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In the last decade it has become possible to resolve the geometric structure of organic molecules with intramolecular resolution using high resolution scanning probe microscopy (SPM), and specifically using the subset of SPM known as noncontact atomic force microscopy (ncAFM). In world leading groups it has become routine not only to perform sub-molecular imaging of the chemical, electronic, and electrostatic properties of single molecules, but also to use this technique to track complex on-surface chemical reactions, investigate novel reaction products, and even synthesise new molecular structures one bond at a time. These developments represent the cutting edge of characterisation at the single chemical bond level, and have revolutionised our understanding of surface-based chemical processes.

OBJECTIVE To evaluate the effect of ultra high-resolution computed tomography (UHRCT) and model-based iterative reconstruction (MBIR) on the detectability of simulated submillimeter artery. METHODS A small vessel phantom ranging from 0.4 to 2.0 mm in diameter and edge phantoms of low to high attenuation values were scanned by UHRCT (super-high-resolution mode and normal-resolution-mode) and conventional CT, and data were reconstructed by MBIR and filtered back projection (FBP). Vessel detectability was assessed subjectively and the effective size at which 50% of response was achieved (ES50 [mm]) was calculated. Modulation transfer function (MTF) was calculated by an edge spread function method. RESULTS ES50 of super high-resolution mode (0.36 mm for MBIR and 0.50 mm for FBP) was significantly smaller than those of normal-resolution mode (P < 0.01). In the MTF analysis, the MTF of MBIR improved as the edge phantom attenuation increased, whereas that of FBP was stable. CONCLUSIONS Both UHRCT and MBIR are effective for the detectability of simulated submillimeter artery.

This paper provides an overview of several seismic inversion approaches and their application to very- and ultra-high-resolution marine seismic datasets. The importance of seismic inversion is related to the current demands of the offshore engineering industry for estimates of elastic stress-related parameters of near-surface and bottom sediments. To meet these demands, the seismic inversion methods which facilitate the estimation of elastic properties of the subsurface should be developed for very high-resolution data. Several problems prevent the successful application of seismic inversion to high-resolution datasets. Firstly, borehole measurements, which are routinely applied to constrain seismic inversion, are often not available for the offshore near-surface. Secondly, very- and ultra-high-resolution seismic data are acquired in high frequency ranges, and low-frequency information is absent in such datasets. The elaboration of seismic inversion methods for ultra-high-resolution data is important for both practical and scientific purposes. In the paper, we share our experience in applying acoustic poststack inversion and prestack AVA inversion to very- and ultra-high-resolution marine seismic datasets.

Mapping the existing land use is the essential activity in the management of an area, especially in densely urbanized areas. Knowing the development, amount, and extent of specific land use will be...

Purpose To evaluate the advantages of ultra-high-resolution computed tomography (U-HRCT) scans for the quantitative measurement of emphysematous lesions over conventional HRCT scans. Materials and methods This study included 32 smokers under routine clinical care who underwent chest CT performed by a U-HRCT scanner. Chronic obstructive pulmonary disease (COPD) was diagnosed in 13 of the 32 participants. Scan data were reconstructed by 2 different protocols: i) U-HRCT mode with a 1024×1024 matrix and 0.25-mm slice thickness and ii) conventional HRCT mode with a 512×512 matrix and 0.5-mm slice thickness. On both types of scans, lesions of emphysema were quantitatively assessed as percentage of low attenuation volume (LAV%

A 2D-liquid chromatographic fractionation method was combined with direct infusion electrospray ionization Fourier transform-ion cyclotron resonance mass spectrometry to better resolve the high complexity of the organic material in atmospheric particles. The number of assigned molecular formulas increased by a factor of 2.3 for the fractionated sample (18 144) compared to a bulk sample analysis without fractionation (7819), while simultaneously allowing the identification of 71 240 isomeric compounds. Accounting for these isomers has an impact on the means and distributions of different descriptive sample parameters. More than 15 000 compounds were exclusively identified in the fractionated sample providing insights regarding the formation of organosulfates, reduced N-containing compounds, and polyaromatic compounds. Further, a new method for assigning organonitrates and poly-organonitrates based on Kendrick mass defect analysis is presented. The current study implicates that analytical separation leads to much more detailed insights into particle organics composition, while more commonly applied direct infusion MS studies can strongly underestimate composition complexity and lead to biased assignments of bulk organic properties. Overall, the particle organics composition is far more complex than previously shown, while separation through better chromatographic techniques helps to understand formation processes of atmospheric particle constituents.

Background The utility of an ultra‐high‐resolution electroanatomical mapping system (UHR‐EAM, Rhythmia) for repeat atrial fibrillation (AF) ablation has not been evaluated. Hypothesis A second AF ablation procedure performed using UHR‐EAM may demonstrate different outcomes compared with that using a conventional electroanatomical mapping system (C‐EAM, CARTO3). Method This observational study enrolled consecutive patients who underwent a second AF ablation procedure using UHR‐EAM (n = 103) and C‐EAM (n = 153). The second ablation procedure included re‐isolation of reconnected pulmonary veins (PVs) and elimination of clinical or induced non‐PV AF triggers and atrial tachycardia (AT). Other empirical ablations were additionally conducted at the discretion of the operators. Results Re‐isolation of PVs was achieved in 196 patients who had ≥1 left atrial‐PV reconnection. The elimination rate of AT was higher in the UHR‐EAM group than the C‐EAM group (87% vs 65%, P = .040), while that of non‐PV AF triggers was similar (63% vs 63%, P = 1.00). The UHR‐EAM demonstrated shorter radiofrequency application time (21.8 ± 16.8 vs 28.0 ± 21.3 minutes, P = .017), but longer fluoroscopic time (26.2 ± 12.6 vs 21.4 ± 9.3 minutes, P = .0001). No severe complication developed. The total 1‐year AF/AT‐free survival rates were similar between the two groups (off AADs, 59.2% vs 56.2%, P = .62; on AADs, 65.0% vs 69.3%, P = .49). Conclusion The efficacy and safety outcomes of repeat AF ablation using UHR‐EAM was comparable to those using C‐EAM.

