Significance: Optical coherence tomography (OCT) is widely used as a potential diagnostic tool for a variety of diseases including various types of cancer. However, sensitivity and specificity analyses of OCT in different cancers yield results varying from 11% to 100%. Hence, there is a need for more detailed statistical analysis of blinded reader studies.
Aim: Extensive statistical analysis is performed on results from a blinded study involving OCT of breast tumor margins to assess the impact of reader variability on sensitivity and specificity.
Approach: Five readers with varying levels of experience reading OCT images assessed 50 OCT images of breast tumor margins collected using an intraoperative OCT system. Statistical modeling and analysis was performed using the R language to analyze reader experience and variability.
Results: Statistical analysis showed that the readers’ prior experience with OCT images was directly related to the probability of the readers’ assessment agreeing with histology. Additionally, results from readers with prior experience specific to OCT in breast cancer had a higher probability of agreement with histology compared to readers with experience with OCT in other (noncancer) diseases.
Conclusions: The results from this study demonstrate the potential impact of reader training and experience in the assessment of sensitivity and specificity. They also demonstrate even greater potential improvement in diagnostic performance by combining results from multiple readers. These preliminary findings suggest valuable directions for further study.
Breast-conserving surgery is a frequent option for women with stage I and II breast cancer, and with radiation treatment,
can be as effective as a mastectomy. However, adequate margin detection remains a challenge, and too often additional
surgeries are required. Optical coherence tomography (OCT) provides a potential method for real-time, high-resolution
imaging of breast tissue during surgery. Intra-operative OCT imaging of excised breast tissues has been previously
demonstrated by several groups. In this study, a novel handheld surgical probe-based OCT system is introduced, which
was used by the surgeon to image in vivo, within the tumor cavity, and immediately following tumor removal in order to
detect the presence of any remaining cancer. Following resection, study investigators imaged the excised tissue with the
same probe for comparison. We present OCT images obtained from over 15 patients during lumpectomy and
mastectomy surgeries. Images were compared to post-operative histopathology for diagnosis. OCT images with micron
scale resolution show areas of heterogeneity and disorganized features indicative of malignancy, compared to more
uniform regions of normal tissue. Video-rate acquisition shows the inside of the tumor cavity as the surgeon sweeps the
probe along the walls of the surgical cavity. This demonstrates the potential of OCT for real-time assessment of surgical
tumor margins and for reducing the unacceptably high re-operation rate for breast cancer patients.
KEYWORDS: 3D acquisition, Imaging systems, Tomography, Luminescence, Signal detection, Sensors, Target detection, 3D metrology, Image resolution, 3D image processing
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 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.
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..
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.
Hand-held optical imaging devices are currently developed by several research groups as a noninvasive and non-ionizing
method towards clinical imaging of breast cancer. The devices developed to date are typically utilized towards
spectroscopic imaging via reflectance-based measurements. Additionally, a couple of devices have been used to perform
3D tomography with the addition of a second modality (e.g. ultrasound). A hand-held optical device that is unique in its
ability to perform rapid 2D imaging and 3D tomography (without the use of a second modality) has been developed in
our Optical Imaging laboratory. Herein, diffuse optical imaging studies are performed in breast cancer subjects. For
these studies, the subject lay in a recliner chair and both breast tissues were imaged with the hand-held optical device
which uses 785 nm laser source and an intensified CCD camera-based detector. Preliminary results demonstrate the
ability to image invasive ductal carcinoma and lymphatic spread, as compared to the patient's medical records (e.g. xray,
ultrasound, MRI). Multiple imaging studies with a subject undergoing chemotherapy demonstrated the potential to
monitor response to treatment. Currently, studies are carried out to tomographically determine the 3D location of the
tumor(s) in breast cancer subjects using the hand-held optical device.
KEYWORDS: Tissue optics, Breast, Tissues, 3D image processing, 3D acquisition, Tomography, Imaging systems, In vivo imaging, Optical tomography, Human subjects
Hand-held optical imagers are currently developed toward clinical imaging of breast tissue. However, the hand-held
optical devices developed to are not able to coregister the image to the tissue geometry for 3D tomography. We have
developed a hand-held optical imager which has demonstrated automated coregistered imaging and 3D tomography in
phantoms, and validated coregistered imaging in normal human subjects. Herein, automated coregistered imaging is
performed in a normal human subject with a 0.45 cm3 spherical target filled with 1 μM indocyanine green (fluorescent
contrast agent) placed superficially underneath the flap of the breast tissue. The coregistered image data is used in an
approximate extended Kalman filter (AEKF) based reconstruction algorithm to recover the 3D location of the target
within the breast tissue geometry. The results demonstrate the feasibility of performing 3D tomographic imaging and
recovering a fluorescent target in breast tissue of a human subject for the first time using a hand-held based optical
imager. The significance of this work is toward clinical imaging of breast tissue for cancer diagnostics and therapy
monitoring.
KEYWORDS: Tissues, In vitro testing, Breast, In vivo imaging, Target detection, 3D image processing, Imaging systems, Tomography, Luminescence, Natural surfaces
A hand-held optical imaging device has been developed in our laboratory towards fast 2D imaging and 3D tomography
for breast cancer diagnosis. The device has the unique abilities: (1) to contour to different tissue curvatures using a
flexible probe face; (2) perform fast 2D imaging by employing simultaneous over sequential source illumination; and
(3) self coregistration towards (future) 3D tomography. The objective of the current work is to demonstrate fast
coregistered 2D imaging on breast tissue of healthy female subjects. Fluorescence imaging experiments are performed
in vitro and in vivo to demonstrate coregistered imaging as well as the ability to detect deep targets from multiple surface
scans. A 0.45 cc spherical target filled with 1 μM indocyanine green is embedded at various depths of a cubical phantom
filled with chicken breast (in vitro models). For in vivo studies, the fluorescent target is placed under the flap of the
breast tissue to represent a tumor for fluorescence imaging. Multiple scans (fast continuous-wave images of
fluorescence intensity) are collected and coregistered at different locations on the breast tissue. This study demonstrates
the potential of the hand-held optical device towards future in vivo surface imaging and tomographic imaging for 3D
tumor localization.
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.
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.
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