Attenuation Contrast Research Articles

An Optimized Attenuation Compensation and Contrast Enhancement Algorithm Without Pseudocharacteristics in Intravascular OCT Imaging

We present an optimized attenuation compensation and contrast enhancement algorithm to improve the quality of the intravascular optical coherence tomography (IVOCT) images and overcome the drawbacks of the previous algorithms, including pseudocharacteristics such as the variation of the tissue attenuation and the artifact shadows. We first analyze the variation of the tissue attenuation caused by the effect of the compensation and enhancement in theory. We compare the values of the estimated tissue attenuation in the baseline and enhanced IVOCT images with calcium, lipid, or fibrous plaques, respectively, to find an optimal enhancement coefficient preserving the attenuation characteristics. Then, we make a comparison of the IVOCT images with different values of the enhancement coefficient to evaluate the effects of each algorithm based on the improvement of visibility in depth, the contrast enhancement, and the preservation of characteristics. We point out that the optimizing attenuation coefficient for attenuation compensation and contrast enhancement algorithm could achieve the quality improvement of IVOCT images, as well as avoiding the pseudocharacteristics.

Visualization of water drying in porous materials by X-ray phase contrast imaging.

We present in this study results from X-ray tomographic microscopy with synchrotron radiation performed both in attenuation and phase contrast modes on a limestone sample during two stages of water drying. No contrast agent was used in order to increase the X-ray attenuation by water. We show that only by using the phase contrast mode it is possible to achieve enough water content change resolution to investigate the drying process at the pore-scale. We performed 3D image analysis of the time-differential phase contrast tomogram. We show by the results of such analysis that it is possible to obtain a reliable characterization of the spatial redistribution of water in the resolved pore system in agreement with what expected from the theory of drying in porous media and from measurements performed with other approaches. We thus show the potential of X-ray phase contrast imaging for pore-scale investigations of reactive water transport processes which cannot be imaged by adding a contrast agent for exploiting the standard attenuation contrast imaging mode.

High-resolution X-ray and neutron computed tomography of partially saturated granular materials subjected to projectile penetration

To improve fundamental understandings of projectile penetration through partially saturated sand at a meso-scale and provide controlled experimental data to validate future numerical simulations, high-resolution computed tomography of granular materials after projectile penetration using two different imaging modalities (X-rays and neutrons) was implemented. This paper presents the novel imaging techniques and results of studying the variation of geometric structure (arrangement of solids, voids, liquid films) at a meso-scale after the penetration of projectiles (ex-situ) under controlled conditions. Attenuation contrast obtained from X-rays and neutrons provided complementary information that would not have been possible to obtain by using X-rays only. X-rays identified silica particles and their boundaries at 14.8 µm/pixel resolution, while neutrons spatially resolved small amounts of moisture at 15.6 µm/pixel resolution due to a large neutron cross-section of hydrogen. Lead (Pb) contained in most projectile tips is opaque to X-rays but transparent to neutrons at the energy range generally used for imaging. Indeed, the need for using multi-modal imaging is further emphasized for non-invasive damage diagnostics. Partially saturated crystalline sand specimens with bulk gravimetric water contents of 5~6% were studied at two different initial packing states (dense and loose) using two different types of commercially available projectiles. A novel image registration technique combined 3-D attenuation data obtained at different spatial resolution with two imaging modalities (X-ray and neutron). The role of moisture in sand on penetration resistance and related effects on the meso-structure has not been studied in detail in the past, and the results from the current study show important preliminary insights on this topic. The effects of projectile impact and penetration on particle rearrangements, fractures, and water re-distributions are summarized as a function of the initial specimen state of compaction and projectile parameters (mass, impact velocity, twist during penetration, and with use of full metal jacket ammunition). Observations of damage patterns including penetration depth and cavity formation are summarized in this paper, and the findings form an important basis for an improved understanding of penetration mechanics in porous materials and related multiscale modeling framework.

