Association of Ground Glass Opacities with Systemic Inflammation and Progression of Emphysema.

RATIONAL: Ground glass opacities (GGO) in the absence of interstitial lung disease are understudied. OBJECTIVE: To assess the association of GGO with white blood cells (WBCs) and progression of quantified chest CT emphysema. METHODS: We analyzed data of participants in the Subpopulations and Intermediate Outcome Measures In COPD Study (SPIROMICS). Chest radiologists and pulmonologists labeled regions of the lung as GGO and adaptive multiple feature method (AMFM) trained the computer to assign those labels to image voxels and quantify the volume of the lung with GGO (%GGOAMFM). We used multivariable linear regression, zero-inflated negative binomial, and proportional hazards regression models to assess the association of %GGOAMFM with WBC, changes in %emphysema, and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: Among 2,714 participants, 1,680 had COPD and 1,034 had normal spirometry. Among COPD participants, based on the multivariable analysis, current smoking and chronic productive cough was associated with higher %GGOAMFM. Higher %GGOAMFM was cross-sectionally associated with higher WBCs and neutrophils levels. Higher %GGOAMFM per interquartile range at visit 1 (baseline) was associated with an increase in emphysema at one-year follow visit by 11.7% (Relative increase; 95%CI 7.5-16.1%;P<0.001). We found no association between %GGOAMFM and one-year FEV1 decline but %GGOAMFM was associated with exacerbations and all-cause mortality during a median follow-up time of 1,544 days (Interquartile Interval=1,118-2,059). Among normal spirometry participants, we found similar results except that %GGOAMFM was associated with progression to COPD at one-year follow-up. CONCLUSIONS: Our findings suggest that GGOAMFM is associated with increased systemic inflammation and emphysema progression.

Light-Driven Metabolic Pathways in Non-Photosynthetic Biohybrid Bacteria.

Biomanufacturing via microorganisms relies on carbon substrates for molecular feedstocks and a source of energy to carry out enzymatic reactions. This creates metabolic bottlenecks and lowers the efficiency for substrate conversion. Nanoparticle biohybridization with proteins and whole cell surfaces can bypass the need for redox cofactor regeneration for improved secondary metabolite production in a non-specific manner. Here we propose using nanobiohybrid organisms (Nanorgs), intracellular protein-nanoparticle hybrids formed through the spontaneous coupling of core-shell quantum dots (QDs) with histidine-tagged enzymes in non-photosynthetic bacteria, for light-mediated control of bacterial metabolism. This proved to eliminate metabolic constrictions and replace glucose with light as the source of energy in Escherichia coli, with an increase in growth by 1.7-fold in 75 % reduced nutrient media. Metabolomic tracking through carbon isotope labeling confirmed flux shunting through targeted pathways, with accumulation of metabolites downstream of respective targets. Finally, application of Nanorgs with the Ehrlich pathway improved isobutanol titers/yield by 3.9-fold in 75 % less sugar from E. coli strains with no genetic alterations. These results demonstrate the promise of Nanorgs for metabolic engineering and low-cost biomanufacturing.

"From Vision to Reality: Virtual Reality's Impact on Baffle Planning in Congenital Heart Disease".

This study aims to evaluate the feasibility and utility of virtual reality (VR) for baffle planning in congenital heart disease (CHD), specifically by creating patient-specific 3D heart models and assessing a user-friendly VR interface. Patient-specific 3D heart models were created using high-resolution imaging data and a VR interface was developed for baffle planning. The process of model creation and the VR interface were assessed for their feasibility, usability, and clinical relevance. Collaborative and interactive planning within the VR space were also explored. The study findings demonstrate the feasibility and usefulness of VR in baffle planning for CHD. Patient-specific 3D heart models generated from imaging data provided valuable insights into complex spatial relationships. The developed VR interface allowed clinicians to interact with the models, simulate different baffle configurations, and assess their impact on blood flow. The VR space's collaborative and interactive planning enhanced the baffle planning process. This study highlights the potential of VR as a valuable tool in baffle planning for CHD. The findings demonstrate the feasibility of using patient-specific 3D heart models and a user-friendly VR interface to enhance surgical planning and patient outcomes. Further research and development in this field are warranted to harness the full benefits of VR technology in CHD surgical management.

