Advanced optical microscopy methods for in vivo imaging of sub-cellular structures in thick biological tissuesl

Optical microscopy has become an indispensable tool for visualizing sub-cellular structures andbiological processes.However,scattering in biological tissues is a major obstacle that preventshigh-resolution images from being obtained from deep regions of tissue.We review commontechniques,such as multiphoton microscopy(MPM)and optical coherence microscopy(OCM),for diffraction limited imaging beyond an imaging depth of 0.5 mm.Novel implementations havebeen emerging in recent years giving higher imaging speed,deeper penetration,and better imagequality.Focal modulation microscopy(FMM)is a novel method that combines confocal spatialfltering with focal modulation to reject out-of-focus background.FMM has demonstrated animaging depth comparable to those of MPM and OCM,near-real-time image acquisition,and thecapability for multiple contrast mechanisms.

Implications of Delayed Reopening in Controlling the COVID-19 Surge in Southern and West-Central USA

In the wake of the rapid surge in the COVID-19-infected cases seen in Southern and West-Central USA in the period of June-July 2020,there is an urgent need to develop robust,data-driven models to quantify the effect which early reopening had on the infected case count increase.In particular,it is imperative to address the question:How many infected cases could have been prevented,had the worst affected states not reopened early?To address this question,we have developed a novel COVID-19 model by augmenting the classical SIR epidemiological model with a neural network module.The model decomposes the contribution of quarantine strength to the infection time series,allowing us to quantify the role of quarantine control and the associated reopening policies in the US states which showed a major surge in infections.We show that the upsurge in the infected cases seen in these states is strongly corelated with a drop in the quarantine/lockdown strength diagnosed by our model.Further,our results demonstrate that in the event of a stricter lockdown without early reopening,the number of active infected cases recorded on 14 July could have been reduced by more than 40%in all states considered,with the actual number of infections reduced being more than 100,000 for the states of Florida and Texas.As we continue our fight against COVID-19,our proposed model can be used as a valuable asset to simulate the effect of several reopening strategies on the infected count evolution,for any region under consideration.

Attentional Ptycho-Tomography(APT)for three-dimensional nanoscale X-ray imaging with minimal data acquisition and computation time

Noninvasive X-ray imaging of nanoscale three-dimensional objects,such as integrated circuits(ICs),generally requires two types of scanning:ptychographic,which is translational and returns estimates of the complex electromagnetic field through the IC;combined with a tomographic scan,which collects these complex field projections from multiple angles.Here,we present Attentional Ptycho-Tomography(APT),an approach to drastically reduce the amount of angular scanning,and thus the total acquisition time.APT is machine learning-based,utilizing axial self-Attention for Ptycho-Tomographic reconstruction.APT is trained to obtain accurate reconstructions of the ICs,despite the incompleteness of the measurements.The training process includes regularizing priors in the form of typical patterns found in IC interiors,and the physics of X-ray propagation through the IC.We show that APT with×12 reduced angles achieves fidelity comparable to the gold standard Simultaneous Algebraic Reconstruction Technique(SART)with the original set of angles.When using the same set of reduced angles,then APT also outperforms Filtered Back Projection(FBP),Simultaneous Iterative Reconstruction Technique(SIRT)and SART.The time needed to compute the reconstruction is also reduced,because the trained neural network is a forward operation,unlike the iterative nature of these alternatives.Our experiments show that,without loss in quality,for a 4.48×93.2×3.92µm^(3) IC(≃6×10^(8) voxels),APT reduces the total data acquisition and computation time from 67.96 h to 38 min.We expect our physics-assisted and attention-utilizing machine learning framework to be applicable to other branches of nanoscale imaging,including materials science and biological imaging.

Electrodynamics of transformation-based invisibility cloaking

The existing knowledge on the electrodynamics of invisibility cloaking based on transformation optics is reviewed from an integrated science and engineering perspective.Several significant electromagnetic problems that have resulted in intense discussions in the past few years are summarized in terms of propagation,scattering,radiation and fabrication.Finally,the road ahead toward invisibility cloaking and transformation optics is discussed from the viewpoint of the author.

Learning to synthesize:robust phase retrieval at low photon counts

The quality of inverse problem solutions obtained through deep learning is limited by the nature of the priors learned from examples presented during the training phase.Particularly in the case of quantitative phase retrieval,spatial frequencies that are underrepresented in the training database,most often at the high band,tend to be suppressed in the reconstruction.Ad hoc solutions have been proposed,such as pre-amplifying the high spatial frequencies in the examples;however,while that strategy improves the resolution,it also leads to high-frequency artefacts,as well as low-frequency distortions in the reconstructions.Here,we present a new approach that learns separately how to handle the two frequency bands,low and high,and learns how to synthesize these two bands into full-band reconstructions.We show that this“learning to synthesize”(LS)method yields phase reconstructions of high spatial resolution and without artefacts and that it is resilient to high-noise conditions,e.g.,in the case of very low photon flux.In addition to the problem of quantitative phase retrieval,the LS method is applicable,in principle,to any inverse problem where the forward operator treats different frequency bands unevenly,i.e.,is ill-posed.

Dynamical machine learning volumetric reconstruction of objects’ interiors from limited angular views

Limited-angle tomography of an interior volume is a challenging, highly ill-posed problem with practical implications in medical and biological imaging, manufacturing, automation, and environmental and food security. Regularizing priors are necessary to reduce artifacts by improving the condition of such problems. Recently, it was shown that one effective way to learn the priors for strongly scattering yet highly structured 3D objects, e.g. layered and Manhattan, is by a static neural network [Goy et al. Proc. Natl. Acad. Sci. 116, 19848–19856 (2019)]. Here, we present a radically different approach where the collection of raw images from multiple angles is viewed analogously to a dynamical system driven by the object-dependent forward scattering operator. The sequence index in the angle of illumination plays the role of discrete time in the dynamical system analogy. Thus, the imaging problem turns into a problem of nonlinear system identification, which also suggests dynamical learning as a better fit to regularize the reconstructions. We devised a Recurrent Neural Network (RNN) architecture with a novel Separable-Convolution Gated Recurrent Unit (SC-GRU) as the fundamental building block. Through a comprehensive comparison of several quantitative metrics, we show that the dynamic method is suitable for a generic interior-volumetric reconstruction under a limited-angle scheme. We show that this approach accurately reconstructs volume interiors under two conditions: weak scattering, when the Radon transform approximation is applicable and the forward operator well defined;and strong scattering, which is nonlinear with respect to the 3D refractive index distribution and includes uncertainty in the forward operator.