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Jerome Mertz

Publications and source records attributed to Jerome Mertz.

At least 19 recordsLinked to original sources

Tailored Speckle Illumination Microscopy with Enhanced Sectioning and Image Quality

Optical speckle patterns have been widely used for illumination in computational imaging, optical sectioning microscopy, and super-resolution imaging. However, commonly used speckles satisfy Rayleigh statistics, which are not ideal for diverse imaging applications. Here we tailor three-dimensional speckle intensity statistics for dynamic speckle illumination microscopy based on linear fluorescence. Optical sectioning is enhanced by axially varying speckle contrast, and image reconstruction noise is minimized with in-focus speckles of binary intensities. The customized speckle statistics are shown to tolerate sample-induced aberration and scattering. We apply tailored speckle illumination to mouse brain vascular imaging and demonstrate much improved image quality than optical-sectioning structured illumination. These results establish customization of speckle intensity statistics as a promising strategy for robust, high-throughput fluorescence imaging in thick, scattering biological specimens.

physics.optics

Far-field compressive ultrasound beamforming

We present a compressive beamforming method for coherent plane-wave compounding (CPWC) ultrasound imaging based on a far-field decomposition of the received radiofrequency (RF) data into virtual plane waves. This decomposition recasts the imaging operation entirely in the spatial frequency domain ($k$-space), allowing direct and flexible control over $k$-space sampling distributions based on the principle of coarrays. We present vernier-type sampling strategies designed to optimize the tradeoff between image contrast and resolution with minimum redundancy, including strategies that favor dense low-frequency sampling for high contrast, shifted schemes that extend the frequency support for improved resolution, and confocal or hybrid compounding schemes that approximate the spatial-frequency transfer function of conventional DAS beamforming. Our method, called KK beamforming, is validated with a calibration phantom and in-vivo human tissue data, demonstrating compression factors of an order of magnitude while maintaining image qualities comparable to conventional DAS. We further demonstrate that KK beamforming yields improvements in computational speed owing to its reduced memory footprint and more efficient cache utilization of the compressed data and associated look-up tables.

eess.SP

Implications of temporal sampling in voltage imaging microscopy

Significance: Voltage imaging microscopy has emerged as a powerful tool to investigate neural activity both in vivo and in vitro. Various imaging approaches have been developed, including point-scanning, line-scanning and wide-field microscopes, however the effects of their different temporal sampling methods on signal fidelity have not yet been fully investigated. Aim: To provide an analysis of the inherent advantages and disadvantages of temporal sampling in scanning and wide-field microscopes and their effect on the fidelity of voltage spike detection. Approach: We develop a mathematical framework based on a mixture of analytical modeling and computer simulations with Monte-Carlo approaches. Results: Scanning microscopes outperform wide-field microscopes in low signal-to-noise conditions and when only a small subset of spikes needs to be detected. Wide-field microscopes outperform scanning microscopes when the measurement is temporally undersampled and a large fraction of the spikes needs to be detected. Both modalities converge in performance as sampling increases and the frame rate reaches the decay rate of the voltage indicator. Conclusions: Our work provides guidance for the selection of optimal temporal sampling parameters for voltage imaging. Most importantly it advises against using scanning voltage imaging microscopes at frame rates below 500 Hz.

physics.optics

Widefield pump-probe microscopy with coherent background subtraction by angle-compensated temporal shearing

Pump-probe microscopy enables label-free imaging of structural and chemical features of samples. However, signals in pump-probe microscopy are typically small and often must be measured in the presence of large backgrounds. As a result, achieving measurements with a high signal-to-noise ratio is challenging, particularly when using sensors that are easily saturated, such as CMOS cameras. We present a method for enhancing signal-to-noise ratio while avoiding detector saturation. In this approach, temporally separated (sheared) reference and probe pulses transmit through a sample before and after the arrival of a pump pulse. The probe and reference pulses are then temporally recombined with opposing phases and nearly matched amplitudes, resulting in interferometric background subtraction. This recombining operation is performed by a novel common-path interferometer. Unlike previous techniques for temporal shearing, this interferometer demonstrates negligible phase and group delay dispersion with angle of incidence, allowing convenient widefield imaging. To our knowledge, this is the first common-path interferometer with such a property. We demonstrate the technique by measuring transient absorption signals in gold nanorod films with a signal-to-background ratio enhanced by over 100% and a signal-to-noise ratio enhanced by about 70%.

