Search

Distinguishing malignant from benign liver lesions based on magnetic resonance imaging (MRI) is an important but often challenging task, especially in noncirrhotic livers. We developed and externally validated a radiomics model to quantitatively assess T2-weighted MRI to distinguish the most common malignant and benign primary solid liver lesions in noncirrhotic livers. Data sets were retrospectively collected from three tertiary referral centers (A, B, and C) between 2002 and 2018. Patients with malignant (hepatocellular carcinoma and intrahepatic cholangiocarcinoma) and benign (hepatocellular adenoma and focal nodular hyperplasia) lesions were included. A radiomics model based on T2-weighted MRI was developed in data set A using a combination of machine learning approaches. The model was internally evaluated on data set A through cross-validation, externally validated on data sets B and C, and compared to visual scoring of two experienced abdominal radiologists on data set C. The overall data set included 486 patients (A: 187, B: 98, and C: 201). The radiomics model had a mean area under the curve (AUC) of 0.78 upon internal validation on data set A and a similar AUC in external validation (B: 0.74 and C: 0.76). In data set C, the two radiologists showed moderate agreement (Cohen's κ: 0.61) and achieved AUCs of 0.86 and 0.82. Our T2-weighted MRI radiomics model shows potential for distinguishing malignant from benign primary solid liver lesions. External validation indicated that the model is generalizable despite substantial MRI acquisition protocol differences. Pending further optimization and generalization, this model may aid radiologists in improving the diagnostic workup of patients with liver lesions. [ABSTRACT FROM AUTHOR]

To explore factors that were associated with meniscus volume in knees free of radiographic osteoarthritis (OA) features and symptoms of OA. In the third Rotterdam Study cohort, clinical, radiographic, and magnetic resonance data were obtained at baseline (BL) and after 5 years of follow-up. Meniscus volumes and their change over time were calculated after semi-automatic segmentation on Magnetic Resonance Imaging. Knees with radiographic OA features (Kellgren and Lawrence>0) or clinical diagnosis of OA (American College of Rheumatology) at BL were excluded. Ten OA risk factors were adjusted in the multivariable analysis (generalized estimating equations), treating two knees within subjects as repeated measurements. From 1065 knees (570 subjects), the average (standard deviation) age and Body mass index (BMI) of included subjects were 54.3 (3.7) years and 26.5 (4.4) kg/m2. At BL, nine factors (varus alignment, higher BMI, meniscus pathologies, meniscus extrusion, cartilage lesions, injury, greater physical activity level, quadriceps muscle strength, and higher age) were significantly associated with greater meniscus volume. Five factors (injury, meniscus pathologies, meniscus extrusion, higher age, and change of BMI) were significantly associated with meniscus volume loss. Modifiable factors (varus alignment, BMI, physical activity level, and quadriceps muscle strength) and non-modifiable factors (higher age, injury, meniscus pathologies, meniscus extrusion, and cartilage lesions) were all associated with meniscus volume or meniscus volume loss over time. [ABSTRACT FROM AUTHOR]

To improve image quality of multi-contrast imaging with the proposed Autocalibrated Parallel Imaging Reconstruction for Extended Multi-Contrast Imaging (APIR4EMC). APIR4EMC reconstructs multi-contrast images in an autocalibrated parallel imaging reconstruction framework by adding contrasts as virtual coils. Compensation of signal evolution along the echo train of different contrasts is performed to improve signal prediction for missing samples. As a proof of concept, we performed prospectively accelerated phantom and in-vivo brain acquisitions with T1, T1-fat saturated (Fatsat), T2, PD, and FLAIR contrasts. The k-space sampling patterns of these acquisitions were jointly optimized. Images were jointly reconstructed with the proposed APIR4EMC method as well as individually with GRAPPA. Root mean square error (RMSE) to fully sampled reference images and g-factor maps were computed for both methods in the phantom experiment. Visual evaluation was performed in the in-vivo experiment. Compared to GRAPPA, APIR4EMC reduced artifacts and improved SNR of the reconstructed images in the phantom acquisitions. Quantitatively, APIR4EMC substantially reduced noise amplification (g-factor) as well as RMSE compared to GRAPPA. Signal evolution compensation reduced artifacts. In the in-vivo experiments, 1 mm 3 isotropic 3D images with contrasts of T1, T1-Fatsat, T2, PD, and FLAIR were acquired in as little as 7.5 min with the acceleration factor of 9. Reconstruction quality was consistent with the phantom results. Compared to single contrast reconstruction with GRAPPA, APIR4EMC reduces artifacts and noise amplification in accelerated multi-contrast imaging. [ABSTRACT FROM AUTHOR]

