Intraoperative optical coherence tomography for assessing human lymph nodes for metastatic cancer

Abstract

BackgroundEvaluation of lymph node (LN) status is an important factor for detecting metastasis and thereby staging breast cancer. Currently utilized clinical techniques involve the surgical disruption and resection of lymphatic structure, whether nodes or axillary contents, for histological examination. While reasonably effective at detection of macrometastasis, the majority of the resected lymph nodes are histologically negative. Improvements need to be made to better detect micrometastasis, minimize or eliminate lymphatic disruption complications, and provide immediate and accurate intraoperative feedback for in vivo cancer staging to better guide surgery.MethodsWe evaluated the use of optical coherence tomography (OCT), a high-resolution, real-time, label-free imaging modality for the intraoperative assessment of human LNs for metastatic disease in patients with breast cancer. We assessed the sensitivity and specificity of double-blinded trained readers who analyzed intraoperative OCT LN images for presence of metastatic disease, using co-registered post-operative histopathology as the gold standard.ResultsOur results suggest that intraoperative OCT examination of LNs is an appropriate real-time, label-free, non-destructive alternative to frozen-section analysis, potentially offering faster interpretation and results to empower superior intraoperative decision-making.ConclusionsIntraoperative OCT has strong potential to supplement current post-operative histopathology with real-time in situ assessment of LNs to preserve both non-cancerous nodes and their lymphatic vessels, and thus reduce the associated risks and complications from surgical disruption of lymphoid structures following biopsy.

Investigation of optical coherence micro-elastography as a method to visualize micro-architecture in human axillary lymph nodes

“…Methods such as high-frequency ultrasound (HF-US) [13] and photoacoustic tomography (PAT) [14] have been investigated, reporting spatial resolutions of ~100 μm (HF-US) or ~50 μm (PAT); additionally, PAT has been used in conjunction with external contrast agents. To obtain improved spatial resolution without the need for labelling agents, optical modalities, such as optical coherence tomography (OCT), often described as the optical analog to ultrasonography, have been proposed [15–22]. The detection of backscattered light, rather than sound, provides OCT with a spatial resolution of 1–20 μm, but only to a depth of 1–2 mm in turbid tissue.…”

“…OCT has the potential to rapidly scan entire ex vivo lymph nodes intraoperatively, improving upon the sampling issues of intraoperative histopathology techniques. However, it is unclear if lymph node metastases can be adequately delineated based on endogenous optical scattering contrast alone [21, 22]. …”

Review of intraoperative optical coherence tomography: technology and applications [Invited]

“…A similar study, conducted with a commercial HHOCT device, suggested that intraoperative margin analysis in shave margin specimens could reduce reoperation rates at the cost of small increases in resected tissue volume [95]. The Boppart group has also advanced OCT for non-destructive detection of breast cancer metastasis in lymph nodes [196,197]. They proposed using OCT to examine the lymph node cortex in situ for metastatic disease, eliminating the need for lymph node dissection and the associated risk of lymphedema.…”

“…They proposed using OCT to examine the lymph node cortex in situ for metastatic disease, eliminating the need for lymph node dissection and the associated risk of lymphedema. Their recent study in [197] demonstrated a mean sensitivity of 58.8% and specificity of 81.% for identifying reactive/metastatic lymph nodes. The detection sensitivity was complicated by image artifacts and limited depth penetration through tissue overlying the lymph nodes of interest.…”

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

“…1), 52 as well as for imaging the surgical margins of resected tumor specimens 19,20,[53][54][55] and loco-regional lymph nodes in human breast cancer surgeries. 56 Related to OCT, optical coherence elastography provides 3-D maps of tissue mechanical properties, on the micrometer to millimeter scale. Here, a mechanical load is applied to tissue and the resultant displacement is measured using OCT.…”