Non-invasive imaging of carcinogen-induced early neoplasia using ultrahigh-resolution optical coherence tomography.
OBJECTIVE
Improved diagnostics capable of non-invasive detection of early stage carcinogenesis would benefit basic research, and potentially aid in clinical cancer diagnosis and management. The two-stage carcinogenesis protocol is widely used for studying the multi-stage nature of tumor development in mice and provides insight into tumor development in other animal models and humans. The objective of this study was to investigate the feasibility of non-invasive optical coherence tomography (OCT) for in vivo imaging of microanatomical changes in the epidermis and dermis during early carcinogenesis using a mouse skin model.


METHODS
10 NIH mice were treated with DMBA and TPA following the well-established two-stage carcinogenesis protocol. OCT imaging of treated skin from live mice was performed at five time points (Week 4-8) after tumor initiation to reveal the structural changes in the epidermis and dermis associated with the earliest, premalignant stages of tumor development. OCT images were compared with histology findings. In addition, OCT signals were quantitatively analyzed to evaluate tissue optical property changes during early carcinogenesis.


RESULTS
Early structural changes in the epidermis, dermis and hair follicles during carcinogenesis were clearly delineated in vivo using OCT. OCT images correlated well with histological findings. Quantitative OCT signal analysis revealed a statistically significant change in the extinction coefficient for untreated (40.5 +/- 17.0 mm(-1)) and treated (9.6 +/- 3.6 mm(-1)) mouse epidermis (P < 0.005). The dermis extinction coefficient for the treated mouse skin (3.7 +/- 0.9 mm(-1)) was lower than the untreated one (4.7 +/- 1.6 mm(-1)), but was not statistically significant (P > 0.10). Furthermore, the papilloma extinction coefficient (2.9 +/- 0.3 mm(-1)) was significantly lower than the extinction coefficient for the treated epidermis (P < 0.005) and dermis (P < 0.01).


CONCLUSIONS
OCT is a viable tool for assessing the earliest stages of carcinogenesis and has potential for early detection of neoplasia in skin, as well as in epithelial linings of other organs.
Cobb
Michael J
MJ
Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Chen
Yuchuan
Y
Bailey
S Lawrence
SL
Kemp
Christopher J
CJ
Li
Xingde
X
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D003952:Diagnostic Imaging / Q000379:methods; D005240:Feasibility Studies; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009367:Neoplasm Staging; D012815:Signal Processing, Computer-Assisted; D012867:Skin / Q000033:anatomy & histology / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D013997:Time Factors; D041623:Tomography, Optical Coherence / Q000295:instrumentation / Q000379:methods*
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene