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Rationale: The role of MUC5B mucin expression in IPF pathogenesis is unknown. Bleomycin-exposed rodent models do not exhibit sustained fibrosis or airway remodeling. Unlike mice, ferrets have human-like distribution of MUC5B expressing cell types and natively express the risk-conferring variant that induces high MUC5B expression in humans. We hypothesized that ferrets would consequently exhibit aberrant repair to propagate fibrosis similar to human IPF., Methods: Bleomycin (5U/kg) or saline-control was micro-sprayed intratracheally then wild-type ferrets were evaluated through 22 wks. Clinical phenotype was assessed with lung function. Fibrosis was assessed with µCT imaging and comparative histology with Ashcroft scoring. Airway remodeling was assessed with histology and quantitative immunofluorescence., Results: Bleomycin ferrets exhibited sustained restrictive physiology including decreased inspiratory capacity, decreased compliance, and shifted Pressure-Volume loops through 22 wks. Volumetric µCT analysis revealed increased opacification of the lung bleomycin-ferrets. Histology showed extensive fibrotic injury that matured over time and MUC5B-positive cystic structures in the distal lung suggestive of honeycombing. Bleomycin ferrets had increased proportion of small airways that were double-positive for CCSP and alpha-tubulin compared to controls, indicating an aberrant 'proximalization' repair phenotype. Notably, this aberrant repair was associated with extent of fibrotic injury at the airway level., Conclusions: Bleomycin-exposed ferrets exhibit sustained fibrosis through 22 wks and have pathologic features of IPF not found in rodents. Ferrets exhibited proximalization of the distal airways and other pathologic features characteristic of human IPF. MUC5B expression through native cell types may play a key role in promoting airway remodeling and lung injury in IPF.