MRA as the Preferred Test for Pulmonary Embolism During the Iodinated Contrast Media Shortage of 2022: A Single-Center Experience.

BACKGROUND. Closure of a GE Healthcare facility in Shanghai, China, in 2022 disrupted the iodinated contrast media supply. Technologic advances have addressed limitations associated with the use of pulmonary MRA for diagnosis of pulmonary embolism (PE). OBJECTIVE. The purpose of this study was to describe a single institution's experience in the use of pulmonary MRA as an alternative to CTA for the diagnosis of PE in the general population during the iodinated contrast media shortage in 2022. METHODS. This retrospective single-center study included all CTA and MRA examinations performed to exclude PE from April 1 through July 31 (18 weekly periods) in 2019 (before the COVID-19 pandemic and contrast media shortage), 2021 (during the pandemic but before the shortage), and 2022 (during both the pandemic and the shortage). From early May through mid-July of 2022, MRA served as the preferred test for PE diagnosis, to preserve iodinated contrast media. CTA and MRA reports were reviewed. The total savings in iodinated contrast media volume resulting from preferred use of MRA was estimated. RESULTS. The study included 4491 examinations of 4006 patients (mean age, 57 ± 18 [SD] years; 1715 men, 2291 women): 1245 examinations (1111 CTA, 134 MRA) in 2019, 1547 examinations (1403 CTA, 144 MRA) in 2021, and 1699 examinations (1282 CTA, 417 MRA) in 2022. In 2022, the number of MRA examinations was four (nine when normalized to a 7-day period) in week 1, and this number increased to a maximum of 63 in week 10 and then decreased to 10 in week 18. During weeks 8-11, more MRA examinations (range, 45-63 examinations) than CTA examinations (range, 27-46 examinations) were performed. In 2022, seven patients with negative MRA underwent subsequent CTA within 2 weeks; CTA was negative in all cases. In 2022, 13.9% of CTA examinations (vs 10.3% of MRA examinations) were reported as having limited image quality. The estimated 4-month savings resulting from preferred use of MRA in 2022, under the assumption of uniform simple linear growth in CTA utilization annually and a CTA dose of 1 mL/kg, was 27 L of iohexol (350 mg I/mL). CONCLUSION. Preferred use of pulmonary MRA for PE diagnosis in the general population helped to conserve iodinated contrast media during the 2022 shortage. CLINICAL IMPACT. This single-center experience shows pulmonary MRA to be a practical substitute for pulmonary CTA in emergency settings.

Quantitative Chest CT Assessment of Small Airways Disease in Post-Acute SARS-CoV-2 Infection.

Background The long-term effects of SARS-CoV-2 infection on pulmonary structure and function remain incompletely characterized. Purpose To test whether SARS-CoV-2 infection leads to small airways disease in patients with persistent symptoms. Materials and Methods In this single-center study at a university teaching hospital, adults with confirmed COVID-19 who remained symptomatic more than 30 days following diagnosis were prospectively enrolled from June to December 2020 and compared with healthy participants (controls) prospectively enrolled from March to August 2018. Participants with post-acute sequelae of COVID-19 (PASC) were classified as ambulatory, hospitalized, or having required the intensive care unit (ICU) based on the highest level of care received during acute infection. Symptoms, pulmonary function tests, and chest CT images were collected. Quantitative CT analysis was performed using supervised machine learning to measure regional ground-glass opacity (GGO) and using inspiratory and expiratory image-matching to measure regional air trapping. Univariable analyses and multivariable linear regression were used to compare groups. Results Overall, 100 participants with PASC (median age, 48 years; 66 women) were evaluated and compared with 106 matched healthy controls; 67% (67 of 100) of the participants with PASC were classified as ambulatory, 17% (17 of 100) were hospitalized, and 16% (16 of 100) required the ICU. In the hospitalized and ICU groups, the mean percentage of total lung classified as GGO was 13.2% and 28.7%, respectively, and was higher than that in the ambulatory group (3.7%, P < .001 for both comparisons). The mean percentage of total lung affected by air trapping was 25.4%, 34.6%, and 27.3% in the ambulatory, hospitalized, and ICU groups, respectively, and 7.2% in healthy controls (P < .001). Air trapping correlated with the residual volume-to-total lung capacity ratio (ρ = 0.6, P < .001). Conclusion In survivors of COVID-19, small airways disease occurred independently of initial infection severity. The long-term consequences are unknown. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Elicker in this issue.