Background The electrophysiological characteristics of residual conduction gaps between the left atrium (LA) and pulmonary veins (PVs) after HotBalloon-based wide antral ablation (HBWA) of atrial fibrillation (AF) remain incompletely understood. This study aimed to characterize the residual gaps by means of ultra-high-resolution mapping.Methods and Results:A total of 55 AF patients underwent HBWA by a predetermined protocol (6-shot total-based antral approach). LA-PV maps were created using 64-electrode minibasket catheters. In total, 55 residual gaps were identified among 26 (47%) patients. Residual gaps included 33 left superior (LS: 60%), 10 left inferior (18%), 6 right superior (11%), and 6 right inferior (11%) PVs. Those gaps demonstrated both extremely lower bipolar amplitudes (0.11 [interquartile range: 0.06-0.27] mV) and conduction velocities (0.75±0.27 m/s); however, the length was confined (10.3±4.1 mm) except for the LSPV anterior carina (12.2±2.4 mm) region. Among the carina regions, all gaps had far-field potentials consistently added to the PV potentials. Left atrial appendage pacing to split the far-field activity identified confined gap regions (6.7±1.9 mm). Touch-up ablation eliminated the residual PV potentials in all cases. Conclusions HBWA resulted in a certain degree of residual gap conduction in particular antral regions. These gaps exhibited narrow lengths with lower amplitudes, and often had far-field recordings from the left atrial appendage. Combined with pacing maneuvers, ultra-high-resolution activation maps could both visualize all confined gaps and ensure a bare minimum of touch-up ablations in all patients with gap conduction.

The rhizosphere is an important hotspot for microbial activity, organic carbon input, and carbon turnover in soils. The interplay of these rhizosphere components results in small scale gradients of organic molecules in the zone around a root. Mass spectrometric imaging (MSI) can reveal the spatial distribution of individual plant metabolites in the soil, which cannot be achieved using bulk analysis. Using non-fragmenting ionization techniques such as laser desorption ionization (LDI) allows for the detection of intact molecules without the need for labeling with e.g. fluorescent tags.Direct MSI for the chemical imaging of intact molecules of the rhizosphere has been recognized as a still existing analytical gap. Here we present a novel method allowing mass spectrometric molecular rhizosphere imaging directly in a complex soil matrix.Our novel approach consists of sampling the roots and the surrounding soil of Zea mays plants in either field- or lab-scale experiments using small metal cylinders. After excavation, the loam soil pellets were embedded in gelatin and cryosectioned to 100 µm sections. After selecting regions of interest on the soil section, the root and the soil surrounding the root was analysed using ultra-high resolution laser desorption ionization Fourier-transform ion cyclotron resonance mass spectrometry (LDI-FT-ICR-MS).Given the large background of soil-derived organic carbon, the high mass resolution and sensitivity of FT-ICR-MS allow distinguishing root-derived molecules from soil organic matter based on their exact masses. We show that our method is capable to recover rhizosphere gradients of a dihexose (C12H22O11, e.g. sucrose, maltose) directly in the soil with a spatial resolution of 25 µm.Molecular gradients for the dihexose showed a high abundance of this metabolite in the root and a strong depletion of the signal intensity within 150 µm from the root surface. Analysing several sections from the same soil pellet allowed to recover 3D molecular gradients from one root segment. Utilizing the potential to easily change the mass window a variety of potential metabolites can be analysed in the same region around the root. Thus the chemical diversity of potential root exudates can be revealed.Our workflow enables the study of root-derived organic carbon with high spatial resolution directly in a soil context. For the first time, direct molecular imaging of the rhizosphere via LDI-FT-ICR-MS will allow for a non-target or targeted analysis of complex soil samples.Visualizing the root structure via X-ray computed tomography in a soil sample before the embedding would enable a guided sampling approach to analyse molecular distributions at certain parts of the root. Moreover, the molecular LDI-MSI results could be correlated with elemental imaging via laser ablation – inductively coupled plasma – mass spectrometry directly at the same sample position - allowing for an even more detailed insight into chemical processes in the rhizosphere.

An automated hologram acquisition system for big-data analysis and for improving the statistical precision of phase analysis has been upgraded with automated particle detection technology. The coordinates of objects in low-magnification images are automatically detected using zero-mean normalized cross-correlation with preselected reference images. In contrast with the conventional scanning acquisitions from the whole area of a microgrid and/or a thin specimen, the new method allows efficient data collections only from the desired fields of view including the particles. The acquisition time of the cubic/triangular nanoparticles that were observed was shortened by about one-fifty eighth that of the conventional scanning acquisition method because of efficient data collections. The developed technology can improve statistical precision in electron holography with shorter acquisition time and is applicable to the analysis of electromagnetic fields for various kinds of nanoparticles.

