Jiajia Ge

Three-dimensional fluorescence-enhanced optical tomography using a hand-held probe based imaging system

Hand-held based optical imaging systems are a recent development towards diagnostic imaging of breast cancer. To date, all the hand-held based optical imagers are used to perform only surface mapping and target localization, but are not capable of demonstrating tomographic imaging. Herein, a novel hand-held probe based optical imager is developed towards three-dimensional (3-D) optical tomography studies. The unique features of this optical imager, which primarily consists of a hand-held probe and an intensified charge coupled device detector, are its ability to; (i) image large tissue areas (5×10sq.cm) in a single scan, (ii) perform simultaneous multiple point illumination and collection, thus reducing the overall imaging time; and (iii) adapt to varying tissue curvatures, from a flexible probe head design. Experimental studies are performed in the frequency domain on large slab phantoms (∼650ml) using fluorescence target(s) under perfect uptake (1:0) contrast ratios, and varying target depths (1-2cm) and X-Y locations. The effect of implementing simultaneous over sequential multiple point illumination towards 3-D tomography is experimentally demonstrated. The feasibility of 3-D optical tomography studies has been demonstrated for the first time using a hand-held based optical imager. Preliminary fluorescence-enhanced optical tomography studies are able to reconstruct 0.45ml target(s) located at different target depths (1-2cm). However, the depth recovery was limited as the actual target depth increased, since only reflectance measurements were acquired. Extensive tomography studies are currently carried out to determine the resolution and performance limits of the imager on flat and curved phantoms.

Automated coregistered imaging using a hand-held probe-based optical imager

Near-infrared optical imaging holds a promise as a noninvasive technology toward cancer diagnostics and other tissue imaging applications. In recent years, hand-held based imagers are of great interest toward the clinical translation of the technology. However hand-held imagers developed to date are typically designed to obtain surface images and not tomography information due to lack of coregistration facilities. Herein, a recently developed hand-held probe-based optical imager in our Optical Imaging Laboratory has been implemented with novel coregistration facilities toward real-time and tomographic imaging of tissue phantoms. Continuous-wave fluorescence-enhanced optical imaging studies were performed using an intensified charge coupled device camera based imaging system in order to demonstrate the feasibility of automated coregistered imaging of flat phantom surfaces, using a flexible probe that can also contour to curvatures. Three-dimensional fluorescence tomographic reconstructions were also demonstrated using coregistered frequency-domain measurements obtained using the hand-held based optical imager. It was also observed from preliminary studies on cubical phantoms that multiple coregistered scans differentiated deeper targets (approximately 3 cm) from artifacts that were not feasible from a single coregistered scan, demonstrating the possibility of improved target depth detectability in the future.

Hand-Held Optical Devices for Breast Cancer: Spectroscopy and 3-D Tomographic Imaging

Diffuse optical imaging (DOI) is a promising noninvasive and nonionizing method for breast imaging. Several research groups have developed hand-held-based optical imaging devices which are portable and patient-comfortable toward clinical translation of the technology. The different hand-held optical devices developed to date are reviewed herein with a focus on the clinical applications. The hand-held device developed at Florida International University is unique in its ability to perform 3-D tomography using DOI alone via self-coregistration facilities. Results demonstrate the ability of the device to perform 2-D imaging and 3-D tomography in human breast tissue.

Design and development of a hand-held optical probe toward fluorescence diagnostic imaging

Near-infrared optical imaging is an emerging noninvasive technology toward breast cancer diagnosis. The optical imaging systems available to date are limited either by flexibility to image any given breast volume, patient comfort, or instrument portability. Here, a hand-held optical probe is designed and developed, 1. employing a unique measurement scheme of simultaneous multiple point illumination and collection for rapid data acquisition and minimal patient discomfort, and 2. employing a curved probe head such that it allows flexible imaging of tissue curvatures. Simulation studies are carried out on homogeneous slab phantoms (5x10x8 cc) to determine an appropriate source-detector configuration for the probe head. These design features are implemented in the development of the probe, which consisted of six simultaneous illuminating and 165 simultaneous collecting fibers, spaced 0.5 cm apart on a 5x10 sq-cm probe head. Simulation studies on 3-D slab and curved phantoms demonstrate an increase in the total area of predicted fluorescence amplitude and overall signal strength on using simultaneous multiple point sources over a single point source. The probe is designed and developed such that on coupling with a detection system in the future, the hand-held probe based imager can be clinically assessed toward cancer diagnostic imaging.

Fluorescence tomographic imaging using a handheld-probe-based optical imager: extensive phantom studies

Handheld-probe-based optical imagers are a popular approach toward breast imaging because of their potential portability and maximum patient comfort. A novel handheld-probe-based optical imager has been developed and its feasibility for three-dimensional fluorescence tomographic imaging demonstrated. Extensive tomography studies were performed on large slab phantoms (650 ml) to assess the performance limits of the handheld imager. Experiments were performed by using different target volumes (0.1-0.45 cm3), target depths (1-3 cm), and fluorescence (Indocyanine Green) absorption contrast ratios in a nonfluorescing (1:0) and constant fluorescing backgrounds (1000:1 to 5:1). The estimated sensitivity and specificity of the handheld imager are 43% and 95%, respectively.

