Quantitative and qualitative monitoring of neovascular growth is required in many vascular tissue engineering applications. For example, the contribution of progenitor cells in growing microvasculature has been demonstrated; however, the process of vascularization from progenitor cells is not well understood. Therefore, there is a need for an imaging technique that is consistent, easy to use, and can quantitatively assess the dynamics of vascular growth or regression in a three-dimensional environment. In this study, we evaluate the ability of combined ultrasound and photoacoustic imaging to assess the dynamics of vascular growth. The experiments were performed using hydrogels that spontaneously promote tube formation from implanted mesenchymal stem cells (MSCs). Specifically, PEGylated fibrin gels, supporting the development of capillary growth were implanted in a Lewis rat. After one week, the rat was euthanized and the gel implants were excised and positioned in water cuvettes for imaging. Simultaneous ultrasound and photoacoustic images were obtained using single-element, focused ultrasound transducers interfaced with a nanosecond pulsed laser source. To image samples, ultrasound transducers operating at either 25 MHz or 48 MHz and interfaced with laser sources operating at either 532 nm or within 680-800 nm wavelengths were used. The 3-D ultrasound and photoacoustic images were acquired by mechanically scanning the transducer over the region of interest and capturing spatially co-registered and temporally consecutive photoacoustic transients and ultrasound pulse-echo signals. The ultrasound and photoacoustic images agree well with the overall anatomy and vascular structure in the gel samples. The results suggest that the photoacoustic and ultrasound imaging could be used to sequentially monitor the growth of neovasculature in-vivo.
The effectiveness of an imaging technique is often based on the ability to image quantitatively both morphological and physiological functions of the tissue. Here we present several ultrasound-based imaging techniques capable of visualizing both structural and functional properties of living tissue. Each imaging system utilizes custom-made, targeted nanoparticles developed to probe specific molecular events. Therefore, images of these nanoparticles display molecular processes in the body. Furthermore, the developed nanoparticle contrast agents can also be used for image-guided molecular therapy. For each imaging system, the basic physics and principles behind each approach are described. Experimental aspects of each imaging system including fabrication of integrated imaging probes and associated imaging hardware, and design of targeted contrast agents are discussed. Finally, biomedical and clinical applications of the developed imaging approaches ranging from microscopic to macroscopic imaging of cardiovascular diseases, cancer detection, diagnosis, therapy and therapy monitoring are demonstrated and discussed.
Gold nanoparticles targeting epidermal growth factor receptor via antibody conjugation undergo molecular specific aggregation when they bind to receptors on cell surfaces, leading to a red shift in their plasmon resonance frequency. Capitalizing on this effect, we demonstrate the efficacy of the molecular specific photoacoustic imaging technique using subcutaneous tumor-mimicking gelatin implants in ex-vivo mouse tissue. The results of our study suggest that highly selective and sensitive detection of cancer cells is possible using multiwavelength photoacoustic imaging and molecular specific gold nanoparticles.
The beam profiles of pulsed lasers are currently measured using either complementary metal oxide semiconductor(CMOS) or charge coupled device(CCD) cameras. Despite providing high-resolution beam profiles, these devices cannot work with high power lasers. If additional optical attenuators are used, beam distortions may occur. In this paper we demonstrate a high-resolution photoacoustic technique capable of measuring the beam profile of pulsed lasers. The beam profiles of a pulsed neodymium-doped yttrium aluminium garnet(Nd:YAG) laser and a pulsed optical parametric oscillator(OPO) laser system were measured using a polydimethylsiloxane film and a single element high-frequency ultrasonic transducer. The advantages and limitations of the developed photoacoustic technique are discussed.