Hyperpolarized 83Kr magnetic resonance imaging of alveolar degradation in a rat model of emphysema

Hyperpolarized 83Kr surface quadrupolar relaxation (SQUARE) generates MRI contrast that was previously shown to correlate to surface to volume ratios in porous model surface systems. The underlying physics of SQUARE contrast is conceptually different from any other current MRI methodology as the method utilizes the nuclear electric properties of the spin I = 9/2 isotope 83Kr. To explore the usage of this non-radioactive isotope for pulmonary pathophysiology, MRI SQUARE contrast was acquired in excised rat lungs obtained from an elastase induced model of emphysema. A significant 83Kr T1 relaxation time increase in the SQUARE contrast was found in the elastase treated lungs compared to the baseline data from control lungs. The SQUARE contrast suggests a reduction in pulmonary surface to volume ratio in the emphysema model that was validated by histology. The finding supports usage of 83Kr SQUARE as new biomarker for surface to volume ratio changes in emphysema

Anaerobic Carbon Monoxide Dehydrogenase Diversity in the Homoacetogenic Hindgut Microbial Communities of Lower Termites and the Wood Roach

Anaerobic carbon monoxide dehydrogenase (CODH) is a key enzyme in the Wood-Ljungdahl (acetyl-CoA) pathway for acetogenesis performed by homoacetogenic bacteria. Acetate generated by gut bacteria via the acetyl-CoA pathway provides considerable nutrition to wood-feeding dictyopteran insects making CODH important to the obligate mutualism occurring between termites and their hindgut microbiota. To investigate CODH diversity in insect gut communities, we developed the first degenerate primers designed to amplify cooS genes, which encode the catalytic (β) subunit of anaerobic CODH enzyme complexes. These primers target over 68 million combinations of potential forward and reverse cooS primer-binding sequences. We used the primers to identify cooS genes in bacterial isolates from the hindgut of a phylogenetically lower termite and to sample cooS diversity present in a variety of insect hindgut microbial communities including those of three phylogenetically-lower termites, Zootermopsis nevadensis, Reticulitermes hesperus, and Incisitermes minor, a wood-feeding cockroach, Cryptocercus punctulatus, and an omnivorous cockroach, Periplaneta americana. In total, we sequenced and analyzed 151 different cooS genes. These genes encode proteins that group within one of three highly divergent CODH phylogenetic clades. Each insect gut community contained CODH variants from all three of these clades. The patterns of CODH diversity in these communities likely reflect differences in enzyme or physiological function, and suggest that a diversity of microbial species participate in homoacetogenesis in these communities

Temperature-ramped 129Xe spin-exchange optical pumping

We describe temperature-ramped spin-exchange optical pumping (TR-SEOP) in an automated high-throughput batch-mode 129Xe hyperpolarizer utilizing three key temperature regimes: (i) “hot”where the 129Xe hyperpolarization rate is maximal, (ii) “warm”-where the 129Xe hyperpolarization approaches unity, and (iii) “cool” where hyperpolarized 129Xe gas is transferred into a Tedlar bag with low Rb content (<5 ng per ∼1 L dose) suitable for human imaging applications. Unlike with the conventional approach of batch-mode SEOP, here all three temperature regimes may be operated under continuous high-power (170 W) laser irradiation, and hyperpolarized 129Xe gas is delivered without the need for a cryocollection step. The variable-temperature approach increased the SEOP rate by more than 2-fold compared to the constant-temperature polarization rate (e.g., giving effective values for the exponential buildup constant γSEOP of 62.5 ± 3.7 × 10−3 min−1 vs 29.9 ± 1.2 × 10−3 min−1) while achieving nearly the same maximum %PXe value (88.0 ± 0.8% vs 90.1% ± 0.8%, for a 500 Torr (67 kPa) Xe cell loadingcorresponding to nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) enhancements of ∼3.1 × 105 and ∼2.32 × 108 at the relevant fields for clinical imaging and HP 129Xe production of 3 T and 4 mT, respectively); moreover, the intercycle “dead” time was also significantly decreased. The higher-throughput TR-SEOP approach can be implemented without sacrificing the level of 129Xe hyperpolarization or the experimental stability for automation-making this approach beneficial for improving the overall 129Xe production rate in clinical settings

