The protective barriers of the CNS present challenges during the treatment and monitoring of diseases. In particular, the blood brain barrier is a major hindrance to the delivery of imaging contrast agents and therapeutics to the brain. In this work, we use gas microbubble-assisted focused ultrasound to transiently open the blood brain barrier and locally deliver silica coated gold nanorods across the barrier. This particular nanoagent possesses a strong optical absorption which enables and visualization of the delivered particles using ultrasound-guided photoacoustic imaging. The results of these studies demonstrate the potential of ultrasound-guided photoacoustics to image contrast agents delivered via microbubble-assisted focused ultrasound for longitudinal diagnostic imaging and for therapeutic monitoring of neurological diseases.

Imaging of cellular electric potential via calcium-ion sensitive contrast agents is a useful tool, but current it lacks sufficient depth penetration. We explore contrast-enhanced photoacoustic (PA) imaging, using Arsenazo III dye, to visualize cardiac myocyte depolarization . Phantom results show strong linearity of PA signal with dye concentration ( > 0.95), and agree spectrally with extinction measurements with varying calcium concentration. Cell studies indicate a significant (> 100-fold) increase in PA signal for dye-treated cells, as well as a 10-fold increase in peak-to-peak variation during a 30-second window. This suggests contrast-enhanced PA imaging may have sufficient sensitivity and specificity for depth-resolved visualization of tissue depolarization in real-time.

A method for selectively inducing apoptosis in tumor nodules is presented, with close-to-cellular level resolution, using 3D-resolved widefield temporal focusing illumination. Treatment times on the order of seconds were achieved using Verteporfin as the photosensitizer, with doses of 30 g ml and below. Results were achieved on both 2D and 3D cell cultures, demonstrating that treatment was possible through approximately one hundred microns of dense tumor nodules.

In this letter, we, for the first time, report on coherent anti-Stokes Raman scattering (CARS) spectroscopy of an ensemble of silicon nanowires (SiNWs) formed by wet chemical etching of crystalline silicon with a mask of silver nanoparticles. The fabricated SiNWs have diameter ranged from 30 to 200 nm and demonstrate both visible and infrared photolumine cence (PL) and spontaneous Raman signal, with their intensities depending on presence of silver nanoparticles in SiNWs. The efficiency of CARS in SiNW ensembles is found to be significantly higher than that in crystalline silicon. The results of CARS and PL measurements are explained in terms of resonant excitation of the electron states attributed to silicon nanoparticles.

Accurate non-invasive assessment of tissue elasticity is required for early diagnostics of many tissue abnormalities. We have developed a focused air-pulse system that produces a low-pressure and short-duration air stream, which can be used to excite transient surface waves (SWs) in soft tissues. System characteristics were studied using a high-resolution analog pressure transducer to describe the excitation pressure. Results indicate that the excitation pressure provided by the air-pulse system can be easily controlled by the air source pressure, the angle of delivery, and the distance between the tissue surface and the port of the air-pulse system. Furthermore, we integrated this focused air-pulse system with phase-sensitive optical coherence tomography (PhS-OCT) to make non-contact measurements of tissue elasticity. The PhS-OCT system is used to assess the group velocity of SW propagation, which can be used to determine Young's modulus. Pilot experiments were performed on gelatin phantoms with different concentrations (10%, 12% and 14% w/w). The results demonstrate the feasibility of using this focused air-pulse system combined with PhS-OCT to estimate tissue elasticity. This easily controlled non-contact technique is potentially useful to study the biomechanical properties of ocular and other tissues .

Scattering dominates light propagation in biological tissue, and therefore restricts both resolution and penetration depth in optical imaging within thick tissue. As photons travel into the diffusive regime-typically 1 mm beneath human skin, their trajectories transition from ballistic to diffusive due to increased number of scattering events, which makes it impossible to focus, much less track, photon paths. Consequently, imaging methods that rely on controlled light illumination are ineffective in deep tissue. This problem has recently been addressed by a novel method capable of dynamically focusing light in thick scattering media via time reversal of ultrasonically encoded (TRUE) diffused light. Here, using photorefractive materials as phase conjugate mirrors, we show a direct visualization and dynamic control of optical focusing with this light delivery method, and demonstrate its application for focused fluorescence excitation and imaging in thick turbid media. These abilities are increasingly critical to understanding the dynamic interactions of light with biological matter and processes at different system levels, as well as their applications for biomedical diagnosis and therapy.