Application of gain-modulated image intensifier in biomedical imaging

In recent years, the incorporation of image intensifiers into charge-coupled-device (CCD) devices has resulted in intensified CCD (ICCD) systems, which possess high sensitivity in low light conditions, as well as high temporal resolution. Such ICCD systems are typically used in fluorescence applications such as fluorescence lifetime imaging (FLI), but seldom used in the context of diffuse optical tomography (DOT). Thus, this project is focused towards developing novel experimental methods and instrumentation for both DOT and FLI systems, especially with the incorporation of image intensifiers. Diffuse optical tomography (DOT) is a promising, non-invasive biomedical imaging technique that is especially suitable for imaging of the breast, brain, muscle and joints. DOT makes use of transmission measurements for various source-detector pairs on the sample surface, which can be used to reconstruct a 3D spatial distribution of optical properties within the sample, namely absorption and scattering coefficients. Since accurate determination of both absorption and scattering properties in homogeneous diffuse medium is critical in DOT applications, we came up with a new experimental technique to measure both absorption and reduced scattering coefficients (μa and μs′) in transmission geometry, based on a homodyne approach using a RF-modulated laser source and a gain-modulated image intensifier. In addition, we also explored similar setups for xi DOT image reconstruction, in various domains and geometries, and presented the corresponding experimental procedures and image reconstruction results. On the other hand, fluorescence lifetime imaging (FLI) is a powerful imaging technique which can provide valuable information about the molecular microenvironment of a fluorophore within a medium. More specifically, it is sensitive to local pH changes and the presence of quenchers such as oxygen and ions, which can be potentially useful for diagnosis and monitoring of diseases. Frequency-domain systems have significant advantages over time-domain systems in terms of cost savings and simpler instrumentation. Thus, in this report, we presented our own frequency-domain experimental setup and procedures, and conducted a preliminary study on fluorescence dyes for system validation. This provides an initial insight into the design of FLI experiments using the image intensifier, as well as paves the way for future work involving frequency-domain FLI systems.DOCTOR OF PHILOSOPHY (SCBE