Optical coherence tomography: the intraoperative assessment of lymph nodes in breast cancer

Abstract

During breast-conserving surgeries, axillary lymph nodes draining from the primary tumor site are removed for disease staging. Although a high number of lymph nodes are often resected during sentinel and lymph-node dissections, only a relatively small percentage of nodes are found to be metastatic, a fact that must be weighed against potential complications such as lymphedema. Without a real-time in vivo or in situ intraoperative imaging tool to provide a microscopic assessment of the nodes, postoperative paraffin section histopathological analysis currently remains the gold standard in assessing the status of lymph nodes. This paper investigates the use of optical coherence tomography (OCT), a high-resolution real-time microscopic optical-imaging technique, for the intraoperative ex vivo imaging and assessment of axillary lymph nodes. Normal (13), reactive (1), and metastatic (3) lymph nodes from 17 human patients with breast cancer were imaged intraoperatively with OCT. These preliminary clinical studies have identified scattering changes in the cortex, relative to the capsule, which can be used to differentiate normal from reactive and metastatic nodes. These optical scattering changes are correlated with inflammatory and immunological changes observed in the follicles and germinal centers. These results suggest that intraoperative OCT has the potential to assess the real-time node status in situ, without having to physically resect and histologically process specimens to visualize microscopic features.

Fig. 1

(a) Photograph of the clinical system with (b) clinical spectral domain optical coherence tomography system schematic. Light from a superluminescent diode (SLD) centered at 1,310 nm is directed into the optical circulator (OC) that passes the light into the fiber coupler (FC) that splits the light into the reference arm (5%) and the sample arm (95%). The light is collimated through a set of fiber collimators (Col). The reflected light from each arm is coupled back together through a set of polarization paddles (PP) and interfered with each other through the 5/95 fiber coupler (FC) and spectrally dispersed onto a line scan camera that serves as the detector.

Fig. 2

(a) Normal lymph node – OCT images from a normal sentinel lymph node with (b) corresponding H&E histology demonstrate an intact capsule structure, which is easily distinguishable from the cortex of the lymph node. The OCT images are highlighted (orange boxes) with the regions that correlate with the histology images.

Fig. 3

(a) Reactive lymph node – OCT image from a reactive axillary lymph node with (b) corresponding H&E histology. In this case, the increased cellular density in the cortex when the lymph node becomes reactive contributes to the increased scattering signal observed under OCT. The change in scattering intensity begins to match the scattering intensity of the capsule, decreasing the ability to distinguish the capsule from the cortex under the OCT images (arrows).

Fig. 4

Three-dimensional rendering of a normal lymph node. (a) OCT image volume acquired from a normal sentinel lymph node is shown with (b) the corresponding H&E histology. The normal lymph node shows a clear capsule that is easily differentiated from the low-scattering cortex. The OCT images correlate to the regions in the histology that are highlighted by the red boxes. The OCT image block measures 5 × 5 × 1.7 mm³.

Fig. 5

Three-dimensional rendering of a metastatic lymph node. (a) OCT image volume acquired from a metastatic axillary lymph node in a single session is shown with (b) the corresponding H&E histology. As with reactive lymph nodes, increased scattering from the node is observed in the OCT data, and the ability to differentiate distinct boundaries between the node capsule and cortex has been lost. The OCT images correlate to the regions in the histology that are highlighted by the red boxes. The OCT image block measures 5 × 5 × 1.7 mm³.