Background: Understanding the characteristics of multiparametric MRI (mpMRI) in patients from different racial/ethnic backgrounds is important for reducing the observed gaps in clinical outcomes., Purpose: To investigate the diagnostic performance of mpMRI and quantitative MRI parameters of prostate cancer (PCa) in African American (AA) and matched White (W) men., Study Type: Retrospective., Subjects: One hundred twenty-nine patients (43 AA, 86 W) with histologically proven PCa who underwent mpMRI before radical prostatectomy., Field Strength/sequence: 3.0 T, T2-weighted turbo spin echo imaging, a single-shot spin-echo EPI sequence diffusion-weighted imaging, and a gradient echo sequence dynamic contrast-enhanced MRI with an ultrafast 3D spoiled gradient-echo sequence., Assessment: The diagnostic performance of mpMRI in AA and W men was assessed using detection rates (DRs) and positive predictive values (PPVs) in zones defined by the PI-RADS v2.1 prostate sector map. Quantitative MRI parameters, including K trans and v e of clinically significant (cs) PCa (Gleason score ≥ 7) tumors were compared between AA and W sub-cohorts after matching age, prostate-specific antigen (PSA), and prostate volume., Statistical Tests: Weighted Pearson's chi-square and Mann-Whitney U tests with a statistically significant level of 0.05 were used to examine differences in DR and PPV and to compare parameters between AA and matched W men, respectively., Results: A total number of 264 PCa lesions were identified in the study cohort. The PPVs in the peripheral zone (PZ) and posterior prostate of mpMRI for csPCa lesions were significantly higher in AA men than in matched W men (87.8% vs. 68.1% in PZ, and 89.3% vs. 69.6% in posterior prostate). The K trans of index csPCa lesions in AA men was significantly higher than in W men (0.25 ± 0.12 vs. 0.20 ± 0.08 min -1 ; P < 0.01)., Data Conclusion: This study demonstrated race-related differences in the diagnostic performances and quantitative MRI measures of csPCa that were not reflected in age, PSA, and prostate volume., Evidence Level: 3 TECHNICAL EFFICACY: Stage 2., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder that causes uncontrolled kidney cyst growth, leading to kidney volume enlargement and renal function loss over time. Total kidney volume (TKV) and cyst burdens have been used as prognostic imaging biomarkers for ADPKD., Objective: This study aimed to evaluate nnUNet for automatic kidney and cyst segmentation in T2-weighted (T2W) MRI images of ADPKD patients., Methods: 756 kidney images were retrieved from 95 patients in the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) cohort (95 patients × 2 kidneys × 4 follow-up scans). The nnUNet model was trained, validated, and tested on 604, 76, and 76 images, respectively. In contrast, all images of each patient were exclusively assigned to either the training, validation, or test sets to minimize evaluation bias. The kidney and cyst regions defined using a semi-automatic method were employed as ground truth. The model performance was assessed using the Dice Similarity Coefficient (DSC), the intersection over union (IoU) score, and the Hausdorff distance (HD)., Results: The test DSC values were 0.96±0.01 (mean±SD) and 0.90±0.05 for kidney and cysts, respectively. Similarly, the IoU scores were 0.91± 0.09 and 0.81±0.06, and the HD values were 12.49±8.71 mm and 12.04±10.41 mm, respectively, for kidney and cyst segmentation., Conclusion: The nnUNet model is a reliable tool to automatically determine kidney and cyst volumes in T2W MRI images for ADPKD prognosis and therapy monitoring., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: To investigate whether the early perfusion change in hepatocellular carcinoma (HCC) predicts the long-term therapeutic response to atezolizumab plus bevacizumab., Methods: We retrospectively selected 19 subjects (median age: 62 years, 4 females, and 15 males) having advanced HCC and treated with atezolizumab alone (n = 3) or in combination with bevacizumab (n = 16). The 4-phased CT or MRI imaging was performed for each subject before and at 9 ± 2 and 21 ± 5 weeks after therapy initiation. The tumor-to-liver signal ratio in the arterial phase was used to estimate the tumor perfusion. The change in tumor perfusion from the baseline to the 1st follow-up exam was correlated with the tumor response evaluated using mRECIST at the 2nd follow-up exam. The difference between favorably responding and non-responding groups was statistically analyzed using one-way ANOVA., Results: The mean tumor long axis in the baseline image was 59 ± 47 mm. The HCC perfusion changes were -26 ± 18% for complete (or partial) response (CR/PR, n = 8), -24 ± 12% for stable disease (SD, n = 8), and 9 ± 13% for progressive disease (PD, n = 3). The HCC perfusion change of the CR/PR groups was significantly lower than that of the PD group (p = 0.0040). The HCC perfusion changes between the SD and PD groups were also significantly different (p = 0.0135). The sensitivity and specificity of the early perfusion change to predict the long-term progression of the disease were 100 and 94%, respectively., Conclusion: The early change in HCC perfusion may predict the long-term therapeutic response to atezolizumab plus bevacizumab, promoting personalized treatment for HCC patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as acute respiratory distress syndrome. In survivors, long-term effects such as the development of respiratory ailments are reported for the organoarsenical sulfur mustard; however, no long-term pulmonary effects are documented for lewisite and DPCA. No animal models exist to explore the relationship between skin exposure to vesicants and constrictive bronchiolitis. We developed and characterized a mouse model to study the long-term effects of cutaneous exposure on the lungs after exposure to a sublethal dose of organoarsenicals. We exposed mice to lewisite, DPCA, or a less toxic surrogate organoarsenic chemical, phenyl arsine oxide, on the skin. The surviving mice were followed for 20 weeks after skin exposure to arsenicals. Lung microcomputed tomography, lung function, and histology demonstrated increased airway resistance, increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and peribronchial lymphocyte infiltration in mice exposed to arsenical on skin.

Substantial clinical evidence supports the notion that ciliary function in the airways is important in COVID-19 pathogenesis. Although ciliary damage has been observed in both in vitro and in vivo models, the extent or nature of impairment of mucociliary transport (MCT) in in vivo models remains unknown. We hypothesize that SARS-CoV-2 infection results in MCT deficiency in the airways of golden Syrian hamsters that precedes pathological injury in lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes in the MCT apparatus. Both genomic and subgenomic viral RNA pathological and physiological changes were monitored in parallel. We show that SARS-CoV-2 infection caused a 67% decrease in MCT rate as early as 2 days postinfection (dpi) in hamsters, principally due to 79% diminished airway coverage of motile cilia. Correlating quantitation of physiological, virological, and pathological changes reveals steadily descending infection from the upper airways to lower airways to lung parenchyma within 7 dpi. Our results indicate that functional deficits of the MCT apparatus are a key aspect of COVID-19 pathogenesis, may extend viral retention, and could pose a risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell function may indicate disease progression. Therapies directed toward the MCT apparatus deserve further investigation.

