Solid tumours are typically first diagnosed by palpation, revealing increased stiffness, while cancer cells are usually reported to be softer. The mechanical characteristics are not universal and depend on the cell type and the stage of development. Current techniques are usually point or 2D measurement techniques that lack depth penetration in 3D samples. We are developing optical coherence mechano-microscopy integrated with a confocal fluorescence microscope as a platform to investigate the mechanical phenotypes of 3D cancer models, mimicking the conditions in the native tumour microenvironment. This platform enables unique measurement of the 3D elasticity (i.e. Young’s modulus) of metastatic and non-metastatic breast cancer cell spheroids embedded in GelMAl, presenting the extracellular matrix, co-registered with fluorescence images. Our findings show that cells at the centre of non-metastatic cancer cell spheroids are softer (5.8 kPa) than the cells at the periphery (12.7 kPa). In contrast, migrating cells at the periphery of the metastatic cancer cell spheroids are softer (5.7 kPa) than the less motile cells at the centre of these spheroids (8.0 kPa).
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.
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.
Disease alters both the micro-structural and micro-mechanical properties of tissue. These changes in mechanical properties manifest at the macro-scale, enabling clinicians to diagnose disease through manual palpation. This has been a primary motivator for elastography, however, in the development of elastography, manual palpation’s key advantages of dexterity and simplicity are lost. Combining manual palpation and elastography would, potentially, preserve these advantages whilst also providing clinicians with quantitative, high-resolution imaging necessary to overcome the subjective and inherently low spatial resolution of manual palpation. Optical coherence elastography (OCE) is particularly well-suited to imaging subtle changes in mechanical properties owing to its high spatial resolution and sensitivity to nanometer-scale displacement. Additionally, as OCE is an optics-based technique, it is readily implemented in compact probes, such as those already demonstrated in needles and endoscopes. Here, we propose a finger-mounted OCE probe, based on quantitative micro-elastography (QME) in a forward-facing configuration, and using the operator’s finger to apply compressive loading. A compliant silicone layer, with known mechanical properties, is placed on the sample and enables quantification of the sample’s elasticity. This finger-mounted probe is designed to preserve the dexterity of manual palpation, whilst providing quantitative, high-resolution images. In this study, we demonstrate the accuracy of finger-mounted OCE to be >70% in measuring the elasticity of tissue mimicking phantoms, and highlight the ability to delineate materials with different mechanical properties. Further, we present results performed on kangaroo muscle tissue and outline the developments required to translate this into a clinically feasible diagnostic tool.
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