Multi-projection fluorescence optical tomography using a handheld-probe-based optical imager: phantom studies

A handheld-probe-based optical imager has recently been developed toward three-dimensional tomography. In this study, the improvement of target depth recovery was demonstrated using a multi-projection technique on large slab phantoms using 0.45 cc fluorescing target(s) (with 1:0 contrast ratio) of 1.5 to 2.5 cm deep. Tomographic results using single- and multi- (here dual) projection measurements (with and without a priori information of target location) were compared. In all experimental cases, the use of multi-projection measurements along with a priori information recovered target depth and location closer to their true values, demonstrating its applicability for clinical translation.

Multi-projection based fluorescence optical tomography using a hand-held probe based optical imager

Hand-held based optical imagers have become a new research interest for its maximum patient comfort, less bulky instrument and potential for clinical translation towards breast cancer diagnostics. However, its ability for optical tomography is either limited by depth recovery since only reflectance measurements were obtained using a hand-held design for imaging. In this study, we introduced a self-guided multi-projection technique, which can take advantage of potential portability of hand-held probe based system, towards improvement of target depth recovery during fluorescence optical tomography studies.

Fluorescence Tomographic Imaging Using a Hand-Held Optical Imager: Extensive Phantom Studies

Hand-held probe based optical imager has become popular towards breast imaging for its potential portability and maximum patient comfort (no compression involved), but are currently limited on three-dimensional (3-D) tumor localization. A novel hand-held probe based optical imager with unique source and detector set-up was recently developed in our laboratory towards tomographic breast imaging. With 3-D fluorescence tomography feasibility of this novel optical imager demonstrated in previous studies, extensive phantom studies under various conditions were performed to assess current system limitation on 3-D tumor/target recovery. The 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 the fluorescence contrast agent. The fluorescence optical measurements acquired on phantom surface were applied towards an Approximate Extended Kalman Filter (AEKF) algorithm for 3-D mapping of fluorescence absorption coefficient over entire phantom volume. In most cases, the target was successfully reconstructed. Currently, the limitations in terms of resolution, depth, and volume recovery of the embedded target are assessed. Upon further experimental validation based on in-vitro and in-vivo studies, the clinical translation of this technology is promising.

Clinical Translation of a Novel Hand-Held Based Optical Imager: In Vitro and In Vivo Studies

Hand-held based optical imaging devices are currently developed by researchers toward clinical translation of the technology. However, the devices developed to date are limited in that they are unable to contour to different tissue curvatures, and they are not capable of coregistration which is necessary for 3D tomography. A novel hand-held based optical imager has been developed in our Optical Imaging Laboratory and tested on homogeneous tissue phantoms. The unique features of the device include (i) flexibility to contour to different tissue curvatures, (ii) simultaneous illumination for rapid data acquisition, and (iii) real-time coregistration capabilities to enable 3D tomography. Herein, studies are performed to demonstrate the ability of the hand-held device to image in vitro samples designed to better mimic the heterogeneous nature of human breast tissue. A fluorescent target (0.45 cc) filled with 1 μM indocyanine green (ICG) was used to represent a tumor and placed at different depths up to 2.5 cm within a 10x10x10 cm3 acrylic cube filled with minced chicken breast and 1% Liposyn. The hand-held device was used to recover the target location from 2D surface contour plots of the fluorescent signal. Parallely, preliminary in vivo studies have been carried out on normal human subjects using a simulated fluorescent target (0.45cc), where the probe was placed on the tissue surface with gentle compression. These studies demonstrate the potential for clinical translation of our hand-held based optical imager for real-time tomographic imaging.

Real-time co-registered imaging using a novel hand-held optical imager

Several hand-held based optical imaging devices have been developed towards breast imaging, which are portable, patient-comfortable, and use non-ionizing radiation. The devices developed to date are limited in that they have flat probe faces and are incapable of real-time coregistration (as needed for 3-D tomographic imaging). A hand-held based optical imager has been developed in our lab, which has unique features of (i) simultaneous over sequential source illumination, which enables rapid data acquisition, (ii) a flexible probe face, which enables it to contour to any tissue curvature, and (iii) self coregistration facilities towards 3-D tomographic imaging. Real-time coregistration is demonstrated using the imager via fluorescence-enhanced studies in the continuous-wave mode, performed on slab phantoms (filled with 1% Liposyn solution) and in vitro samples (chicken breast). Additionally, preliminary studies were conducted using curved phantoms. In all cases, a 0.45-cc target filled with 1 μM Indocyanine green was used to represent a tumor. Real-time 2-D surface images of the phantom were obtained via multiple scans at different target depths. Preliminary surface imaging studies demonstrated that the summation of multiple scans distinctly differentiated the target from artifacts (up to 3 cm deep), which was not possible from individual scans.