The nature of work and the way it is organized continues to change profoundly. The continuing debate on flexible work arrangements reveals the perceived need of policy makers to react to these changes in a balanced manner. Despite the demand of organizations and employees alike, the negative implications of flexible work arrangements threaten to counteract the equally valid arguments for their benefits. The new autonomy of the individual employee is mirrored by a management style that emphasizes results rather than specifying the way to achieve them. Despite the cherished liberties of the new workplace, studies indicate that stress due to unhealthy work practices has become a major concern for preventive care in these environments. Based on a study with IT professionals we set out to dispute the effectiveness of mainstream measures of preventive care that aim at (re-)regulating work. Instead, we propose an employee-centred approach to preventive care that aims at sensitizing employees to structural defects of new ways of working (through biofeedback and reflection on work patterns) and helping employees in crafting their work practices. Initial results of our empirical study, which combines biometric as well as qualitative data, indicate both the need and the potential for employee-centred preventive care. We demonstrate how bio feedback can inform the coaching of individuals in their quest for sustainable work practices. [ABSTRACT FROM AUTHOR]

Background: Long-acting reversible contraceptives, including hormonal levonorgestrel-releasing intrauterine systems, are the most effective methods of reversible contraception. However, unfavorable bleeding, particularly during the first months of use, is one of the most important reasons for discontinuation or avoidance. Minimizing this as early as possible would be highly beneficial. Nonsteroidal anti-inflammatory drugs inhibiting prostaglandin synthesis are known to reduce bleeding and pain at time of menses. A levonorgestrel-releasing intrauterine system has been developed with an additional reservoir containing indomethacin, designed to be released during the initial postplacement period.Objective: This proof-of-concept study aimed to establish whether the addition of indomethacin to the currently available levonorgestrel-releasing intrauterine system (average in vivo levonorgestrel release rate of 8 μg/24 h during the first year of use) reduces the number of bleeding and spotting days during the first 90 days of use compared with the unmodified system. The dose-finding analysis included 3 doses of indomethacin-low (6.5 mg), middle (12.5 mg), and high (15.4 mg)-to determine the ideal dose of indomethacin to reduce bleeding and spotting days with minimal side-effects.Study Design: This was a multicenter, single-blinded, randomized, controlled phase II trial conducted between June 2018 and June 2019 at 6 centers in Europe. Three indomethacin dose-ranging treatment groups (low-, middle-, and high-dose indomethacin/levonorgestrel-releasing intrauterine system) were compared with the unmodified levonorgestrel-releasing intrauterine system group, with participants randomized in a 1:1:1:1 ratio. The primary outcome was the number of uterine bleeding and spotting days over a 90-day reference (treatment) period. Secondary outcomes were the number of women showing endometrial histology expected for intrauterine levonorgestrel application and the frequency of treatment-emergent adverse events. Point estimates and 2-sided 90% credible intervals were calculated for mean and median differences between treatment groups and the levonorgestrel-releasing intrauterine system without indomethacin. Point and interval estimates were determined using a Bayesian analysis.Results: A total of 174 healthy, premenopausal women, aged 18 to 45 years, were randomized, with 160 women eligible for the per-protocol analysis set. Fewer bleeding and spotting days were observed in the 90-day reference period for the 3 indomethacin/levonorgestrel-releasing intrauterine system dose groups than for the levonorgestrel-releasing intrauterine system without indomethacin group. The largest reduction in bleeding and spotting days was achieved with low-dose indomethacin/levonorgestrel-releasing intrauterine system, which demonstrated a point estimate difference of -32% (90% credible interval, -45% to -19%) compared with levonorgestrel-releasing intrauterine system without indomethacin. Differences for high- and middle-dose indomethacin/levonorgestrel-releasing intrauterine system groups relative to levonorgestrel-releasing intrauterine system without indomethacin were -19% and -16%, respectively. Overall, 97 women (58.1%) experienced a treatment-emergent adverse event considered related to the study drug, with similar incidence across all treatment groups including the unmodified levonorgestrel-releasing intrauterine system. These were all mild or moderate in intensity, with 6 leading to discontinuation. Endometrial biopsy findings were consistent with effects expected for the levonorgestrel-releasing intrauterine system.Conclusion: All 3 doses of indomethacin substantially reduced the number of bleeding and spotting days in the first 90 days after placement of the levonorgestrel-releasing intrauterine system, thus providing proof of concept. Adding indomethacin to the levonorgestrel-releasing intrauterine system can reduce the number of bleeding and spotting days in the initial 90 days postplacement, without affecting the safety profile, and potentially improving patient acceptability and satisfaction. [ABSTRACT FROM AUTHOR]