physics.optics

3D space-variant modal deconvolution with computed point spread functions

Deconvolution is the most widely used aberration correction technique in microscopy, however most techniques assume that the aberrations are the same for each point in the image, which is rarely true. Methods for tracking spatially varying aberrations require burdensome calibration or computation, or require symmetries in the aberration patterns. Here, we expand on existing modal deconvolution methods to demonstrate 3D fluorescence deconvolution in imaging systems that exhibit no simple symmetry. Our method is based on a space-variant generalization of Richardson-Lucy deconvolution that makes use of ZEMAX\textsuperscript{\textregistered}-derived point spread functions without the requirement of guide stars or calibration measurements. We validate the performance of our method by applying it to snapshot multiplane imaging of both bead samples and biological specimens, and show that modal decomposition is a practical solution for deconvolving spatially varying aberrations that do not display clear symmetries.

physics.optics

Back-illumination interference tomography for imaging weak scattering in thick tissues

Biological tissues are composed of discrete compartments of biochemical media that often exhibit subtle differences in refractive index. Light propagating through these compartments partially diffracts in a forward direction with a pi/2 phase shift. We introduce a microscopy technique to image this scattering signal in thick tissues, called back-illumination interference tomography (BIT). An incoherent source is demagnified and imaged past the focal plane of a high numerical aperture objective lens, producing a small, semicoherent source of backscattered light. This backscattered light undergoes a phase inversion over the narrow depth of field of the microscope, providing interference contrast to weakly scattering objects at the focal plane. BIT offers a fundamentally different source of contrast to conventional illumination and oblique back-illumination microscopy. Compared to these techniques, we show that BIT improves contrast to blood cells in vitro in microfluidic chambers and in vivo in a human capillary. Finally, we apply BIT to unstained, unlabeled bulk human tissue ex vivo and compare side-by-side to adjacent frozen sections stained with Hematoxylin and Eosin. These results demonstrate the potential of BIT to provide high resolution, high speed, 3D imaging of unprocessed biological tissues.

physics.optics

Plane-wave compounding with adaptive joint coherence factor weighting

Coherent Plane Wave Compounding (CPWC) is widely used for ultrasound imaging. This technique involves sending plane waves into a sample at different transmit angles and recording the resultant backscattered echo at different receive positions. The time-delayed signals from the different combinations of transmit angles and receive positions are then coherently summed to produce a beamformed image. Various techniques have been developed to characterize the quality of CPWC beamforming based on the measured coherence across the transmit or receive apertures. Here, we propose a more fine-grained approach where the signals from every transmit/receive combination are separately evaluated using a quality metric based on their joint spatio-angular coherence. The signals are then individually weighted according to their measured Joint Coherence Factor (JCF) prior to being coherently summed. To facilitate the comparison of JCF beamforming compared to alternative techniques, we further propose a method of image display standardization based on contrast matching. We show results from tissue-mimicking phantoms and human soft-tissue imaging. Fine-grained JCF weighting is found to improve CPWC image quality compared to alternative approaches.

eess.IV

Interferometric speckle visibility spectroscopy (iSVS) for measuring decorrelation time and dynamics of moving samples with enhanced signal-to-noise ratio and relaxed reference requirements

Diffusing wave spectroscopy (DWS) is a group of techniques used to measure the dynamics of a scattering medium in a non-invasive manner. DWS methods rely on detecting the speckle light field from the moving scattering media and measuring the speckle decorrelation time to quantify the scattering mediums dynamics. For DWS, the signal-to-noise (SNR) is determined by the ratio between measured decorrelation time to the standard error of the measurement. This SNR is often low in certain applications because of high noise variances and low signal intensity, especially in biological applications with restricted exposure and emission levels. To address this photon-limited signal-to-noise ratio problem, we investigated, theoretically and experimentally, the SNR of an interferometric speckle visibility spectroscopy (iSVS) compared to more traditional DWS methods. We found that iSVS can provide excellent SNR performance through its ability to overcome camera noise. We also proved iSVS system has more relaxed constraints on the reference beam properties than most other interferometric systems. For an iSVS to function properly, we simply require the reference beam to exhibit local temporal stability, while incident angle, reference phase, and intensity uniformity do not need to be constrained. This flexibility can potentially enable more unconventional iSVS implementation schemes.

