Wide-field quantitative micro-elastography of human breast tissue

Abstract

Currently, 20-30% of patients undergoing breast-conserving surgery require a second surgery due to insufficient surgical margins in the initial procedure. We have developed a wide-field quantitative micro-elastography system for the assessment of tumor margins. In this technique, we map tissue elasticity over a field-of-view of ~46 × 46 mm. We performed wide-field quantitative micro-elastography on thirteen specimens of freshly excised tissue acquired from patients undergoing mastectomy. We present wide-field optical coherence tomography (OCT) images, qualitative (strain) micro-elastograms and quantitative (elasticity) micro-elastograms, acquired in 10 minutes. We demonstrate that wide-field quantitative micro-elastography can extend the range of tumors visible using OCT-based elastography by providing contrast not present in either OCT or qualitative microelastography and, in addition, can reduce imaging artifacts caused by a lack of contact between tissue and the imaging window. Also, we describe how the combined evaluation of OCT, qualitative micro-elastograms and quantitative micro-elastograms can improve the visualization of tumor.

Optical palpation for the visualization of tumor in human breast tissue

“…Statistical analysis performed in this study has shown that tumor exhibits median stress of 60 kPa, higher than that of adipose and stroma, in cases when the preload was controlled between 15% and 25%. The elevated stress, which is sensitive to the underlying elasticity of features in tissue, measured for invasive tumor in this study is consistent with QME studies; where it was shown that invasive tumor exhibits elevated elasticity in comparison to benign dense tissue . Stress is a qualitative measurement; therefore, the measured stress in the layer is proportional to the preload applied.…”

“…Finally, we anticipate that by mimicking the sense of touch, a tool that surgeons routinely use to assess tissue, optical palpation may provide images that can prove more intuitive to interpret than other forms of intraoperative imaging. However, the significant advantages of QME over optical palpation are the quantification of elasticity , the ability to perform depth sectioning of mechanical contrast, up to ~1 mm , and higher spatial resolution (which is discussed in the Supporting Information in Appendix S1).…”

“…However, stress is a qualitative measurement of elasticity, and the measured stress is proportional to the preload. A related technique, quantitative micro‐elastography (QME), reports tissue elasticity, defined here as the slope of the stress‐strain curve at the point of preload, that is, the tangent modulus . Despite the quantification of elasticity provided by QME, in this study, we suggest that optical palpation may provide a less complex and more cost‐effective solution for margin assessment in a large subset of tumors, particularly in invasive tumors, which tend to present as larger regions of tumor.…”

“…Wide‐field en face images are generated by mosaicking en face subimages with an overlap of 1 mm to ensure accurate alignment can be achieved and to minimize areas of low OCT intensity due to coherence gate curvature . Wide‐field en face OCT images are generated (at a single pixel depth) ~100 μm below the layer‐specimen interface.…”

“…A custom binary segmentation algorithm is used to identify regions of dense tissue and to produce binary masks. Due to the complex mechanical structure of the tissue, in some cases, negative elasticity is estimated in QME . As negative elasticity is not physically meaningful, these pixels are also segmented from the final image.…”