Breast-conserving surgery (BCS) for treatment of breast cancer requires complete removal of the tumor. 20-30% of patients undergoing BCS require multiple surgeries due to cancer at or near the boundary (margin) of the excised tissue as assessed by postoperative histopathology. Intraoperative detection of involved margins could significantly reduce the number of patients requiring repeat surgeries. We built and deployed a portable optical coherence elastography system capable of rapid, 3D imaging of whole margins (46x46 mm) of excised breast specimens (wide local excisions, WLEs) removed during BCS. The system produces images of the microstructure and stiffness of the tissue using a phase-sensitive, compression-based elastography approach. The goal of this study was to determine the diagnostic accuracy (sensitivity and specificity), using this system, of OCT versus OCT plus micro-elastography for detecting cancer within 0.75 mm of the margin of the excised tissue. >70 women undergoing BCS were enrolled in the study. We scanned two margins from each fresh, intact surgical specimen within 2 hours of excision. We selected 10x10x0.75mm regions of interest (ROIs) from each margin scanned that are representative of the makeup of breast tissue. Post-operative histology, co-registered with the scans, was used as a gold standard, and a pathologist determined the tissue types present within each ROI based on corresponding histology. Recruitment for the study is complete, and a blinded reader analysis of one ROI from each margin is being performed by two surgeons, a pathologist, a radiologist, and an engineer. Results for sensitivity and specificity will be presented.
Probing the mechanical properties of skin at high resolution could aid in the assessment of skin pathologies by, for example, detecting the extent of cancerous skin lesions and assessing pathology in burn scars. Here, we present two elastography techniques based on optical coherence tomography (OCT) to probe the local mechanical properties of skin. The first technique, optical palpation, is a high-resolution tactile imaging technique, which uses a complaint silicone layer positioned on the tissue surface to measure spatially-resolved stress imparted by compressive loading. We assess the performance of optical palpation, using a handheld imaging probe on a skin-mimicking phantom, and demonstrate its use on human skin. The second technique is a strain imaging technique, phase-sensitive compression OCE that maps depth-resolved mechanical variations within skin. We show preliminary results of in vivo phase-sensitive compression OCE on a human skin lesion.
We demonstrate the first application of the recently proposed method of optical palpation to in vivo imaging of human skin. Optical palpation is a tactile imaging technique that probes the spatial variation of a sample’s mechanical properties by producing an en face map of stress measured at the sample surface. This map is determined from the thickness of a translucent, compliant stress sensor placed between a loading element and the sample and is measured using optical coherence tomography. We assess the performance of optical palpation using a handheld imaging probe on skin-mimicking phantoms, and demonstrate its use on human skin lesions. Our results demonstrate the capacity of optical palpation to delineate the boundaries of lesions and to map the mechanical contrast between lesions and the surrounding normal skin.
Optical coherence elastography (OCE) is an emerging imaging technique that probes microscale mechanical contrast in tissues with the potential to differentiate healthy and malignant tissues. However, conventional OCE techniques are limited to imaging the first 1 to 2 mm of tissue in depth. We demonstrate, for the first time, OCE measurements deep within human tissues using needle OCE, extending the potential of OCE as a surgical guidance tool. We use needle OCE to detect tissue interfaces based on mechanical contrast in both normal and malignant breast tissues in freshly excised human mastectomy samples, as validated against histopathology. Further, we demonstrate the feasibility of in situ measurements >4 cm from the tissue surface using ultrasound guidance of the OCE needle probe. With further refinement, our method may potentially aid in accurate detection of the boundary of the tumor to help ensure full removal of all malignant tissues, which is critical to the success of breast-conserving surgery.
Optical coherence elastography (OCE) maps the mechanical properties of tissue microstructure and has potential applications in both fundamental investigations of biomechanics and clinical medicine. We report the first analysis of contrast in OCE, including evaluation of the accuracy with which OCE images (elastograms) represent mechanical properties and the sensitivity of OCE to mechanical contrast within a sample. Using phase-sensitive compression OCE, we generate elastograms of tissue-mimicking phantoms with known mechanical properties and identify limitations on contrast imposed by sample mechanics and the imaging system, including signal-processing parameters. We also generate simulated elastograms using finite element models to perform mechanical analysis in the absence of imaging system noise. In both experiments and simulations, we illustrate artifacts that degrade elastogram accuracy, depending on sample geometry, elasticity contrast between features, and surface conditions. We experimentally demonstrate sensitivity to features with elasticity contrast as small as 1.1∶1 and calculate, based on our imaging system parameters, a theoretical maximum sensitivity to elasticity contrast of 1.002∶1 . The results highlight the microstrain sensitivity of compression OCE, at a spatial resolution of tens of micrometers, suggesting its potential for the detection of minute changes in elasticity within heterogeneous tissue.
Optical coherence elastography (OCE) provides images of tissue elasticity and has potential for several clinical applications, including guidance of tumor resection. However, advancement toward clinical implementation of OCE is currently limited by the technique’s small imaging depth in tissue (1-2 mm), as well as a lack of validation of the elastic contrast generated in OCE. We have overcome the depth limitation of current OCE techniques by developing a method for performing OCE via a needle probe. Our technique, needle OCE, uses an OCT needle probe to perform axial measurements of tissue deformation during needle insertion, and has demonstrated potential for subsurface detection of the boundaries of diseased tissue. In this paper, we demonstrate how elastic contrast is generated in needle OCE by performing measurements in tissue phantoms and porcine airway wall. In addition, we have developed a finite element model of tissue deformation in compression OCE as a first step toward better understanding of the generation and interpretation of contrast in OCE images. We show initial results demonstrating excellent agreement between measured and simulated deformation in a tissue phantom.
Optical coherence elastography (OCE) is a strain imaging technique that characterizes the elastic properties of tissues
with microscopic resolution in three dimensions. In OCE, the displacement introduced to tissue by mechanical excitation
is measured using optical coherence tomography. The local strain is calculated from the spatial derivative of
displacement to generate strain images, known as elastograms. To validate elastograms, we compare them to a finite
element analysis model of sample deformation. We also present preliminary OCE measurements performed on excised
human breast tissue, and demonstrate discrimination of tissue types based on their elastic properties.
We incorporate for the first time optical coherence elastography (OCE) into a needle probe and demonstrate its ability to
provide depth-resolved information about the mechanical properties of soft tissues. This allows analysis of tissues
located much deeper than has previously been possible with other forms of OCE. OCE exploits the microscopic
resolution of optical coherence tomography (OCT) to produce high-resolution maps of tissue mechanical properties.
While OCE has potential to delineate diseased and healthy tissues (e.g., stiff tumor in soft tissue), standard techniques
are limited by the penetration depth of OCT in tissue (2-3 mm). Our OCE needle probe overcomes this limitation, as it
may be inserted deep within the body to perform measurements. We tested needle-based OCE in tissue-mimicking
phantoms and ex vivo porcine airway tissue comprising layers of varying stiffness. Results demonstrate mechanical
differentiation of tissues and identification of tissue interfaces. The proof-of-principle results presented here pave the
way for future measurements in human breast tissue that will aim to establish needle-based OCE as a viable technique
for intraoperative guidance of breast cancer surgery.
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