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.

An integrated functional mapping and source localization platform for brain research

The premise of this dissertation is to create a highly integrated platform that combines the most current recording technologies for brain research through the development of new algorithms for three-dimensional (3D) functional mapping and 3D source localization. The recording modalities that were integrated include: Electroencephalography (EEG), Optical Topographic Maps (OTM), Magnetic Resonance Imaging (MRI), and Diffusion Tensor Imaging (DTI). This work can be divided into two parts: The first part involves the integration of OTM with MRI, where the topographic maps are mapped to both the skull and cortical surface of the brain. This integration process is made possible through the development of new algorithms that determine the probes location on the MRI head model and warping the 2D topographic maps onto the 3D MRI head/brain model. Dynamic changes of the brain activation can be visualized on the MRI head model through a graphical user interface. The second part of this research involves augmenting a fiber tracking system, by adding the ability to integrate the source localization results generated by commercial software named Curry. This task involved registering the EEG electrodes and the dipole results to the MRI data. Such Integration will allow the visualization of fiber tracts, along with the source of the EEG, in a 3D transparent brain structure. The research findings of this dissertation were tested and validated through the participation of patients from Miami Children Hospital (MCH). Such an integrated platform presented to the medical professionals in the form of a user-friendly graphical interface is viewed as a major contribution of this dissertation. It should be emphasized that there are two main aspects to this research endeavor: (1) if a dipole could be situated in time at its different positions, its trajectory may reveal additional information on the extent and nature of the brain malfunction; (2) situating such a dipole trajectory with respect to the fiber tracks could ensure the preservation of these fiber tracks (axons) during surgical interventions, preserving as a consequence these parts of the brain that are responsible for information transmission.