Assimilating biophysical metrics from remote sensing platforms into crop-yield forecasting models can increase overall model performance. Recent advances in remote sensing technologies provide an unprecedented resource for Earth observation that has both, spatial and temporal resolutions appropriate for precision agriculture applications. Furthermore, computationally efficient assimilation techniques can integrate these new satellite-derived products into modeling frameworks. To date, such modeling approaches work at the regional scale, with comparatively few studies examining the integration of remote sensing and crop-yield modeling at intra-field resolutions. In this study, we investigate the potential of assimilating daily, 3 m satellite-derived leaf area index (LAI) into the Agricultural Production Systems sIMulator (APSIM) for crop yield estimation in a rainfed corn field located in Nebraska. The impact of the number of satellite images and the definition of homogeneous spatial units required to re-initialize input parameters was also evaluated. Results show that the observed spatial variability of LAI within the maize field can effectively drive the crop simulation model and enhance yield forecasting that takes into account intra-field variability. The detection of intra-field biophysical metrics is particularly valuable since it may be employed to infer inefficiency problems at different stages of the season, and hence drive specific and localized management decisions for improving the final crop yield.

Varved lake sediments are recognized as valuable archives of paleoclimatic information due to their precise chronological control. However, paleoclimate reconstructions based on the composition of biochemical varves are relatively rare (Zolitschka et al., 2015). We applied novel high-resolution scanning techniques to the varved sediments of Lake Żabińskie, Poland to obtain spatially resolved geochemical data at a resolution of 60 μm covering the period 1966-2019. Relative abundances of elements were measured in resin-embedded sediment slabs using a Bruker M4 Tornado micro-XRF scanner. Chloropigments-a and bacteriopheopigments-a were measured on a wet sediment core using a Specim Hyperspectral core scanner (Butz et al., 2015). The high resolution of the scanning data, and the relatively thick well-preserved varves (average thickness = 6.4 mm), enables a close examination of seasonal scale sediment composition and varve formation processes. Time series of geochemical variables within each varve year were classified into 4 varve type groups based on the dissimilarity measure ψ for multivariate time series (Benito and Birks, 2020; Gordon and Birks, 1974). Based on a Multivariate Analysis Of Variance test, these groups of years experienced significant (p ReferencesBenito, B. M. and Birks, H. J. B.: distantia: an open‐source toolset to quantify dissimilarity between multivariate ecological time‐series, Ecography (Cop.)., 43(5), 660–667, doi:10.1111/ecog.04895, 2020.Butz, C., Grosjean, M., Fischer, D., Wunderle, S., Tylmann, W. and Rein, B.: Hyperspectral imaging spectroscopy: a promising method for the biogeochemical analysis of lake sediments, J. Appl. Remote Sens., 9(1), 096031, doi:10.1117/1.jrs.9.096031, 2015.Gordon, A. D. and Birks, H. J. B.: Numerical methods in Quaternary palaeoecology: II. Comparison of pollen diagrams, New Phytol., 73(1), 221–249, doi:10.1111/j.1469-8137.1974.tb04621.x, 1974.Zolitschka, B., Francus, P., Ojala, A. E. K. and Schimmelmann, A.: Varves in lake sediments - a review, Quat. Sci. Rev., 117, 1–41, doi:10.1016/j.quascirev.2015.03.019, 2015.

Warming of the circumpolar north is accelerating permafrost thaw, with implications for landscapes, hydrology, ecosystems and the global carbon cycle. In subarctic Canada, abrupt permafrost thaw is creating widespread thermokarst lakes. Little attention has been given to small waterbodies with area less than 10,000 m2, yet these are biogeochemically more active than larger lakes. Additionally, the landscapes where they develop show intense shrubification and terrestrialization processes, with increases in area and height of shrub and tree communities. Tall vegetation that is colonizing waterbody margins can cast shadows that impact productivity, thermal regime and the water spectral signal, which in satellite data generates pixels with mixed signatures between sunlit and shaded surfaces. We undertook UAV surveys using optical and multispectral sensors at long-term monitoring sites of the Center for Northern Studies (CEN) in subarctic Canada, from the sporadic (SAS/KWAK) to the discontinuous (BGR) permafrost zones in the boreal forest-tundra transition zone. This ultra-high spatial resolution data enabled spectral characterization and 3D reconstruction of the study areas. Ultra-high resolution digital surface models were produced to model shadowing at satellite overpass time (WorldView, PlanetScope and Sentinel-2). We then analyzed the impacts of surrounding vegetation and cast shadows on lake surface spectral reflectance derived from satellite imagery. Ultra-high resolution UAV data allows generating accurate shadow models and can be used to improve the assessment of errors and accuracy of satellite data analysis. Particularly, we identify different spectral signal impacts of cast shadows according to lake color, which highlight the need for special attention of this issue onto lakes with more turbidity.This research is funded by the Portuguese Foundation for Science and Technology (FCT) under the project THAWPOND (PROPOLAR), by the Centre of Geographical Studies (FCT I.P. UIDB/00295/2020 and UIDP/00295/2020), with additional support from ArcticNet (NCE), Sentinel North (CFREF) and CEN and is a contribution to T-MOSAiC. PF is funded by FCT (SFRH/BD/145278/2019).

