Michael Liebling

Bio: Michael Liebling is an academic researcher from Idiap Research Institute. The author has contributed to research in topics: Iterative reconstruction & Deconvolution. The author has an hindex of 24, co-authored 81 publications receiving 2692 citations. Previous affiliations of Michael Liebling include University of California, Berkeley & University of California, Santa Barbara.

Reversing Blood Flows Act through klf2a to Ensure Normal Valvulogenesis in the Developing Heart

Abstract: Heart valve anomalies are some of the most common congenital heart defects, yet neither the genetic nor the epigenetic forces guiding heart valve development are well understood. When functioning normally, mature heart valves prevent intracardiac retrograde blood flow; before valves develop, there is considerable regurgitation, resulting in reversing (or oscillatory) flows between the atrium and ventricle. As reversing flows are particularly strong stimuli to endothelial cells in culture, an attractive hypothesis is that heart valves form as a developmental response to retrograde blood flows through the maturing heart. Here, we exploit the relationship between oscillatory flow and heart rate to manipulate the amount of retrograde flow in the atrioventricular (AV) canal before and during valvulogenesis, and find that this leads to arrested valve growth. Using this manipulation, we determined that klf2a is normally expressed in the valve precursors in response to reversing flows, and is dramatically reduced by treatments that decrease such flows. Experimentally knocking down the expression of this shear-responsive gene with morpholine antisense oligonucleotides (MOs) results in dysfunctional valves. Thus, klf2a expression appears to be necessary for normal valve formation. This, together with its dependence on intracardiac hemodynamic forces, makes klf2a expression an early and reliable indicator of proper valve development. Together, these results demonstrate a critical role for reversing flows during valvulogenesis and show how relatively subtle perturbations of normal hemodynamic patterns can lead to both major alterations in gene expression and severe valve dysgenesis.

The Embryonic Vertebrate Heart Tube Is a Dynamic Suction Pump

Abstract: The embryonic vertebrate heart begins pumping blood long before the development of discernable chambers and valves. At these early stages, the heart tube has been described as a peristaltic pump. Recent advances in confocal laser scanning microscopy and four-dimensional visualization have warranted another look at early cardiac structure and function. We examined the movement of cells in the embryonic zebrafish heart tube and the flow of blood through the heart and obtained results that contradict peristalsis as a pumping mechanism in the embryonic heart. We propose a more likely explanation of early cardiac dynamics in which the pumping action results from suction due to elastic wave propagation in the heart tube.

Complex-wave retrieval from a single off-axis hologram.

Abstract: We present a new digital two-step reconstruction method for off-axis holograms recorded on a CCD camera. First, we retrieve the complex object wave in the acquisition plane from the hologram's samples. In a second step, if required, we propagate the wave front by using a digital Fresnel transform to achieve proper focus. This algorithm is sufficiently general to be applied to sophisticated optical setups that include a microscope objective. We characterize and evaluate the algorithm by using simulated data sets and demonstrate its applicability to real-world experimental conditions by reconstructing optically acquired holograms.

Fresnelets: new multiresolution wavelet bases for digital holography

Abstract: We propose a construction of new wavelet-like bases that are well suited for the reconstruction and processing of optically generated Fresnel holograms recorded on CCD-arrays. The starting point is a wavelet basis of L/sub 2/ to which we apply a unitary Fresnel transform. The transformed basis functions are shift-invariant on a level-by-level basis but their multiresolution properties are governed by the special form that the dilation operator takes in the Fresnel domain. We derive a Heisenberg-like uncertainty relation that relates the localization of Fresnelets with that of their associated wavelet basis. According to this criterion, the optimal functions for digital hologram processing turn out to be Gabor (1948) functions, bringing together two separate aspects of the holography inventor's work. We give the explicit expression of orthogonal and semi-orthogonal Fresnelet bases corresponding to polynomial spline wavelets. This special choice of Fresnelets is motivated by their near-optimal localization properties and their approximation characteristics. We then present an efficient multiresolution Fresnel transform algorithm, the Fresnelet transform. This algorithm allows for the reconstruction (backpropagation) of complex scalar waves at several user-defined, wavelength-independent resolutions. Furthermore, when reconstructing numerical holograms, the subband decomposition of the Fresnelet transform naturally separates the image to reconstruct from the unwanted zero-order and twin image terms. This greatly facilitates their suppression. We show results of experiments carried out on both synthetic (simulated) data sets as well as on digitally acquired holograms.

Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry

Abstract: A fast-Fourier-transform method of topography and interferometry is proposed. By computer processing of a noncontour type of fringe pattern, automatic discrimination is achieved between elevation and depression of the object or wave-front form, which has not been possible by the fringe-contour-generation techniques. The method has advantages over moire topography and conventional fringe-contour interferometry in both accuracy and sensitivity. Unlike fringe-scanning techniques, the method is easy to apply because it uses no moving components.

Deep Convolutional Neural Network for Inverse Problems in Imaging

Abstract: In this paper, we propose a novel deep convolutional neural network (CNN)-based algorithm for solving ill-posed inverse problems. Regularized iterative algorithms have emerged as the standard approach to ill-posed inverse problems in the past few decades. These methods produce excellent results, but can be challenging to deploy in practice due to factors including the high computational cost of the forward and adjoint operators and the difficulty of hyperparameter selection. The starting point of this paper is the observation that unrolled iterative methods have the form of a CNN (filtering followed by pointwise non-linearity) when the normal operator ( $H^{*}H$ , where $H^{*}$ is the adjoint of the forward imaging operator, $H$ ) of the forward model is a convolution. Based on this observation, we propose using direct inversion followed by a CNN to solve normal-convolutional inverse problems. The direct inversion encapsulates the physical model of the system, but leads to artifacts when the problem is ill posed; the CNN combines multiresolution decomposition and residual learning in order to learn to remove these artifacts while preserving image structure. We demonstrate the performance of the proposed network in sparse-view reconstruction (down to 50 views) on parallel beam X-ray computed tomography in synthetic phantoms as well as in real experimental sinograms. The proposed network outperforms total variation-regularized iterative reconstruction for the more realistic phantoms and requires less than a second to reconstruct a $512\times 512$ image on the GPU.

Quantitative phase imaging in biomedicine

Abstract: Quantitative phase imaging (QPI) has emerged as a valuable method for investigating cells and tissues. QPI operates on unlabelled specimens and, as such, is complementary to established fluorescence microscopy, exhibiting lower phototoxicity and no photobleaching. As the images represent quantitative maps of optical path length delays introduced by the specimen, QPI provides an objective measure of morphology and dynamics, free of variability due to contrast agents. Owing to the tremendous progress witnessed especially in the past 10–15 years, a number of technologies have become sufficiently reliable and translated to biomedical laboratories. Commercialization efforts are under way and, as a result, the QPI field is now transitioning from a technology-development-driven to an application-focused field. In this Review, we aim to provide a critical and objective overview of this dynamic research field by presenting the scientific context, main principles of operation and current biomedical applications. Over the past 10–15 years, quantitative phase imaging has moved from a research-driven to an application-focused field. This Review presents the main principles of operation and representative basic and clinical science applications.

Mechanical control of tissue and organ development

Abstract: Many genes and molecules that drive tissue patterning during organogenesis and tissue regeneration have been discovered. Yet, we still lack a full understanding of how these chemical cues induce the formation of living tissues with their unique shapes and material properties. Here, we review work based on the convergence of physics, engineering and biology that suggests that mechanical forces generated by living cells are as crucial as genes and chemical signals for the control of embryological development, morphogenesis and tissue patterning.

Principles and techniques of digital holographic microscopy

Abstract: Digital holography is an emerging field of new paradigm in general imaging applications. We present a review of a subset of the research and development activities in digital holography, with emphasis on microscopy techniques and applications. First, the basic results from the general theory of holography, based on the scalar diffraction theory, are summarized, and a general description of the digital holographic microscopy process is given, including quantitative phase microscopy. Several numerical diffraction methods are described and compared, and a number of representative configurations used in digital holography are described, including off-axis Fresnel, Fourier, image plane, in-line, Gabor, and phase-shifting digital holographies. Then we survey numerical techniques that give rise to unique capabilities of digital holography, including suppression of dc and twin image terms, pixel resolution control, optical phase unwrapping, aberration compensation, and others. A survey is also given of representative application areas, including biomedical microscopy, particle field holography, micrometrology, and holographic tomography, as well as some of the special techniques, such as holography of total internal reflection, optical scanning holography, digital interference holography, and heterodyne holography. The review is intended for students and new researchers interested in developing new techniques and exploring new applications of digital holography.