Antonio M. Caravaca-Aguirre

High-speed scattering medium characterization with application to focusing light through turbid media

We introduce a phase-control holographic technique to characterize scattering media with the purpose of focusing light through it. The system generates computer-generated holograms implemented via a deformable mirror device (DMD) based on micro-electro-mechanical technology. The DMD can be updated at high data rates, enabling high speed wavefront measurements using the transmission matrix method. The transmission matrix of a scattering material determines the hologram required for focusing through the scatterer. We demonstrate this technique measuring a transmission matrix with 256 input modes and a single output mode in 33.8 ms and creating a focus with a signal to background ratio of 160. We also demonstrate focusing through a temporally dynamic, strongly scattering sample with short speckle decorrelation times.

Genetic algorithm optimization for focusing through turbid media in noisy environments

We introduce genetic algorithms (GA) for wavefront control to focus light through highly scattering media. We theoretically and experimentally compare GAs to existing phase control algorithms and show that GAs are particularly advantageous in low signal-to-noise environments.

Real-time resilient focusing through a bending multimode fiber

Multimode optical fibers are attractive for biomedical and sensing applications because they possess a small cross section and can bend over small radii of curvature. However, mode phase-velocity dispersion and random mode coupling change with bending, temperature, and other perturbations, producing scrambling interference among propagating modes; hence preventing its use for focusing or imaging. To tackle this problem we introduce a system capable of re-focusing light through a multimode fiber in 37ms, one order of magnitude faster than demonstrated in previous reports. As a result, the focus spot can be maintained during significant bending of the fiber, opening numerous opportunities for endoscopic imaging and energy delivery applications. We measure the transmission matrix of the fiber by projecting binary-amplitude computer generated holograms using a digital micro-mirror device controlled by a field programmable gate array. The system shows two orders of magnitude enhancements of the focus spot relative to the background.

High contrast three-dimensional photoacoustic imaging through scattering media by localized optical fluence enhancement

We demonstrate enhanced three-dimensional photoacoustic imaging behind a scattering material by increasing the fluence in the ultrasound transducer focus. We enhance the optical intensity using wavefront shaping before the scatterer. The photoacoustic signal induced by an object placed behind the scattering medium serves as feedback to optimize the wavefront, enabling one order of magnitude enhancement of the photoacoustic amplitude. Using the enhanced optical intensity, we scan the object in two-dimensions before post-processing of the data to reconstruct the image. The temporal profile of the photoacoustic signal provides the information used to reconstruct the third dimension.

Super-resolution photoacoustic imaging through a scattering wall.

The use of wavefront shaping to compensate for scattering has brought a renewed interest as a potential solution to imaging through scattering walls. A key to the practicality of any imaging through scattering technique is the capability to focus light without direct access behind the scattering wall. Here we address this problem using photoacoustic feedback for wavefront optimization. By combining the spatially non-uniform sensitivity of the ultrasound transducer to the generated photoacoustic waves with an evolutionary competition among optical modes, the speckle field develops a single, high intensity focus significantly smaller than the acoustic focus used for feedback. Notably, this method is not limited by the size of the absorber to form a sub-acoustic optical focus. We demonstrate imaging behind a scattering medium using two different imaging modalities with up to ten times improvement in signal-to-noise ratio and five to six times sub-acoustic resolution.

SINGLE MULTIMODE FIBER ENDOSCOPE

Multimode fibers can guide thousands of modes capable of delivering spatial information. Unfortunately, mode dispersion and coupling have so far prevented their use in endoscopic applications. To address this long-lasting challenge, we present a robust scanning fluorescence endoscope. A spatial light modulator shapes the input excitation wavefront to focus light on the distal tip of the fiber and to rapidly scan the focus over the region of interest. A detector array collects the fluorescence emission propagated back from the sample to the proximal tip of the fiber. We demonstrate that proper selection of the multimode fiber is critical for a robust calibration and for high signal-to-background ratio performance. We compare different types of multimode fibers and experimentally show that a focus created through a graded-index fiber can withstand a few millimeters of fiber distal tip translation. The resulting scanning endoscopic microscope images fluorescent samples over a field of view of 80µm with a resolution of 2µm.

Laser speckle contrast imaging with extended depth of field for in-vivo tissue imaging

This work presents, to our knowledge, the first demonstration of the Laser Speckle Contrast Imaging (LSCI) technique with extended depth of field (DOF). We employ wavefront coding on the detected beam to gain quantitative information on flow speeds through a DOF extended two-fold compared to the traditional system. We characterize the system in-vitro using controlled microfluidic experiments, and apply it in-vivo to imaging the somatosensory cortex of a rat, showing improved ability to image flow in a larger number of vessels simultaneously.

Thermal expansion feedback for wave-front shaping

We present a technique for focusing inside scattering media that combines optical-coherence-tomography (OCT) and wave-front-shaping (WFS). We use OCT as a non-invasive feedback for WFS optimization of a separate penetrating laser, based on light-induced thermal-expansions.

High-speed phase-control of wavefronts with binary amplitude DMD for light control through dynamic turbid media

The optical imaging depth in biological materials is limited by the scattering of light in tissue. New methods which control light propagation through scattering media have been introduced with the potential to overcome the scattering of light in biological materials. These techniques shape the incident wavefront to pre-compensate for the scattering effects of light propagation in the material and beyond. However, living biological materials have speckle decorrelation times on the millisecond timescale. This fast rate of change makes liquid crystal spatial light modulation (LC-SLM) devices too slow for this task. To achieve the required wavefront control with high modulation speeds we present binary-amplitude off-axis computer-generated holography implemented on a digital micro-mirror device (DMD). Binary amplitude off-axis holography is a method for the generation of arbitrary wavefronts, and in particular uniform-amplitude phase-modulated images. As a result, we are able to simultaneously encode phase modulated wavefronts at the high frame rate of binary amplitude DMDs. This wavefront encoding technique allows for focusing through temporally dynamic turbid materials at a rate which approaches the decorrelation time of living biological tissue. We demonstrate this technique by high speed wavefront optimization for focusing through turbid media as well as through a dynamic, strongly scattering sample with short speckle decorrelation times. With this approach we attain an order of magnitude improvement in measurement speed over the previous fastest wavefront determination method and three orders of magnitude improvement over LC-SLM methods.

Minimally invasive multimode optical fiber microendoscope for deep brain fluorescence imaging

A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive multi-photon approaches for deep (>2mm) structures, while gradient refractive index (GRIN) endoscopes are relatively thick and can cause significant damage upon insertion. Here, we present a novel micro-endoscope design to image neural activity at arbitrary depths via an ultra-thin multi-mode optical fiber (MMF) probe that has 5-10X thinner diameter than commercially available micro-endoscopes. We demonstrate micron-scale resolution, multi-spectral and volumetric imaging. In contrast to previous approaches, we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator (GCaMP). Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.