Climate change, in particular the rise in tropical sea surface temperatures, is the greatest threat to coral reef ecosystems today and causes climatic extremes affecting the livelihood of tropical societies. The combination of long-term global warming and interannual El Niño-related warm events has severely affected corals and coral reefs throughout the tropical ocean basins. Mass coral bleaching, a result of large-scale temperature stress, was first observed during the 1982/83 El Niño, and was followed by much more severe, global scale bleaching events during the El Niño years of 1997/98 and 2010, culminating in the most wide-spread and most destructive global bleaching episode to date, which lasted from 2014-2017. The interval between recurrent mass coral bleaching events driven by anomalously high sea surface temperatures is becoming too short for a full recovery of mature coral reef assemblages and will have dramatic effects on future coral reef growth. Assessing how future warming will change coral reef ecosystems and tropical climate variability is therefore of extreme urgency.The recently established Priority Programme „Tropical Climate Variability and Coral Reefs – A Past to Future Perspective on Current Rates of Change at Ultra-High Resolution“ (SPP 2299; https://www.spp2299.tropicalclimatecorals.de/) of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) aims to enhance our current understanding of tropical marine climate variability and its impact on coral reef ecosystems in a warming world, by quantifying climatic and environmental changes during both the ongoing warming and past warm periods on timescales relevant for society. Ultra-high resolution coral geochemistry provides a tool to understand the temporal response of corals and coral reefs to ongoing climate and environmental change, to reconstruct past tropical climate and environmental variability and to use these data in conjunction with advanced statistical methods, earth system modelling and observed ecosystem responses for improved projections of future changes in tropical climate and coral reef ecosystems.The Priority Programme is organised around three major research topics in order to fuel interdisciplinary collaboration among various disciplines: (a) Large-scale ocean, climate & environment reconstructions, (b) Coral & reef-scale response to current environmental stress, and (c) Climate, reef & proxy modelling – Climate & proxy advanced statistics. The strongly interdisciplinary Priority Programme will bring together expertise in the fields of climate, environmental and ecosytem research in a sustainable manner, and aims to provide an ultra-high resolution past to future perspective on current rates of change to project how tropical marine climate variability and coral reef ecosystems will change in a warming world.

Proglacial lakes are becoming ubiquitous at the termini of many glaciers worldwide, leading to increased glacier mass loss and terminus retreat due to the influence such lakes are having upon ice dynamics. However, despite the highly dynamic nature and relative insensitivity to climate of many lake-terminating glaciers, an understanding of the key processes forcing their behaviour is lacking. As a result, it is difficult at present to accurately assess and predict the future response of these glaciers to continued warming. In addition, current methods of investigating lake-terminating glacier dynamics primarily involve the use of satellite remote sensing, which despite its clear importance in cryospheric studies does suffer from important limitations. A novel alternative is the use of repeat unmanned aerial vehicle (UAV) imagery, which can provide high resolution (cm-scale) imagery of the ice surface at varying spatial and temporal scales, depending on the needs of the researcher. As a result, this study utilised ultra-high resolution repeat UAV imagery to provide insights into the changing dynamics of Fjallsjökull, a lake-terminating glacier in southeast Iceland, over two periods during the 2019 summer melt season. The findings indicate that the overall dynamics of the glacier are controlled by the ~120 m deep subglacial channel under the study region, which is causing the glacier to flow faster as it enters deeper water, leading to increased ice acceleration, thinning and retreat. Such a correspondence between ice velocity and surface thinning suggests the implementation of the positive feedback mechanism “dynamic thinning” in this region of Fjallsjökull, with such heightened rates of surface thinning and frontal retreat continuing in future until the glacier recedes out of the subglacial channel into shallower water. Within this overall pattern, however, more localised, short-term changes in glacier dynamics are also observed which are likely to be forced primarily by subaqueous melting at the waterline, rather than being solely influenced by the basal topography. Although further work is required to add additional support to these findings, they clearly indicate the complex nature of the calving process and the dynamics of calving glaciers in general, highlighting the need for continued monitoring of lake-terminating glaciers at varying spatial and temporal scales.

Background and importance Nivolumab (Opdivo) is a human IgG4 monoclonal antibody from the group of immunomodulators which bind to the programmed death receptor 1 (PD-1). As a complex protein, physical aggregation and chemical degradation can occur throughout its life, and even modest environmental stresses can cause extensive damage.1 As indicated in its technical report,2 the unopened vials can be stored at a controlled room temperature up to 25°C with room light for up to 48 hours. Aim and objectives To assess the impact on the isoform profile of nivolumab 10 mg/mL (Opdivo) promoted by exposure to light in its own opened vial at a controlled temperature of 25°C to evaluate likely risks from unintentional mishandling in real hospital conditions. Material and methods Nivolumab (Opdivo, 10 mg/mL) was placed in an accelerated stress test chamber to simulate sunlight (Solarbox 3000e RH, Cofomegra, Milan, Italy) for 24 hours at 25°C. Irradiation was set at 250 W/m2, between 320 and 800 nm.3 A validated reverse phase ultra high resolution liquid chromatography coupled to high resolution mass spectrometry and exact mass ((RP)UHPLC-UV-(HESI/Orbitrap)-MS) method was used to analyse intact nivolumab. UV-chromatograms and total ion chromatograms (TICs) were recorded and the deconvoluted mass spectra gave the nivolumab mass isoform profile. Results UV chromatograms and TICs suggested no degradation products after light exposure. However, isoform profiles clearly showed changes in the light submitted nivolumab samples. An important increase in the number of isoforms even with changes in their masses, including the main isoform, was detected. Conclusion and relevance Exposure to light may cause modifications in the nivolumab isoform profile which suggests protein degradation. This work shows the importance of protecting opened vials of the medicine Opdivo from light (and by extension, bags for infusion) when they are at room temperature (up to 25°C). References and/or acknowledgements Nejadnik MR, et al. J Pharm Sci 2018;107:2013–19. Nivolumab Technical Report. https://www.ema.europa.eu/en/documents/product-information/opdivo-epar-product-information_en.pdf Scientific discussion ICH Q1B photostability testing of new active substances and medicinal products. European Medicines Agency (EMEA) 1998 https://www.ema.europa.eu/en/documents/scientific-guideline/ich-q-1-b-photostability-testing-new-active-substances-medicinal-products-step-5_en.pdf Funded by project FIS: PI-17/00547 (Instituto Carlos III, Spain), which means that it was also partially supported by European Regional Development Funds. AT-L is currently receiving an FPU predoctoral grant (reference FPU18/03131) from the Ministry of Universities, Spain. Conflict of interest No conflict of interest

