Can radiomic feature analysis differentiate adrenal metastases from lipid-poor adenomas on single-phase contrast-enhanced CT abdomen?

AIM: To assess if radiomic feature analysis could help to differentiate between the lipid-poor adenomas and metastases to the adrenal glands. MATERIALS AND METHODS: Eighty-six patients (women:men 42:44; mean age 66 years) with biopsy-proven adrenal metastases and 55 patients (women:men 39:16; mean age 67 years) with lipid-poor adenomas who underwent contrast-enhanced, portal-venous phase CT of the abdomen. Radiomic features were extracted using the PyRadiomics extension for 3D Slicer. Following elastic net regularisation, seven of 1,132 extracted radiomic features were selected to build a radiomic signature. This was combined with patient demographics to create a predictive nomogram. The calibration curves in both the training and validation cohorts were assessed using a Hosmer-Lemeshow test. RESULTS: The radiomic signature alone yielded an area under the curve of 91.7% in the training cohort (n=93) and 87.1% in the validation cohort (n=48). The predictive nomogram, which combined age, a previous history of malignancy, and the radiomic signature, had an AUC of 97.2% in the training cohort and 90.4% in the validation cohort. CONCLUSION: The present nomogram has the potential to differentiate between a lipid-poor adrenal adenoma and adrenal metastasis on portal-venous CT.

Impact of COVID-19 on CT-diagnosed acute appendicitis and diverticulitis: was there collateral damage?

AIM: To evaluate the change in diagnosis rates, disease severity at presentation, and treatment of acute appendicitis and diverticulitis during the COVID-19 shutdown. MATERIALS AND METHODS: Following institutional review board approval, 6,002 CT examinations performed at five hospitals for suspected acute appendicitis and/or diverticulitis over the 12 weeks preceding and following the shutdown were reviewed retrospectively. Semi-automated language analysis (SALA) of the report classified 3,676 CT examinations as negative. Images of the remaining 2,326 CT examinations were reviewed manually and classified as positive or negative. Positive cases were graded as non-perforated; perforated, contained; and perforated, free. RESULTS: CT examinations performed for suspected appendicitis and/or diverticulitis decreased from 3,558 to 2,200 following the shutdown. The rates of positive diagnoses before and after shutdown were 4% (144) and 4% (100) for appendicitis and 8% (284) and 7% (159) for diverticulitis (p>0.2 for both). For positive CT examinations, the rates of perforation, hospitalisation, surgery, and catheter drainage changed by -2%, -3%, -2%, and -3% for appendicitis (n=244, p>0.3 for all) and +6% (p=0.2) +9% (p=0.06), +4% (p=0.01) and +1% (p=0.6) for diverticulitis (n=443). CONCLUSION: CT examinations performed for suspected appendicitis or diverticulitis declined after the shutdown, likely reflecting patients leaving urban centres and altered triage of non-COVID-19 patients. The diagnosis rates, disease severity at presentation, and treatment approach otherwise remained mostly unchanged.

Thorium amidates function as single-source molecular precursors for thorium dioxide.

We report the synthesis of four homoleptic thorium(iv) amidate complexes as single-source molecular precursors for thorium dioxide. Each can be sublimed at atmospheric pressure, with the substituents on the amidate ligands significantly impacting their volatility and thermal stability. These complexes decompose via alkene elimination to give ThO2 without need for a secondary oxygen source. ThO2 samples formed from pyrolysis of C-alkyl amidates were found to have higher purity and crystallinity than ThO2 samples formed from C-aryl amidates.

Image-guided biopsy in the age of personalised medicine: strategies for success and safety.

Oncology has progressed into an era of personalised medicine, whereby the therapeutic regimen is tailored to the molecular profile of the patient's cancer. Determining personalised therapeutic options is achieved by using tumour genomics and proteomics to identify the specific molecular targets against which candidate drugs can interact. Several dozen targeted drugs, many for multiple cancer types are already widely in clinical use. Molecular profiling of tumours is contingent on high-quality biopsy specimens and the most common method of tissue sampling is image-guided biopsy. Thus, for radiologists performing these biopsies, the paradigm has now shifted away from obtaining specimens simply for histopathological diagnosis to acquiring larger amounts of viable tumour cells for DNA, RNA, or protein analysis. These developments have highlighted the central role now played by radiologists in the delivery of personalised cancer care. This review describes the principles of molecular profiling assays and biopsy techniques for optimising yield, and describes a scoring system to assist in patient selection for percutaneous biopsy.

