Prostate cancer represents 7% of all new cancer cases worldwide. There remain important challenges in the diagnosis and treatment of prostate cancers, particularly to increase biopsy accuracy and to enable nerve-sparing surgery. Here, we explore the capability of wide-field optical coherence tomography (OCT) and optical coherence elastography (OCE), spanning up to 45x45 mm in the lateral field of view and to depths of 1 mm, to accurately identify prostate microarchitecture. In this study, we present novel methodology to systematically validate OCT and OCE images through co-registration with standard histology on 15 human prostate specimens and demonstrate the potential for intraoperative use.
Quantitative Micro-Elastography (QME), an emerging compression optical coherence elastography technique, is used to measure the mechanical properties of tissue on the microscale. As QME requires contact between the loading plate and the sample, knowledge of the boundary conditions at the contact surface, including friction, is required to accurately calculate elasticity. In previous implementations of QME, a lubricant is applied at the contact surfaces, and it is assumed that this results in negligible friction. In this work, for the first time, we demonstrate that experimental factors including the application method and viscosity of the lubricant, as well as the mechanical contrast between the compliant layer and the sample affect friction and, therefore, the accuracy of QME. For instance, in the absence of appropriate lubrication, errors as large as 92% were observed, while the development of an optimized lubrication protocol provided accurate elasticity measurements for a wide range of samples elasticity (from 3 kPa to 130 kPa) to within 10% error.
In this work, we present the development of a compact, wireless imaging probe using a cost effective camera based optical elastography technique, stereoscopic optical palpation, towards intraoperative tumour assessment for breast cancer surgery. We demonstrate the working principle of this probe and test its capability of tumour margin assessment on freshly excised tissues. With further development, this probe holds the potential to be used as a real time cancer imaging tool that can help surgeons more effectively remove cancer during the operation, reducing the need for follow-up surgery. The probe has the potential to be used in rural and remote areas.
Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique that visualizes micro-scale tissue stiffness. Current benchtop QME shows great potential for identifying cancer in excised breast tissue (96% diagnostic accuracy), but cannot image cancer directly in the patients. We present the development of a handheld QME probe to directly image the surgical cavity in vivo during breast-conserving surgery (BCS) and a preliminary clinical demonstration. The results from 21 patients indicate that in vivo QME can identify residual cancer based on the elevated stiffness by directly imaging the surgical cavity, potentially contributing to a more complete cancer excision during BCS.
Assessing mechanical properties of tissue plays an important role in disease diagnosis and clinical examination. Here, we present a low resource and cost-effective method of using digital camera technologies to map mechanical properties of tissue, termed camera-based optical palpation. We applied this technique to breast cancer detection and burn scar assessment, validating its capability of generating high mechanical contrast between various tissue regions for clinical applications. We also implemented camera-based optical palpation in a smartphone, demonstrating its potential for telehealth applications in rural and remote areas, improving equity of access to optimal treatment for people all around the world.
Re-excision following breast-conserving surgery (BCS) due to suspected residual cancer left from the primary surgery causes substantial physical, psychological, and financial burdens for patients. This study provides a first-in-human clinical study of in vivo quantitative micro-elastography (QME) for in-cavity identification of residual cancer. A custom-built handheld QME probe is used to directly scan the surgical cavity for imaging the micro-scale tissue stiffness during BCS. In vivo QME of 21 patients, validated by co-registered histopathology of the excised specimens, demonstrates the capability to detect residual cancer based on its elevated micro-scale stiffness, potentially contributing to a more complete cancer removal.
This presentation reports a comparison between two handheld quantitative micro elastography (QME) methods: PZT actuated compression QME and manual compression QME. PZT actuated compression QME utilizes a PZT actuator to provide a periodic compression against the scanned sample, whilst manual compression QME utilizes the continuous motion of the user’s hand holding the probe to create compression against the sample. From our results, each method has its own advantages, and both methods are capable of measuring elasticity of the sample and distinguishing stiff tumor from regions of soft benign tissue on excised human breast specimens.
We propose a tilt interferometer to search for gravitational wave (GW) signals at high frequencies. The torque caused by a cross-polarized gravitational wave passing through the mirrors in an interferometer can result in a tilt motion, which generates a TEM10 transverse mode of the cavity. The GW signal can then be detected as a beating between the TEM00 and TEM10 modes. There are two types of mirror motion that are relevant: the aforementioned rotation, as well as a translation in parallel to the front surface of the end mirror, in the local reference frame of the input test masses. We estimate that possible implementations could achieve a strain sensitivity of ∼ 7 10−22 Hz−1/2 in the frequency band of 100-500 kHz, limited by thermal and shot noises. A preliminary design for a prototype detector with a 74m optical cavity is presented.
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.