Prevalence and significance of incidental findings on computed tomography pulmonary angiograms: A retrospective cohort study.

OBJECTIVE: The purpose of this study was to analyze the prevalence and significance of incidental findings on computed tomography pulmonary angiography (CTPA) studies and to assess the diagnostic yield of CTPA in identifying an alternate diagnosis to pulmonary embolism (PE) on PE negative exams. METHODS: All patients who had a CTPA exam for PE evaluation between Jan 2016 and Dec 2018 with a negative PE result were included in the study. A total of 2083 patients were identified. We retrospectively queried the electronic medical record and the radiology report and recorded the following: Age, Sex, BMI, Patient location and Incidental findings. The incidental findings were classified into type 1 (Alternate diagnosis other than PE which could explain the patient's symptoms), type 2 (non-emergent findings which needed further work up) and type 3 findings (non-emergent findings which did not need further work up). Logistic regression analysis was performed to determine what factors affected the probability of finding a type 1 incidental (alternate diagnosis) or a type 2 incidental. RESULTS: 74.5% of the patients in our study had at least one incidental finding. Type 1 incidental findings (alternate diagnosis to PE) were found in 864 patients (41.5%). The most common type 1 finding was pneumonia followed by fluid overload. Male sex, increased age and lower BMI were significantly associated with increased odds of a type 1 incidental(p < 0.05). Similarly, all the patient locations had significantly different odds of finding a type-1 incidental, with ICU having the highest odds, followed by inpatient, ED and outpatient locations (p < 0.05). 563 patients (27%) had at least one type 2 incidental findings and the most common type 2 findings were progressive lung malignancy/ metastatic disease and new pulmonary nodule. Increased age was significantly associated with the probability of a type 2 finding (p < 0.05). CONCLUSIONS: CTPA may suggest an alternative diagnosis to pulmonary embolism in approximately 40% of the patients with a negative study. The probability of finding an alternate diagnosis (type 1 incidental) is higher in elderly patients and in patients referred from ICU and inpatient units.

Imaging primer for CT angiography in peripheral vascular trauma.

The use of computed tomography angiography (CTA) for the evaluation of peripheral vascular trauma has become increasingly prevalent in the past decade with the development of multidetector CT (MDCT) and multiple studies subsequently demonstrating high sensitivity, specificity, and diagnostic accuracy when compared with conventional angiography. Additional benefits of MDCT include the ability to rapidly acquire the images, perform multiplanar and 3D reconstructions, and assess the adjacent soft tissues and bones. Rapid intravenous injection of iodinated contrast material is required for optimal arterial enhancement. CTA manifestations of an arterial injury may be direct, and include active contrast extravasation, pseudoaneurysm, arteriovenous fistula (AVF), intimal injury, dissection, or occlusion. There are also indirect signs which have a high association with vascular injury, and should raise suspicion, when present. Pitfalls related to image acquisition or patient factors can be mitigated with appropriate planning and post-processing techniques.

Pulmonary embolism rule out: positivity and factors affecting the yield of CT angiography.