The role of percutaneous CT-guided biopsy of an adrenal lesion in patients with known or suspected lung cancer.

PURPOSE: To determine the sensitivity, specificity, and complication rate of percutaneous adrenal biopsy in patients with known or suspected lung cancer. METHODS: This study was approved by the Institutional Review Board at our institution as a retrospective analysis; therefore, the need for informed consent was waived. All percutaneous adrenal biopsies performed between April 1993 and May 2019 were reviewed. 357 of 582 biopsies were performed on 343 patients with known or suspected lung cancer (M:F 164:179; mean age 66 years). The biopsy results were classified into malignant, benign, or non-diagnostic. The final diagnosis was established by pathology (biopsy and/or surgical resection) or imaging follow-up on CT for at least 12 months following the biopsy. Patients with less than 12 months follow-up were excluded (n = 44). Complications were recorded. RESULTS: The final diagnosis was metastatic lung cancer in 235 cases (77.8%), metastasis from an extrapulmonary primary in 2 cases (0.7%), pheochromocytoma in 2 cases (0.7%), and benign lesions in 63 cases (20.9%). Percutaneous adrenal gland biopsy had a sensitivity of 97% and specificity of 100% for lung cancer metastases. The non-diagnostic rate was 0.6%. Larger lesions were more likely to be malignant (p = 0.0000) and to be correctly classified as a lung metastasis (p = 0.025). The incidence of minor complications was 1.1%. There were no major complications. CONCLUSION: Over 20% of adrenal lesions in patients with known or suspected lung cancer were not related to lung cancer. Percutaneous adrenal gland biopsy is a safe procedure, with high sensitivity and specificity for lung cancer metastases.

Manipulating nanoscale structure to control functionality in printed organic photovoltaic, transistor and bioelectronic devices.

Printed electronics is simultaneously one of the most intensely studied emerging research areas in science and technology and one of the fastest growing commercial markets in the world today. For the past decade the potential for organic electronic (OE) materials to revolutionize this printed electronics space has been widely promoted. Such conviction in the potential of these carbon-based semiconducting materials arises from their ability to be dissolved in solution, and thus the exciting possibility of simply printing a range of multifunctional devices onto flexible substrates at high speeds for very low cost using standard roll-to-roll printing techniques. However, the transition from promising laboratory innovations to large scale prototypes requires precise control of nanoscale material and device structure across large areas during printing fabrication. Maintaining this nanoscale material control during printing presents a significant new challenge that demands the coupling of OE materials and devices with clever nanoscience fabrication approaches that are adapted to the limited thermodynamic levers available. In this review we present an update on the strategies and capabilities that are required in order to manipulate the nanoscale structure of large area printed organic photovoltaic (OPV), transistor and bioelectronics devices in order to control their device functionality. This discussion covers a range of efforts to manipulate the electroactive ink materials and their nanostructured assembly into devices, and also device processing strategies to tune the nanoscale material properties and assembly routes through printing fabrication. The review finishes by highlighting progress in printed OE devices that provide a feedback loop between laboratory nanoscience innovations and their feasibility in adapting to large scale printing fabrication. The ability to control material properties on the nanoscale whilst simultaneously printing functional devices on the square metre scale is prompting innovative developments in the targeted nanoscience required for OPV, transistor and biofunctional devices.

Comparison of 18F-FDG avidity at PET of benign and malignant pure ground-glass opacities: a paradox? Part II: artificial neural network integration of the PET/CT characteristics of ground-glass opacities to predict their likelihood of malignancy.

AIM: To assess the ability of artificial neural networks (ANNs) to predict the likelihood of malignancy of pure ground-glass opacities (GGOs), using observations from computed tomography (CT) and 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) images and relevant clinical information. MATERIALS AND METHODS: One hundred and twenty-five cases of pure GGOs described in a previous article were used to train and evaluate the performance of an ANN to predict the likelihood of malignancy in each of the GGOs. Eighty-five cases selected randomly were used for training the network and the remaining 40 cases for testing. The ANN was constructed from the image data and basic clinical information. The predictions of the ANN were compared with blinded expert estimates of the likelihood of malignancy. RESULTS: The ANN showed excellent predictive value in estimating the likelihood of malignancy (AUC = 0.98±0.02). Employing the optimal cut-off point from the receiver operating characteristic (ROC) curve, the ANN correctly identified 11/11 malignant lesions (sensitivity 100%) and 27/29 benign lesions (specificity 93.1%). The expert readers found 23 lesions indeterminate and correctly identified 17 lesions as benign. CONCLUSION: ANNs have potential to improve diagnostic certainty in the classification of pure GGOs, based upon their CT appearance, intensity of FDG uptake, and relevant clinical information, and may therefore, be useful to help direct clinical and imaging follow-up.