Incomplete excision of cancerous tissue is a major issue in breast-conserving surgery, with up to 30% of cases requiring re-excision. In vivo quantitative micro-elastography (QME) using a hand-held probe is a promising path towards improved intraoperative margin assessment, potentially improving removal of cancerous tissue during the initial procedure. QME is an OCE technique that requires a modified 3D OCT scan in which each lateral position is acquired in two states, differing by a small compressive axial deformation. Analysis of the axial strain between the two states generates a 3D micro-elastogram that facilitates identification of cancerous tissue.
Compressive deformation is typically provided by a piezoelectric actuator. However, this approach presents significant disadvantages for hand-held scanning, most notably: the relatively large size of the actuator; high driving voltages; and the difficulty of hermetically sealing and sterilizing moving parts. Alternatively, deformation may be provided by manual compression, avoiding many of the issues associated with piezoelectric actuation. This approach has yet to be demonstrated in 3D, limiting its utility in surgical applications.
Here, we present hand-held 3D QME using a manual compression technique. Our technique requires the user to apply a steadily varying pressure to the tissue in order to generate 3D micro-elastograms. We describe the signal processing developed to enable this approach and present results from both structured phantoms and freshly excised human breast tissue, validated by histology. Furthermore, we analyze repeatability by presenting results from multiple users and benchmark our technique against the piezoelectric-actuated approach.
Approximately a quarter of patients undergoing breast conserving surgery will need further surgery as close or involved surgical margins suggest they may have residual tumour in the breast. Handheld imaging probes capable of scanning the surgical cavity during the surgery have the potential to improve intraoperative assessment of surgical margins in breast conserving surgery thus allow real time assessment of completeness of tumour excision. In this paper, we present a handheld optical coherence elastography (OCE) probe, allowing us to acquire a 3D quantitative elastogram of a 6×6×1.5 mm volume in 3.4 seconds. Our technique is based on a compression OCE technique, referred to as quantitative micro-elastography (QME), where a compliant silicone layer is incorporated to measure stress at the tissue surface. To perform handheld scanning, we implemented a rapid scan pattern to enable B-scan rates of 215 Hz using a microelectromechanical system (MEMS) scanner: minimizing the time difference between B-scan pairs used to generate displacement maps thus minimizing the motion artefact caused by hand motion. We present handheld scans acquired from silicone phantoms where the motion artefact is barely noticeable. In addition, freshly dissected human breast tissue from a mastectomy was scanned with the handheld probe. The breast tissue elastograms are validated using standard histology and demonstrate our ability to distinguish stiff regions of tumour from benign tissue using this probe.
In many applications of optical coherence elastography (OCE), it is necessary to rapidly acquire images in vivo, or within intraoperative timeframes, over fields-of-view far greater than can be achieved in one OCT image acquisition. For example, tumour margin assessment in breast cancer requires acquisition over linear dimensions of 4-5 centimetres in under 20 minutes. However, the majority of existing techniques are not compatible with these requirements, which may present a hurdle to the effective translation of OCE. To increase throughput, we have designed and developed an OCE system that simultaneously captures two 3D elastograms from opposite sides of a sample. The optical system comprises two interferometers: a common-path interferometer on one side of the sample and a dual-arm interferometer on the other side. This optical system is combined with scanning mechanisms and compression loading techniques to realize dual-scanning OCE. The optical signals scattered from two volumes are simultaneously detected on a single spectrometer by depth-encoding the interference signal from each interferometer. To demonstrate dual-scanning OCE, we performed measurements on tissue-mimicking phantoms containing rigid inclusions and freshly isolated samples of murine hepatocellular carcinoma, highlighting the use of this technique to visualise 3D tumour stiffness. These findings indicate that our technique holds promise for in vivo and intraoperative applications.
The mechanical forces that living cells experience represent an important framework in the determination of a range of intricate cellular functions and processes. Current insight into cell mechanics is typically provided by in vitro measurement systems; for example, atomic force microscopy (AFM) measurements are performed on cells in culture or, at best, on freshly excised tissue. Optical techniques, such as Brillouin microscopy and optical elastography, have been used for ex vivo and in situ imaging, recently achieving cellular-scale resolution. The utility of these techniques in cell mechanics lies in quick, three-dimensional and label-free mechanical imaging. Translation of these techniques toward minimally invasive in vivo imaging would provide unprecedented capabilities in tissue characterization. Here, we take the first steps along this path by incorporating a gradient-index micro-endoscope into an ultrahigh resolution optical elastography system. Using this endoscope, a lateral resolution of 2 µm is preserved over an extended depth-of-field of 80 µm, achieved by Bessel beam illumination. We demonstrate this combined system by imaging stiffness of a silicone phantom containing stiff inclusions and a freshly excised murine liver tissue. Additionally, we test this system on murine ribs in situ. We show that our approach can provide high quality extended depth-of-field images through an endoscope and has the potential to measure cell mechanics deep in tissue. Eventually, we believe this tool will be capable of studying biological processes and disease progression in vivo.
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