Dynamic Infrared Imaging in the Hamster Cheek Pouch Model of Oral Cancer: searching for prognostic parameters of tumor response and normal tissue radiotoxicity in BNCT

MARIA S. HERRERA; CLAUDIO PADRA; NATALIA SALVA; GUSTAVO A SANTA CRUZ; ANDREA MONTE HUGHES; AMANDA SCHWINT

Congreso; The 17th International Congress on Neutron Capture Therapy; 2016

Biomedical infrared thermography is a non-invasive and functional imaging method that providesinformation on the normal and abnormal status and response of tissues in terms of spatial andtemporal variations in body infrared radiance. Employing radiometric measurements andalgorithms that convert infrared radiance to temperature, this technique can be used to quantifytemperature distribution on body surfaces. It is especially attractive in cancer research due to thehypervascular and hypermetabolic activity of solid tumors. Moreover, healthy tissues like skin ormucosa exposed to radiation can be examined since inflammation, changes in water content,exudation, desquamation, erosion and necrosis are factors that modify their thermal properties.Based on our earlier experience using this technique in our melanoma patients as well as in animalresearch, in this work we combined Dynamic Infrared Imaging (DIRI) with theoretical andexperimental studies to contribute to the understanding and evaluation of BNCT-induced tumorcontrol and radiotoxicity in the hamster cheek pouch model of oral cancer. Particularly, we focusedon the observation of temperature changes under transient conditions associated with watertransfer in the tissue-air interface of tumor and normal tissue in the pouch.We examined 70 hamsters with DIRI, divided into 6 groups: non-irradiated normal hamster cheekpouch; DMBA-cancerized pouch + BNCT mediated by boronophenylalanine (BPA-BNCT) orbeam-only; normal pouch + BPA-BNCT or beam-only; and sham group (DMBA-cancerizedpouch without treatment). For DIRI studies, the pouch was everted under anesthesia, during 12minutes. Tissue thermal responses were assessed before, during and after forced temperaturechanges at tissue-air interface (provocation test). Since tissue temperature varied exponentiallywith time, we used as a first approximation, the well-known lumped capacity analysis method.Under this assumption, we modeled each transient process considering the heat transfer from tissueto ambient through convection and evaporation, to determine the typical time constant and degreeof evaporation occurring on the tissue surface. We also used thermographic data to determineconduction and convection thermal parameters through an inverse problem, solving numericallythe 1-dimensional transient bioheat problem formulated by Pennes equation.Group comparisons were performed using paired or unpaired t-test and one-way ANOVA with asignificance level lower than 0.05.We were able to characterize thermal responses of tumors and normal tissue through acomprehensive validation of the proposed models. In particular, tissue transient processes underprovocation tests could be used as a non-invasive method to characterize tissue physiology. Wefound significant differences in the studied parameters between tumors treated with BPA-BNCTand sham or beam-only groups. This fact might be explored further as an indicator of tumorresponse in a long-term study including DIRI. Finally, we observed differences in the recoverytime constants after the provocation tests for normal pouches exposed to BNCT compared to nonirradiatednormal pouches, which would possibly be related with their water content.In summary, DIRI could provide ancillary non-invasive in vivo information related to thephysiological status of tumor and normal tissue and their response to BNCT, in the hamstercheek pouch oral cancer model.