title: Advancing optical imaging for breast margin assessment: an analysis of excisional time, cautery, and patent blue dye on underlying sources of contrast.
abstract: Breast conserving surgery (BCS) is a recommended treatment for breast cancer patients where the goal is to remove the tumor and a surrounding rim of normal tissue. Unfortunately, a high percentage of patients return for additional surgeries to remove all of the cancer. Post-operative pathology is the gold standard for evaluating BCS margins but is limited due to the amount of tissue that can be sampled. Frozen section analysis and touch-preparation cytology have been proposed to address the surgical needs but also have sampling limitations. These issues represent an unmet clinical need for guidance in resecting malignant tissue intra-operatively and for pathological sampling. We have developed a quantitative spectral imaging device to examine margins intra-operatively. The context in which this technology is applied (intra-operative or post-operative setting) is influenced by time after excision and surgical factors including cautery and the presence of patent blue dye (specifically Lymphazurin™, used for sentinel lymph node mapping). Optical endpoints of hemoglobin ([THb]), fat ([β-carotene]), and fibroglandular content via light scattering (<µ(s)'>) measurements were quantified from diffuse reflectance spectra of lumpectomy and mastectomy specimens using a Monte Carlo model. A linear longitudinal mixed-effects model was used to fit the optical endpoints for the cautery and kinetics studies. Monte Carlo simulations and tissue mimicking phantoms were used for the patent blue dye experiments. [THb], [β-carotene], and <µ(s)'> were affected by <3.3% error with <80 µM of patent blue dye. The percent change in [β-carotene], <µ(s)'>, and [β-carotene]/<µ(s)'> was <14% in 30 minutes, while percent change in [THb] was >40%. [β-carotene] and [β-carotene]/<µ(s)'> were the only parameters not affected by cautery. This work demonstrates the importance of understanding the post-excision kinetics of ex-vivo tissue and the presence of cautery and patent blue dye for breast tumor margin assessment, to accurately interpret data and exploit underling sources of contrast.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, USA.
authors.forename: Torre M
authors.initials: TM
authors.lastname: Bydlon
authors.forename: William T
authors.initials: WT
authors.lastname: Barry
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Kennedy
authors.forename: J Quincy
authors.initials: JQ
authors.lastname: Brown
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Gallagher
authors.forename: Lee G
authors.initials: LG
authors.lastname: Wilke
authors.forename: Joseph
authors.initials: J
authors.lastname: Geradts
authors.forename: Nimmi
authors.initials: N
authors.lastname: Ramanujam
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology / Q000601:surgery*; D002425:Cautery; D004396:Coloring Agents / Q000737:chemistry*; D005260:Female; D006801:Humans; D008408:Mastectomy; D015412:Mastectomy, Segmental; D061848:Optical Imaging; D012394:Rosaniline Dyes / Q000737:chemistry*
chemical_list: D004396:Coloring Agents; D012394:Rosaniline Dyes; C025484:iso-sulfan blue