eess.IV

Roadmap on Wavefront Shaping and deep imaging in complex media

The last decade has seen the development of a wide set of tools, such as wavefront shaping, computational or fundamental methods, that allow to understand and control light propagation in a complex medium, such as biological tissues or multimode fibers. A vibrant and diverse community is now working on this field, that has revolutionized the prospect of diffraction-limited imaging at depth in tissues. This roadmap highlights several key aspects of this fast developing field, and some of the challenges and opportunities ahead.

physics.optics

Flatfield Ultrafast Imaging with Single-Shot Non-Synchronous Array Photography

We present a method for acquiring a sequence of time-resolved images in a single shot, called Single-Shot Non-Synchronous Array Photography (SNAP). In SNAP, a pulsed laser beam is split by a diffractive optical element into an array of angled beamlets whose illumination fronts remain perpendicular to the optical axis. Different time delays are imparted to each beamlet by an echelon, enabling them to probe a scene in rapid succession. The beamlets are then imaged onto different regions of a camera by a lenslet array. Because the illumination fronts remain flat (head-on) independently of beamlet angle, the temporal resolution of SNAP is fundamentally limited only by the laser pulse duration, akin to a "global shutter" in conventional imaging. We demonstrate SNAP by capturing the evolution of a laser induced plasma filament for 20 frames at an average rate of 4.2 Tfps.

physics.optics

Ultrasound differential phase contrast using backscattering and the memory effect

We describe a simple and fast technique to perform ultrasound differential phase contrast (DPC) imaging in arbitrarily thick scattering media. Though configured in a reflection geometry, DPC is based on transmission imaging and is a direct analogue of optical differential interference contrast (DIC). DPC exploits the memory effect and works in combination with standard pulse-echo imaging, with no additional hardware or data requirements, enabling complementary phase contrast (in the transverse direction) without any need for intensive numerical computation. We experimentally demonstrate the principle of DPC using tissue phantoms with calibrated speed-of-sound inclusions.

eess.IV

Speed-of-sound imaging by differential phase contrast with angular compounding

We describe a technique to reveal speed-of-sound (SoS) variations within an echogenic sample. The technique uses the same receive data as standard pulse-echo imaging based on plane-wave compounding, and can be operated in parallel. Point-like scatterers randomly distributed throughout the sample serve as local probes of the downstream transmit-beam phase shifts caused by aberrating structures within the sample. Phase shifts are monitored in a differential manner, providing signatures of transverse gradients of the local sample SoS. The contrast of the signatures is augmented by a method of angular compounding, which provides ``focus" control of the image sharpness, which, in turn, enables a visual localization of aberrating inclusions within the sample on the fly. The localization can be performed in 2D when operated with standard B-mode imaging, or in 3D when operated with C-mode imaging. Finally, we present a wave-acoustic forward model that provides insight into the principle of differential phase contrast (DPC) imaging, and roughly recapitulates experimental results obtained with an elastography phantom. In particular, we demonstrate that our technique easily reveals relative SoS variations as small as 0.5\% in real time. Such imaging may ultimately be useful for clinical diagnosis of pathologies in soft tissue.

eess.IV

Simultaneous multiplane imaging with reverberation multiphoton microscopy

Multiphoton microscopy (MPM) has gained enormous popularity over the years for its capacity to provide high resolution images from deep within scattering samples1. However, MPM is generally based on single-point laser-focus scanning, which is intrinsically slow. While imaging speeds as fast as video rate have become routine for 2D planar imaging, such speeds have so far been unattainable for 3D volumetric imaging without severely compromising microscope performance. We demonstrate here 3D volumetric (multiplane) imaging at the same speed as 2D planar (single plane) imaging, with minimal compromise in performance. Specifically, multiple planes are acquired by near-instantaneous axial scanning while maintaining 3D micron-scale resolution. Our technique, called reverberation MPM, is well adapted for large-scale imaging in scattering media with low repetition-rate lasers, and can be implemented with conventional MPM as a simple add-on.

