Noninvasive enhanced mid-IR imaging of breast cancer developmentin vivo

Abstract

Lumpectomy coupled with radiation therapy and/or chemotherapy is commonly used to treat breast cancer patients. We are developing an enhanced thermal IR imaging technique that has the potential to provide real-time imaging to guide tissue excision during a lumpectomy by delineating tumor margins. This enhanced thermal imaging method is a combination of IR imaging (8 to 10 μm ) and selective heating of blood (∼0.5°C ) relative to surrounding water-rich tissue using LED sources at low powers. Postacquisition processing of these images highlights temporal changes in temperature and the presence of vascular structures. In this study, fluorescent, standard thermal, and enhanced thermal imaging modalities, as well as physical caliper measurements, were used to monitor breast cancer tumor volumes over a 30-day study period in 19 mice implanted with 4T1-RFP tumor cells. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after day 22. The tumor volumes estimated from enhanced thermal imaging, standard thermal imaging, and caliper measurements all show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging, standard IR imaging, and caliper measurements with enhanced thermal imaging, indicating that enhanced thermal imaging monitors tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses associated with the tumor margin. In the future, this IR technique might be used to estimate tumor margins in real time during surgical procedures.

Focal dynamic thermal imaging for label-free high-resolution characterization of materials and tissue heterogeneity

“…While these results are exciting, the spatial resolution limitations of widefield DTI techniques may not allow robust estimation of tumor heterogeneity and margin assessment, which would further expand the utility of dynamic thermal imaging. Additional heat challenge techniques have applied visible light sources including green LEDs that created heat due to absorption by hemoglobin to identify the vascular boundary of tumors 29 . Herein, FDTI had 95% and 91% accuracy in small cohorts of breast cancer mouse and rat models, respectively, using classification based on single point FDTI measurements of cold tumors.…”

Post-operative monitoring of tissue perfusion in skin flaps in a murine model using enhanced thermal imaging

“…ETI uses illumination with low powered LED's (λ = 530 nm) to selectively heat blood rich regions. [12][13][14][15][16] Blood absorbs strongly at this wavelength allowing the selective increase in its temperature relative to the surrounding tissue. A mid-infrared camera (sensitive from 7 -10 µm) is then able to capture the small increase in temperature in the targeted region.…”

Tissue clearing may alter emission and absorption properties of common fluorophores

“…Traditionally, tissues have been embedded and cut in serial sections, granting two-dimensional tools and techniques access to three- dimensional samples 1 . Common techniques like volume imaging, including confocal and light sheet microscopy, now routinely enable accurate molecular and structural analysis of intact 3D tissues 2 , even live 3 . However, the optical analysis of large cellular aggregates still poses challenges.…”