X-ray computed tomography of wood-adhesive bondlines: attenuation and phase-contrast effects

Microscale X-ray computed tomography (XCT) is discussed as a technique for identifying 3D adhesive distribution in wood-adhesive bondlines. Visualization and material segmentation of the adhesives from the surrounding cellular structures require sufficient gray-scale contrast in the reconstructed XCT data. Commercial wood-adhesive polymers have similar chemical characteristics and density to wood cell wall polymers and therefore do not provide good XCT attenuation contrast in their native form. Here, three different adhesive types, namely phenol formaldehyde, polymeric diphenylmethane diisocyanate, and a hybrid polyvinyl acetate, are tagged with iodine such that they yield sufficient X-ray attenuation contrast. However, phase-contrast effects at material edges complicate image quality and segmentation in XCT data reconstructed with conventional filtered backprojection absorption contrast algorithms. A quantitative phase retrieval algorithm, which isolates and removes the phase-contrast effect, was demonstrated. The article discusses and illustrates the balance between material X-ray attenuation and phase-contrast effects in all quantitative XCT analyses of wood-adhesive bondlines.

SU-F-207-07: Dual-Energy Computed Tomography Detection Limit of Various Radiopaque Contrast Agents That Can Be Infused Within Absorbable Inferior Vena Cava Filters

Purpose: Absorbable IVC filters are shown to be safe and efficacious in preventing pulmonary embolism. These absorbable filters disappear from the body after their required duration, alleviating costly removal procedures and downstream complications. Monitoring the positioning and integrity of absorbable devices using dual-energy computed tomography (DECT) would improve treatment efficacy. The purpose of this study is to determine the limit of detection and the energy dependence of DECT for various contrast agents that may be infused within the IVC filters including gold nanoparticles (AuNP) having diameters of 2 and 4 nm. Methods: All imaging studies were performed on a GE Discovery CT750 system in Gemstone Spectral Imaging (GSI) mode. Plastic vials containing the contrast agent solutions of water and blood were placed in a water bath, and images were acquired with the GSI-5 preset. The images were reformatted into the coronal plane and 5mm diameter ROIs were placed within each solution on a GE Advantage Workstation. Monoenergetic reconstructions were generated from 40 – 140 keV. Results: Mass attenuation (contrast per unit density) for AuNPs was greater than iron, but less than barium and iodine. Contrast was 10.2 (± 3.6) HU for 4 nm AuNP at 0.72 mg/ml and 12.1 (± 4.2) for 2 nm AuNP at 0.31 mg/ml at 70 keV suggesting reasonable chance of visualization at these concentrations for 70 keV reconstruction. The contrast as a function of CT energy is similar in both water and blood. Iodine is most dependent, followed closely by barium and iron, and trailed by a large margin by the AuNP. This was unexpected given Au's large atomic number and the predominance of photoelectric effect at low energy. Conclusion: Infusion of IVC filters with AuNP is feasible. Discrimination of AuNP-infused IVC filters from surrounding anatomy warrants further investigation.

The 3D Attenuation Structure of Deception Island (Antarctica)

The seismic and volcanological structure of Deception Island (Antarctica) is an intense focus topic in Volcano Geophysics. The interpretations given by scientists on the origin, nature, and location of the structures buried under the island strongly diverge. We present a high-resolution 3D P-wave attenuation tomography model obtained by using the coda normalization method on 20,293 high-quality waveforms produced by active sources. The checkerboard and synthetic anomaly tests guarantee the reproduction of the input anomalies under the island down to a depth of 4 km. The results, once compared with our current knowledge on the geological, geochemical, and geophysical structure of the region, depict Deception as a piecemeal caldera structure coming out of the Bransfield Trough. High-attenuation anomalies contouring the northeastern emerged caldera rim correlate with the locations of sediments. In our interpretation, the main attenuation contrast, which appears under the collapsed southeastern caldera rim, is related to the deeper feeding systems. A unique P-wave high-attenuation spherical-like anomaly in the inner bay extends between depths of 1 and 3 km. The northern contour of the anomaly coincides with the calderic rim both at 1 and 2 km, while smaller anomalies connect it with deeper structures below 3 km, dipping toward the Bransfield Trough. In our interpretation, the large upper anomaly is caused by a high-temperature shallow (1–3 km deep) geothermal system, located beneath the sediment-filled bay in the collapsed blocks and heated by smaller, deeper contributions of molten materials (magma) rising from southeast.

Ancient administrative handwritten documents: X-ray analysis and imaging.

