1-Methyl-3-(naphthalen-2-yl)cyclo-penta-diene.

The title compound, C16H14, an asymmetric naphthyl-/methyl-substituted cyclo-penta-diene was synthesized and one isomer of five accessible through sigmatropic rearrangement was isolated and characterized by 1H NMR and X-ray diffraction. The crystal packing features an inter-molecular C-H⋯π inter-action.

Oral CT Contrast Agents: What's New and Why, From the AJR Special Series on Contrast Media.

Current CT oral contrast agents improve the conspicuity and confidence for bowel and peritoneal findings in many clinical scenarios, particularly for outpatient and oncologic abdominopelvic imaging. Yet, existing positive and neutral oral contrast agents may diminish the detectability of certain radiologic findings, frequently in the same scans in which the oral contrast agent improves the detectability of other findings. With ongoing improvements in CT technology, particularly multi-energy CT, opportunities are opening for new types of oral contrast agents to further improve anatomic delineation and disease detection using CT. The CT signal of new dark oral contrast agents and of new high-Z oral contrast agents promise to combine the strengths of both positive and neutral oral CT contrast agents by providing distinct CT appearances in comparison with bodily tissues, iodinated IV contrast agents, and other classes of new CT contrast agents. High-Z oral contrast agents will unlock previously inaccessible capabilities of multi-energy CT, particularly photon-counting detector CT, for differentiating simultaneously administered IV and oral contrast agents; this technique will allow generation of rich 3D, intuitive, perfectly co-registered, high-resolution image sets with individual contrast-agent "colors" that provide compelling clarity for intertwined intraabdominal anatomy and disease processes.

Synthesis, crystal structure, EPR, and DFT studies of an unusually distorted vanadium(II) complex.

We report the synthesis and structure of the most highly distorted four-coordinate d3 ion known to date that also serves as the second known example of a bis(biphenolato) transition metal complex. We demonstrate the application of density functional theory to calculate the magnetic parameters derived from the experimental and simulated EPR spectra.

An Intravascular Tantalum Oxide-based CT Contrast Agent: Preclinical Evaluation Emulating Overweight and Obese Patient Size.

Purpose To compare the CT imaging performance of a carboxybetaine zwitterionic-coated tantalum oxide (TaCZ) nanoparticle CT contrast agent with that of a conventional iodinated contrast agent in a swine model meant to simulate overweight and obese patients. Materials and Methods Four swine were evaluated inside three different-sized adipose-equivalent encasements emulating abdominal girths of 102, 119, and 137 cm. Imaging was performed with a 64-detector row CT scanner at six scan delays after intravenous injection of 240 mg element (Ta or I) per kilogram of body weight of TaCZ or iopromide. For each time point, contrast enhancement of the aorta and liver were measured by using regions of interest. Two readers independently recorded the clarity of vasculature using a five-point Likert scale. Findings were compared by using paired t tests and Wilcoxon signed-rank tests. Results Mean peak enhancement was higher for TaCZ than for iopromide in the aorta (270 HU [σ = 24.5] vs 199 HU [σ = 10.2], P < .001) and liver (61.3 HU [σ = 11.7] vs 45.2 HU [σ = 8], P < .001). Vascular clarity was higher for TaCZ than for iopromide in 63% (132 of 208), 82% (170 of 208), and 86% (178 of 208) of the individual vessels at the 102-, 119-, and 137-cm girths, respectively (P < .01). Arterial clarity scores were higher for TaCZ than for iopromide in 62% (208 of 336) of vessels. Venous clarity scores were higher for TaCZ than for iopromide in 89% (128 of 144) of the veins in the venous phase and in 100% (144 of 144) of veins in the delayed phase (P < .01). No vessel showed higher clarity score with iopromide than with TaCZ. Conclusion An experimental tantalum nanoparticle-based contrast agent showed greater contrast enhancement compared with iopromide in swine models meant to simulate overweight and obese patients. © RSNA, 2018.

Liquid tissue surrogates for X-ray and CT phantom studies.