1ABSTRACTAlthough poorly positioned nucleosomes are ubiquitous in the prokaryote genome, they are difficult to identify with existing nucleosome identification methods. Recently available enhanced high-throughput chromatin conformation capture techniques such as Micro-C, DNase Hi-C, and Hi-CO characterize nucleosome-level chromatin proximity, probing the positions of mono-nucleosomes and the spacing between nucleosome pairs at the same time, enabling profiling of nucleosomes in poorly positioned regions. Here we develop a novel computational approach, NucleoMap, to identify nucleosome positioning from ultra-high resolution chromatin contact maps. By integrating nucleosome binding preferences, read density, and pairing information, NucleoMap precisely locates nucleosomes in both eukaryotic and prokaryotic genomes and outperforms existing nucleosome identification methods in precision and recall. We rigorously characterize genome-wide association in eukaryotes between the spatial organization of mono-nucleosomes and their corresponding histone modifications, protein binding activities, and higher-order chromatin functions. We also predict two tetra-nucleosome folding structures in human embryonic stem cells using machine learning methods and analysis their distribution at different structural and functional regions. Based on the identified nucleosomes, nucleosome contact maps are constructed, reflecting the inter-nucleosome distances and preserving the original data’s contact distance profile.

Conventional CT scanners use energy-integrating detectors (EIDs). Photon-counting detector (PCD) computed tomography (CT) utilizes a CT detector technology based on smaller detector pixels capable of counting single photons and in addition discriminating their energy. Goal of this study was to explore the potential of higher spatial resolution for imaging of bone metastases. Four female patients with histologically confirmed breast cancer and bone metastases were included between July and October 2019. All patients underwent conventional EID CT scans followed by a high resolution non-contrast experimental PCD CT scan. Ultra-high resolution (UHR) reconstruction kernels were used to reconstruct axial slices with voxel sizes of 0.3 mm × 0.3 mm (inplane) × 1 mm (z-direction). Four radiologists blinded for patient identity assessed the images and compared the quality to conventional CT using a qualitative Likert scale. In this case series, we present images of bone metastases in breast cancer patients using an experimental PCD CT scanner and ultra-high-resolution kernels. A tendency to both a smaller inter-reader variability in the structural assessment of lesion sizes and in the readers’ opinion to an improved visualization of lesion margins and content was observed. In conclusion, while further studies are warranted, PCD CT has a high potential for therapy monitoring in breast cancer.

Introduction: Conventional resolution coronary CTA (CRCT) is frequently avoided in patients with heavy calcification and prior stents given the diminished diagnostic accuracy. Ultra-high-resolution CT (UHRCT) with detector width of 0.25 mm may overcome partial volume effect limitations. Hypothesis: We hypothesize that UHRCT yields high accuracy for detecting obstructive coronary arterial stenoses in patients with severe coronary artery disease using cardiac catheterization as reference standard. Methods: Nine patients ≥45 years with severe coronary artery disease referred for invasive coronary angiography were prospectively enrolled at a single center. Patients underwent UHRCT within 30 days prior to catheterization and results for significant coronary artery stenoses (≥70%) by visual assessment by blinded expert readers for the two tests were compared. Diagnostic accuracy assessment was performed at a patient-level (N=9) and vessel-level (N=36). Results: Median patient age was 67 (range 53-77). Six patients were obese and 6 had prior stent placement. Estimated radiation dose was 9.3 mSv. Mean Agatston calcium score of patients without stents was 1,688. UHRCT correctly classified all patients as having obstructive or non-obstructive coronary heart disease, respectively, yielding 100% accuracy (95% confidence interval [CI] 64-100%). On a vessel level UHRCT had an accuracy of 93% (95% CI 78-98%). Conclusions: Our initial experience with UHRCT in patients with severe coronary calcification or prior stenting suggests high accuracy for detecting and excluding obstructive stenoses. These results warrant further studies to confirm a role of UHRCT in this challenging population.

Detailed mapping studies of accessory pathway (AP) conduction have not been previously performed using ultra-high resolution mapping systems. We sought to evaluate the clinical utility of ultra-high resolution mapping systems and the novel “Lumipoint” algorithm in AP ablation. This study included 17 patients who underwent AP mapping using minielectrode basket catheters and Rhythmia systems. Ablation was performed with 4-mm irrigated-tip catheters. Antegrade and retrograde AP conduction was observed in 6 and 16 patients. Atrial activation map was obtained during orthodromic tachycardia and ventricular pacing in 13 (76.5%) and 14 (82.3%) patients, and the earliest activation area was identical. Ventricular activation maps were created during atrial pacing in 3 patients. All maps showed focal activation patterns on global activation histograms, and the valley on the histogram highlighted the earliest activation area. “Complex activation” features further highlighted limited areas with continuous electrical activity during the time period in the majority. APs were located at the mitral and tricuspid annuli in 15 and 2 patients, and all were successfully eliminated with 3.4 ± 0.6 s applications. No patients had recurrences during a median follow-up of 15 [10.5–22.5] months. At successful ablation sites, the local atrial and ventricular electrogram amplitudes and ratio tended to be greater, and fusion or continuous electrical activity between the atrial and ventricular components was more frequently observed on the minielectrode than ablation catheter (17/17 vs. 12/17, p = 0.005). Ultra-high resolution activation mapping and a novel algorithm facilitated the AP localization. The local electrogram characteristics differed between the minielectrode and ablation catheters.

