Light is confined within a mouse brain tissue. a Bright field microscope image of a 240 µm thick coronal brain slice from a mouse. b Blue light imaged through the brain slice tissue with no ultrasound. Laser beam is traveling along z-direction, impinging on the brain slice from the bottom and being imaged from the top, as shown in Fig. 2a. c Blue light imaged through the tissue couples to a sculpted waveguide, when ultrasound is turned on. d Line cross-section of the confined optical waveguide mode through the brain slice tissue near the top edge of the slice. The line-cut is through the line indicated by the red arrows in Fig. 7c. The measured extinction ratio (ER1) is ~5
Our work demonstrates that patterned ultrasound can be leveraged to produce a variety of light piping components within the medium itself. Of particular interest is biological and neural tissue, where light techniques are fundamental to many sensing and actuation strategies, but penetration remains a problem. To be clear, this technique does not address absorption; instead, it plays the same role as waveguides do, i.e., confinement and guiding of light to counterbalance beam expansion due to scattering and diffraction. Our results in a homogeneous medium with negligible scattering show that ballistic photons can be confined and guided using the ultrasonically-defined optical waveguides. In a scattering medium both ballistic and scattered photons exist. While our experimental results demonstrate that this method works in a scattering medium, it would be important to study how the ultrasonically sculpted optical waveguide affects both scattered and ballistic photons in a turbid medium.
Additionally, the demonstrated technique does not require high average ultrasonic power. Both the ultrasound and the laser can be pulsed. The effective light-ultrasound interaction through the medium happens only during the tiny fraction of the ultrasonic wave period set by the modulation of the laser and the relative phase between the laser modulation and the ultrasound standing wave. In addition, different optical processes of biological interest respond to light over different time scales. For example, opsins integrate incoming photons over the course of milliseconds; by comparison, the ultrasonic waves used here have periods in the microseconds. As a result, neither the light source nor the ultrasonic wave have to be continuously on but can be pulsed rapidly. For diagnostic and therapeutic applications, the established maximum values of de-rated spatial-peak pulse-average intensity (ISPPA), spatial-peak temporal average intensity (ISPTA), and mechanical index (MI) as defined by FDA are 190 W cm−2, 720 mW cm−2, and 1.9, respectively. We performed ultrasonic power measurements outside the transducer to probe the tail of the ultrasonic pressure waves to obtain the maximum power required for realizing optical waveguides discussed in this paper (see Methods). For the extreme case, when all elements of the ultrasonic phased array are synchronously driven at 20 V, we measured ISPPA = 50.365 W cm−2, ISPTA = 503.7 mW cm−2, and MI = 1.246, respectively, at the highest pressure intensity region for a pulsed ultrasound at a duty cycle of 1%, (during the on time, the transducer elements are driven with approximately 40 cycles, corresponding to ~40 μs, with a pulse repetition frequency (PRF) of 250 Hz), which are all within the safety limit. The ultrasonic wave could be pulsed at much smaller duty cycles to reduce its thermal effect even further.
Reconfigurable optical pattern generation in tissue using this acousto-optic technique is not limited to the two examples demonstrated in this paper. One can imagine steering a single virtual optical waveguide simply by physically moving the array of ultrasonic transducers or selectively turning on and off individual transducer elements in a digital manner or continuously changing the pattern of light by continuously changing the phases and amplitudes of the array elements.
It appears likely that with the advanced ultrasound beam-steering technologies now in development for various medical applications such as High Intensity Focused Ultrasound (HiFU) complex pressure patterns can be created in tissue. Of course, when contemplating applications in the central nervous system, the ultrasound propagation loss in the skull can present a challenge and this will likely necessitate the use of craniotomy windows or burr holes to place an array of ultrasonic transducers on the surface of the brain. Using our acousto-optic technique, ultrasound transducers can be placed outside the brain to launch ultrasonic waves from the surface to guide and steer light from a laser or light emitting diode through the craniotomy window. Initial simulation results (data not shown), indicate that planar, multi-element surface arrays (as opposed to cylindrically-symmetric arrays like those employed in this work) can transiently produce cylindrical pressure regions tissue similar to those demonstrated in this paper that extend into the tissue by beam-forming. With this approach, light can be guided, steered, and focused deep into the brain tissue without inserting any invasive light guide into the tissue. Lastly, while we demonstrated all of our results based on ultrasonic standing waves, there is also a great potential for using pulsed ultrasound to sculpt transient optical waveguides with arbitrary shapes and trajectories. Nevertheless, taken together, our results suggest the tantalizing notion that a variety of optical components can be instantiated within tissue.