PURPOSE: To develop a simple method for producing liquid-tissue-surrogate (LTS) materials that accurately represent human soft tissues in terms of density and X-ray attenuation coefficient. METHODS AND MATERIALS: We evaluated hypothetical mixtures of water, glycerol, butanol, methanol, sodium chloride, and potassium nitrate; these mixtures were intended to emulate human adipose, blood, brain, kidney, liver, muscle, pancreas, and skin. We compared the hypothetical densities, effective atomic numbers (Zeff ), and calculated discrete-energy CT attenuation [Hounsfield Units (HU)] of the proposed materials with those of human tissue elemental composition as specified in International Commission on Radiation Units (ICRU) Report 46. We then physically produced the proposed LTS materials for adipose, liver, and pancreas tissue, and we measured the polyenergetic CT attenuation (also expressed as HU) of these materials within a 32 cm phantom using a 64-slice clinical CT scanner at 80 kVp, 100 kVp, 120 kVp, and 140 kVp. RESULTS: The predicted densities, Zeff , and calculated discrete-energy CT attenuation of our proposed formulations generally agreed with those of ICRU within < 1% or < 10 HU. For example, the densities of our hypothetical materials agreed precisely with ICRU's reported values and were 0.95 g/mL for adipose tissue, 1.04 g/mL for pancreatic tissue, and 1.06 g/mL for liver tissue; the discrete-energy CT attenuation at 60 keV of our hypothetical materials (and ICRU-specified compositions) were -107 HU (-113 HU) for adipose #3, -89 HU (-90 HU) for adipose #2, 56 HU (55 HU) for liver tissue, and 31 HU (31 HU) for pancreatic tissue. The densities of our physically produced materials (compared to ICRU-specified compositions) were 0.947 g/mL (0.0%) for adipose #2, 1.061 g/mL (+2.0%) for pancreatic tissue, and 1.074 g/mL (+1.3%) for liver tissue. The empirical polyenergetic CT attenuation measurements of our LTS materials (and the discrete-energy HU of the ICRU compositions at the mean energy of each spectrum) at 80 kVp were -104 HU (-113 HU) for adipose #3, -87 HU (-90 HU) for adipose #2, 59 HU (55 HU) for liver tissue, and 33 HU (31 HU) for pancreatic tissue; at 120 kVp, these were -83 HU (-83 HU) for adipose #3, -68 HU (-63 HU) for adipose #2, 55 HU (52 HU) for liver tissue, and 35 HU (33 HU) for pancreatic tissue. CONCLUSION: Our method for formulating tissue surrogates allowed straightforward production of solutions with CT attenuation that closely matched the target tissues' expected CT attenuation values and trends with kVp. The LTSs' inexpensive and widely available constituent chemicals, combined with their liquid state, should enable rapid production and versatile use among different phantom and experiment types. Further study is warranted, such as the inclusion of contrast agents. These liquid tissue surrogates may potentially accelerate development and testing of advanced CT imaging techniques and technologies.

The Effect of Patient Diameter on the Dual-Energy Ratio of Selected Contrast-Producing Elements.

OBJECTIVES: The aim of this study was to assess whether the low- to high-kVp computed tomography (CT) number ratio at dual-energy CT is affected by changes in patient diameter. METHODS: Seven contrast-producing elements were housed sequentially within an abdomen phantom. Fat rings enlarged the phantom diameter from 26 to 44 cm. The phantom was scanned using single-energy CT at tube potentials of 80 and 140 kVp and rapid-kVp-switching dual-energy CT. RESULTS: CT numbers decreased proportionally (∼20% CT number reduction for smallest to largest phantom diameters) for low- and high-energy acquisitions but resulted in consistent dual-energy ratios for each contrast element. For 17 of 21 material pair combinations, the dual-energy ratio ranges of the two elements did not overlap, implying that discrimination should remain possible for these material pairs at all patient sizes. CONCLUSIONS: The dual-energy ratio for different contrast materials is largely unaffected by changes in phantom diameter. This should allow for robust separation of most contrast material combinations irrespective of patient size.

Opportunities for new CT contrast agents to maximize the diagnostic potential of emerging spectral CT technologies.

The introduction of spectral CT imaging in the form of fast clinical dual-energy CT enabled contrast material to be differentiated from other radiodense materials, improved lesion detection in contrast-enhanced scans, and changed the way that existing iodine and barium contrast materials are used in clinical practice. More profoundly, spectral CT can differentiate between individual contrast materials that have different reporter elements such that high-resolution CT imaging of multiple contrast agents can be obtained in a single pass of the CT scanner. These spectral CT capabilities would be even more impactful with the development of contrast materials designed to complement the existing clinical iodine- and barium-based agents. New biocompatible high-atomic number contrast materials with different biodistribution and X-ray attenuation properties than existing agents will expand the diagnostic power of spectral CT imaging without penalties in radiation dose or scan time.

A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

OBJECTIVES: The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. MATERIALS AND METHODS: We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. RESULTS: Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. CONCLUSIONS: We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.

CT Image Contrast of High-Z Elements: Phantom Imaging Studies and Clinical Implications.

