12 November 2012
Rapid screening of cancer margins in tissue with multimodal confocal microscopy
Daniel S. Gareau, Hana Jeon, Kishwer S. Nehal, Milind Rajadhyaksha
Background: Complete and accurate excision of cancer is guided by the examination of
histopathology. However, preparation of histopathology is labor intensive and slow,
leading to insufficient sampling of tissue and incomplete and/or inaccurate excision of
margins. We demonstrate the potential utility of multimodal confocal mosaicing microscopy
for rapid screening of cancer margins, directly in fresh surgical excisions, without the
need for conventional embedding, sectioning, or processing.
Materials and methods: A multimodal confocal mosaicing microscope was developed to
image basal cell carcinoma margins in surgical skin excisions, with the resolution that
shows nuclear detail. Multimodal contrast is with fluorescence for imaging nuclei and
reflectance for cellular cytoplasm and dermal collagen. Thirty-five excisions of basal cell
carcinomas from Mohs surgery were imaged, and the mosaics analyzed by comparison
with the corresponding frozen pathology.
Results: Confocal mosaics are produced in about 9 min, displaying tissue in fields of view of
12mm with 2 magnification. A digital staining algorithm transforms black and white
contrast to purple and pink, which simulates the appearance of standard histopathology.
Mosaicing enables rapid digital screening, which mimics the examination of
Conclusions: Multimodal confocal mosaicing microscopy offers a technology platform to
potentially enable real-time pathology at the bedside. The imaging may serve as an adjunct
to conventional histopathology to expedite screening of margins and guide surgery toward
more complete and accurate excision of cancer.