Rationale: The majority of chronic obstructive pulmonary disease (COPD) patients have chronic bronchitis, for which specific therapies are unavailable. Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is observed in chronic bronchitis, but has not been proven in a controlled animal model with airway disease. Furthermore, the potential of CFTR as a therapeutic target has not been tested in vivo, given limitations to rodent models of COPD. Ferrets exhibit cystic fibrosis-related lung pathology when CFTR is absent and COPD with bronchitis following cigarette smoke exposure., Objectives: To evaluate CFTR dysfunction induced by smoking and test its pharmacological reversal by a novel CFTR potentiator, GLPG2196, in a ferret model of COPD with chronic bronchitis., Methods: Ferrets were exposed for 6 months to cigarette smoke to induce COPD and chronic bronchitis and then treated with enteral GLPG2196 once daily for 1 month. Electrophysiological measurements of ion transport and CFTR function, assessment of mucociliary function by one-micron optical coherence tomography imaging and particle-tracking microrheology, microcomputed tomography imaging, histopathological analysis and quantification of CFTR protein and mRNA expression were used to evaluate mechanistic and pathophysiological changes., Measurements and Main Results: Following cigarette smoke exposure, ferrets exhibited CFTR dysfunction, increased mucus viscosity, delayed mucociliary clearance, airway wall thickening and airway epithelial hypertrophy. In COPD ferrets, GLPG2196 treatment reversed CFTR dysfunction, increased mucus transport by decreasing mucus viscosity, and reduced bronchial wall thickening and airway epithelial hypertrophy., Conclusions: The pharmacologic reversal of acquired CFTR dysfunction is beneficial against pathological features of chronic bronchitis in a COPD ferret model., Competing Interests: Conflict of interest: S.M. Rowe has received consulting fees from Abbvie related to the design and conduct of clinical trials in cystic fibrosis. M. Borgonovi and K. Conrath are employees of Galapagos. All other authors declare no competing interests., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Providing sufficient testing capacities and accurate results in a time-efficient way are essential to prevent the spread and lower the curve of a health crisis, such as the COVID-19 pandemic. In line with recent research investigating how simulation-based models and tools could contribute to mitigating the impact of COVID-19, a discrete event simulation model is developed to design optimal saliva-based COVID-19 testing stations performing sensitive, non-invasive, and rapid-result RT-qPCR tests processing. This model aims to determine the adequate number of machines and operators required, as well as their allocation at different workstations, according to the resources available and the rate of samples to be tested per day. The model has been built and experienced using actual data and processes implemented on-campus at the University of Illinois at Urbana-Champaign, where an average of around 10,000 samples needed to be processed on a daily basis, representing at the end of August 2020 more than 2% of all the COVID-19 tests performed per day in the USA. It helped identify specific bottlenecks and associated areas of improvement in the process to save human resources and time. Practically, the overall approach, including the proposed modular discrete event simulation model, can easily be reused or modified to fit other contexts where local COVID-19 testing stations have to be implemented or optimized. It could notably support on-site managers and decision-makers in dimensioning testing stations by allocating the appropriate type and quantity of resources., Competing Interests: The authors have declared that no competing interests exist.

Despite the high morbidity and mortality among patients with extensive cutaneous burns in the intensive care unit due to the development of acute respiratory distress syndrome, effective therapeutics remain to be determined. This is primarily because the mechanisms leading to acute lung injury (ALI) in these patients remain unknown. We test the hypothesis that cutaneous chemical burns promote lung injury due to systemic activation of neutrophils, in particular, toxicity mediated by the deployment of neutrophil extracellular traps (NETs). We also demonstrate the potential benefit of a peptidyl arginine deiminase 4 (PAD4) inhibitor to prevent NETosis and to preserve microvascular endothelial barrier function, thus reducing the severity of ALI in mice. Our data demonstrated that phenylarsine oxide (PAO) treatment of neutrophils caused increased intracellular Ca2+-associated PAD4 activity. A dermal chemical burn by lewisite or PAO resulted in PAD4 activation, NETosis, and ALI. NETs disrupted the barrier function of endothelial cells in human lung microvascular endothelial cell spheroids. Citrullinated histone 3 alone caused ALI in mice. Pharmacologic or genetic abrogation of PAD4 inhibited lung injury following cutaneous chemical burns. Cutaneous burns by lewisite and PAO caused ALI by PAD4-mediated NETosis. PAD4 inhibitors may have potential as countermeasures to suppress detrimental lung injury after chemical burns.