• We propose a theoretical metric to evaluate undersampling patterns for Q-MRI scans. • The metric was verified with prospectively undersampled scans for mapping T1 and T2. • Good patterns for Q-MRI scans could be obtained by low-discrepancy sampling. [Display omitted] To realize Quantitative MRI (QMRI) with clinically acceptable scan time, acceleration factors achieved by conventional parallel imaging techniques are often inadequate. Further acceleration is possible using model-based reconstruction. We propose a theoretical metric called TEUSQA: Time Efficiency for UnderSampled QMRI Acquisitions to inform sequence design and sample pattern optimisation. TEUSQA is designed for a particular class of reconstruction techniques that directly estimate tissue parameters, possibly using prior information to regularize the estimation. TEUSQA can be used to evaluate undersampling patterns for multi-contrast QMRI sequences targeting any tissue parameter. To verify the time efficiency predicted by TEUSQA, we performed Monte Carlo simulations and an accelerated parameter mapping with two sequences (Inversion prepared fast spin echo for T 1 and T 2 mapping and 3D GRASE for T 2 and B0 inhomogeneity mapping). Using TEUSQA, we assessed several ways to generate undersampling patterns in silico , providing insight into the relation between sample distribution and time efficiency for different acceleration factors. The time efficiency predicted by TEUSQA was within 15% of that observed in the Monte Carlo simulations and the prospective acquisition experiment. The assessment of undersampling patterns showed that a class of good patterns could be obtained by low-discrepancy sampling. We believe that TEUSQA offers a valuable instrument for developers of novel QMRI sequences pushing the boundaries of acceleration to achieve clinically feasible protocols. Finally, we applied a time-efficient undersampling pattern selected using TEUSQA for a 32-fold accelerated scan to map T 1 & T 2 mapping of a healthy volunteer. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: Aneurysm morphodynamics is potentially relevant for assessing aneurysm rupture risk. A method is proposed for automated quantification and visualization of intracranial aneurysm morphodynamics from electrocardiogram (ECG)-gated computed tomography angiography (CTA) data. Materials and Methods: A prospective study was performed in 19 aneurysms from 14 patients with diagnostic workup for recently discovered aneurysms (n = 15) or follow-up of untreated known aneurysms (n = 4). The study was approved by the Institutional Review Board of the hospital and written informed consent was obtained from each patient. An image postprocessing method was developed for quantifying aneurysm volume changes and visualizing local displacement of the aneurysmal wall over a heart cycle using multiphase ECG-gated (four-dimensional) CTA. Percentage volume changes over the heart cycle were determined for aneurysms, surrounding arteries, and the skull. Results: Pulsation of the aneurysm and its surrounding vasculature during the heart cycle could be assessed from ECG-gated CTA data. The percentage aneurysmal volume change ranged from 3% to 18%. Conclusion: ECG-gated CTA can be used to study morphodynamics of intracranial aneurysms. The proposed image analysis method is capable of quantifying the volume changes and visualizing local displacement of the vascular structures over the cardiac cycle. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: The aim of this study was to automatically detect and quantify calcium lesions for the whole heart as well as per coronary artery on non-contrast-enhanced cardiac computed tomographic images. Materials and Methods: Imaging data from 366 patients were randomly selected from patients who underwent computed tomographic calcium scoring assessments between July 2004 and May 2009 at Erasmum MC, Rotterdam. These data included data sets with 1.5-mm and 3.0-mm slice spacing reconstructions and were acquired using four different scanners. The scores of manual observers, who annotated the data using commercially available software, served as ground truth. An automatic method for detecting and quantifying calcifications for each of the four main coronary arteries and the whole heart was trained on 209 data sets and tested on 157 data sets. Statistical testing included determining Pearson''s correlation coefficients and Bland-Altman analysis to compare performance between the system and ground truth. Wilcoxon''s signed-rank test was used to compare the interobserver variability to the system''s performance. Results: Automatic detection of calcified objects was achieved with sensitivity of 81.2% per calcified object in the 1.5-mm data set and sensitivity of 86.6% per calcified object in the 3.0-mm data set. The system made an average of 2.5 errors per patient in the 1.5-mm data set and 2.2 errors in the 3.0-mm data set. Pearson''s correlation coefficients of 0.97 (P < .001) for both 1.5-mm and 3.0-mm scans with respect to the calcium volume score of the whole heart were found. The average R values over Agatston, mass, and volume scores for each of the arteries (left circumflex coronary artery, right coronary artery, and left main and left anterior descending coronary arteries) were 0.93, 0.96, and 0.99, respectively, for the 1.5-mm scans. Similarly, for 3.0-mm scans, R values were 0.94, 0.94, and 0.99, respectively. Risk category assignment was correct in 95% and 89% of the data sets in the 1.5-mm and 3-mm scans. Conclusions: An automatic vessel-specific coronary artery calcium scoring system was developed, and its feasibility for calcium scoring in individual vessels and risk category classification has been demonstrated. [Copyright &y& Elsevier]