physics.optics

Video-rate large-scale imaging with Multi-Z confocal microscopy

Fast, volumetric imaging over large scales has been a long-standing goal in biological microscopy. Scanning techniques such as fluorescence confocal microscopy can acquire 2D images at high resolution and high speed, but extending the acquisition to multiple planes at different depths requires an axial scanning mechanism that drastically reduces the acquisition speed. To address this challenge, we report an augmented variant of confocal microscopy where the key innovation consists to use a series of reflecting pinholes axially distributed in the detection plane, each one probing a different depth within the sample. As no axial scanning mechanism is involved, our technique provides simultaneous multiplane imaging over fields of view larger than a millimeter at video-rate. We demonstrate the general applicability of our technique to neuronal imaging of both Caenorhabditis elegans and mouse brains in-vivo.

physics.bio-ph

High-resolution 3D phase imaging using a partitioned detection aperture: a wave-optic analysis

Quantitative phase imaging has become a topic of considerable interest in the microscopy community. We have recently described one such technique based on the use of a partitioned detection aperture, which can be operated in a single shot with an extended source [Opt. Lett. 37, 4062 (2012)]. We follow up on this work by providing a rigorous theory of our technique using paraxial wave optics, where we derive fully three-dimensional spread functions for both phase and intensity. Using these functions we discuss methods of phase reconstruction for in- and out-of-focus samples, insensitive to weak attenuations of light. Our approach provides a strategy for detection-limited lateral resolution with an extended depth of field, and is applicable to imaging smooth and rough samples.

physics.optics

Axial range of conjugate adaptive optics in two-photon microscopy

We describe an adaptive optics technique for two-photon microscopy in which the deformable mirror used for aberration compensation is positioned in a plane conjugate to the plane of the aberration. We demonstrate in a proof-of-principle experiment that this technique yields a large field of view advantage in comparison to standard pupil-conjugate adaptive optics. Further, we show that the extended field of view in conjugate AO is maintained over a relatively large axial translation of the deformable mirror with respect to the conjugate plane. We conclude with a discussion of limitations and prospects for the conjugate AO technique in two-photon biological microscopy.

physics.optics

Conjugate adaptive optics in widefield microscopy with an extended-source wavefront sensor

Adaptive optics is a strategy to compensate for sample-induced aberrations in microscopy applications. Generally, it requires the presence of "guide stars" in the sample to serve as localized reference targets. We describe an implementation of conjugate adaptive optics that is amenable to widefield (i.e. non-scanning) microscopy, and can provide aberration corrections over potentially large fields of view without the use of guide stars. A unique feature of our implementation is that it is based on wavefront sensing with a single-shot partitioned-aperture sensor that provides large dynamic range compatible with extended samples. Combined information provided by this sensor and the imaging camera enable robust image de-blurring based on a rapid estimation of sample and aberrations obtained by closed-loop feedback. We present the theoretical principle of our technique and proof of concept experimental demonstrations.

physics.optics

High-throughput Imaging of Self-luminous Objects through a Single Optical Fiber

Imaging through a single optical fiber offers attractive possibilities in many applications such as microendoscopy or remote sensing. However, the direct transmission of an image through an optical fiber is difficult because spatial information is scrambled upon propagation. We demonstrate an image transmission strategy where spatial information is first converted to spectral information. Our strategy is based on a principle of spread-spectrum encoding, borrowed from wireless communications, wherein object pixels are converted into distinct spectral codes that span the full bandwidth of the object spectrum. Image recovery is performed by numerical inversion of the detected spectrum at the fiber output. We provide a simple demonstration of spread-spectrum encoding using Fabry-Perot etalons. Our technique enables the 2D imaging of self-luminous (i.e. incoherent) objects with high throughput in principle independent of pixel number. Moreover, it is insensitive to fiber bending, contains no moving parts, and opens the possibility of extreme miniaturization.

physics.optics