Manuela Roman

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.

Gen-2 Hand-Held Optical Imager towards Cancer Imaging: Reflectance and Transillumination Phantom Studies

Hand-held near-infrared (NIR) optical imagers are developed by various researchers towards non-invasive clinical breast imaging. Unlike these existing imagers that can perform only reflectance imaging, a generation-2 (Gen-2) hand-held optical imager has been recently developed to perform both reflectance and transillumination imaging. The unique forked design of the hand-held probe head(s) allows for reflectance imaging (as in ultrasound) and transillumination or compressed imaging (as in X-ray mammography). Phantom studies were performed to demonstrate two-dimensional (2D) target detection via reflectance and transillumination imaging at various target depths (1–5 cm deep) and using simultaneous multiple point illumination approach. It was observed that 0.45 cc targets were detected up to 5 cm deep during transillumination, but limited to 2.5 cm deep during reflectance imaging. Additionally, implementing appropriate data post-processing techniques along with a polynomial fitting approach, to plot 2D surface contours of the detected signal, yields distinct target detectability and localization. The ability of the gen-2 imager to perform both reflectance and transillumination imaging allows its direct comparison to ultrasound and X-ray mammography results, respectively, in future clinical breast imaging studies.

Noninvasive Surface Imaging of Breast Cancer in Humans using a Hand-held Optical Imager.

X-ray mammography, the current gold standard for breast cancer detection, has a 20% false-negative rate (cancer is undetected) and increases in younger women with denser breast tissue. Diffuse optical imaging (DOI) is a safe (nonionizing), and relatively inexpensive method for noninvasive imaging of breast cancer in human subjects (including dense breast tissues) by providing physiological information (e.g. oxy- and deoxy- hemoglobin concentration). At the Optical Imaging Laboratory, a hand-held optical imager has been developed which employs a breast contourable probe head to perform simultaneous illumination and detection of large surfaces towards near real-time imaging of human breast cancer. Gen-1 and gen-2 versions of the handheld optical imager have been developed and previously demonstrated imaging in tissue phantoms and healthy human subjects. Herein, the hand-held optical imagers are applied towards in vivo imaging of breast cancer subjects in an attempt to determine the ability of the imager to detect breast tumors. Five female human subjects (ages 51-74) diagnosed with breast cancer were imaged with the gen-1 optical imager prior to surgical intervention. One of the subjects was also imaged with the gen-2 optical imager. Both imagers use 785 nm laser diode sources and ICCD camera detectors to generate 2D surfaces maps of total hemoglobin absorption. The subjects lay in supine position and images were collected at various locations on both the ipsilateral (tumor-containing) and contralateral (non-tumor containing) breasts. The optical images (2D surface maps of optical absorption due to total hemoglobin concentration) show regions of higher intensity at the tumor location, which is indicative of increased vasculature and higher blood content due to the presence of the tumor. Additionally, a preliminary result indicates the potential to image lymphatic spread. This study demonstrates the potential of the hand-held optical devices to noninvasively image breast cancer in human subjects.

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..

Resolution of a Gen-2 handheld optical imager: diffuse and fluorescence imaging studies

A generation-2 (Gen-2) handheld optical imager capable of two-dimensional surface and three-dimensional tomographic imaging has recently been developed. Herein, the ability of the handheld imager to detect and resolve two targets under diffuse and fluorescence imaging conditions has been demonstrated via tissue phantom studies. Two-dimensional surface imaging studies demonstrated that two 0.96 cm diameter Indocyannine Green targets were detected and resolved ~0.5  cm apart (between edges) at a target depth of 1 cm during diffuse imaging and up to 2 cm depth during fluorescence imaging. Preliminary 3D tomographic imaging capability to resolve the two targets was also demonstrated, but requires extensive future studies.

Phantom and in-vivo imaging using a Gen-2 hand-held optical imager: reflectance and transmission studies

A novel Gen-2 hand-held optical imager was developed with capabilities to contour to different tissue curvatures, perform simultaneous illumination and detection and imager large tissue surfaces. Experimental studies using cubical phantoms demonstrated that the imager can detect targets up to 2.5 cm and 5 cm deep via reflectance and transmission measurements, respectively. The target was also localized as regions of high absorption during multi-scan imaging of curved breast phantoms via both reflectance and transmission modes. Preliminary in-vivo breast imaging demonstrated that the target can be detected via varying the pressure applied during imaging, as observed from reflectance-based imaging studies on healthy adults with superficially placed target(s) in the intra-mammary fold.

Resolution studies of a hand-held optical imager

A Gen-2 hand-held optical imager has been developed capable of 2D surface imaging and 3D tomography. In the current work, the capability of the imager to resolve two closely placed targets is assessed via 2D and 3D tomographic studies. Resolution studies have been carried out under various experimental conditions using slab phantoms. Preliminary 2D surface images of reflected measurements have demonstrated the ability of the system to resolve 0.95cm diameter targets placed 0.5cm apart at 2cm depth. Three dimensional tomography reconstructions are currently performed to assess the resolution capacity under different experimental conditions.

A Gen-2 Hand-Held Optical Imager: Phantom and Preliminary in-vivo Breast Imaging Studies

Diffuse optical imaging is a promising non-invasive and non-ionizing modality for breast cancer diagnosis. Hand-held optical imagers are developed toward rapid clinical translation due to their portability and patient-comfort. In our Optical Imaging Laboratory, a Gen-2 hand-held optical imager has been developed capable of two-dimensional (2D) and three-dimensional (3D) imaging, and has a flexible probe head designed to contour to different breast tissue curvatures. The optical imager is composed of an intensified charge-couple device (ICCD) based detector, and six 785nm laser diodes (connected the probe heads via optical fibers). Herein, phantom studies were performed in order to validate the target detection capabilities of the imager. Experimental studies using slab phantoms demonstrated that the imager can detect targets up to 2.5 and 5 cm deep via reflectance and transmission measurements, respectively. In addition, resolution studies have demonstrated the ability of the system to resolve two 0.95cm diameter targets, placed 0.5cm apart and at a depth of 2cm. Preliminary in-vivo breast imaging studies have been carried out on healthy human subjects. These studies have demonstrated that targets can be detected by varying the pressure applied during imaging with superficially placed target(s) in the intra-mammary fold.