Abstract: As a result from the development of silicon thin-film solar cells that had been conducted at Applied Materials over the last few years, we present a new kind of microcrystalline silicon oxide (μc-SiO x :H) based p-layer for the application in amorphous/microcrystalline (a-Si:H/μc-Si:H) tandem solar cells on ZnO substrates. The refractive index of this p-layer can be adjusted in the range 2–3.5 and therefore serves as a refractive index matching layer between ZnO (n∼2) and silicon (n∼4). By applying such a layer the reflection of solar cells can be reduced to 3%. This results in a significant short circuit current increase in thin-film solar cells. As a follow up to the recently published results of large area thin film silicon modules by us , we describe in this paper in detail the material properties of this new silicon oxide p-layer, the optimization of electrical and optical properties in solar cells and also the impact on the light induced degradation of a-Si/μc-Si tandem junction cells. [Copyright &y& Elsevier]

Abstract: Recently, Applied Materials has demonstrated the ability to manufacture large area a-Si/μc-Si thin film modules with total area efficiencies of 10% and above. Reducing the production costs is now the key objective for an economic success of this technology. Decreasing the absorber layer thickness or increasing the deposition rate can reduce the cost significantly because the PECVD deposition of the silicon layers is one of the main cost contributors. But this would also reduce the conversion efficiency of amorphous/microcrystalline tandem cells (a-Si/μc-Si TJ cells). Therefore, optimizing TJ cells for maximal productivity requires a careful balancing of layer thicknesses and deposition rates. In this paper we studied the impact of deposition rates and absorber layer thicknesses for top and bottom cells. The reduction of the bottom cell (BC) thickness from 2μm to less than 1μm showed only a small impact on the stabilized module efficiency while having a big impact on the productivity of a production line. The influence of the top cell (TC) deposition rate on the other hand results in a big decrease of the efficiency while having only a small impact on the line output. 10.2% stable mini-module efficiency could be achieved with 900nm BC thickness, reducing the deposition time by 50%. [Copyright &y& Elsevier]

In this study, TaqMan™ PCR was used to assess viral replication of HIV-1 infected cells in vitro. This PCR technique was compared with p24 ELISA as a standard method to monitor HIV-1 replication in cell culture. Hut78 T-lymphoblastoid cells were infected with different titres of HIV-1IIIb (MOI 0.05–0.0005). The course of HIV-1 replication was monitored by determination of p24 concentrations by ELISA in cell culture supernatants and by quantitation of HIV-1 gag RNA by TaqMan™ RT-PCR. Additionally, the number of HIV-1 proviral copies was assessed by TaqMan™ PCR. Monitoring of HIV-1 replication by p24 ELISA and TaqMan™ RT-PCR revealed comparable kinetics of infection. Both methods provided similar data on the exponential increase and on plateauing of HIV-1 replication. Furthermore, both methods were equally sensitive. However, a 7 log linearity of TaqMan™ HIV-1 gag PCR was demonstrated without dilution of the specimen, in contrast to p24 ELISA, where because of its narrow range of detectable p24 concentrations, sample dilution was necessary. Although determination of the number of proviral copies by TaqMan™ PCR does not measure HIV-1 replication, the kinetics of proviral copy number following in vitro inoculation of cells with HIV-1 was nearly the same as the kinetics of HIV-1 RNA copy numbers. In conclusion, TaqMan™ real-time RT-PCR was demonstrated as a reliable and sensitive tool to quantify and monitor HIV-1 replication in cell culture. It is suggested, therefore, that this technique be an alternative method to monitor HIV-1 replication in vitro. [Copyright &y& Elsevier]