Rationale and Objectives: The study goal was to test whether the improved accuracy in quantitative dynamic contrast-enhanced magnetic resonance imaging measurement using a point-of-care portable perfusion phantom (P4) leads to better stratification of prostate cancer grade., Materials and Methods: A prospective clinical study was conducted recruiting 44 patients scheduled for multi-parameter MRI prostate exams. All participants were imaged with the P4 placed under their pelvic regions. Tissue sampling was carried out for 25 patients at 22 ± 18 (mean ± SD) days after multi-parameter MRI. On histologic examination, a total of 31 lesions were confirmed as prostate cancer. Tumors were classified into low grade (n = 14), intermediate grade (n = 10), and high grade (n = 7). Tumor perfusion was assessed by volume transfer constant, K trans , before and after P4-based error correction, and the K trans of low, intermediate and high-grade tumors were statistically compared., Results: After P4-based error correction, the K trans of low, intermediate, and high-grade tumors were 0.109 ± 0.026 min -1 (95% CI: 0.0094 to 0.124 min -1 ), 0.163 ± 0.049 min -1 (95% CI: 0.129 to 0.198 min -1 ) and 0.356 ± 0.156 min -1 (95% CI: 0.215 to 0.495 min -1 ), respectively, with statistically significant difference among the groups (low vs intermediate: p = 0.002; intermediate vs high: p = 0.002; low vs high: p < 0.001). The sensitivity and specificity of K trans value, 0.14 min -1 , to detect the clinically significant prostate cancer were 88% and 93%, respectively, after P4 based error correction, but those before error correction were 88% and 86%, respectively., Conclusion: The P4 allows to reduce errors in quantitative dynamic contrast-enhanced magnetic resonance imaging measurement, enhancing accuracy in stratification of prostate cancer grade., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

While the COVID-19 pandemic has led to many disruptions in industrial value chains, the adoption of circular economy (CE) principles appears to be a commendable solution for more robust, resilient, and sustainable industrial supply chains. In this study, the standpoints and visions of two consecutive classes of engineering students - following the course "Circular Economy & Industrial Systems" at the Université Paris-Saclay - are given on how they value CE strategies to mitigate the impact of COVID-19 on industrial practices. Capturing and understanding the viewpoints of the engineers of tomorrow on such a pressing issue is key to train and provide them with the suitable methods and tools to build a more circular and sustainable society. At the end of their eight-week training class, including theoretical background on industrial ecology tools, workshops, and a hands-on project, part of the final exam included a one-hour essay in which the students had to argue their position on the following questions: (i) "Circular Economy as an answer to the COVID-19 crisis?" for the class of 2020, and (ii) "Circular Economy as an answer for green recovery and value chain resiliency in the COVID-19 context?" for the class of 2021. Interestingly, the evolution of viewpoints between the beginning of the COVID-19 crisis (exam conducted in May 2020 for the first class) and one year after (exam conducted in Mars 2021 for the second class) is discussed and illustrated. Also, the answers and insights provided by engineering students on these questions are positioned within the state-of-the-art literature on the topic. Last but not least, key recommendations and challenges on how CE could alleviate COVID-related disruptions and production shortages are synthesized in a SWOT (strengths, weaknesses, threats, and opportunities) diagram., (© 2021 The Author(s). Published by Elsevier B.V.)

The discovery of ferroelectricity in HfO 2 -based materials in 2011 provided new research directions and opportunities. In particular, for atomic layer deposited Hf 0.5 Zr 0.5 O 2 (HZO) films, it is possible to obtain homogenous thin films with satisfactory ferroelectric properties at a low thermal budget process. Based on experiment demonstrations over the past 10 years, it is well known that HZO films show excellent ferroelectricity when sandwiched between TiN top and bottom electrodes. This work reports a comprehensive study on the effect of TiN top and bottom electrodes on the ferroelectric properties of HZO thin films (10 nm). Investigations showed that during HZO crystallization, the TiN bottom electrode promoted ferroelectric phase formation (by oxygen scavenging) and the TiN top electrode inhibited non-ferroelectric phase formation (by stress-induced crystallization). In addition, it was confirmed that the TiN top and bottom electrodes acted as a barrier layer to hydrogen diffusion into the HZO thin film during annealing in a hydrogen-containing atmosphere. These features make the TiN electrodes a useful strategy for improving and preserving the ferroelectric properties of HZO thin films for next-generation memory applications.

