Fluorescence-enhanced optical imaging on three-dimensional phantoms using a hand-held probe based frequency-domain intensified charge coupled device (ICCD) optical imager

Fluorescence-enhanced optical imaging is an emerging non-invasive and non-ionizing modality towards breast cancer diagnosis. Various optical imaging systems are currently available, although most of them are limited by bulky instrumentation, or their inability to flexibly image different tissue volumes and shapes. Hand-held based optical imaging systems are a recent development for its improved portability, but are currently limited only to surface mapping. Herein, a novel optical imager, consisting primarily of a hand-held probe and a gain-modulated intensified charge coupled device (ICCD) detector, is developed towards both surface and tomographic breast imaging. The unique features of this hand-held probe based optical imager are its ability to; (i) image large tissue areas (5×10 sq. cm) in a single scan, (ii) reduce overall imaging time using a unique measurement geometry, and (iii) perform tomographic imaging for tumor three-dimensional (3-D) localization. Frequency-domain based experimental phantom studies have been performed on slab geometries (650 ml) under different target depths (1-2.5 cm), target volumes (0.45, 0.23 and 0.10 cc), fluorescence absorption contrast ratios (1:0, 1000:1 to 5:1), and number of targets (up to 3), using Indocyanine Green (ICG) as fluorescence contrast agents. An approximate extended Kalman filter based inverse algorithm has been adapted towards 3-D tomographic reconstructions. Single fluorescence target(s) was reconstructed when located: (i) up to 2.5 cm deep (at 1:0 contrast ratio) and 1.5 cm deep (up to 10:1 contrast ratio) for 0.45 cc-target; and (ii) 1.5 cm deep for target as small as 0.10 cc at 1:0 contrast ratio. In the case of multiple targets, two targets as close as 0.7 cm were tomographically resolved when located 1.5 cm deep. It was observed that performing multi-projection (here dual) based tomographic imaging using a priori target information from surface images, improved the target depth recovery over using single projection based imaging. From a total of 98 experimental phantom studies, the sensitivity and specificity of the imager was estimated as 81-86% and 43-50%, respectively. With 3-D tomographic imaging successfully demonstrated for the first time using a hand-held based optical imager, the clinical translation of this technology is promising upon further experimental validation from in-vitro and in-vivo studies.

Nonlinear optical effects manifested by electromagnetic induced transparency in cold atoms

This dissertation reports experimental studies of nonlinear optical effects manifested by electromagnetically induced transparency (EIT) in cold Rb atoms. The cold Rb atoms are confined in a magneto-optic trap (MOT) obtained with the standard laser cooling and trapping technique. Because of the near zero Doppler shift and a high phase density, the cold Rb sample is well suited for studies of atomic coherence and interference and related applications, and the experiments can be compared quantitatively with theoretical calculations. It is shown that with EIT induced in the multi-level Rb system by laser fields, the linear absorption is suppressed and the nonlinear susceptibility is enhanced, which enables studies of nonlinear optics in the cold atoms with slow photons and at low light intensities. Three independent experiments are described and the experimental results are presented. First, an experimental method that can produce simultaneously co-propagating slow and fast light pulses is discussed and the experimental demonstration is reported. Second, it is shown that in a three-level Rb system coupled by multi-color laser fields, the multi-channel two-photon Raman transitions can be manipulated by the relative phase and frequency of a control laser field. Third, a scheme for all-optical switching near single photon levels is developed. The scheme is based on the phase-dependent multi-photon interference in a coherently coupled four-level system. The phase dependent multi-photon interference is observed and switching of a single light pulse by a control pulse containing ∼20 photons is demonstrated. These experimental studies reveal new phenomena manifested by quantum coherence and interference in cold atoms, contribute to the advancement of fundamental quantum optics and nonlinear optics at ultra-low light intensities, and may lead to the development of new techniques to control quantum states of atoms and photons, which will be useful for applications in quantum measurements and quantum photonic devices.