B Background: b Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract. Predicting the c-KIT mutational status of GISTs led to an AUC of 0.52 (95% CI 0.32-0.72) for predicting all c-KIT mutations, an AUC of 0.51 (95% CI 0.29-0.72) for predicting a c-KIT exon 9 mutation, and an AUC of 0.61 (95% CI 0.47-0.74) for predicting a c-KIT exon 11 mutation. B Conclusions b : The results of this pilot study showed the potential of radiomics to distinguish GIST from other GI tumors, but no potential in predicting c-KIT mutational status of GISTs. [Extracted from the article]

Retinal vascular diseases are a leading cause for blindness and partial sight certifications. By applying adaptive optics (AO) to conventional imaging modalities, the microstructures of the retinal vasculature can be observed with high spatial resolution, hence offering a unique opportunity for the exploration of the human microcirculation. The objective of this systematic review is to describe the current state of retinal vascular biomarkers imaged by AO flood illumination ophthalmoscopy (FIO) and AO scanning laser ophthalmoscopy (SLO). A literature research was conducted in the PubMed and Scopus databases on July 9, 2020. From 217 screened studies, 42 were eligible for this review. All studies underwent a quality check regarding their content. A meta-analysis was performed for the biomarkers reported for the same pathology in at least three studies using the same modality. The most frequently studied vascular biomarkers were the inner diameter (ID), outer diameter (OD), parietal thickness (PT), wall cross-sectional area (WCSA), and wall-to-lumen ratio (WLR). The applicability of AO vascular biomarkers has been mostly explored in systemic hypertension using AO FIO and in diabetes using AO SLO. The result of the meta-analysis for hypertensive patients showed that WLR, PT, and ID were significantly different when compared to healthy controls, while WCSA was not (P < 0.001, P = 0.002, P < 0.001, and P = 0.070, respectively). The presented review shows that, although a substantial number of retinal vascular biomarkers have been explored in AO en face imaging, further clinical research and standardization of procedures is needed to validate such biomarkers for the longitudinal monitoring of arterial hypertension and other diseases. [ABSTRACT FROM AUTHOR]

Abstract: Since CO2 enrichment alters the composition of live plant tissues, the ongoing global increase of atmospheric CO2 concentration is expected to affect plant–animal interactions. Although this is a widely explored field, test systems studied so far have not included mature trees. Our study uses the Swiss Canopy Crane and the web-FACE CO2 enrichment system in a 35m tall temperate deciduous forest. We studied the in situ abundance of dominant leaf-galls and leaf-miners on 13 mature oaks before the treatment started, and in two sub-groups, one of which received CO2 enrichment from 2001 to 2004. We expected that gall-inducing cynipids (Neuroterus quercusbaccarum and N. numismalis) would show similar loads with spangle-galls on the two tree groups, due to their capacity to manipulate their host plant and the quality of gall tissues. On the other hand, we expected that leaf-miners (Tischeria ekebladella) would show higher infestation on trees with high-quality (i.e. low C/N ratio, etc.) foliage leading to less mines on CO2 enriched oaks. Partially in line with our hypothesis, spangle-gall density showed only a positive short-term pulse effect (N. quercusbaccarum only) and did not differ across treatments after 4years. In contrast to our hypothesis, the leaf-miner species did not respond persistently to CO2 enrichment either; it even showed higher infestation on CO2 enriched oaks in the 1styear after the onset of enrichment. In conclusion, CO2 enrichment had no lasting effect in all three taxa, despite the substantial and consistent change in leaf chemistry of oak due to growth in elevated CO2. [Copyright &y& Elsevier]