Building intermixed donor-acceptor architectures for water-processable organic photovoltaics.

A modified synthesis method for aqueous nanoparticle printing inks, based upon vacuum-assisted solvent removal, is reported. Poly(3-hexylthiophene):phenyl C61 butyric acid methyl ester nanoparticle inks were prepared via this modified miniemulsion method, leading to both an improvement in photoactive layer morphology and a substantial reduction in the ink fabrication time. A combination of UV-visible spectroscopy, photoluminescence spectroscopy and scanning transmission X-ray microscopy measurements revealed a nanoparticle morphology comprising highly intermixed donor-acceptor domains. Consistent with these measurements, dynamic mechanical thermal analysis of the nanoparticles showed a glass transition temperature (Tg) of 104 °C, rather than a pure polymer phase or pure fullerene phase Tg. Together the spectroscopy, microscopy and thermomechanical data indicate that rapid solvent removal generates a more blended nanoparticle morphology. As such, this study highlights a new experimental lever for optimising nanostructure in the photoactive layer of nanoparticulate organic photovoltaic devices by enabling highly intermixed donor-acceptor architectures to be built from customised nanoparticulate inks.

Comparison of the 18F-FDG avidity at PET of benign and malignant pure ground-glass opacities: a paradox?

AIM: To determine if pure ground-glass opacities (GGOs) and the subgroup of ground-glass nodules (GGNs) typically demonstrate higher 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG) uptake at positron-emission tomography (PET) when benign than when malignant. MATERIALS AND METHODS: Informed consent was waived for this institutional review board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA) compliant, retrospective study. A review of all 1,864 combined PET/computed tomography (CT) examinations performed in 2011 on a single system to identify pure GGOs with mean diameter ≥1 cm yielded 166 GGOs. Two blinded subspecialty-trained thoracic radiologists independently assessed GGO size, morphology, attenuation, and location on CT. A blinded nuclear radiologist procured the SUVmax for each GGO. Final diagnosis of malignancy (n=21) was made based on histopathology or upon increased size and attenuation; a final diagnosis of benignity (n=106) was made if GGO resolved, was new within 3 months, evolved in a manner consistent with pulmonary fibrosis, or was stable for ≥60 months; 29 were indeterminate and were excluded, along with 10 cases with unreliable SUVmax measurements, yielding 127 GGOs, of which 68 were GGNs, in 76 patients. RESULTS: The SUVmax was significantly higher in benign than malignant GGOs (p=0.0017) and in the GGN subgroup (p=0.03). A threshold SUVmax >1.5 for GGOs, including GGNs, assured benignity in this cohort. CONCLUSION: Benign GGOs and the benign GGN subgroup demonstrated significantly higher FDG uptake at PET than malignant GGOs/GGNs. Awareness of this finding may prevent misinterpretation of highly 18FDG-avid pure GGOs/GGNs as definitively malignant, which could lead to unnecessary thoracic surgery and its associated risks.

Sub-micron level investigation reveals the inaccessibility of stabilized carbon in soil microaggregates.

Direct evidence-based approaches are vital to evaluating newly proposed theories on the persistence of soil organic carbon and establishing the contributions of abiotic and biotic controls. Our primary goal was to directly identify the mechanisms of organic carbon stabilization in native-state, free soil microaggregates without disrupting the aggregate microstructure using scanning transmission x-ray microscopy coupled with near edge x-ray absorption fine structure spectroscopy (STXM-NEXAFS). The influence of soil management practices on microaggregate associated-carbon was also assessed. Free, stable soil microaggregates were collected from a tropical agro-ecosystem in Cruz Alta, Brazil. The long-term experimental plots (>25 years) comparing two tillage systems: no-till and till with a complex crop rotation. Based on simultaneously collected multi-elemental associations and speciation, STXM-NEXAFS successfully provided submicron level information on organo-mineral associations. Simple organic carbon sources were found preserved within microaggregates; some still possessing original morphology, suggesting that their stabilization was not entirely governed by the substrate chemistry. Bulk analysis showed higher and younger organic carbon in microaggregates from no-till systems than tilled systems. These results provide direct submicron level evidence that the surrounding environment is involved in stabilizing organic carbon, thus favoring newly proposed concepts on the persistence of soil organic carbon.