OBJECTIVE: CT pulmonary angiography (CTPA) is one of the most commonly ordered CT imaging tests. It is often believed to be overutilised with few recent studies showing a yield of less than 2%. This study aimed to determine the overall positivity rate of CTPA examinations and understand the factors that affect the yield of the CTPA examination. METHODS: We retrospectively analysed 2713 patients who received the CTPA exam between 2016 and 2018. Type of study ordered (CTPA chest or CTPA chest with abdomen and pelvis CT), patient location (emergency department (ED), outpatient, inpatient, intensive care unit (ICU)) and patient characteristics-age, sex and body mass index (BMI) were recorded. A logistic regression analysis was performed to determine what factors affect the positivity rate of CT scans for pulmonary embolism (PE). RESULTS: With 296 positive test results, the overall CTPA positivity was 10.9%. Male sex was associated with higher CTPA positivity, gender difference was maximum in 18-year to 35-year age group. Overweight and obese patients had significantly higher positivity as compared with BMI<25 (p<0.05). Higher positivity rate was seen in the BMI 25-40 group (11.9%) as compared with BMI>40 (10.1%) (p<0.05). Significant difference (p<0.001) was also found in CTPA examination yield from ICU (15.3%) versus inpatients (other than ICU) (12.4%) versus ED (9.6%), and outpatients (8.5%). The difference in CTPA yield based on the type of CT order (CTPA chest vs CTPA chest with CT abdomen and pelvis), patient's age and sex was not significant. CONCLUSION: CTPA yield of 10.9% in this study is comparable to acceptable positivity rate for the USA and is higher than recent studies showing positivity of <2%. Patient characteristics like obesity and ICU or inpatient location are associated with higher rate of CT positivity.

Four-dimensional virtual reality cine cardiac models using free open-source software.

This is a proof-of-concept study to create a four-dimensional (4-D) cine model of the heart and visualize it in virtual reality by using freely available open-source software and inexpensive hardware. Four-dimensional cine models allow for real-time visualization of cardiac structures during processes such as complex congenital heart disease. Such models can be used for patient and trainee education, and potentially for surgical planning. Currently, 3-D printed models are more commonly used, but they are static, showing only one selected phase of the cardiac cycle. Second, they are limited by the selection of clipping planes before printing. Four-dimensional segmentation and virtual reality visualization overcome these limitations. Currently, most of the work in virtual/augmented reality models involves the segmentation of one cardiac phase or the use of expensive software for multiphase segmentation. In this study, we show an approach for multiphase cardiac segmentation as well as its display using free open-source software and relatively inexpensive hardware.

Nanorg Microbial Factories: Light-Driven Renewable Biochemical Synthesis Using Quantum Dot-Bacteria Nanobiohybrids.

Living cells do not interface naturally with nanoscale materials, although such artificial organisms can have unprecedented multifunctional properties, like wireless activation of enzyme function using electromagnetic stimuli. Realizing such interfacing in a nanobiohybrid organism (or nanorg) requires (1) chemical coupling via affinity binding and self-assembly, (2) the energetic coupling between optoelectronic states of artificial materials with the cellular process, and (3) the design of appropriate interfaces ensuring biocompatibility. Here we show that seven different core-shell quantum dots (QDs), with excitations ranging from ultraviolet to near-infrared energies, couple with targeted enzyme sites in bacteria. When illuminated by light, these QDs drive the renewable production of different biofuels and chemicals using carbon-dioxide (CO2), water, and nitrogen (from air) as substrates. These QDs use their zinc-rich shell facets for affinity attachment to the proteins. Cysteine zwitterion ligands enable uptake through the cell, facilitating cell survival. Together, these nanorgs catalyze light-induced air-water-CO2 reduction with a high turnover number (TON) of ∼106-108 (mols of product per mol of cells) to biofuels like isopropanol (IPA), 2,3-butanediol (BDO), C11-C15 methyl ketones (MKs), and hydrogen (H2); and chemicals such as formic acid (FA), ammonia (NH3), ethylene (C2H4), and degradable bioplastics polyhydroxybutyrate (PHB). Therefore, these resting cells function as nanomicrobial factories powered by light.

Post Transcatheter Mitral Valve-In-Valve Repair Cardiac Pseudoaneurysm.

Online supplemental material is available for this article.

Near-Infrared-Light-Triggered Antimicrobial Indium Phosphide Quantum Dots.

The emergence of multidrug-resistant (MDR) pathogens represents one of the most urgent global public health crises. Light-activated quantum dots (QDs) are alternative antimicrobials, with efficient transport, low cost, and therapeutic efficacy, and they can act as antibiotic potentiators, with a mechanism of action orthogonal to small-molecule drugs. Furthermore, light-activation enhances control over the spatiotemporal release and dose of the therapeutic superoxide radicals from QDs. However, the limited deep-tissue penetration of visible light needed for QD activation, and concern over trace heavy metals, have prevented further translation. Herein, we report two indium phosphide (InP) QDs that operate in the near-infrared and deep-red light window, enabling deeper tissue penetration. These heavy-metal-free QDs eliminate MDR pathogenic bacteria, while remaining non-toxic to host human cells. This work provides a pathway for advancing QD nanotherapeutics to combat MDR superbugs.