Handwritten characters in administrative antique documents from three centuries have been detected using different synchrotron X-ray imaging techniques. Heavy elements in ancient inks, present even for everyday administrative manuscripts as shown by X-ray fluorescence spectra, produce attenuation contrast. In most cases the image quality is good enough for tomography reconstruction in view of future applications to virtual page-by-page `reading'. When attenuation is too low, differential phase contrast imaging can reveal the characters from refractive index effects. The results are potentially important for new information harvesting strategies, for example from the huge Archivio di Stato collection, objective of the Venice Time Machine project.

Quantitative imaging using high-energy X-ray phase-contrast CT with a 70 kVp polychromatic X-ray spectrum.

Imaging of large and dense objects with grating-based X-ray phase-contrast computed tomography requires high X-ray photon energy and large fields of view. It has become increasingly possible due to the improvements in the grating manufacturing processes. Using a high-energy X-ray phase-contrast CT setup with a large (10 cm in diameter) analyzer grating and operated at an acceleration tube voltage of 70 kVp, we investigate the complementarity of both attenuation and phase contrast modalities with materials of various atomic numbers (Z). We confirm experimentally that for low-Z materials, phase contrast yields no additional information content over attenuation images, yet it provides increased contrast-to-noise ratios (CNRs). The complementarity of both signals can be seen again with increasing Z of the materials and a more comprehensive material characterization is thus possible. Imaging of a part of a human cervical spine with intervertebral discs surrounded by bones and various soft tissue types showcases the benefit of high-energy X-ray phase-contrast system. Phase-contrast reconstruction reveals the internal structure of the discs and makes the boundary between the disc annulus and nucleus pulposus visible. Despite the fact that it still remains challenging to develop a high-energy grating interferometer with a broad polychromatic source with satisfactory optical performance, improved image quality for phase contrast as compared to attenuation contrast can be obtained and new exciting applications foreseen.

Rest and stress transluminal attenuation gradient and contrast opacification difference for detection of haemodynamically significant stenoses in patients with suspected coronary artery disease

Rest and stress transluminal attenuation gradient and contrast opacification difference for detection of haemodynamically significant stenoses in patients with suspected coronary artery disease

Establishment of optimal scan delay for multi-phase computed tomography using bolus-tracking technique in canine pancreas.

To establish a protocol for a multi-phase computed tomography (CT) of the canine pancreas using the bolus-tracking technique, dynamic scan and multi-phase CT were performed in six normal beagle dogs. The dynamic scan was performed for 60 sec at 1-sec intervals after the injection (4 ml/sec) of a contrast medium, and intervals from aortic enhancement appearance to aortic, pancreatic parenchymal and portal vein peaks were measured. The multi-phase CT with 3 phases was performed three times using a bolus-tracking technique. Scan delays were 0, 15 and 30 in first multi-phase scan; 5, 20 and 35 in second multi-phase scan; and 10, 25 and 40 sec in third multi-phase scan, respectively. Attenuation values and contrast enhancement pattern were analyzed from the aorta, pancreas and portal vein. The intervals from aortic enhancement appearance to aortic, pancreatic parenchymal and portal vein peaks were 3.8 ± 0.7, 8.7 ± 0.9 and 13.3 ± 1.5 sec, respectively. The maximum attenuation values of the aorta, pancreatic parenchyma and portal vein were present at scan sections with no scan delay, a 5-sec delay and a 10-sec delay, respectively. When a multi-phase CT of the canine pancreas is triggered at aortic enhancement appearance using a bolus-tracking technique, the recommended optimal delay times of the arterial and pancreatic parenchymal phases are no scan delay and 5 sec, respectively.

Experimental comparison of grating- and propagation-based hard X-ray phase tomography of soft tissue

When imaging soft tissues with hard X-rays, phase contrast is often preferred over conventional attenuation contrast due its superior sensitivity. However, it is unclear which of the numerous phase tomography methods yields the optimized results at given experimental conditions. Therefore, we quantitatively compared the three phase tomography methods implemented at the beamline ID19 of the European Synchrotron Radiation Facility: X-ray grating interferometry (XGI), and propagation-based phase tomography, i.e., single-distance phase retrieval (SDPR) and holotomography (HT), using cancerous tissue from a mouse model and an entire heart of a rat. We show that for both specimens, the spatial resolution derived from the characteristic morphological features is about a factor of two better for HT and SDPR compared to XGI, whereas the XGI data generally exhibit much better contrast-to-noise ratios for the anatomical features. Moreover, XGI excels in fidelity of the density measurements, and is also more robust against low-frequency artifacts than HT, but it might suffer from phase-wrapping artifacts. Thus, we can regard the three phase tomography methods discussed as complementary. The application will decide which spatial and density resolutions are desired, for the imaging task and dose requirements, and, in addition, the applicant must choose between the complexity of the experimental setup and the one of data processing.