PURPOSE: To quantify the computed tomographic (CT) image contrast produced by potentially useful contrast material elements in clinically relevant imaging conditions. MATERIALS AND METHODS: Equal mass concentrations (grams of active element per milliliter of solution) of seven radiodense elements, including iodine, barium, gadolinium, tantalum, ytterbium, gold, and bismuth, were formulated as compounds in aqueous solutions. The compounds were chosen such that the active element dominated the x-ray attenuation of the solution. The solutions were imaged within a modified 32-cm CT dose index phantom at 80, 100, 120, and 140 kVp at CT. To simulate larger body sizes, 0.2-, 0.5-, and 1.0-mm-thick copper filters were applied. CT image contrast was measured and corrected for measured concentrations and presence of chlorine in some compounds. RESULTS: Each element tested provided higher image contrast than iodine at some tube potential levels. Over the range of tube potentials that are clinically practical for average-sized and larger adults-that is, 100 kVp and higher-barium, gadolinium, ytterbium, and tantalum provided consistently increased image contrast compared with iodine, respectively demonstrating 39%, 56%, 34%, and 24% increases at 100 kVp; 39%, 66%, 53%, and 46% increases at 120 kVp; and 40%, 72%, 65%, and 60% increases at 140 kVp, with no added x-ray filter. CONCLUSION: The consistently high image contrast produced with 100-140 kVp by tantalum compared with bismuth and iodine at equal mass concentration suggests that tantalum could potentially be favorable for use as a clinical CT contrast agent.

Reversible catalytic dehydrogenation of alcohols for energy storage.

Reversibility of a dehydrogenation/hydrogenation catalytic reaction has been an elusive target for homogeneous catalysis. In this report, reversible acceptorless dehydrogenation of secondary alcohols and diols on iron pincer complexes and reversible oxidative dehydrogenation of primary alcohols/reduction of aldehydes with separate transfer of protons and electrons on iridium complexes are shown. This reactivity suggests a strategy for the development of reversible fuel cell electrocatalysts for partial oxidation (dehydrogenation) of hydroxyl-containing fuels.

Highly selective electrocatalytic dehydrogenation at low applied potential catalyzed by an Ir organometallic complex.

A homogeneous organometallic Ir complex was shown to catalyze the electro-oxidation of 4-methoxybenzyl alcohol to p-anisaldehyde at a very low applied potential with remarkably high selectivity and Faradaic efficiency. In the chemical catalysis, when stoichiometric oxidant and anionic base were used to separately accept electrons and protons, aldehyde selectivity was in agreement with electrolysis results.

Preclinical assessment of a zwitterionic tantalum oxide nanoparticle X-ray contrast agent.

Tantalum oxide nanoparticles show great potential as the next generation of X-ray contrast media. Recently, we reported advances in tantalum oxide nanoparticles and identified improvements that were required for such particles to progress further. Namely, the viscosity of concentrated particles, the amount of retention in reticuloendothelial (RES) tissues, and the effect of large quantities of particles on the kidneys after administration were all identified as critical factors which needed further study, understanding, and development. Here, we report on a zwitterionic siloxane polymer nanoparticle coating that reduced the viscosity of concentrated solutions of particles by a factor of 5, decreased tissue retention of injected particles by a factor of 10, and, importantly, did not induce pathological responses in the kidneys.

Biological performance of a size-fractionated core-shell tantalum oxide nanoparticle x-ray contrast agent.

OBJECTIVES: Metal-containing nanoparticles show great promise as x-ray contrast media and could enable reduced radiation dose, increased contrast, and the visualization of smaller anatomic features. In this study, we report progress toward these goals using a size-fractionated core-shell tantalum oxide nanoparticle contrast agent. MATERIALS AND METHODS: A core-shell tantalum oxide nanoparticle contrast agent was synthesized and size fractionated for preclinical investigation of biodistribution, blood half-life, organ retention, and histopathology. Fractionated agent was injected at anticipated clinical dose and at 3 times the anticipated clinical dose to evaluate biological performance. Computed tomography (CT) imaging studies were also performed to evaluate short-term clearance kinetics and new imaging applications. RESULTS: Improved control of 2-diethylphosphatoethylsilane-TaO nanoparticle size resulted in significantly reduced retention of injected tantalum. In vivo and in vitro CT imaging studies demonstrated short-term biodistribution differences in the kidney between small-molecule iodinated contrast media and fractionated 2-diethylphosphatoethylsilane-TaO, as well as preliminary data about new "Ta-only" imaging applications using multienergy CT image acquisition. CONCLUSIONS: Size-fractionated core-shell tantalum oxide nanoparticles with a well-defined particle size distribution have several key features required of clinically viable vascular imaging compounds and may be used in developing multienergy CT imaging applications.

Synthesis, characterization, and computed tomography imaging of a tantalum oxide nanoparticle imaging agent.

Water-soluble ≤6 nm tantalum oxide nanoparticles have been synthesized and characterized in solution using HPLC-ICP, DLS, and multinuclear NMR. Nanoparticle formulation permitted intravenous injection, in vivo imaging, and subsequent renal clearance. A clinical CT scanner provided excellent resolution following agent injection, and distribution to the arterial system was visualized. In vitro CT imaging studies indicated that at equal molar concentration of tantalum and iodine, tantalum produced greater image contrast than iodine across the diagnostic X-ray spectrum with contrast benefit increasing with peak X-ray energy.