High-Throughput Block Optical DNA Sequence Identification.

Optical techniques for molecular diagnostics or DNA sequencing generally rely on small molecule fluorescent labels, which utilize light with a wavelength of several hundred nanometers for detection. Developing a label-free optical DNA sequencing technique will require nanoscale focusing of light, a high-throughput and multiplexed identification method, and a data compression technique to rapidly identify sequences and analyze genomic heterogeneity for big datasets. Such a method should identify characteristic molecular vibrations using optical spectroscopy, especially in the "fingerprinting region" from ≈400-1400 cm-1 . Here, surface-enhanced Raman spectroscopy is used to demonstrate label-free identification of DNA nucleobases with multiplexed 3D plasmonic nanofocusing. While nanometer-scale mode volumes prevent identification of single nucleobases within a DNA sequence, the block optical technique can identify A, T, G, and C content in DNA k-mers. The content of each nucleotide in a DNA block can be a unique and high-throughput method for identifying sequences, genes, and other biomarkers as an alternative to single-letter sequencing. Additionally, coupling two complementary vibrational spectroscopy techniques (infrared and Raman) can improve block characterization. These results pave the way for developing a novel, high-throughput block optical sequencing method with lossy genomic data compression using k-mer identification from multiplexed optical data acquisition.

Conformational Smear Characterization and Binning of Single-Molecule Conductance Measurements for Enhanced Molecular Recognition.

Electronic conduction or charge transport through single molecules depends primarily on molecular structure and anchoring groups and forms the basis for a wide range of studies from molecular electronics to DNA sequencing. Several high-throughput nanoelectronic methods such as mechanical break junctions, nanopores, conductive atomic force microscopy, scanning tunneling break junctions, and static nanoscale electrodes are often used for measuring single-molecule conductance. In these measurements, "smearing" due to conformational changes and other entropic factors leads to large variances in the observed molecular conductance, especially in individual measurements. Here, we show a method for characterizing smear in single-molecule conductance measurements and demonstrate how binning measurements according to smear can significantly enhance the use of individual conductance measurements for molecular recognition. Using quantum point contact measurements on single nucleotides within DNA macromolecules, we demonstrate that the distance over which molecular junctions are maintained is a measure of smear, and the resulting variance in unbiased single measurements depends on this smear parameter. Our ability to identify individual DNA nucleotides at 20× coverage increases from 81.3% accuracy without smear analysis to 93.9% with smear characterization and binning (SCRIB). Furthermore, merely 7 conductance measurements (7× coverage) are needed to achieve 97.8% accuracy for DNA nucleotide recognition when only low molecular smear measurements are used, which represents a significant improvement over contemporary sequencing methods. These results have important implications in a broad range of molecular electronics applications from designing robust molecular switches to nanoelectronic DNA sequencing.

Single Nucleobase Identification Using Biophysical Signatures from Nanoelectronic Quantum Tunneling.

Nanoelectronic DNA sequencing can provide an important alternative to sequencing-by-synthesis by reducing sample preparation time, cost, and complexity as a high-throughput next-generation technique with accurate single-molecule identification. However, sample noise and signature overlap continue to prevent high-resolution and accurate sequencing results. Probing the molecular orbitals of chemically distinct DNA nucleobases offers a path for facile sequence identification, but molecular entropy (from nucleotide conformations) makes such identification difficult when relying only on the energies of lowest-unoccupied and highest-occupied molecular orbitals (LUMO and HOMO). Here, nine biophysical parameters are developed to better characterize molecular orbitals of individual nucleobases, intended for single-molecule DNA sequencing using quantum tunneling of charges. For this analysis, theoretical models for quantum tunneling are combined with transition voltage spectroscopy to obtain measurable parameters unique to the molecule within an electronic junction. Scanning tunneling spectroscopy is then used to measure these nine biophysical parameters for DNA nucleotides, and a modified machine learning algorithm identified nucleobases. The new parameters significantly improve base calling over merely using LUMO and HOMO frontier orbital energies. Furthermore, high accuracies for identifying DNA nucleobases were observed at different pH conditions. These results have significant implications for developing a robust and accurate high-throughput nanoelectronic DNA sequencing technique.