XeNA: an automated ‘open-source’ 129Xe hyperpolarizer for clinical use

Here we provide a full report on the construction, components, and capabilities of our consortium’s “open-source” large-scale (~ 1 L/h) 129Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The ‘hyperpolarizer’ is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800 Torr Xe in 0.5 L) in either stopped-flow or single-batch mode—making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell 129Xe nuclear spin polarization values of ~ 30%–90% have been measured for Xe loadings of ~ 300–1600 Torr. Typical 129Xe polarization build-up and T1 relaxation time constants were ~ 8.5 min and ~ 1.9 h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~ 200 W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long 129Xe relaxation times (up to nearly 6 h) were observed in Tedlar bags following transport to a clinical 3 T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine

Magnetic resonance imaging in children: common problems and possible solutions for lung and airways imaging

Pediatric chest MRI is challenging. High-resolution scans of the lungs and airways are compromised by long imaging times, low lung proton density and motion. Low signal is a problem of normal lung. Lung abnormalities commonly cause increased signal intenstities. Among the most important factors for a successful MRI is patient cooperation, so the long acquisition times make patient preparation crucial. Children usually have problems with long breath-holds and with the concept of quiet breathing. Young children are even more challenging because of higher cardiac and respiratory rates giving motion blurring. For these reasons, CT has often been preferred over MRI for chest pediatric imaging. Despite its drawbacks, MRI also has advantages over CT, which justifies its further development and clinical use. The most important advantage is the absence of ionizing radiation, which allows frequent scanning for short- and long-term follow-up studie

Green synthesis of a thermo/photochromic doped cellulose polymer: a biocompatible film for potential application in cold chain visual tracking†

To mitigate food losses and ensure a robust cold chain in transportation, sensors play a pivotal role in swiftly and visibly monitoring storage conditions. The most commonly used indicators for reporting temperature violations are based on devices capable of signaling when a threshold temperature has been reached or exceeded or on disposable colorimetric sensors. A potential alternative, which uses reusable colorimetric sensors, may come from utilizing systems capable of displaying reversible color changes upon temperature variations; in this regard, molecules exhibiting thermo- and photochromic properties such as N-salicylideneaniline derivatives (anils) have emerged as promising candidates due to the simplicity of their synthesis and their ability to respond to temperature and light stimuli. In this study we have synthesized a family of anils through mechanochemistry, focusing on H/F substituents on the bromoaniline residue. The compounds were fully characterized using XRD and thermal techniques, and their thermo- and photochromic properties were explored via infrared spectroscopy. Among the series, the most suitable compound, i.e., a photochromic one showing a neat color change (from white to red/orange) quickly naked eye-detectable and whose back reaction is slow or virtually negligible at low temperatures, was identified and incorporated into a carboxymethyl cellulose (CMC) biopolymer matrix to produce a composite film, which was further characterized via XRD, thermal analyses and mechanical tests. The selected compound maintained its photochromic behavior upon embedding, and UV irradiation induced a color change in the film from colorless to red, while reversibility was evaluated at different temperatures (−19 °C, 4 °C and RT) using UV-vis spectroscopy. The composite film maintained a deep red color at −19 °C and 4 °C for seven weeks, while rapidly reversing to white/yellowish at room temperature, making it a suitable candidate for the development of sensors for cold chain transport and scenarios requiring rapid visual inspection of storage conditions.University of Bologna (RFO-Scheme

Conventional CT and PET/CT imaging in the evaluation and management of subsolid pulmonary nodules: an overview of the literature and author recommendations

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Filtration-histogram based texture analysis and CALIPER based pattern analysis as quantitative CT techniques in idiopathic pulmonary fibrosis: head-to-head comparison

