Three-Dimensional Imaging of Tumors Through Tissue

We will 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 millimeters penetration. LHI measures intensity-modulated fluorescence originating from the heterodyning of two laser beams in a small intersection volume; thus, it permits localized measurement. That fluorescence is modulated at the beat frequency of the two beams (40MHz). Heterodyning discriminates against interfering background fluorescence; therefore, it permits 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 II prototype to measure skin cancer and sub-surface soft tissue neoplasya in human subjects.