Wide-field optical coherence micro-elastography for intraoperative assessment of human breast cancer margins

Abstract

Incomplete excision of malignant tissue is a major issue in breast-conserving surgery, with typically 20 -30% of cases requiring a second surgical procedure arising from postoperative detection of an involved margin. We report advances in the development of a new intraoperative tool, optical coherence micro-elastography, for the assessment of tumor margins on the micro-scale. We demonstrate an important step by conducting whole specimen imaging in intraoperative time frames with a wide-field scanning system acquiring mosaicked elastograms with overall dimensions of ~50 × 50 mm, large enough to image an entire face of most lumpectomy specimens. This capability is enabled by a wide-aperture annular actuator with an internal diameter of 65 mm. We demonstrate feasibility by presenting elastograms recorded from freshly excised human breast tissue, including from a mastectomy, lumpectomies and a cavity shaving. Vitkin, "Hybrid method of strain estimation in optical coherence elastography using combined sub-wavelength phase measurements and supra-pixel displacement tracking," J. Biophotonics 9(5), 499-509 (2016

Optical coherence elastography – OCT at work in tissue biomechanics [Invited]

“…Of course, the need for quantitation remains debatable, and must be assessed application by application. Already, as discussed herein, there are signs that some groups are moving beyond demonstrations of novelty, to systematic investigations of an application, such as intraoperative breast tumor margin identification [52, 151,155] and monitoring therapeutic procedures on the cornea [115]. Undoubtedly, the field will continue to grow, as there are many remaining opportunities for novelty in methods; very little research done to date on probe design, such as would be suitable for endoscopy; combination of experimental data with models and computational methods to overcome artifacts and enhance accuracy is in its infancy; and there is a very large application space to explore.…”

“…Schmitt's images were superior to most subsequent published work until about 2014, when a group led by one of us demonstrated much more compelling images of soft tissue contrast [52], a recent example of which is shown in Fig. 4 [151]. Why did this advance take so long?…”

“…In the case of breast cancer lumpectomies, the goal is to assess the margins of the sample for the presence of tumor to guide the surgery, with the goal of reducing the high rates (20-40%) of re-excision currently experienced [156,157]. Evidence accumulated from more than 58 specimens [52, 151,155] shows strong correlation between tumor or benign stroma diagnosed in histology and the texture of the en face strain elastograms. Distinguishing between benign and malignant solid tissue has been a challenge faced by OCT at conventional resolutions (5-15 μm) [158].…”

Label-free optical imaging technologies for rapid translation and use during intraoperative surgical and tumor margin assessment

“…Images of strain or elastograms present identifying features based on mechanical contrast. 57,58 Intraoperative Raman spectroscopy has been used to create molecular contrast maps of ex vivo specimen margins based on spectral features indicative of normal versus tumor tissues, 59 and more recently, photoacoustic microscopy has recently been used to assess surgical specimens and margins, relying on inherent absorption contrast differences between normal and tumor tissues. There are significant impediments to the adoption of label-free optical imaging technologies in current oncological surgery.…”

Biomedical device innovation methodology: applications in biophotonics

“…OCT in combination with elastography and/or microelastography has a large number of potential clinical applications, but it was the ability of the founders of OncoRes Medical (Perth, Western Australia, Australia) to focus and define the unmet need of tumor margin assessment in breastconserving surgery that led to accelerated development and opportunities for investment. [40][41][42][43][44] Hearing loss is a prevalent, chronic condition that affects tens of millions of Americans and has a significant social and professional impact. 45,46 Individuals with hearing loss wait on average a decade for an intervention after initially experiencing hearing loss.…”