Tumor Margin Assessment in Breast Cancer

As breast cancer screening has increased and improved, breast cancer lesions are detected at earlier stages. Each year, over 180,000 new cases of invasive breast cancer (or 26% of all newly diagnosed cancer cases in women) and over 65,000 cases of ductal carcinoma in situ (DCIS) are reported in the United States. Breast cancerremains the second leading cause of cancer deaths among women in the United States, second only to lung cancer. In recent years, the decrease in the mortality rate from breast cancer has been attributed to increased awareness, earlier detection, and improved treatment and management options leading to increased five year survival rates. Current treatment options include the surgical removal of the lesion via breast-conserving surgery (lumpectomy) followed by irradiation or mastectomy.High-resolution, real-time OCT can be used to intraoperatively guide the surgical resection of solid tumors by identifying tumor margins and scanning for metastatic cells or distant foci of tumor cells.

Photograph of the clinical spectral domain optical coherence tomography (SD-OCT) system housed in a standard medical endoscopy cart (left). This clinical system is portable and compact allowing for its use in surgical suites. OCT images are 2-D cross-sectional planes (x-z) oriented perpendicular to the surface of the tissue. Multiple OCT images can be acquired by stepping the beam in the transverse (y) direction.

Negative tumor margin. OCT (a) and corresponding H&E-stained histology (b) of normal breast tissue near the surface of a lumpectomy specimen. The large adipose cells with point-like scattering nuclei dominate the OCT image, which also contains a region of the microvasculature (arrows).

Positive tumor margins. The OCT image (a) shows a distinct heterogeneously-scattering region (arrows) with small, highly scattering foci indicative of collections of tumor cells. These features clearly extend to the top surface of the specimen (to the surgical margin). Corresponding H&E-stained histology (b) and ER+ immunohistochemistry (c) images show corresponding features, confirming the presence of a positive margin.

Nguyen FT, Zysk AM, Chaney EJ, Kotynek JG, Oliphant UJ, Bellafiore FJ, Rowland KM, Johnson PA, Boppart SA. Intraoperative evaluation of breast tumor margins with optical coherence tomography. Cancer Research, 69(22): 8790-8796, 2009. PDF

 

 

Handheld surgical imaging probe and portable OCT system for in vivo assessment of the WLE resection bed. A, schematic showing the OCT system components. B, the handheld surgical probe is used by the surgeon to image inside the in vivo resection bed and across the excised tumor specimens. C, the OCT system is integrated in a portable cart for easy transportation into the operating room and positioning near the sterile surgical field. SLD, superluminescent diode; FC, fiber optic coupler; PP, fiber polarization paddle controller; RM, reference mirror.

Video OCT cross-sectional images of a positive tumor margin from the in vivo resection bed and ex vivo excised tissue. Images are from a 72-year-old female WLE patient with invasive ductal carcinoma of the left breast. Diagrams on the left indicate the imaged regions (dashed boxes) of the resection bed or the excised specimen (not to scale), and the solid black lines in the black dashed boxes indicate the top of the corresponding OCT image. The red and blue dashed regions correspond to areas identified as cancer and normal areas, respectively. A, OCT image of the positive in vivo lateral tumor margin. B, OCT image of the positive ex vivo lateral specimen margin, with corresponding histology. C, OCT image of the positive additional ex vivo lateral margin tissue (same tissue as imaged in vivo in A), with corresponding histology. D, OCT image of the final negative in vivo lateral margin. Areas of interest are magnified and shown in the insets to compare normalstroma and adipose with cancerous regions. Note that histology images are only provided for the corresponding OCT images in B and C, because the images in A and D were acquired in vivo and hence do not have histology images to compare.

Erickson-Bhatt SJ, Nolan RM, Shemonski ND, Adie SG, Putney J, Darga D, McCormick DT, Cittadine AJ, Zysk AM, Marjanovic M, Chaney EJ, Monroy GL, South FA, Cradock KA, Liu ZG, Sundaram M, Ray PS, Boppart SA. Real-time imaging of the resection bed using a handheld probe to reduce incidence of microscopic positive margins in cancer surgery. Cancer Research,75(18): 3706-3712, 2015. PDF

 

 

 

Swept-source PS-OCT system design. FDML: Fourier domain mode-locked laser; LP: Linear polarizer; PBS: Polarizing beam splitter; QWP: Quarter-wave plate.

Fibro-adipose human breast tissue. (a) Structural OCT image. (b) H&E-stained histology. (c) PS-OCT phase retardation image (Media 1). (d) Picrosirius red stained histology. (e) En face PS-OCT projection. Scale bars represent 500 µm.
 

Image processing sequence for the descriptive Coefficient of Variation (CV) statistical metric. (A) Original OCT image of sarcoma, (B) corresponding mask, and (C) calculated coefficient of variation. (D) Raw OCT image of muscle, (E) corresponding mask, and (F) calculated coefficient of variation. Scale bar represents 1 mm and the color bar ranges from 0.1 to 1.1 in steps of 0.1.

South FA, Chaney EJ, Marjanovic M, Adie SG, Boppart SA. Differentiation of ex vivo human breast tissue using polarization-sensitive optical coherence tomograph. Biomedical Optics Express, 5(10): 3417-3426, 2014.

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Mesa KJ, Selmic LE, Pande P, Monroy GL, Reagan J, Samuelson J, Li J, Marjanovic M, Chaney EJ, Boppart SA. Intraoperative OCT for soft tissue sarcoma margin identification. IEEE Journal of Lasers in Surgery and Medicine, 2017. (in press) In Press