Projects

Seeing through fog, looking around corners, and peering deep into biological tissue have traditionally been considered to be impossible tasks in optics. The main challenge is attributable to disordered optical scattering which scrambles the optical field of light from different optical paths. In the last decade, optical wavefront shaping has made great progress to control light through complex disordered scattering media for imaging and focusing^1–6. This class of techniques first measures the optical phase or complex field of light from different scattering paths and then actively manipulates the output field by shaping an input wavefront. To focus light inside scattering media, a ‘guidestar’ mechanisms is required to provide feedback for wavefront measurement and the subsequent wavefront display. The projects aims to develop “guidestars” and wavefront shaping methods for light focusing inside scattering media.

References:

R. Horstmeyer*, H. Ruan*, and C. Yang*, "Guidestar-assisted wavefront-shaping methods for focusing light into biological tissue," Nature Photonics 9, 563–571 (2015).

H. Ruan*, M. Jang*, and C. Yang, "Optical focusing inside scattering media with time-reversed ultrasound microbubble encoded light," Nature Communications 6, 8968 (2015).

H. Ruan, T. Haber, Y. Liu, J. Brake, J. Kim, J. Berlin, and C. Yang, "Focusing light inside scattering media with magnetic particle guided wavefront shaping," Optica, 4 1337 (2017).

Noninvasive light focusing deep inside living biological tissue has long been a goal in biomedical optics. However, the optical scattering of biological tissue prevents conventional optical systems from tightly focusing visible light beyond several hundred micrometers. The recently developed wavefront shaping technique time-reversed ultrasonically encoded (TRUE) focusing enables noninvasive light delivery to targeted locations beyond the optical diffusion limit. However, until now, TRUE focusing has only been demonstrated inside nonliving tissue samples. We present the first example of TRUE focusing in 2-mm-thick living brain tissue and demonstrate its application for optogenetic modulation of neural activity in 800-mm-thick acute mouse brain slices at a wavelength of 532 nm. We found that TRUE focusing enabled precise control of neuron firing and increased the spatial resolution of neuronal excitation fourfold when compared to conventional lens focusing. This work is an important step in the application of TRUE focusing for practical biomedical uses.

Reference:

H. Ruan*, J. Brake*, J. E. Robinson, Y. Liu, M. Jang, C. Xiao, C. Zhou, V. Gradinaru, and C. Yang, "Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light," Science Advances, aao5520 (2017).

How do photons travel inside biological tissue? What’s the percentage of the photons can reach a target voxel inside a sample? How many of the photons that reach the target are modulated or tagged by the optical properties of the target? How many of these tagged photons can return to the surface of the sample and get detected? The Monte Carlo and diffuse approximation models developed in this project help answer all these important questions. This work gives us a sense on the theoretical limit of using light to probe the optical information inside biological tissue.

Reference:

M. Jang, H. Ruan, B. Judkewitz, and C. Yang, "Model for estimating the penetration depth limit of the time-reversed ultrasonically encoded optical focusing technique," Optics Express 22, 5787–5807 (2014).

In this project, we theoretically and numerically show that by using a transmission matrix inversion method to achieve focusing, within a limited field of view and under a low noise condition in transmission matrix measurements, the peak-to-background ratio of the focus can be higher than that achieved by conventional methods such as optical phase conjugation or feedback-based wavefront shaping. Experimentally, using a phase-modulation spatial light modulator, we increase the PBR by 66% over that achieved by conventional methods based on phase conjugation. In addition, we demonstrate that, within a limited field of view and under a low noise condition in transmission matrix measurements, our matrix inversion method enables light focusing to multiple foci with greater fidelity than those of conventional methods.

Reference:

J. Xu, H. Ruan, Y. Liu, H. Zhou, and C. Yang, “Focusing light through scattering media by transmission matrix inversion,” Optics Express 25, 27234 (2017)

For conventional optical imaging systems, it’s difficult to achieve both high resolution and large field of view. In other words, it’s difficult to increase the throughput of optical systems in convention. My colleagues Mooseok Jang and Yu Horie came up with a smart idea to break this limit when they were playing tennis. The idea is to use a disordered engineered metasurface to generate scattered light of high angular components and to use wavefront shaping technique to focus light through the metasurface. We demonstrate high numerical aperture (NA > 0.5) focusing in an ~8 mm field of view. An estimated addressable points is ~2.2 × 108, one orders of magnitude larger than conventional imaging systems.

Reference:

M. Jang, Y. Horie, A. Shibukawa, J. Brake, Y. Liu, S. M. Kamali, A. Arbabi, H. Ruan, A. Faraon, and C. Yang, "Wavefront shaping with disorder-engineered metasurfaces," Nat. Photonics 12, 84–90 (2018).

A method that uses digital heterodyne holography reconstruction to extract scattered light modulated by a singlecycle ultrasound (US) burst is demonstrated and analyzed. An US burst is used to shift the pulsed laser frequency by a series of discrete harmonic frequencies which are then locked on a CCD. The analysis demonstrates that the unmodulated light’s contribution to the detected signal can be canceled by appropriate selection of the pulse repetition frequency. It is also shown that the modulated signal can be maximized by selecting a pulse sequence which consists of a pulse followed by its inverted counterpart. The system is used to image a 12 mm thick chicken breast with 2 mm wide optically absorbing objects embedded at the midplane. Furthermore, the method can be revised to detect the nonlinear US modulated signal by locking at the second harmonic US frequency.

Reference:

H. Ruan, M. L. Mather, and S. P. Morgan, "Pulsed ultrasound modulated optical tomography utilizing the harmonic response of lock-in detection," Appl. Opt. 52, 4755–62 (2013).

As coherent light interacts with scattering media, a laser speckle pattern develops. For a dynamic sample, the laser speckle pattern changes over time. The correlation between the speckle patterns measured at different times depends on the motion of the scattering media. This correlation is of particular interest because 1) it can be used as a signal to evaluate the dynamic property of samples, e.g. blood flow index; 2) it poses a limitation in some coherent optical imaging techniques such as ultrasound modulated optical tomography and optical wavefront shaping. In this project, we investigated this decorrelation characteristic time through a 1.5-mm-thick dorsal skin flap of a living mouse and found that it ranges from 50 ms to 2.5 s depending on the level of immobilization. This study provides information on relevant time scales for applying OPC to living tissues.

Reference:

M. Jang*, H. Ruan*, I. M. Vellekoop, B. Judkewitz, E. Chung, and C. Yang, "Relation between speckle decorrelation and optical phase conjugation (OPC)-based turbidity suppression through dynamic scattering media: a study on in vivo mouse skin," Biomed. Opt. Express 6, 72–85 (2015).

While taking photos is fun, building a digital camera from sketch is exciting. In this master student project, we built a digital camera on a board level. We designed three print circuit boards – an I2C controlled power management module, an A/D module converting camera VGA signals to digital signals, and a FPGA board to grab images to the memory and the SD card. The FPGA was programmed with a system on chip (SoC), which allows us to program in C and write images to the SD card in FAT32 format.

In the big data era, monitoring signals for a large number of sensors is highly demanded. However, a typical oscilloscope can only allow us to monitor signals from only 4 channels. In this project, we developed our own data acquisition system that can measure signals up to 10 channels simultaneously. We developed a signal display GUI in Visual Studio that allows us to monitor signals in real-time. This system was later deployed to monitor sensors from a diesel engine.