Anatomical complexities of optical diagnostic targets in vivo: to discover the abnormal, one has to know first the normal

Optical diagnosis of cancers requires detection of differential concentrations of (1) various absorbers and scatterers or (2) native or exogenous fluorophores to distinguish cancers from surrounding tissues. The differential concentrations are due to the biology of the cancer cells and the host responses to the cancer growth. For most patients, the cancer will be intermixed with a complex 3-dimensional array of "normal" tissue and benign lesions. This complexity will challenge the optical biopsy investigator but, with the recent advances in our understanding of light transport, optical diagnostic techniques and devices can be developed to complement and supplement current cancer screening techniques.