and prostate cancer.

High Definition Imaging

Image quality in infrared spectroscopic imaging can be improved dramatically by an appropriate redesign of instruments. Theoretical insights obtained from modeling light propagation through the entire instrument have guided a design that has resulted in high-definition imaging wherein the important image details are now accessible. This has improved the accuracy of cancer detection using infrared spectroscopic imaging.

High resolution mid-infrared spectroscopic imaging was demonstrated recently in our paper that received recognition from various scientific communities. We presented a new way of understanding and designing infrared imaging instruments based on a modular approach that utilizes an operator formalism. This technique of instrument construction provides an intimate connection between theory and experiment. There is a direct, one-to-one correspondence between an optical component (like a lens) in an experiment and an operator in the theory. Replacing one component in an experiment is equivalent to replacing one operator and vice versa. Therefore, changes to an instrument design can be understood and analyzed easily and this rapid feedback loop between theory and experiment enables the design of significantly better instruments. We demonstrated the power of these ideas by developing a high-definition mid-infrared spectroscopic imaging instrument which provides significantly higher image detail than in current commercial instruments. The figure on the left is an example of data from such an instrument where a chemical map of tissue is obtained using our proposed instrument. This provides excellent tissue detail by the press of a button without laborious chemical stains that are normally required.

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