Quantitative sparse array vascular elastography: the impact of tissue attenuation and modulus contrast on performance.

Quantitative sparse array vascular elastography visualizes the shear modulus distribution within vascular tissues, information that clinicans could use to reduce the number of strokes each year. However, the low transmit power sparse array (SA) imaging could hamper the clinical usefulness of the resulting elastograms. In this study, we evaluated the performance of modulus elastograms recovered from simulated and physical vessel phantoms with varying attenuation coefficients (0.6, 1.5, and [Formula: see text]) and modulus contrasts ([Formula: see text], [Formula: see text], and [Formula: see text]) using SA imaging relative to those obtained with conventional linear array (CLA) and plane-wave (PW) imaging techniques. Plaques were visible in all modulus elastograms, but those produced using SA and PW contained less artifacts. The modulus contrast-to-noise ratio decreased rapidly with increasing modulus contrast and attenuation coefficient, but more quickly when SA imaging was performed than for CLA or PW. The errors incurred varied from 10.9% to 24% (CLA), 1.8% to 12% (SA), and [Formula: see text] (PW). Modulus elastograms produced with SA and PW imagings were not significantly different ([Formula: see text]). Despite the low transmit power, SA imaging can produce useful modulus elastograms in superficial organs, such as the carotid artery.

Photon counting spectral CT component analysis of coronary artery atherosclerotic plaque samples.

To evaluate the capabilities of photon counting spectral CT to differentiate components of coronary atherosclerotic plaque based on differences in spectral attenuation and iodine-based contrast agent concentration. 10 calcified and 13 lipid-rich non-calcified histologically demonstrated atheromatous plaques from post-mortem human coronary arteries were scanned with a photon counting spectral CT scanner. Individual photons were counted and classified in one of six energy bins from 25 to 70 keV. Based on a maximum likelihood approach, maps of photoelectric absorption (PA), Compton scattering (CS) and iodine concentration (IC) were reconstructed. Intensity measurements were performed on each map in the vessel wall, the surrounding perivascular fat and the lipid-rich and the calcified plaques. PA and CS values are expressed relative to pure water values. A comparison between these different elements was performed using Kruskal-Wallis tests with pairwise post hoc Mann-Whitney U-tests and Sidak p-value adjustments. RESULTS for vessel wall, surrounding perivascular fat and lipid-rich and calcified plaques were, respectively, 1.19 ± 0.09, 0.73 ± 0.05, 1.08 ± 0.14 and 17.79 ± 6.70 for PA; 0.96 ± 0.02, 0.83 ± 0.02, 0.91 ± 0.03 and 2.53 ± 0.63 for CS; and 83.3 ± 10.1, 37.6 ± 8.1, 55.2 ± 14.0 and 4.9 ± 20.0 mmol l(-1) for IC, with a significant difference between all tissues for PA, CS and IC (p < 0.012). This study demonstrates the capability of energy-sensitive photon counting spectral CT to differentiate between calcifications and iodine-infused regions of human coronary artery atherosclerotic plaque samples by analysing differences in spectral attenuation and iodine-based contrast agent concentration. Photon counting spectral CT is a promising technique to identify plaque components by analysing differences in iodine-based contrast agent concentration, photoelectric attenuation and Compton scattering.

Simulated cystic renal lesions: quantitative X-ray phase-contrast CT--an in vitro phantom study.