Purpose: To introduce a method that allows the generation of ultra high-resolution (submillimeter) heterogeneous digital PET brain phantoms and to provide a new publicly available [(Formula presented.) ]FDG phantom as an example. Method: The radiotracer distribution of the phantom is estimated by minimizing the Kullback–Leibler distance between the parameterized unknown phantom distribution and a radiotracer-specific template used as a reference. The phantom is modelled using the histological and tissue classified volumes of the BigBrain atlas to provide both high resolution and heterogeneity. The Hammersmith brain atlas is also included to allow the estimation of different activity values in different anatomical regions of the brain. Using this method, a realistic [(Formula presented.) ]FDG phantom was produced, where a single real [(Formula presented.) ]FDG scan was used as the reference to match. An MRI T1-weighted image, obtained from the BigBrain atlas, and a pseudo-CT are included to complete the dataset. A full PET-MRI dataset was simulated and reconstructed with MR-guided methods for the new [(Formula presented.) ]FDG phantom. Results: An ultra high-resolution (400 μm voxel size) and heterogeneous phantom for [(Formula presented.) ]FDG was obtained. The radiotracer activity follows the patterns observed in the scan used as a reference. The simulated PET-MRI dataset provided a realistic simulation that was able to be reconstructed with MR-guided methods. By visual inspection, the reconstructed images showed similar patterns to the real data and the improvements in contrast and noise with respect to the standard MLEM reconstruction were more modest compared to simulations done with a simpler phantom, which was created from the same MRI image used to assist the reconstruction. Conclusions: A method to create high-resolution heterogeneous digital brain phantoms for different PET radiotracers has been presented and successfully employed to create a new publicly available [(Formula presented.) ]FDG phantom. The generated phantom is of high resolution, is heterogeneous, and simulates the uptake of the radiotracer in the different regions of the brain.

Marine renewable energy technologies have a great potential in supplying clean electricity to millions of people across the globe, if technical and economic conditions are in right. So far, ocean energy projects are commonly started by SMEs or educational institutions with limited budgets. Therefore, any effort to reduce expenses is of great value. One of the areas involving substantial expenses are the inevitable seabed inspection prior to deployment of marine renewable energy device. Detailed seabed inspections can also reduce the risk of associated with deployment of structures on uneven seabed, especially marine renewable energy devices with gravity foundations. By reducing the costs and risks of such surveys prior and during the installation phases, the feasibility of marine renewable energy projects can be more favoured and competitive. In this perspective, this study proposes a cost and time effective technique for seabed surveys. The proposed technique involves the use of high precision and inexpensive sonar systems and underwater optical cameras integrated into a versatile and compact subsea monitoring platform. It also involves simple and practical data acquisition and processing protocols that do not requires hi expertise for operation. The results obtained showed that high resolution bathymetric maps and detailed seabed inspections imagery can be acquired. This study concludes that a simple and inexpensive subsea monitoring platform comprising a multibeam, dual beam and video cameras can be effective for high resolution seabed inspection and bathymetric measurements for marine energy applications.

We evaluated lower dose (LD) hepatic dynamic ultra-high-resolution computed tomography (U-HRCT) images reconstructed with deep learning reconstruction (DLR), hybrid iterative reconstruction (hybrid-IR), or model-based IR (MBIR) in comparison with standard-dose (SD) U-HRCT images reconstructed with hybrid-IR as the reference standard to identify the method that allowed for the greatest radiation dose reduction while preserving the diagnostic value. Evaluated were 72 patients who had undergone hepatic dynamic U-HRCT; 36 were scanned with the standard radiation dose (SD group) and 36 with 70% of the SD (lower dose [LD] group). Hepatic arterial and equilibrium phase (HAP, EP) images were reconstructed with hybrid-IR in the SD group, and with hybrid-IR, MBIR, and DLR in the LD group. One radiologist recorded the standard deviation of attenuation in the paraspinal muscle as the image noise. The overall image quality was assessed by 3 other radiologists; they used a 5-point confidence scale ranging from 1 (unacceptable) to 5 (excellent). Superiority and equivalence with prespecified margins were assessed. With respect to the image noise, in the HAP and EP, LD DLR and LD MBIR images were superior to SD hybrid-IR images; LD hybrid-IR images were neither superior nor equivalent to SD hybrid-IR images. With respect to the quality scores, only LD DLR images were superior to SD hybrid-IR images. DLR preserved the quality of abdominal U-HRCT images even when scanned with a reduced radiation dose. • Lower dose DLR images were superior to the standard-dose hybrid-IR images quantitatively and qualitatively at abdominal U-HRCT. • Neither hybrid-IR nor MBIR may allow for a radiation dose reduction at abdominal U-HRCT without compromising the image quality. • Because DLR allows for a reduction in the radiation dose and maintains the image quality even at the thinnest slice section, DLR should be applied to abdominal U-HRCT scans.

Background: The corona-virus disease 2019 (COVID-19) pandemic has caused a serious public health risk. Compared with conventional high-resolution CT (C-HRCT, matrix 512), ultra-high resolution CT (U-HRCT, matrix 1024) can increase the effective pixel per unit volume by about 4 times. Our study is to evaluate the value of target reconstruction of U-HRCT in the accurate diagnosis of COVID-19. Methods: A total of 13 COVID-19 cases, 44 cases of other pneumonias, and 6 cases of ground-glass nodules were retrospectively analyzed. The data were categorized into groups A (C-HRCT) and B (U-HRCT), following which iDose4-3 and iDose4-5 were used for target reconstruction, respectively. CT value, noise, and signal-to-noise ratio (SNR) in different reconstructed images were measured. Two senior imaging doctors scored the image quality and the structure of the lesions on a 5-point scale. Chi-square test, variance analysis, and binary logistic regression analysis were used for statistical analysis. Results: U-HRCT image can reduce noise and improve SNR with an increase of the iterative reconstruction level. The SNR of U-HRCT image was lower than that of the C-HRCT image of the same iDose4 level, and the noise of U-HRCT was higher than that of C-HRCT image; the difference was statistically significant (P < 0.05). Logistic regression analysis showed that peripleural distribution, thickening of blood vessels and interlobular septum, and crazy-paving pattern were independent indictors of the COVID-19 on U-HRCT. U-HRCT was superior to C-HRCT in showing the blood vessels, bronchial wall, and interlobular septum in the ground-glass opacities; the difference was statistically significant (P < 0.05). Conclusions: Peripleural distribution, thickening of blood vessels and interlobular septum, and crazy-paving pattern on U-HRCT are favorable signs for COVID-19. U-HRCT is superior to C-HRCT in displaying the blood vessels, bronchial walls, and interlobular septum for evaluating COVID-19.

