Steven Regalado

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.

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.

Fluorescence-enhanced imaging using a novel hand-held based optical imager: phantom studies

Near-infrared (NIR) optical imaging is an emerging noninvasive modality for breast cancer diagnosis. The currently available optical imaging systems towards tomography studies are limited either by instrument portability, patient comfort, or flexibility to image any given tissue volume. Hence, a novel hand-held probe based gain modulated intensified CCD camera imaging system is developed such that it can possibly overcome some of the above limitations. The unique features of this hand-held probe based optical imaging system are: (i) to perform simultaneous multiple point illumination and detection, thus decreasing the total imaging time and improving overall signal strength; (ii) to adapt to the tissue contours, thus decreasing the light leakage at contact surface; and (iii) to obtain trans-illumination measurements apart from reflectance measurements, thus improving the depth information. Phantom studies are performed to demonstrate the feasibility of performing fluorescence optical imaging under different target depths using cubical phantoms (10×6.5×10 cc). The effect of simultaneous multiple point illumination over sequential single point illumination is demonstrated from experimental phantom studies.

A hand-held probe-based optical imager with self co-registration facilities

A novel hand-held probe-based optical imager with self co-registration facilities is developed towards breast cancer diagnosis. Initial experimental studies on slab tissue phantoms have demonstrated the feasibility of co-registered measurements towards future tomography studies.

Hand-held probe based optical imaging system towards breast cancer diagnosis

Near-infrared (NIR) optical imaging is an emerging noninvasive modality for breast cancer diagnosis. However, the currently available optical imaging systems towards tomography studies are limited either by instrument portability, patient comfort, or flexibility to image any given tissue volume. Herein, a hand-held based optical imaging system is developed such that it can possibly overcome some of the above limitations. The unique features of the hand-held optical probe are: (i) to perform simultaneous multiple point illumination and detection, thus decreasing the total imaging time and improving the overall signal strength; (ii) to adapt to the contour of tissue surface, thus decreasing the leakage of excitation and emission signal at contact surface; and (iii) to obtain trans-illumination measurements apart from reflectance measurements, thus improving the depth information. The increased detected signal strength as well as total interrogated tissue volume is demonstrated by simulation studies (i.e. forward model) over a 5×10×10 cc slab phantom. The appropriate number and layout of the source and detection points on the probe head is determined and the hand-held optical probe is developed. A frequency-domain ICCD (intensified charge coupled device) detection system, which allows simultaneous multiple points detection, is developed and coupled to the hand-held probe in order to perform fluorescence-enhanced optical imaging of tissue phantoms. In the future, imaging of homogenous liquid phantoms will be used for the assessment of this hand-held system, followed by extensive imaging studies on different phantoms types under various experimental conditions.

SU‐DD‐A4‐02: A Novel Optical Imager Towards Breast Cancer Diagnosis

Purpose: To design and develop a portable optical imager for early‐stage breast cancer diagnostics, providing great depth information, enhanced data acquisition rates, and minimal patient discomfort. Method and Materials: A unique measurement geometry of simultaneous multiple point source illumination was implemented in the design and development of the hand‐held based optical probe. Simultaneous multiple point detection was carried out using an intensified charge‐coupled camera (ICCD) that can be operated in the continuous wave and frequency domain measurement approaches. The hand‐held based imaging probe has been coupled to the ICCD detection system and the performance characteristics (in terms of measurement accuracy and precision) of the imager is characterized through initial phantom studies under homogeneous conditions. Results: Preliminary simulated studies using simultaneous multiple point illuminationmeasurement geometry over the universally used single point illumination geometry demonstrated an increase in the detected signal strength as well as total interrogated tissue volumes. An optimal number of source and detector fibers used to develop the probe head, minimized the dead volume and improved the data acquisition times. Conclusion: A novel fluorescence‐enhanced imagingsystem was developed using a hand‐held probe and an ICCD camera, enabling the flexible and rapid imaging of any given tissue volume. Further work involves phantom based experimental studies towards 3D optical imaging and tomographic analysis. The final goal is to translate the current laboratory‐based techniques into routine clinical use.