To determine if grating-based x-ray phase-contrast computed tomography (CT) can allow differentiation of simulated simple, protein-rich, hemorrhagic, and enhancing cystic renal lesions in an in vitro phantom. An in vitro phantom specifically designed to simulate simple, protein-rich, hemorrhagic, and enhancing renal cysts was scanned with an experimental grating-based phase-contrast CT setup consisting of a Talbot-Lau interferometer with a rotating anode x-ray tube and a single photon counting detector. Various combinations of serum and saline (100% and 0% to 0% and 100%), blood and saline, blood and serum (100% and 0% to 6.25% and 93.75% for both), and an iodinated contrast agent and saline (7.6-1.6 mg per milliliter of saline) were used to reproduce the chemical composition of the different types of cysts. A thickened solution of an iodinated contrast agent calibrated with a clinical multidetector CT scanner served as contrast agent-enhanced renal parenchyma (195 HU at 80 kVp, 400 mAs and 98 HU at 140 kVp, 200 mAs). Standard attenuation- and phase-contrast images were reconstructed from the raw projection data. Quantitative values for attenuation and phase contrast and image noise were determined. Contrast-to-noise ratios were calculated. Simulated lesions were assessed for visual differentiability by means of pairwise comparison of the attenuation- and phase-contrast images and both images simultaneously. Attenuation-contrast imaging showed large differences in Hounsfield units with increasing concentrations of iodine (118.9 HU for 1.6 mg/mL vs 331.4 HU for 7.6 mg/mL). Values for phase-contrast imaging were substantially distinguishable for saline, serum, and blood (7.9, 23.7, and 52.8 HU, respectively). Both imaging modalities combined allowed differentiation of all four types of simulated cysts (100% saline, 100% serum, 100% blood, and 1.6-7.6 mg of iodine per milliliter of saline) with one imaging acquisition. Grating-based phase-contrast CT allows differentiation of simulated simple, protein-rich, hemorrhagic, and enhancing renal cysts in an in vitro phantom through simultaneous assessment of their distinct attenuation- and phase-contrast signal.

Contrast enhancement of iohexol-cisplatin-gelatin complex under computed tomography imaging

Abstract X-ray computed tomography (CT) is one of the most powerful non-invasive diagnostic techniques nowadays. The iodinated molecules used as CT contrast agents in the clinic have short circulation times in the body, which significantly restrict its applications. Furthermore, some patients are hypersensitive to iodine. So, researchers have made tremendous efforts to improve the property of iodine. Besides, cis-diammineplatinum (II) dichloride (cisplatin), a major chemo agent for cancer treatment, possess higher X-ray attenuation coefficient being a CT contrast agent. The incorporation of cisplatin with an iodinated agent could facilitate the quality of CT images and damage cancer cells simultaneously. To reduce toxicity of a contrast agent, polymer matrix, gelatin, was incorporated for avoiding contact with nontarget cells. In this study, we combined the iodine contrast agent, 1,3-N-bis (2,3-dihydroxypropyl)-5-[N-(2,3-dihydroxypropyl)acetamido]-2,4,6-triiodobenzene-1,3-dicarboxamide (iohexol), with cisplatin, and then examined them in a micro CT with different X-ray tube voltages (50 kV, 80 kV, 100 kV) to find optimal scanning conditions for imaging. As expected, iohexol combined with cisplatin enhanced X-ray attenuation and image contrast. The optimal CT image could be acquired at iohexol and cisplatin concentrations of 50 mg/ml and 3 mg/ml, respectively, under 80 kV irradiation. Finally, the iohexol-cisplatin-gelatin solution was then fabricated into nanoparticles of sizes about 240 nm, which may suitable for in vivo delivery.

Contrasting inherent optical properties and particle characteristics between an under-ice phytoplankton bloom and open water in the Chukchi Sea

Variability in the inherent optical properties (IOPs) of seawater and characteristics of the particle assemblage were examined along a transect in the Chukchi Sea during July 2011. This transect encompassed samples from open waters of the marginal ice zone exhibiting low concentrations of chlorophyll-a (Chla<1mgm−3), as well as an extensive phytoplankton bloom (Chla>30mgm−3) beneath consolidated pack ice. Measurements included the spectral coefficients for particulate beam attenuation, backscattering, and absorption, bulk indicators of particle concentration and composition, and the particle size distribution. Within the bloom microphytoplankton contributed >95% to the total Chla, and relatively small amounts of nonalgal particles were present. This assemblage exhibited low Chla-specific phytoplankton absorption coefficients (0.006m2mg−1 at 676nm) indicating a strong influence of pigment packaging, and a weak spectral dependence of the particulate backscattering coefficient. In contrast, the phytoplankton community in nutrient-depleted surface waters outside the sea ice had a strong contribution of picoplankton to Chla (54%) and an increased abundance of nonalgal particles. The Chla-specific phytoplankton absorption coefficient approached maximum values at 676nm (0.023m2mg−1) and particle backscattering had much stronger spectral dependence. Additional samples from near the sea floor exhibited characteristics of either mineral-dominated assemblages or a mixture of mineral and organic particles, and also displayed optical differentiation from the surface samples. The marked contrast in absorption, attenuation, and backscattering properties of these ecological regimes suggest that they can be discriminated from optical measurements available on a variety of in situ and remote-sensing platforms.