OBJECTIVE: To assess the prognostic performance of two quantitative CT (qCT) techniques in idiopathic pulmonary fibrosis (IPF) compared to established clinical measures of disease severity (GAP index). METHODS: Retrospective analysis of high-resolution CT scans for 59 patients (age 70.5 ± 8.8 years) with two qCT methods. Computer-aided lung informatics for pathology evaluation and ratings based analysis classified the lung parenchyma into six different patterns: normal, ground glass, reticulation, hyperlucent, honeycombing and pulmonary vessels. Filtration histogram-based texture analysis extracted texture features: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPPs), skewness and kurtosis at different spatial scale filters. Univariate Kaplan-Meier survival analysis assessed the different qCT parameters' performance to predict patient outcome and refine the standard GAP staging system. Multivariate cox regression analysis assessed the independence of the significant univariate predictors of patient outcome. RESULTS: The predominant parenchymal lung pattern was reticulation (16.6% ± 13.9), with pulmonary vessel percentage being the most predictive of worse patient outcome (p = 0.009). Higher SD, entropy and MPP, in addition to lower skewness and kurtosis at fine texture scale (SSF2), were the most significant predictors of worse outcome (p < 0.001). Multivariate cox regression analysis demonstrated that SD (SSF2) was the only independent predictor of survival (p < 0.001). Better patient outcome prediction was achieved after adding total vessel percentage and SD (SSF2) to the GAP staging system (p = 0.006). CONCLUSION: Filtration-histogram texture analysis can be an independent predictor of patient mortality in IPF patients. ADVANCES IN KNOWLEDGE: qCT analysis can help in risk stratifying IPF patients in addition to clinical markers

[18F]FDG PET/CT Predicts Patient Survival in Patients with Systemic Sclerosis-Associated Interstitial Lung Disease

There are few effective prognostic biomarkers in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). We investigated the potential of [18F]FDG PET/CT to predict mortality in this population. Methods: In total, 45 patients with SSc-ILD (12 men and 33 women; age, 58.9 ± 9.9 y) were prospectively recruited for [18F]FDG PET/CT, forming the largest cohort of this type to our knowledge. All patients underwent clinical assessment, including multidisciplinary team review, high-resolution CT evaluation, and pulmonary function tests. The maximum pulmonary uptake on [18F]FDG PET/CT (SUVmax), minimum pulmonary uptake in unaffected or background lung (SUVmin), and target-to-background ratio (TBR) (SUVmax/SUVmin) were quantified using region-of-interest analysis. Kaplan-Meier analysis identified associations with mortality. Associations between [18F]FDG PET/CT measurements, pulmonary function tests, and the established model based on sex, age, and lung physiology (known as ILD-GAP) to predict mortality were performed. Stepwise forward Wald-Cox analysis assessed the independence of significant [18F]FDG PET/CT measurements from the ILD-GAP index. Synergies between pulmonary [18F]FDG PET/CT measurements and ILD-GAP index for risk stratification in patients with SSc-ILD were investigated. Results: Forty-five patients with SSc-ILD were followed for a mean of 44.8 ± 26.1 mo, with 15 deaths (33%) recorded. The mean ± SD SUVmax was 3.2 ± 1.1, SUVmin was 0.5 ± 0.3, and TBR was 6.8 ± 2.6. Increased mortality was associated with high pulmonary SUVmax (P = 0.027), high SUVmin (P = 0.002), low TBR (P = 0.016), low forced vital capacity (P = 0.021), low carbon monoxide diffusion coefficient (P = 0.021), low transfer factor (P = 0.012), high ILD-GAP score (P = 0.010), and high ILD-GAP index (P = 0.005). Multivariate Cox regression analysis revealed that pulmonary SUVmin (hazard ratio, 4.2; 95% CI, 1.3-13.4; P = 0.017) and ILD-GAP index (hazard ratio, 3.9; 95% CI, 1.2-12.8; P = 0.024) were the only independent predictors of overall survival. Combining [18F]FDG uptake with ILD-GAP score data in a modified ILD-GAP index refined the ability to predict mortality (P < 0.002). Conclusion: High-background [18F]FDG uptake in normal-appearing lung independently predicts overall survival in SSc-ILD and may stratify patients' risk when combined with ILD-GAP score data in a modified ILD-GAP index. High pulmonary [18F]FDG uptake is associated with increased mortality in patients with SSc-ILD