Three-dimensional localization of nanoscale battery reactions using soft X-ray tomography.

Battery function is determined by the efficiency and reversibility of the electrochemical phase transformations at solid electrodes. The microscopic tools available to study the chemical states of matter with the required spatial resolution and chemical specificity are intrinsically limited when studying complex architectures by their reliance on two-dimensional projections of thick material. Here, we report the development of soft X-ray ptychographic tomography, which resolves chemical states in three dimensions at 11 nm spatial resolution. We study an ensemble of nano-plates of lithium iron phosphate extracted from a battery electrode at 50% state of charge. Using a set of nanoscale tomograms, we quantify the electrochemical state and resolve phase boundaries throughout the volume of individual nanoparticles. These observations reveal multiple reaction points, intra-particle heterogeneity, and size effects that highlight the importance of multi-dimensional analytical tools in providing novel insight to the design of the next generation of high-performance devices.

Organic matter in extraterrestrial water-bearing salt crystals.

Direct evidence of complex prebiotic chemistry from a water-rich world in the outer solar system is provided by the 4.5-billion-year-old halite crystals hosted in the Zag and Monahans (1998) meteorites. This study offers the first comprehensive organic analysis of the soluble and insoluble organic compounds found in the millimeter-sized halite crystals containing brine inclusions and sheds light on the nature and activity of aqueous fluids on a primitive parent body. Associated with these trapped brines are organic compounds exhibiting wide chemical variations representing organic precursors, intermediates, and reaction products that make up life's precursor molecules such as amino acids. The organic compounds also contain a mixture of C-, O-, and N-bearing macromolecular carbon materials exhibiting a wide range of structural order, as well as aromatic, ketone, imine, and/or imidazole compounds. The enrichment in 15N is comparable to the organic matter in pristine Renazzo-type carbonaceous chondrites, which reflects the sources of interstellar 15N, such as ammonia and amino acids. The amino acid content of the Zag halite deviates from the meteorite matrix, supporting an exogenic origin of the halite, and therefore, the Zag meteorite contains organics synthesized on two distinct parent bodies. Our study suggests that the asteroidal parent body where the halite precipitated, potentially asteroid 1 Ceres, shows evidence for a complex combination of biologically and prebiologically relevant molecules.

Physical origins of current and temperature controlled negative differential resistances in NbO2.

Negative differential resistance behavior in oxide memristors, especially those using NbO2, is gaining renewed interest because of its potential utility in neuromorphic computing. However, there has been a decade-long controversy over whether the negative differential resistance is caused by a relatively low-temperature non-linear transport mechanism or a high-temperature Mott transition. Resolving this issue will enable consistent and robust predictive modeling of this phenomenon for different applications. Here we examine NbO2 memristors that exhibit both a current-controlled and a temperature-controlled negative differential resistance. Through thermal and chemical spectromicroscopy and numerical simulations, we confirm that the former is caused by a ~400 K non-linear-transport-driven instability and the latter is caused by the ~1000 K Mott metal-insulator transition, for which the thermal conductance counter-intuitively decreases in the metallic state relative to the insulating state.The development of future computation devices will be aided by a better understanding of the physics underlying material behaviors. Using thermoreflectance and spatially resolved X-ray microscopy, Kumar et al. elucidate the origin of two types of negative differential resistance in NbO2 memristors.

Spatially uniform resistance switching of low current, high endurance titanium-niobium-oxide memristors.

We analyzed micrometer-scale titanium-niobium-oxide prototype memristors, which exhibited low write-power (<3 µW) and energy (<200 fJ per bit per µm2), low read-power (∼nW), and high endurance (>millions of cycles). To understand their physico-chemical operating mechanisms, we performed in operando synchrotron X-ray transmission nanoscale spectromicroscopy using an ultra-sensitive time-multiplexed technique. We observed only spatially uniform material changes during cell operation, in sharp contrast to the frequently detected formation of a localized conduction channel in transition-metal-oxide memristors. We also associated the response of assigned spectral features distinctly to non-volatile storage (resistance change) and writing of information (application of voltage and Joule heating). These results provide critical insights into high-performance memristors that will aid in device design, scaling and predictive circuit-modeling, all of which are essential for the widespread deployment of successful memristor applications.

Conduction Channel Formation and Dissolution Due to Oxygen Thermophoresis/Diffusion in Hafnium Oxide Memristors.