A new method for fusion, denoising and enhancement of x-ray images retrieved from Talbot–Lau grating interferometry

This paper introduces a new image denoising, fusion and enhancement framework for combining and optimal visualization of x-ray attenuation contrast (AC), differential phase contrast (DPC) and dark-field contrast (DFC) images retrieved from x-ray Talbot–Lau grating interferometry. The new image fusion framework comprises three steps: (i) denoising each input image (AC, DPC and DFC) through adaptive Wiener filtering, (ii) performing a two-step image fusion process based on the shift-invariant wavelet transform, i.e. first fusing the AC with the DPC image and then fusing the resulting image with the DFC image, and finally (iii) enhancing the fused image to obtain a final image using adaptive histogram equalization, adaptive sharpening and contrast optimization. Application examples are presented for two biological objects (a human tooth and a cherry) and the proposed method is compared to two recently published AC/DPC/DFC image processing techniques. In conclusion, the new framework for the processing of AC, DPC and DFC allows the most relevant features of all three images to be combined in one image while reducing the noise and enhancing adaptively the relevant image features. The newly developed framework may be used in technical and medical applications.

Can dual-energy CT improve the assessment of tumor margins in oral cancer?

The aim was to investigate the image quality of dual-energy computed-tomography (DECT) compared to single-energy images at 80 kV and 140 kV in oral tumors. Forty patients underwent a contrast-enhanced DECT scan on a definition flash-CT. Four reconstructions (80 kV, 140 kV, mixed (M), and optimum-contrast (OC)) were assessed by four blinded readers for subjective image quality (10-point scale/10=best). For objective quality assessment, linear attenuation measurements (line density profiles (LDP)) were positioned at the tumor margin, and the difference between minimum and maximum was calculated. Signal-to-noise ratios (SNR) were measured in the tongue. The mean image quality for all readers was 5.1±0.3, 8.4±0.3, 8.1±0.2, and 8.3±0.2 for the 140 kV, 80 kV, M, and OC, respectively (P<001 between 140 kV and all others). The mean difference between the minimum and maximum within the LDP was 139.4±59.0, 65.7±29.5, 105.1±46.5, and 118.7±59.4 for the 80 kV, 140 kV, M, and OC, respectively (P<001). The SNR for the tongue was 3.8±2.1, 3.8±2.1, 4.2±2.4, and 4.1±2.3 for the 80 kV, 140 kV, M, and OC, respectively. DECT of oral tumors offers high image quality, with subjectively rated image quality and attenuation contrast at the tumor margin similar to that of 80 kV; DECT, however, provides a significantly higher SNR compared to 80 kV.

反应堆中子边缘增强效应成像初步研究

Neutron edge enhancement image is a recently developmental technique which is based not only on the amplitude like in the projection imaging but also on the contribution of phase alteration of the neutron beam. With the additional contrast from the difference of neutron refraction index in the sample which mainly leads to edge enhancement, this method can show more details about the neutron phase materials, especially some low attenuation contrast materials. Numerical simulation of neutron edge enhancement imaging is processed by MATLAB based on reflection theory and some experiments are carried out at a reactor using polychromatic thermal neutron beam line. The simulation and experiment results all show that a proper L / D condition would cause image enhancement at the edge of aluminum materials and the monochromatic neutron source isn't needed. The effect is related to L / D and the distance between sample and scintillator.

Material specific X-ray imaging using an energy-dispersive pixel detector

By imaging the X-ray spectral properties or ‘colours’ we have shown how material specific imaging can be performed. Using a pixelated energy-dispersive X-ray detector we record the absorbed and emitted hard X-radiation and measure the energy (colour) and intensity of the photons. Using this technology, we are not only able to obtain attenuation contrast but also to image chemical (elemental) variations inside objects, potentially opening up a very wide range of applications from materials science to medical diagnostics.