Over the past few years, structures for lossless ion manipulations (SLIM) have used traveling waves (TWs) to move ions over long serpentine paths that can be further lengthened by routing the ions through multiple passages of the same path. Such SLIM “multipass” separations provide unprecedentedly high ion mobility resolving powers but are ultimately limited in their ion mobility range because of the range of mobilities spanned in a single pass; that is, higher mobility ions ultimately “overtake” and “lap” lower mobility ions that have experienced fewer passes, convoluting their arrival time distribution at the detector. To achieve ultrahigh resolution separations over broader mobility ranges, we have developed a new multilevel SLIM possessing multiple stacked serpentine paths. Ions are transferred between SLIM levels through apertures (or ion escalators) in the SLIM surfaces. The initial multilevel SLIM module incorporates four levels and three interlevel ion escalator passages, providing a total path length of 43.2 m. Using the full path length and helium buffer gas, high resolution separations were achieved for Agilent tuning mixture phosphazene ions over a broad mobility range (K(0) ≈ 3.0 to 1.2 cm(2)/(V*s)). High sensitivity was achieved using “in-SLIM” ion accumulation over an extended trapping region of the first SLIM level. High transmission efficiency of ions over a broad mobility range (e.g., K(0) ≈ 3.0 to 1.67 cm(2)/(V*s)) was achieved, with transmission efficiency rolling off for the lower mobility ions (e.g., K(0) ≈ 1.2 cm(2)/(V*s)). Resolving powers of up to ~560 were achieved using all four ion levels to separate reverse peptides (SDGRG(1+) and GRGDS(1+)). A complex mixture of phosphopeptides showed similar coverage could be achieved using one or all four SLIM levels, and doubly charged phosphosite isomers not significantly separated using one SLIM level were well resolved when four levels were used. The new multilevel SLIM technology thus enables wider mobility range ultrahigh-resolution ion mobility separations and expands on the ability of SLIM to obtain improved separations of complex mixtures with high sensitivity.

BackgroundThe novel advanced modeled iterative reconstruction (ADMIRE) algorithm in ultra-high-resolution (UHR) computed tomography (CT) of the temporal bone has not yet been systematically evaluat...

This work introduces, for the first time, a millimeter-wave imaging system with a “synthetic” ultra-wide imaging bandwidth of 98 GHz to provide the ultra-high resolutions required for early-stage skin cancer detection. The proposed approach consists of splitting the required ultra-wide imaging bandwidth into four sub-bands, and assigning each sub-band to a separate imaging element, i.e., an antenna radiator. Each of the sub-band antennas transmits and receives signals only at its corresponding sub-band. The captured signals are then combined and processed to form the image of the target. For each sub-band, a Vivaldi tapered slot antenna fed with a combination of substrate-integrated waveguide and coplanar waveguide is designed and microfabricated. Design techniques are also provided for the four similarly-shaped sub-band antennas for achieving excellent impedance matches ( $S_{11}$ < –10 dB) and nearly constant gains of 10 dBi over the entire 12–110 GHz bandwidth. The design procedure is validated by comparing the simulated results with measurements performed on the fabricated prototypes. Excellent agreements are obtained between simulations and measurements. Finally, the feasibility of detecting early-stage skin tumors in three dimensions is experimentally verified by employing the sub-band antennas in a synthetic ultra-wideband imaging system with a bandwidth of 98 GHz. Two separate setups, each comprising a dispersive skin-mimicking phantom as well as two dispersive spherical tumors, are constructed for imaging experiments. Lateral and axial resolutions of 200 μm are confirmed, and a successful reconstruction of the spherical tumors is achieved in both cases.

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans.SIGNIFICANCE STATEMENTVisual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.

BackgroundAn ongoing outbreak of mystery pneumonia in Wuhan was caused by coronavirus disease 2019 (COVID-19). The infectious disease has spread globally and become a major threat to public health.PurposeWe aim to investigate the ultra-high-resolution CT (UHR-CT) findings of imported COVID-19 related pneumonia from the initial diagnosis to early-phase follow-up.MethodsThis retrospective study included confirmed cases with early-stage COVID-19 related pneumonia imported from the epicenter. Initial and early-phase follow-up UHR-CT scans (within 5 days) were reviewed for characterizing the radiological findings. The normalized total volumes of ground-glass opacities (GGOs) and consolidations were calculated and compared during the radiological follow-up by artificial-intelligence-based methods.ResultsEleven patients (3 males and 8 females, aged 32-74 years) with confirmed COVID-19 were evaluated. Subpleural GGOs with inter/intralobular septal thickening were typical imaging findings. Other diagnostic CT features included distinct margins (8/11, 73%), pleural retraction or thickening (7/11, 64%), intralesional vasodilatation (6/11, 55%). Normalized volumes of pulmonary GGOs (p=0.003) and consolidations (p=0.003) significantly increased during the CT follow-up.ConclusionsThe abnormalities of GGOs with peripleural distribution, consolidated areas, septal thickening, pleural involvement and intralesional vasodilatation on UHR-CT indicate the diagnosis of COVID-19. COVID-19 cases could manifest significantly progressed GGOs and consolidations with increased volume during the early-phase CT follow-up.