Structural changes to airway morphology, such as increased bronchial wall thickness (BWT) and airway wall area, are cardinal features of chronic obstructive pulmonary disease (COPD). Ferrets are a recently established animal model uniquely exhibiting similar clinical and pathological characteristics of COPD as humans, including chronic bronchitis. Our objective was to develop a microcomputed tomography (µCT) method for evaluating structural changes to the airways in ferrets and assess whether the effects of smoking induce changes consistent with chronic bronchitis in humans. Ferrets were exposed to mainstream cigarette smoke or air control twice daily for 6 mo. µCT was conducted in vivo at 6 mo; a longitudinal cohort was imaged monthly. Manual measurements of BWT, luminal diameter (LD), and BWT-to-LD ratio (BWT/LD) were conducted and confirmed by a semiautomated algorithm. The square root of bronchial wall area (√WA) versus luminal perimeter was determined on an individual ferret basis. Smoke-exposed ferrets reproducibly demonstrated 34% increased BWT ( P < 0.001) along with increased LD and BWT/LD versus air controls. Regression indicated that the effect of smoking on BWT persisted despite controlling for covariates. Semiautomated measurements replicated findings. √WA for the theoretical median airway luminal perimeter of 4 mm (Pi4) was elevated 4.4% in smoke-exposed ferrets ( P = 0.015). Increased BWT and Pi4 developed steadily over time. µCT-based airway measurements in ferrets are feasible and reproducible. Smoke-exposed ferrets develop increased BWT and Pi4, changes similar to humans with chronic bronchitis. µCT can be used as a significant translational platform to measure dynamic airway morphological changes.

The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting chronic bronchitis. We investigated the effects of cigarette smoke on mucociliary transport (MCT).Adult ferrets were exposed to cigarette smoke for 6 months, with in vivo mucociliary clearance measured by technetium-labelled DTPA retention. Excised tracheae were imaged with micro-optical coherence tomography. Mucus changes in primary human airway epithelial cells and ex vivo ferret airways were assessed by histology and particle tracking microrheology. Linear mixed models for repeated measures identified key determinants of MCT.Compared to air controls, cigarette smoke-exposed ferrets exhibited mucus hypersecretion, delayed mucociliary clearance (-89.0%, p<0.01) and impaired tracheal MCT (-29.4%, p<0.05). Cholinergic stimulus augmented airway surface liquid (ASL) depth (5.8±0.3 to 7.3±0.6 µm, p<0.0001) and restored MCT (6.8±0.8 to 12.9±1.2 mm·min -1 , p<0.0001). Mixed model analysis controlling for covariates indicated smoking exposure, mucus hydration (ASL) and ciliary beat frequency were important predictors of MCT. Ferret mucus was hyperviscous following smoke exposure in vivo or in vitro , and contributed to diminished MCT. Primary cells from smokers with and without COPD recapitulated these findings, which persisted despite the absence of continued smoke exposure.Cigarette smoke impairs MCT by inducing airway dehydration and increased mucus viscosity, and can be partially abrogated by cholinergic secretion of fluid secretion. These data elucidate the detrimental effects of cigarette smoke exposure on mucus clearance and suggest additional avenues for therapeutic intervention., Competing Interests: Conflict of interest: V.Y. Lin has nothing to disclose. Conflict of interest: N. Kaza has nothing to disclose. Conflict of interest: S.E. Birket has nothing to disclose. Conflict of interest: H. Kim has nothing to disclose. Conflict of interest: L.J. Edwards has nothing to disclose. Conflict of interest: J. LaFontaine has nothing to disclose. Conflict of interest: L. Liu has a patent “Method for functional investigation of respiratory airways and other ciliated tissues using µOCT” pending. Conflict of interest: M. Mazur has nothing to disclose. Conflict of interest: S.A. Byzek has nothing to disclose. Conflict of interest: J. Hanes is founder and owner of company stock (which is subject to certain rules and restrictions under Johns Hopkins University policy) of GrayBug Vision, Inc., and Kala Pharmaceuticals, Inc., outside the submitted work. Conflict of interest: G.J. Tearney has patents 14/240,938 and 12826303.5 pending. Conflict of interest: S.V. Raju has nothing to disclose. Conflict of interest: S.M. Rowe reports grants from Bayer, Forest Research Institute, AstraZeneca, N30/Nivalis, Novartis, Galapagos/AbbVie, Proteostasis, PTC Therapeutics and Eloxx, grants and personal fees for consultancy from Celtaxsys, personal fees for consultancy and advisory board work and in kind support for clinical trial work from Vertex Pharmaceuticals Incorporated, personal fees for consultancy from Bayer and Novartis, outside the submitted work; and has a patent “Use of OCT as a diagnostic modality for diseases of mucus clearance” issued., (Copyright ©ERS 2020.)

