3D Spatial Distribution of Nanoparticles in Mice Brain Metastases by X-ray Phase-Contrast Tomography.

Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.

EUV and Hard X-ray Hartmann Wavefront Sensing for Optical Metrology, Alignment and Phase Imaging.

For more than 15 years, Imagine Optic have developed Extreme Ultra Violet (EUV) and X-ray Hartmann wavefront sensors for metrology and imaging applications. These sensors are compatible with a wide range of X-ray sources: from synchrotrons, Free Electron Lasers, laser-driven betatron and plasma-based EUV lasers to High Harmonic Generation. In this paper, we first describe the principle of a Hartmann sensor and give some key parameters to design a high-performance sensor. We also present different applications from metrology (for manual or automatic alignment of optics), to soft X-ray source optimization and X-ray imaging.

Simulation of Fresnel Zone Plate Imaging Performance with Number of Zones.

In recent years, integral imaging, a promising three-dimensional imaging technology, has attracted more and more attention for its broad applications in robotics, computational vision, and medical diagnostics. In the visible spectrum, an integral imaging system can be easily implemented by inserting a micro-lens array between a image formation optic and a pixelated detector. By using a micro-Fresnel Zone Plate (FZP) array instead of the refractive lens array, the integral imaging system can be applied in X-ray. Due to micro-scale dimensions of FZP in the array and current manufacturing techniques, the number of zones of FZP is limited. This may have an important impact on the FZP imaging performance. The paper introduces a simulation method based on the scalar diffraction theory. With the aid of this method, the effect of the number of zones on the FZP imaging performance is numerically investigated, especially the case of very small number of zones. Results of several simulation of FZP imaging are presented and show the image can be formed by a FZP with a number of zones as low as 5. The paper aims at offering a numerical approach in order to facilitate the design of FZP for integral imaging.

High numerical aperture Hartmann wave front sensor for extreme ultraviolet spectral range.

We present a novel, to the best of our knowledge, Hartmann wave front sensor for extreme ultraviolet (EUV) spectral range with a numerical aperture (NA) of 0.15. The sensor has been calibrated using an EUV radiation source based on gas high harmonic generation. The calibration, together with simulation results, shows an accuracy beyond λ/39 root mean square (rms) at λ=32nm. The sensor is suitable for wave front measurement in the 10 nm to 45 nm spectral regime. This compact wave front sensor is high-vacuum compatible and designed for in situ operations, allowing wide applications for up-to-date EUV sources or high-NA EUV optics.

Emulation of X-ray Light-Field Cameras.

X-ray plenoptic cameras acquire multi-view X-ray transmission images in a single exposure (light-field). Their development is challenging: designs have appeared only recently, and they are still affected by important limitations. Concurrently, the lack of available real X-ray light-field data hinders dedicated algorithmic development. Here, we present a physical emulation setup for rapidly exploring the parameter space of both existing and conceptual camera designs. This will assist and accelerate the design of X-ray plenoptic imaging solutions, and provide a tool for generating unlimited real X-ray plenoptic data. We also demonstrate that X-ray light-fields allow for reconstructing sharp spatial structures in three-dimensions (3D) from single-shot data.

Study of contrast variations with depth in focused plenoptic cameras.

A focused plenoptic camera has the ability to record and separate spatial and directional information of the incoming light. Combined with the appropriate algorithm, a 3D scene could be reconstructed from a single acquisition, over a depth range called plenoptic depth-of-field. In this Letter, we study the contrast variations with depth as a way to assess plenoptic depth-of-field. We take into account the impact of diffraction, defocus, and magnification on the resulting contrast. We measure the contrast directly on both simulated and acquired images. We demonstrate the importance of diffraction and magnification in the final contrast. Contrary to classical optics, the maximum of contrast is not centered around the main object plane, but around a shifted position, with a fast and nonsymmetric decrease of contrast.

Advanced light-field refocusing through tomographic modeling of the photographed scene.

Recently we have shown that light-field photography images can be interpreted as limited-angle cone-beam tomography acquisitions. Here, we use this property to develop a direct-space tomographic refocusing formulation that allows one to refocus both unfocused and focused light-field images. We express the reconstruction as a convex optimization problem, thus enabling the use of various regularization terms to help suppress artifacts, and a wide class of existing advanced tomographic algorithms. This formulation also supports super-resolved reconstructions and the correction of the optical system's limited frequency response (point spread function). We validate this method with numerical and real-world examples.

Elemental and optical imaging evaluation of zwitterionic gold nanoclusters in glioblastoma mouse models.

We report in this study the in vivo biodistribution of ultra-small luminescent gold (Au) particles (∼1.5 nm core size; 17 kDa), so-called nanoclusters (NCs), stabilized by bidentate zwitterionic molecules in subcutaneous (s.c.) and orthotopic glioblastoma mice models. Particular investigations on renal clearance and tumor uptake were performed using highly sensitive advanced imaging techniques such as multi-elemental Laser-Induced Breakdown Spectroscopy (LIBS) imaging and in-line X-ray Synchrotron Phase Contrast Tomography (XSPCT). Results show a blood circulation time of 6.5 ± 1.3 min accompanied by an efficient and fast renal clearance through the cortex of the kidney with a 66% drop between 1 h and 5 h. With a similar size range, these Au NCs are 5 times more fluorescent than the well-described Au25GSH18 NCs in the near-infrared (NIR) region and present significantly stronger tumor uptake and retention illustrated by an in vivo s.c. tumor-to-skin ratio of 1.8 measured by non-invasive optical imaging and an ex vivo tumor-to-muscle of 6.1. This work highlights the pivotal role of surface coating in designing optimum Au NC candidates for cancer treatment.