To establish complementary information for the diagnosis and evaluation of ocular surface diseases, we developed a multi-modal, non-invasive optical imaging platform by combining ultra-high resolution optical coherence tomography (UHR-OCT) with a microvascular imaging system based on slit-lamp biomicroscopy. Our customized UHR-OCT module achieves an axial resolution of &asymp, 2.9 &mu, m in corneal tissue with a broadband light source and an A-line acquisition rate of 24 kHz with a line array CCD camera. The microvascular imaging module has a lateral resolution of 3.5 &mu, m under maximum magnification of &asymp, 187.5&times, with an imaging rate of 60 frames/s, which is sufficient to image the conjunctival vessel network and record the movement trajectory of clusters of red blood cells. By combining the imaging optical paths of different modules, our customized multi-modal anterior eye imaging platform is capable of performing real-time cross-sectional UHR-OCT imaging of the anterior eye, conjunctival vessel network imaging, high-resolution conjunctival blood flow videography, fluorescein staining and traditional slit-lamp imaging on a single device. With self-developed software, a conjunctival vessel network image and blood flow videography were further analyzed to acquire quantitative morphological and hemodynamics parameters, including vessel fractal dimensions, blood flow velocity and vessel diameters. The ability of our multi-modal anterior eye imager to provide both structural and functional information for ophthalmic clinical applications was demonstrated on a healthy human subject and a keratitis patient.

To review the chest computed tomography (CT) findings on the ultra-high-resolution CT (U-HRCT) in patients with the Novel coronavirus disease 2019 (COVID-19). In February 2020, six consecutive patients with COVID-19 pneumonia (median age, 69 years) underwent U-HR CT imaging. U-HR-CT has a larger matrix size of 1024 × 1024 thinner slice thickness of 0.25 mm and can demonstrate terminal bronchioles in the normal lungs; as a result, Reid’s secondary lobules and their abnormalities can be identified. The distribution and hallmarks (ground-glass opacity, consolidation with or without architectural distortion, linear opacity, crazy paving) of the lung opacities on U-HRCT were visually evaluated on a 1 K monitor by two experienced reviewers. The CT lung volume was measured, and the ratio of the measured lung volume to the predicted total lung capacity (predTLC) based on sex, age and height was calculated. All cases showed crazy paving pattern in U-HRCT. In these lesions, the secondary lobules were smaller than those in the un-affected lungs. CT lung volume decreased in two cases comparing predTLC. U-HRCT can evaluate not only the distribution and hallmarks of COVID-19 pneumonia but also visualize local lung volume loss.

Atmospheric rivers (ARs) are narrow, elongated structures, transporting large amounts of water vapor from the tropics towards polar regions. These synoptic scale features play an important role in the global hydrological cycle and for extreme precipitation events. To study how ARs will change in response to greenhouse warming we use a series of century-long fully coupled ultra-high-resolution simulations conducted with CESM 1.2.2 with an approximate horizontal resolution of ~25 km in the atmosphere and 10 km in the ocean. The simulations were carried out for present-day, 2xCO2 and 4xCO2 conditions. In this high atmospheric resolution, we obtain a much more realistic representation of complex orographic features (such as the Rocky Mountains), which can greatly influence the extreme precipitation often associated with ARs. Results from the present-day simulation are compared with ERA-Interim data to validate the model's fidelity in representing ARs. Our analysis focuses on future greenhouse-warming induced changes in AR frequency, geometry, landfalling latitude and strength. We find a global increase in the frequency of ARs amounting to ~0.5% for 2xCO2 and 0.9% for 4xCO2 respectively. In subtropical areas, such as the southwestern part of the United States AR frequencies increase by up to 7%. The presentation will further document the underlying processes for this increase.

Background: Quantitative measurement of airway dimensions using computed tomography (CT) is performed in relatively larger airways due to the limited resolution of CT scans. Nevertheless, the small airway is an important pathological lesion in lung diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Ultra-high resolution scanning may resolve the smaller airway, but its accuracy and limitations are unclear. Methods: Phantom tubes were imaged using conventional (512 × 512) and ultra-high resolution (1024 × 1024 and 2048 × 2048) scans. Reconstructions were performed using the forward-projected model-based iterative reconstruction solution (FIRST) algorithm in 512 × 512 and 1024 × 1024 matrix scans and the adaptive iterative dose reduction 3D (AIDR-3D) algorithm for all scans. In seven subjects with COPD, the airway dimensions were measured using the 1024 × 1024 and 512 × 512 matrix scans. Results: Compared to the conventional 512 × 512 scan, variations in the CT values for air were increased in the ultra-high resolution scans, except in the 1024×1024 scan reconstructed through FIRST. The measurement error of the lumen area of the tube with 2-mm diameter and 0.5-mm wall thickness (WT) was minimal in the ultra-high resolution scans, but not in the conventional 512 × 512 scan. In contrast to the conventional scans, the ultra-high resolution scans resolved the phantom tube with ≥ 0.6-mm WT at an error rate of < 11%. In seven subjects with COPD, the WT showed a lower value with the 1024 × 1024 scans versus the 512 × 512 scans. Conclusions: The ultra-high resolution scan may allow more accurate measurement of the bronchioles with smaller dimensions compared with the conventional scan.