Novel laser emission based microscopy for early detection of colon cancer
Accurate identification of neoplastic or pre-neoplastic lesions is traditionally dependent on microscopic recognition of histological abnormalities and is both time-consuming and subject to human error, particularly for early-stage lesions. Laser-emission microscopy (LEM) is an emerging imaging technology that takes advantage of the finding that highly proliferating cells like those in neoplastic or pre-neoplastic lesions can be differentiated from less proliferative cells by a lower laser emission threshold when stained with a nuclear dye. LEM can be applied to frozen or paraffin-embedded formalin-fixed tissues prepared as for standard histological evaluation. The tissues are sandwiched between two mirrors to form a laser cavity and laser excitation is applied. By comparing the laser emission spectra, highly proliferative tissues can be differentiated from less proliferative tissues. We have applied this technique to distinguish Stage I/II human lung cancer tissues from normal tissues with a Receiver Operating Characteristic (ROC) curve of 0.998, indicating high specificity and sensitivity. Moreover, we have successfully utilized the same technique to distinguish histologically normal colon tissues from mice with adjacent adenomas from histologically normal colon tissues from mice without adenomas, a task that is not possible by conventional histological examination. This indicates the LEM may be a useful technique for detecting the higher proliferative capacity in very early stage pre-neoplastic lesions, before histological changes can be detected using currently available tools. Because this technique can be automated, it may be an efficient adjunct for diagnostic pre-screening or confirmation of pre-neoplastic or neoplastic changes in human colon biopsy tissues. We plan to apply this technique to multiple types of human colon neoplastic and non-neoplastic tissues diagnosed by traditional histological and molecular means, available through tissue repositories in the Department of Pathology at the University of Michigan. In parallel, we will also test normal colonic biopsies (collected from subjects at risk for colon cancer) using the same technology. Ultimately, this will allow us to assess the applicability of LEM as an early diagnostic tool for neoplasia in biopsy samples from a wide variety of human cancers.
Figure: a. Conceptual illustration of the scanning laser-emission based microscopy (LEM). b. A description of the setup. c. Picture showing a human lung tissue sandwiched between mirrors and illuminated by an external excitation light.