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Synergy of light and sound, such as photoacoustic imaging, has demonstrated promising potentials in advancing the state-of-the-art of biomedical imaging by ultrasonically detecting the absorption of light, no matter the light is diffusive or not. As a result, optical contrast can be revealed with ultrasound or sub-ultrasound spatial resolution, which can be exploited to map sensitively the early tissue changes associated with the onset and development of early-stage diseases. The sources of photoacoustic emissions, however, could be very complicated within living biological tissue, as many tissue constituents may absorb light and generate heat to emit the ultrasonic waves, which considerably reduces the contrast between the target and the background. Therefore, exogenous agents, such as nanoparticles, that have absorption spectrum distinctive from that of background tissues have been widely used in the field to enhance the photoacoustic detection contrast and sensitivity at selected optical wavelengths. This talk summarizes our recent efforts in this direction that have explored various nanoparticles for more robust and more sensitive diagnosis and treatment of early-stage liver cancer based on photoacoustic imaging and photothermal effect. While the studies are based on merely small animal models, they may inspire further explorations towards preclinical and clinical trials.

Light and sound are the two most dominant mechanisms with which we naturally perceive this world. Both have their significant impacts yet with inherent limitations. For example, sound is insensitive to soft tissue functional changes, and light is strongly scattered in tissue, resulting in a trade-off between penetration depth and resolution. Here, we present our most recent research efforts of exploiting the synergy of light and sound to overcome this limitation. Specifically, photoacoustics converts diffusive photon into non-scattering ultrasonic waves, enabling a high-contrast sensing of optical absorption with ultrasonic resolution in deep tissue, overcoming the optical diffusion limit from the signal detection perspective. The generation of photoacoustic signals, however, is still throttled by the attenuation of photon flux due to the strong diffusion effect of light in tissue. Therefore, wavefront shaping is introduced, so that multiply scattered light could be manipulated so as to retain optical focusing or sufficient photon flux even at depths in tissue. We will present the recent development of photoacoustic imaging and optical wavefront shaping in our lab. Potential applications, existing challenges, and further improvement are also discussed.Light and sound are the two most dominant mechanisms with which we naturally perceive this world. Both have their significant impacts yet with inherent limitations. For example, sound is insensitive to soft tissue functional changes, and light is strongly scattered in tissue, resulting in a trade-off between penetration depth and resolution. Here, we present our most recent research efforts of exploiting the synergy of light and sound to overcome this limitation. Specifically, photoacoustics converts diffusive photon into non-scattering ultrasonic waves, enabling a high-contrast sensing of optical absorption with ultrasonic resolution in deep tissue, overcoming the optical diffusion limit from the signal detection perspective. The generation of photoacoustic signals, however, is still throttled by the attenuation of photon flux due to the strong diffusion effect of light in tissue. Therefore, wavefront shaping is introduced, so that multiply scattered light could be manipulated so as to retain optical foc...

Acoustically imaging non‐cavitating HIFU lesions is challenging due to the relatively weak contrast between normal and necrosed tissues. However, thermal lesions posses optical scattering and absorption characteristics that can differ significantly from surrounding tissue. Acousto‐optic (AO) sensing refers to the detection of phase modulated photons generated by the nonlinear interaction of diffuse laser light (532 and 1064 nm) and a focused ultrasound beam. AO sensing in excised chicken breast exposed to HIFU (1.1 MHz) is used to sense the onset and spatial extent of lesion formation in real time and to image an existing lesion after HIFU exposure. We also demonstrate that the AO signal can be used to provide real‐time feedback in order to more effectively control the duration of the HIFU exposure. [Work supported by the Center for Subsurface Sensing and Imaging Systems (NSF ERC Award No. EEC‐9986821).]

The acoustic monitoring of non‐cavitating high‐intensity focused ultrasound (HIFU) lesions is challenging due to the relatively weak acoustic contrast between normal and necrosed tissues. Fortunately, thermal lesions posses optical scattering and absorption characteristics that can differ significantly from surrounding tissue. Diffusive optical techniques such as photo‐acoustic imaging and diffusive optical tomography have been successfully employed to image absorbing structures in organs such as breast and brain. We describe a technique in which the nonlinear interaction of diffuse laser light (1064 nm) and the HIFU field is used to sense the onset and spatial extent of lesion formation in excised chicken breast. Changes in AO response correlate with lesion volume. We show that the AO signal can be used to provide real‐time feedback in order to control the duration of the HIFU exposure. The lesions that were formed with AO feedback had a more consistent volume than lesions formed with a fixed duration of...

Tissue heating by high‐intensity focused ultrasound (HIFU) is a promising modality for minimally invasive therapy. However, real‐time treatment monitoring still poses significant challenges, particularly at the lower exposure levels where stable cavitation and/or boiling does not result. Bubble‐‐free HIFU lesions offer little acoustic contrast; however, one does observe significant contrast in both optical scattering and absorption. We employ acousto‐optic (AO) imaging to sense, in real time, optical changes induced by lesion formation. By using a transducer to simultaneously heat a tissue volume and pump the AO interaction, lesions generated in excised chicken breast are monitored in real time. The change in AO response with time is linearly related to the time‐dependent lesion volume, provided the diameter of the lesion does not exceed the width of the optical beam. Therefore, AO sensing can be used to both determine the onset of lesion formation and the resulting volume of the necrosed region. The feas...

Tissue ablation by high‐intensity focused ultrasound (HIFU) leads to changes in the optical absorption and scattering of the tissue. Here acousto‐optic (AO) sensing was used to detect HIFU induced changes in the optical contrast of chicken breast. The tissue was insonified by 1‐MHz HIFU and illuminated by infrared light. The diffuse light that exited the tissue was collected and processed using photo‐refractive crystal based interferometer configured to detect phase modulated light that had interacted with the HIFU. Here the HIFU served both to ablate the tissue and elicit the AO response, and as a lesion forms, the increase in optical absorption and scattering should result in a reduction in modulated light being detected by the interferometer. The HIFU was amplitude modulated with a 50% duty cycle at 50 Hz and the interferometer output was processed through a lock‐in amplifier tuned to the modulation frequency to improve the signal‐to‐noise ratio. Using a focal pressure of 6 MPa (derated from water), the AO signal remained constant for ∼10 s of HIFU, and a “post‐mortem” in this time‐frame found no detectable lesion. Once the AO signal decreased a lesion was always detected and the lesion size correlated with the amount of decay of the AO signal. [Work supported by NSF CenSSIS EEC‐9986821]

Acousto‐optic imaging is a dual‐wave modality that combines ultrasound with diffuse light to achieve deep‐tissue imaging of optical contrast with the spatial resolution of ultrasound. While substantial progress has been made in recent years in detecting and imaging optical inhomogeneities in highly scattering media based on the acousto‐optic response, quantitative measurement of subsurface optical properties remains difficult. A technique for the local and quantitative measure of the optical properties of turbid media, referred to as pressure contrast acousto‐optic imaging, is presented. In this approach, the acousto‐optic signals elicited by ultrasound pulses at two different peak pressures are measured, and the ratio of the amplitudes of these two signals determined. The resulting pressure ratio, once calibrated for a given set of pressure pulses, is found to give a direct measure of the optical transport mean free path of the interaction region between the light and sound. Measurements of the transport...