Clinical translation of a hand-held optical imager for breast cancer diagnostics: In vitro and in vivo tomography studies

Optical imaging is an emerging technology towards non-invasive breast cancer diagnostics. In recent years, portable and patient comfortable hand-held optical imagers are developed towards two-dimensional (2D) tumor detections. However, these imagers are not capable of three-dimensional (3D) tomography because they cannot register the positional information of the hand-held probe onto the imaged tissue. A hand-held optical imager has been developed in our Optical Imaging Laboratory with 3D tomography capabilities, as demonstrated from tissue phantom studies. The overall goal of my dissertation is towards the translation of our imager to the clinical setting for 3D tomographic imaging in human breast tissues. A systematic experimental approach was designed and executed as follows: (i) fast 2D imaging, (ii) coregistered imaging, and (iii) 3D tomographic imaging studies. (i) Fast 2D imaging was initially demonstrated in tissue phantoms (1% Liposyn solution) and in vitro (minced chicken breast and 1% Liposyn). A 0.45 cm3 fluorescent target at 1:0 contrast ratio was detectable up to 2.5 cm deep. Fast 2D imaging experiments performed in vivo with healthy female subjects also detected a 0.45 cm3 fluorescent target superficially placed ∼2.5 cm under the breast tissue. (ii) Coregistered imaging was automated and validated in phantoms with ∼0.19 cm error in the probe’s positional information. Coregistration also improved the target depth detection to 3.5 cm, from multi-location imaging approach. Coregistered imaging was further validated in-vivo , although the error in probe’s positional information increased to ∼0.9 cm (subject to soft tissue deformation and movement). (iii) Three-dimensional tomography studies were successfully demonstrated in vitro using 0.45 cm3 fluorescence targets. The feasibility of 3D tomography was demonstrated for the first time in breast tissues using the hand-held optical imager, wherein a 0.45 cm3 fluorescent target (superficially placed) was recovered along with artifacts. Diffuse optical imaging studies were performed in two breast cancer patients with invasive ductal carcinoma. The images showed greater absorption at the tumor cites (as observed from x-ray mammography, ultrasound, and/or MRI). In summary, my dissertation demonstrated the potential of a hand-held optical imager towards 2D breast tumor detection and 3D breast tomography, holding a promise for extensive clinical translational efforts.

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.