Photoacoustic methods for direct monitoring of nanoparticle enhanced photothermal ablation in biological tissues: visualizing scattering, absorption and thermal effects

Photothermal ablation of biological tissue is a powerful minimally invasive technique capable of selectively destroying high-risk localized lesions using near infrared laser light delivered through thin optical fibers. As such, photothermal therapy (PTT) holds great therapeutic potential particularly in the context of cancer treatment, however, effective implementation has proven challenging due to lack of availability of direct treatment monitoring. Currently, MRI is the modality of choice due to molecular contrast and thermometry capability, unfortunately slow imaging speed as well as high cost and complexity are significant impediments preventing widespread adoption. Photoacoustic imaging (PAI) can in principle overcome these limitations since it provides multispectral molecular contrast and thermometry, while easily implemented at video frame rates. Nevertheless, current embodiments of PAI systems have failed to provide sufficient imaging sensitivity to changes in tissue temperature and optical properties during PTT at clinically relevant scales. We are developing a PTT-specific PAI system with specialized detectors capable of visualizing bulk-tissue optical property changes, as well as temperature, at imaging scales of up to several cm. We show that, despite the traditional interpretation, photoacoustic signals are not limited to depending on only the optical absorption coefficient but can be influenced by temperature. Finally, by combining PTT with novel organic nanoparticles (Porphysomes) and diffuse optical tomography, both developed at our center, we demonstrate theranostic potential through enhanced lesion localization and thermal confinement. These developments have significant implications for guiding minimally invasive photothermal treatments with reduced or eliminated collateral tissue damage and consequently preservation of posttreatment quality of life.