Contrast and sensitivity enhanced molecular imaging using photoacoustic nanoamplifiers

Abstract

Molecular imaging is an emerging imaging principle which can visually represent the biological processes both spatially and temporally down to the sub-cellular level in vivo. The outcome of this research is expected to have a profound impact on facilitating the early diagnosis of diseases, accelerating the development of new drugs, and improving the efficacy of therapy. In general, molecular imaging highly relies on probes to sense the occurrence of molecular biological events, and to generate signals which could be picked up by diagnostic imaging modalities. The advances in the design of molecular probes not only have equipped traditional anatomical medical imaging with new capabilities but also, in some cases, stimulated developments of new imaging modalities and renaissance of existing medical imaging modalities. One of these is photoacoustic imaging, which as an emerging medical imaging modality, unites the merits from both optical imaging and ultrasound imaging. It shares with optical imaging, that it uses non-ionizing radiation and provides higher contrast and higher sensitivity than ultrasound imaging. Unlike optical imaging, which requires ballistic photons for imaging, photoacoustic imaging requires only diffusive photons to excite the ultrasound signal from the imaging target; therefore, it is capable of imaging much deeper into the tissue. In combination with molecular probes, photoacoustic molecular imaging has been demonstrated by several research groups using various photoacoustic molecular probes. However, the molecular probes used for most of these studies were contrast agents simply adopted from other optical imaging modalities. Our research on photoacoustic contrast agents indicated that the mechanism of photoacoustic signal generation from nanometer-sized contrast agents is distinct from that of optically homogeneous materials, such as tissue. We have discovered that, the amplitude of the photoacoustic signal generated from nano-contrast agents depends not only on the optical absorption of the particles, but more importantly, on the dynamic process of the heat conduction from the nanoparticles to the ambient, and the thermal properties of the surrounding materials. Based on our finding, we explored and further improved the photoacoustic response of the nanoparticles by exploiting the heat conduction process between the nanoparticle and its surrounding materials and by manipulating the excitations. This research allows to create optimized molecular specific contrast enhanced photothermal stable probes which can aid photoacoustic imaging and image guided photothermal cancer therapy.