Heterozygosity for human polycystic kidney and hepatic disease 1 ( PKHD1) mutations was recently associated with cystic liver disease and radiographic findings resembling medullary sponge kidney (MSK). However, the relevance of these associations has been tempered by a lack of cystic liver or renal disease in heterozygous mice carrying Pkhd1 gene trap or exon deletions. To determine whether heterozygosity for a smaller Pkhd1 defect can trigger cystic renal disease in mice, we generated and characterized mice with the predicted truncating Pkhd1 C642* mutation in a region corresponding to the middle of exon 20 cluster of five truncating human mutations (between PKHD1 G617fs and PKHD1 G644* ). Mouse heterozygotes or homozygotes for the Pkhd1 C642* mutation did not have noticeable liver or renal abnormalities on magnetic resonance images during their first weeks of life. However, when aged to ~1.5 yr, the Pkhd1 C642* heterozygotes developed prominent cystic liver changes; tissue analyses revealed biliary cysts and increased number of bile ducts without signs of congenital hepatic fibrosis-like portal field inflammation and fibrosis that was seen in Pkhd1 C642* homozygotes. Interestingly, aged female Pkhd1 C642* heterozygotes, as well as homozygotes, developed radiographic changes resembling MSK. However, these changes correspond to proximal tubule ectasia, not an MSK-associated collecting duct ectasia. In summary, by demonstrating that cystic liver and kidney abnormalities are triggered by heterozygosity for the Pkhd1 C642* mutation, we provide important validation for relevant human association studies. Together, these investigations indicate that PKHD1 mutation heterozygosity (predicted frequency 1 in 70 individuals) is an important underlying cause of cystic liver disorders and MSK-like manifestations in a human population.

Increasing interest in the development of alternative energy storage technologies has led to efforts being taken to improve the energy density of dielectric capacitors with high power density. However, dielectric polymer materials still have low energy densities because of their low dielectric constant, whereas Pb-based materials are limited by environmental issues and regulations. Here, the energy storage behaviors of atomic layer-deposited Hf 1- X Zr X O 2 ( X = 0-1) thin films (10 nm) and the phase transformation mechanism associated with an enhancement of their energy density are reported using unipolar pulse measurements. Based on electrical and material characterization, the energy density and energy efficiency are dependent on the Zr content, and stress-induced crystallization by the encapsulating Hf 1- X Zr X O 2 films with TiN top electrodes prior to annealing can enhance the energy density (up to 47 J/cm 3 at a small voltage value of 3.5 MV/cm) while minimizing energy loss even at low process temperatures (400 °C). This work will facilitate the realization of Hf 1- X Zr X O 2 -based capacitors for lead-free electrostatic energy storage applications.

DCE-MRI has been extensively used for diagnosis, prognosis and therapy monitoring of various diseases including cancer. However, it has been reported that the perfusion parameters measured by DCE-MRI largely vary across different research sites, preventing data comparison in multi-institutional clinical trials. Recently, novel perfusion phantoms have been developed to correct scanner-driven errors, enabling quality assurance of quantitative DCE-MRI measurement. However, the sources for the variability in quantitating perfusion parameters are not only MRI scanners but also software packages and imaging protocols set by the operators. In this manuscript, the various sources influencing the variability in quantitative DCE-MRI measurement are reviewed, and the proper solutions to minimize those are discussed.

This technical note describes how to modify a population-based arterial input function to incorporate variation among the individuals. In DCE-MRI, an arterial input function (AIF) is often distorted by pulsated inflow effect and noise. A population-based AIF (pAIF) has high signal-to-noise ratio (SNR), but cannot incorporate the individual variation. AIF variation is mainly induced by variation in cardiac output and blood volume of the individuals, which can be detected by the full width at half maximum (FWHM) during the first passage and the amplitude of AIF, respectively. Thus pAIF scaled in time and amplitude fitting to the individual AIF may serve as a high SNR AIF incorporating the individual variation. The proposed method was validated using DCE-MRI images of 18 prostate cancer patients. Root mean square error (RMSE) of pAIF from individual AIFs was 0.88±0.48mM (mean±SD), but it was reduced to 0.25±0.11mM after pAIF modification using the proposed method (p<0.0001)., (Copyright © 2017 Elsevier Inc. All rights reserved.)