Jean Gonzalez

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.

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.

Motor response investigation in individuals with cerebral palsy using near infrared spectroscopy: pilot study

Cerebral palsy (CP) describes a group of motor impairment syndromes secondary to genetic that may be due to acquired disorders of the developing brain. In this study, near infrared spectroscopy (NIRS) is used to investigate the prefrontal cortical activation and lateralization in response to the planning and execution of motor skills in controls and individuals with CP. The prefrontal cortex, which plays a dominant role in the planning and execution of motor skill stimulus, is noninvasively imaged using a continuous wave-based NIRS system. During the study, 7 controls (4 right-handed and 3 left-handed) and 2 individuals with CP (1 right-handed and 1 left-handed) over 18 years of age performed 30 s of a ball throwing task followed by 30 s rest in a 5-block paradigm. The optical signal acquired from the NIRS system was processed to elucidate the activation and lateralization in the prefrontal region of controls and individuals with CP. The preliminary result indicated a difference in activation between the task and rest conditions in all the participant types. Bilateral dominance was observed in the prefrontal cortex of controls in response to planning and execution of motor skill tasks, while an ipsilateral dominance was observed in individuals with CP. In conjunction, similar contralateral dominance was observed during rest periods, both in controls and individuals with CP.

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.

Anatomical co-registration using spatio-temporal features of a non-contact near-infrared optical scanner

Non-contact based near-infrared (NIR) optical imaging devices are developed for non-invasive imaging of deep tissues in various clinical applications. Most of these devices focus on obtaining the spatial information for anatomical co-registration of blood vessels as in sub-surface vein localization applications. In the current study, the anatomical co-registration of blood vessels based on spatio-temporal features was performed using NIR optical imaging without the use of external contrast agents. A 710 nm LED source and a compact CCD camera system were employed during simple cuff (0 to 60 mmHg) experiment in order to acquire the dynamic NIR data from the dorsum of a hand. The spatio-temporal features of dynamic NIR data were extracted from the cuff experimental study to localize vessel according to blood dynamics. The blood vessels shape is currently reconstructed from the dynamic data based on spatio-temporal features. Demonstrating the spatio-temporal feature of blood dynamic imaging using a portable non-contact NIR imaging device without external contrast agents is significant for applications such as peripheral vascular diseases.

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.

Simultaneous NIRS and kinematics study of planning and execution of motor skill task: towards cerebral palsy rehabilitation

Cerebral palsy (CP) is a term that describes a group of motor impairment syndromes secondary to genetic and/or acquired disorders of the developing brain. In the current study, NIRS and motion capture were used simultaneously to correlate the brain’s planning and execution activity during and with arm movement in healthy individual. The prefrontal region of the brain is non-invasively imaged using a custom built continuous-wave based near infrared spectroscopy (NIRS) system. The kinematics of the arm movement during the studies is recorded using an infrared based motion capture system, Qualisys. During the study, the subjects (over 18 years) performed 30 sec of arm movement followed by 30 sec rest for 5 times, both with their dominant and non-dominant arm. The optical signal acquired from NIRS system was processed to elucidate the activation and lateralization in the prefrontal region of participants. The preliminary results show difference, in terms of change in optical response, between task and rest in healthy adults. Currently simultaneous NIRS imaging and kinematics data are acquired in healthy individual and individual with CP in order to correlate brain activity to arm movement in real-time. The study has significant implication in elucidating the evolution in the functional activity of the brain as the physical movement of the arm evolves using NIRS. Hence the study has potential in augmenting the designing of training and hence rehabilitation regime for individuals with CP via kinematic monitoring and imaging brain activity.

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.