The value of light based technologies

The mission of the Tissue Optical Spectroscopy and Imaging Laboratory at the University of Wisconsin is to develop novel optical diagnostic tools to aid in the clinical diagnosis of cancer. Technologies based on light have the potential to revolutionize early detection for cancer. Light is safe (non-ionizing radiation) and low cost compared to existing diagnostic modalities such as mammography and magnetic resonance imaging (MRI). Light is unique in that it can unravel physiological, metabolic and structural properties of cancer by interacting with a large number of biological molecules that are already present in the tissue. Light can also be used to detect optically labeled probe molecules (antibodies, peptides, etc) that specifically bind to over expressed molecular targets in cancer cells within the tissue. Additionally, these intrinsic and extrinsic sources of optical contrast can be detected rapidly and non-destructively from human tissues in vivo . Thus, compelling reasons exist to exploit light based technologies to aid in the clinical diagnosis of cancer.

Optical detection in tissue

The basic components of an optical system include a light source, a conduit for delivery of the light to and from the tissue and an optical detector. Fiber-optic probes are most commonly used as conduits for delivery of the light to and from the tissue. Light from the source is delivered to a region of interest on the tissue surface. Light interacts with the molecules in the tissue and a fraction of it is remitted from the tissue surface and collected by the detector.

The wavelengths of light used for illumination of the tissue fall within the ultraviolet (UV), visible (VIS) and near infrared (NIR) range of the electromagnetic spectrum. Light interacts with the molecules in tissue through absorption, scattering and fluorescence. Tissue absorption and scattering can be measured using diffuse reflectance spectroscopy techniques. Fluorescence spectroscopy can be used to measure the intrinsic fluorescence, which is modulated by the tissue absorption and scattering properties. The complex interplay between absorbers, fluorophores, and scatterers present in tissue makes interpretation of the fluorescence and diffuse reflectance spectra challenging. Thus, the spectral data needs to be analyzed using appropriate models/algorithms to provide insight into the physiological, metabolic and structural information reflected by these molecules.

Sources of intrinsic optical contrast

There are a large number of absorbers and fluorophores present in tissue and their absorption and fluorescence properties are wavelength dependent.

The primary absorbers in tissue in the UV-VIS (300-700 nm) part of the electromagnetic spectrum. include hemoglobin, beta-carotene, structural proteins, electron carriers and amino acids. The structural proteins, electron carriers and amino acids exhibit fluorescence when excited at specific wavelengths in the UV-VIS. The primary absorbers in the near infrared (NIR) part of the electromagnetic spectrum. include hemoglobin, lipids and water.

The primary elastic scatterers in tissue are cellular and subcellular components including nuclei and mitochondria and the structural proteins in the extracellular matrix.

Sources of extrinsic optical contrast

A newly emerging area in the field of biomedical optics is molecular imaging. In the last few years, global analysis of gene expression by genomic and proteomic approaches has led to the discovery of new cancer-related genes, proteins and biomarkers. The conjugation of optical contrast agents with molecules that can target these specific biomarkers in cancer could dramatically increase the sensitivity and specificity of early detection. Most research efforts in the area of optical molecular imaging have focused on the use of fluorescent contrast agents (for example, cyanine dyes). Recently, nanoparticles are being explored as a new class of contrast agents to provide sensitive and specific molecular imaging of epithelial pre-cancers and cancers. These include gold and silver nanoparticles and quantum dots. These different types of contrast agents can be conjugated with antibodies and DNA probes, etc. for molecular imaging of cancer.

Penetration depth of light in tissue

The primary absorbers in soft tissues are oxygenated and deoxygenated hemoglobin. The absorbance of these two molecules decreases on average with increasing wavelength. This implies that tissues are more transparent at longer wavelengths. It has been shows that the penetration depth of light in tissue ranges from several hundred microns in the UV to several centimeters (photon migration) in the NIR wavelength range.

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