Transition-metal-oxide memristors, or resistive random-access memory (RRAM) switches, are under intense development for storage-class memory because of their favorable operating power, endurance, speed, and density. Their commercial deployment critically depends on predictive compact models based on understanding nanoscale physicochemical forces, which remains elusive and controversial owing to the difficulties in directly observing atomic motions during resistive switching, Here, using scanning transmission synchrotron X-ray spectromicroscopy to study in situ switching of hafnium oxide memristors, we directly observed the formation of a localized oxygen-deficiency-derived conductive channel surrounded by a low-conductivity ring of excess oxygen. Subsequent thermal annealing homogenized the segregated oxygen, resetting the cells toward their as-grown resistance state. We show that the formation and dissolution of the conduction channel are successfully modeled by radial thermophoresis and Fick diffusion of oxygen atoms driven by Joule heating. This confirmation and quantification of two opposing nanoscale radial forces that affect bipolar memristor switching are important components for any future physics-based compact model for the electronic switching of these devices.

Molecular imaging-its current role in cancer.

Medical imaging has undergone extensive growth over the last few decades and now plays a central role in clinical oncology. The future of imaging in the management of oncology patients is molecularly targeted imaging agents. Molecular imaging differs from conventional anatomical imaging in that imaging probes are utilized to visualize target molecules-of-interest. It is envisioned that molecular imaging will have a major impact on oncology and personalized medicine by allowing earlier diagnosis, assessing early response to treatment and by predicting treatment response. It will, hopefully, also have an impact on drug development by streamlining preclinical and clinical tests for new drug candidates.

Dependence on Crystal Size of the Nanoscale Chemical Phase Distribution and Fracture in LixFePO4.

The performance of battery electrode materials is strongly affected by inefficiencies in utilization kinetics and cycle life as well as size effects. Observations of phase transformations in these materials with high chemical and spatial resolution can elucidate the relationship between chemical processes and mechanical degradation. Soft X-ray ptychographic microscopy combined with X-ray absorption spectroscopy and electron microscopy creates a powerful suite of tools that we use to assess the chemical and morphological changes in lithium iron phosphate (LiFePO4) micro- and nanocrystals that occur upon delithiation. All sizes of partly delithiated crystals were found to contain two phases with a complex correlation between crystallographic orientation and phase distribution. However, the lattice mismatch between LiFePO4 and FePO4 led to severe fracturing on microcrystals, whereas no mechanical damage was observed in nanoplates, indicating that mechanics are a principal driver in the outstanding electrode performance of LiFePO4 nanoparticles. These results demonstrate the importance of engineering the active electrode material in next generation electrical energy storage systems, which will achieve theoretical limits of energy density and extended stability. This work establishes soft X-ray ptychographic chemical imaging as an essential tool to build comprehensive relationships between mechanics and chemistry that guide this engineering design.

Observation of a four-electron Auger process in near-K-edge photoionization of singly charged carbon ions.

Single, double, and triple ionization of C(1+) ions by single photons is investigated in the energy range of 286-326 eV, i.e., in the range from the lowest-energy K-vacancy resonances to well beyond the K-shell ionization threshold. Clear signatures of C(1+)(1s2s(2)2p(2) (2)D,(2)P) resonances are found in the triple-ionization channel. The only possible mechanism producing C(4+)(1s(2)) via these resonances is direct triple-Auger decay, i.e., a four-electron process with simultaneous emission of three electrons.

Electron localization in a mixed-valence diniobium benzene complex.

Reaction of the neutral diniobium benzene complex {[Nb(BDI)N t Bu]2(µ-C6H6)} (BDI = N,N'-diisopropylbenzene-ß-diketiminate) with Ag[B(C6F5)4] results in a single electron oxidation to produce a cationic diniobium arene complex, {[Nb(BDI)N t Bu]2(µ-C6H6)}{B(C6F5)4}. Investigation of the solid state and solution phase structure using single-crystal X-ray diffraction, cyclic voltammetry, magnetic susceptibility, and multinuclear NMR spectroscopy indicates that the oxidation results in an asymmetric molecule with two chemically inequivalent Nb atoms. Further characterization using density functional theory (DFT) calculations, UV-visible, Nb L3,2-edge X-ray absorption near-edge structure (XANES), and EPR spectroscopies supports assignment of a diniobium complex, in which one Nb atom carries a single unpaired electron that is not largely delocalized on the second Nb atom. During the oxidative transformation, one electron is removed from the δ-bonding HOMO, which causes a destabilization of the molecule and formation of an asymmetric product. Subsequent reactivity studies indicate that the oxidized product allows access to metal-based chemistry with substrates that did not exhibit reactivity with the starting neutral complex.