Photoexcited quantum dots for killing multidrug-resistant bacteria.

Multidrug-resistant bacterial infections are an ever-growing threat because of the shrinking arsenal of efficacious antibiotics. Metal nanoparticles can induce cell death, yet the toxicity effect is typically nonspecific. Here, we show that photoexcited quantum dots (QDs) can kill a wide range of multidrug-resistant bacterial clinical isolates, including methicillin-resistant Staphylococcus aureus, carbapenem-resistant Escherichia coli, and extended-spectrum ß-lactamase-producing Klebsiella pneumoniae and Salmonella typhimurium. The killing effect is independent of material and controlled by the redox potentials of the photogenerated charge carriers, which selectively alter the cellular redox state. We also show that the QDs can be tailored to kill 92% of bacterial cells in a monoculture, and in a co-culture of E. coli and HEK 293T cells, while leaving the mammalian cells intact, or to increase bacterial proliferation. Photoexcited QDs could be used in the study of the effect of redox states on living systems, and lead to clinical phototherapy for the treatment of infections.

ROS mediated selection for increased NADPH availability in Escherichia coli.

The economical production of chemicals and fuels by microbial processes remains an intense area of interest in biotechnology. A key limitation in such efforts concerns the availability of key co-factors, in this case NADPH, required for target pathways. Many of the strategies pursued for increasing NADPH availability in Escherichia coli involve manipulations to the central metabolism, which can create redox imbalances and overall growth defects. In this study we used a reactive oxygen species based selection to search for novel methods of increasing NADPH availability. We report a loss of function mutation in the gene hdfR appears to increase NADPH availability in E. coli. Additionally, we show this excess NADPH can be used to improve the production of 3HP in E. coli.

Titanium dioxide nanotube membranes for solar energy conversion: effect of deep and shallow dopants.

Nanostructured titanium dioxide (TiO2) has been intensively investigated as a material of choice for solar energy conversion in photocatalytic, photoelectrochemical, photovoltaic, and other photosensitized devices for converting light into chemical feedstocks or electricity. Towards management of light absorption in TiO2, while the nanotubular structure improves light absorption and simultaneous charge transfer to mitigate problems due to the indirect bandgap of the semiconductor, typically dopants are used to improve light absorption of incident solar irradiation in the wide bandgap of TiO2. While these dopants can be critical to the success of these solar energy conversion devices, their effect on photophysical and photoelectrochemical properties and detailed photokinetics are relatively under-studied. Here, we show the effect of deep and shallow metal dopants on the kinetics of photogenerated charged carriers in TiO2 and the resulting effect on photocatalytic and photoelectrochemical processes using these nanotube membranes. We performed a detailed optical, electronic, voltammetry and electrochemical impedance study to understand the effect of shallow and deep metal dopants (using undoped and niobium- and copper-doped TiO2 nanotubes) on light absorption, charge transport and charge transfer processes. Using wireless photocatalytic methylene blue degradation and carbon dioxide reduction, and wired photoelectrochemical device measurements, we elucidate the effect of different dopants on solar-to-fuel conversion efficiency and simultaneously describe the photokinetics using a model, to help design better energy conversion devices.

Comparison of Echocardiography, Cardiac Magnetic Resonance, and Computed Tomographic Imaging for the Evaluation of Left Ventricular Myocardial Function: Part 1 (Global Assessment).

Assessing left ventricular function is an essential part of the cardiovascular evaluation as it plays an important role in managing the patient and predicting prognosis. Recent advances in the imaging modalities currently allow a non-invasive comprehensive assessment of cardiac mechanics and precise estimation of cardiovascular hemodynamics. In this review, we will discuss and compare the currently available techniques and novel approaches utilized by echocardiography, cardiac magnetic resonance, and computed tomography for the assessment of global left ventricular performance.