In this study, micrometer-sized (< 5μm) microbubbles (MBs) were investigated as optical contrast agents. Exogenous contrast agents in optical imaging can enhance the detection of cancerous tissue, however they are limited by their potential side effects such as organ accumulation and toxicity with repeated administration. In ultrasound imaging, microbubbles are FDA approved and used clinically as contrast agents. Microbubbles can also produce a refractive index mismatch between the gas-filled core and surrounding water media, potentially modifying optical properties of tissue when injected intravenously into tissue.
Cancer detection can potentially be achieved by imaging microvasculature functionality through the blood volume fraction measurements with diffuse optical imaging (DOI). In order to study the potential application of using MBs for DOI, the effect of MBs on the bulk optical properties of a skin tissue phantom solution at various volume fraction
of human blood was assessed at various injection doses of Definity® microbubble. The absorption and reduced scattering coefficients were computed and compared in the absence and presence of microbubbles. The presence of microbubbles in the blood caused a statistically significant enhancement in the reduced scattering contrast (~1.3 times) at 660 nm wavelength which increases with the dose of Definity® MBs (166 μL/kg) at 6% blood volume fraction. However, the absorption contrast enhancement remained relatively constant as microbubble dose increased. The scattering contrast enhancement confirmed the feasibility of using MBs as DOI contrast agents to improve the detection of tissue with high blood concentration conditions.
Microbubbles were also investigated as optical coherence tomography (OCT) contrast agents. OCT structural and speckle variance (sv) images, as well as the speckle decorrelation times, were evaluated under no-flow and flow conditions from a skin tissue phantom with two embedded microtubes. Faster decorrelation times and greater structural and svOCT image contrasts were detected with the presence of MBs. The effects of the presence of MBs on the image contrast were maximal (2 times) at no flow in the svOCT imaging mode and reduced with blood average flow velocity from zero to 12 mm/s. This result confirmed the feasibility of using MBs to enhance svOCT visualization of microvasculature morphology.