Tomographic approach for the quantitative scene reconstruction from light field images.

Current computational methods for light field photography model the ray-tracing geometry inside the plenoptic camera. This representation of the problem, and some common approximations, can lead to errors in the estimation of object sizes and positions. We propose a representation that leads to the correct reconstruction of object sizes and distances to the camera, by showing that light field images can be interpreted as limited angle cone-beam tomography acquisitions. We then quantitatively analyze its impact on image refocusing, depth estimation and volumetric reconstructions, comparing it against other possible representations. Finally, we validate these results with numerical and real-world examples.

Ossicular motion related to middle ear transmission delay in gerbil.

The middle ear transmits sound efficiently from the air in the ear canal (EC) to the fluid filled cochlea. In gerbil, middle ear transmission produces a constant pressure gain between the EC and the cochlea of ∼25 dB from 2 to 40 kHz, and a delay-like phase corresponding to a ∼25-30 µs delay. The mechanisms by which the air-born signal is collected and delivered to the cochlea are not thoroughly understood, and the source of the delay is controversial. We investigated these issues by observing ossicular motion along a single line of sight, roughly parallel to the EC and perpendicular to the stapes footplate. Measurements were made at the umbo, the long process of the manubrium, across the malleus-incus joint, at the long process of the incus, and the stapes head. While the overall delay between EC pressure and stapes velocity was fairly constant with frequency, subcomponents of the delay were frequency dependent. Up to ∼17 kHz, most of the overall delay was between the EC and umbo with a much smaller contribution along the ossicles, whereas in the range from ∼17 to 30 kHz, more of the overall delay was along the ossicles.

A sum of simple and complex motions on the eardrum and manubrium in gerbil.

Based on comparisons of ear canal and scala vestibuli pressures the gerbil middle ear transmits sound with a gain of approximately 25 dB that is almost flat from 2 to 40 kHz, and with a delay-like phase corresponding to a 25-30 micros delay. How the middle ear is able to transmit sound with such high temporal and amplitude fidelity is not known, and is particularly mysterious given the complex motion the ossicles and tympanic membrane (TM) are known to undergo. To explore this question, we looked at the velocities of the manubrium and along a line on the TM. The TM motion was complex, and could be approximated as the combination of a wave-like motion and an in-and-out piston-like motion. The manubrium underwent bending at some stimulus frequencies and therefore its motion was not like a rigid body. It had a complex motion with frequency fine structure that seemed likely to be derived from resonances on the drum-like TM.

The role of organ of Corti mass in passive cochlear tuning.

The mechanism for passive cochlear tuning remains unsettled. Early models considered the organ of Corti complex (OCC) as a succession of spring-mass resonators. Later, traveling wave models showed that passive tuning could arise through the interaction of cochlear fluid mass and OCC stiffness without local resonators. However, including enough OCC mass to produce local resonance enhanced the tuning by slowing and thereby growing the traveling wave as it approached its resonant segment. To decide whether the OCC mass plays a role in tuning, the frequency variation of the wavenumber of the cochlear traveling wave was measured (in vivo, passive cochleae) and compared to theoretical predictions. The experimental wavenumber was found by taking the phase difference of basilar membrane motion between two longitudinally spaced locations and dividing by the distance between them. The theoretical wavenumber was a solution of the dispersion relation of a three-dimensional cochlear model with OCC mass and stiffness as the free parameters. The experimental data were only well fit by a model that included OCC mass. However, as the measurement position moved from a best-frequency place of 40 to 12 kHz, the role of mass was diminished. The notion of local resonance seems to only apply in the very high-frequency region of the cochlea.

Recording depth and signal competition in heterodyne interferometry.

A common way to measure submicroscopic motion of the organ of Corti is heterodyne interferometry. The depth over which vibration can be accurately measured with heterodyne interferometry is determined by both the optics, which controls to what extent light from nonfocal planes reaches the photodetectors, and demodulation electronics, which determines to what extent signal generated by out-of-focal-plane light influences the measurements. The influence of a second reflecting surface is investigated theoretically and experimentally. By reviewing the theory of FM demodulation and showing tests with a Revox FM demodulator, it is demonstrated that the influence of a secondary signal on a measurement depends on the modulation index. Both high- and low-modulation index signals are encountered in heterodyne interferometry of the cochlea. Using a He-Ne-like diode laser (lambda = 638 nm), the border between low- and high-modulation signals is at a displacement of about 25-100 nm. Confocal interferometry reduces the magnitude of out-of-focus signals, and therefore their effect on vibration measurement. The response of the confocal system to reflected signals from two surfaces separated by distances encountered within the cochlear partition is shown. The results underscore the benefit of steep optical sectioning for intracochlear measurements.