We propose to apply a new, non-invasive, non-contacting technique, Laser Heterodyne Imaging (LHI) to 3-dimensional imaging of neoplasms. Preliminary measurements have been made through ~1mm of mouse skin and in 1.4mm phantoms, using dyes similar to those used in PDT. With improved apparatus, our goal is several centimeters penetration. LHI measures intensity-modulated fluorescence originating from the heterodyning of two laser beams in a small intersection volume, thus permitting localized measurement. That fluorescence is modulated at the difference frequency of the two beams (40MHz). Heterodyning discriminates against interfering background fluorescence, thus permitting measurements at depth, even through highly turbid biological tissue. LHI can enhance the diagnostic capabilities of Laser Induced Fluorescence by determining tumor boundaries in three dimensions.
Our specific aims are (1) to compare the capabilities of LHI with established clinical techniques through a graded set of experiments (using animal tissue in vitro and in vivo and concluding with an animal model for basal cell carcinoma), (2) to investigate the effect of scattering on performance (attainable depth), (3) to investigate the possibility of using endogenous fluorescent agents, and (4) to define a Phase 2 prototype to measure skin cancer and deeper-seated soft tissue neoplasms, like breast cancer, in human subjects.
