Sarah J. Erickson

Hand-held based near-infrared optical imaging devices: A review

Near-infrared (NIR) optical imaging is a non-invasive and non-ionizing modality that is emerging as a diagnostic/prognostic tool for breast cancer and other applications related to functional brain mapping. In recent years, hand-held based optical imaging devices are developed for clinical translation of the technology, as opposed to the various bulky optical imagers available. Herein, we review the different hand-held based NIR devices developed to date, in terms of the measurement techniques implemented (continuous wave, time or frequency-domain), the imaging methods used, and the specific applications towards which they were applied. The advantages and disadvantages of the different hand-held optical devices are described and also compared with respect to a novel hand-held based device currently developed in our Optical Imaging Laboratory towards three-dimensional tomography studies.

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.

Hand-held optical imager (Gen-2): improved instrumentation and target detectability

Hand-held optical imagers are developed by various researchers towards reflectance-based spectroscopic imaging of breast cancer. Recently, a Gen-1 handheld optical imager was developed with capabilities to perform two-dimensional (2-D) spectroscopic as well as three-dimensional (3-D) tomographic imaging studies. However, the imager was bulky with poor surface contact (~30%) along curved tissues, and limited sensitivity to detect targets consistently. Herein, a Gen-2 hand-held optical imager that overcame the above limitations of the Gen-1 imager has been developed and the instrumentation described. The Gen-2 hand-held imager is less bulky, portable, and has improved surface contact (~86%) on curved tissues. Additionally, the forked probe head design is capable of simultaneous bilateral reflectance imaging of both breast tissues, and also transillumination imaging of a single breast tissue. Experimental studies were performed on tissue phantoms to demonstrate the improved sensitivity in detecting targets using the Gen-2 imager. The improved instrumentation of the Gen-2 imager allowed detection of targets independent of their location with respect to the illumination points, unlike in Gen-1 imager. The developed imager has potential for future clinical breast imaging with enhanced sensitivity, via both reflectance and transillumination imaging.

Three-dimensional fluorescence tomography of human breast tissues in vivo using a hand-held optical imager.

Diffuse optical imaging using non-ionizing radiation is a non-invasive method that shows promise towards breast cancer diagnosis. Hand-held optical imagers show potential for clinical translation of the technology, yet they have not been used towards 3D tomography. Herein, 3D tomography of human breast tissue in vivo is demonstrated for the first time using a hand-held optical imager with automated coregistration facilities. Simulation studies are performed on breast geometries to demonstrate the feasibility of 3D tomographic imaging using a hand-held imager under perfect (1:0) and imperfect (100:1, 50:1) fluorescence absorption contrast ratios. Experimental studies are performed in vivo using a 1 µM ICG filled phantom target placed non-invasively underneath the flap of the breast tissue. Results show the ability to perform automated tracking and coregistered imaging of human breast tissue (with tracking accuracy on the order of ∼1 cm). Three-dimensional tomography results demonstrated the ability to recover a single target placed at a depth of 2.5 cm, from both the simulated (at 1:0, 100:1 and 50:1 contrasts) and experimental cases on actual breast tissues. Ongoing efforts to improve target depth recovery are carried out via implementation of transmittance imaging in the hand-held imager.

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.

Improved detection limits using a hand-held optical imager with coregistration capabilities

Optical imaging is emerging as a non-invasive and non-ionizing method for breast cancer diagnosis. A hand-held optical imager has been developed with coregistration facilities towards flexible imaging of different tissue volumes and curvatures in near real-time. Herein, fluorescence-enhanced optical imaging experiments are performed to demonstrate deeper target detection under perfect and imperfect (100:1) uptake conditions in (liquid) tissue phantoms and in vitro. Upon summation of multiple scans (fluorescence intensity images), fluorescent targets are detected at greater depths than from single scan alone.

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.

Non-contact Deep Tissue Imaging using a Hand-Held Near-infrared OpticalScanner

Fiber-free non-contact near-infrared (NIR) imaging devices using wide-field detectors are emerging apart from the contact and fiber-based NIR devices. Unlike the fiber-based devices that can image deep tissues, the fiber-free noncontact devices have been used only for subsurface imaging (≤1 cm) to date. A new compact (7 × 8 × 12 cm3) handheld Near-Infrared. Optical Scanner (NIROS) has been developed for fiber-free non-contact imaging of deep tissues in both reflectance and transmittance modes. Absorption-contrasted diffuse imaging studies were performed on tissue mimicking cubical phantoms (5.5 × 5.5 × 5.5 cm3 volume) using India. Ink based targets located at various depths (0.5 to 4 cm) in both reflectance and transmittance modes. Preliminary in vivo breast imaging studies in transmittance mode were also performed to determine the deep target detectability of NIROS. The hand-held NIROS could detect targets up to 1.5 cm in reflectance mode and across the entire depth of the phantom (4 cm deep) in transmittance mode, as observed from phantom studies. Absorption-contrasted targets placed as deep as 6 cm were detectable in vivo breast tissues during transmittance imaging, when comfortable pressure was applied via compression. The non-contact hand-held NIROS demonstrated the ability to detect targets deeper than 1 cm (which was the limit attempted to date using other non-contact NIR devices in phantoms or in vivo). The ability of the portable handheld NIROS to perform deep tissue imaging can allow for in vivo breast imaging studies in the future, with a potential as an initial assessment tool for breast cancer pre-screening.

Portable wide-field hand-held NIR scanner

Near-infrared (NIR) optical imaging modality is one of the widely used medical imaging techniques for breast cancer imaging, functional brain mapping, and many other applications. However, conventional NIR imaging systems are bulky and expensive, thereby limiting their accelerated clinical translation. Herein a new compact (6 × 7 × 12 cm3), cost-effective, and wide-field NIR scanner has been developed towards contact as well as no-contact based real-time imaging in both reflectance and transmission mode. The scanner mainly consists of an NIR source light (between 700- 900 nm), an NIR sensitive CCD camera, and a custom-developed image acquisition and processing software to image an area of 12 cm2. Phantom experiments have been conducted to estimate the feasibility of diffuse optical imaging by using Indian-Ink as absorption-based contrast agents. As a result, the developed NIR system measured the light intensity change in absorption-contrasted target up to 4 cm depth under transillumination mode. Preliminary in-vivo studies demonstrated the feasibility of real-time monitoring of blood flow changes. Currently, extensive in-vivo studies are carried out using the ultra-portable NIR scanner in order to assess the potential of the imager towards breast imaging..