• Rates of central line-associated bloodstream infections are the same in internal jugular vein (IJV) and subclavian vein (SCV) central venous catheters (CVCs) after allogeneic hematopoietic cell transplantation (HCT). • The strongest risk factor for local inflammation or fever is >6 neutropenic CVC-days. • The time to local inflammation is longer with CVCs placed in the IJV. • CVC placement in the SCV is not superior to placement in the IJV in allogeneic HCT. • A clear recommendation for a preferred CVC insertion site is not supported in allogeneic HCT. Central venous catheters (CVCs) are extensively used in patients undergoing allogeneic hematopoietic cell transplantation (HCT). In these patients CVC are placed routinely either via the internal jugular vein (IJV) or the subclavian vein (SCV). Purpose of this study was to systematically analyze complications of CVC at different insertion sites in HCT recipients. In this retrospective analysis, all consecutive patients (n = 56) who received a CVC (n = 101) due to allogeneic HCT at our institution between January 2011 and June 2013 were included. Three-lumen standard, nontunneled CVCs were placed via either the IJV (n = 60; 59%) or the SCV (n = 41; 41%). Study endpoints were time to local inflammation at the insertion site, time to fever, time to a combined endpoint of inflammation and fever, central line-associated bloodstream infection (CLABSI), duration of catheterization, catheter lumen obstruction, deep-vein thrombosis, pneumothorax, and catheter-related death. The median duration of catheterization per CVC was almost identical for the IJV and SCV sites (18 days versus 17 days; P not significant). There were no differences in the frequency of CLABSI, deep-vein thrombosis, pneumothorax, and catheter lumen obstruction between IJV and SCV CVC insertion sites. None of the patients died due to a CVC-related cause. Local inflammation occurred less frequently (48% versus 71%; P =.025) and later (median time to local inflammation, 25 days versus 12 days; P =.01) in IJV CVCs versus SCV CVCs. There was a trend toward a median longer time to the occurrence of fever for IJV CVCs compared with SCV CVCs (20 days versus 13 days; P =.07). In the multivariate analysis, diagnosis of acute leukemia (hazard ratio [HR], 1.696; P =.036), SCV CVC (HR, 1.617; P =.039), and neutropenic CVC-days (HR, 2.477; P =.01) were identified as risk factors for the occurrence of local inflammation or fever. In contrast to earlier studies in patients without hematologic malignancies, these data demonstrate that CVCs placed in the SCV are not superior over IJV CVCs. Moreover, local inflammation occurred earlier and more frequently in patients with an SCV CVC. [ABSTRACT FROM AUTHOR]

To reduce artifacts and scan time of GRASE imaging by selecting an optimal sampling pattern and jointly reconstructing gradient echo and spin echo images. We jointly reconstruct images for the different echo types by considering these as additional virtual coil channels in the novel Autocalibrated Parallel Imaging Reconstruction with Sampling Pattern Optimization for GRASE (APIR4GRASE) method. Besides image reconstruction, we identify optimal sampling patterns for the acquisition. The selected optimal patterns were validated on phantom and in-vivo acquisitions. Comparison to the conventional GRASE without acceleration, and to the GRAPPA reconstruction with a single echo type was also performed. Using identified optimal sampling patterns, APIR4GRASE eliminated modulation artifacts in both phantom and in-vivo experiments; mean square error (MSE) was reduced by 78% and 94%, respectively, compared to the conventional GRASE with similar scan time. Both artifacts and g-factor were reduced compared to the GRAPPA reconstruction with a single echo type. APIR4GRASE substantially improves the speed and quality of GRASE imaging over the state-of-the-art, and is able to reconstruct both spin echo and gradient echo images. [ABSTRACT FROM AUTHOR]

• First-line treatment is applied relatively homogeniously among German, Austrian, and Swiss transplant centers except initial treatment of progressive onset. • Second-line treatment varies considerably with new agents entering clinic through the last 10 years. • Even in the presence of evidence clinical practice in treatment of lung manifestations varies considerably. Chronic graft-versus-host disease (cGVHD) remains the leading cause of late morbidity and mortality. Despite the growing number of treatment options in cGVHD, evidence remains sparse. The German-Austrian-Swiss GVHD Consortium performed a survey on clinical practice in treatment of cGVHD among transplant centers in Germany, Austria, and Switzerland in 2009 and 2018 and compared the results. The survey performed in 2009 contained 20 questions on first-line treatment and related issues and 4 questions on second-line scenarios followed by a survey on all systemic and topic treatment options known and applied, with 31 of 36 transplant centers (86%) responding. The survey in 2018 repeated 7 questions on first-line treatment and 3 questions on second-line scenarios followed by an updated survey on all current systemic treatment options known and applied, with 29 of 66 centers (43%) responding. In summary, the results show a large overlap of first-line treatment practice between centers and the 2 surveys because of a lack of new data that changes practice, except significant heterogeneity of treatment of cGVHD progressive onset type, which can be explained by the lack of trials focusing on this high-risk entity. In contrast, treatment options applied to second-line therapy vary considerably, with new agents like ibrutinib and ruxolitinib entering clinical practice. Moreover, treatment of bronchiolitis obliterans syndrome demonstrates heterogeneity in applied therapeutic options and sequence because of a lack of controlled data and different conclusions from already existing evidence. In summary, the survey results demonstrate an increasing number of treatment options applied to cGVHD accompanied by a significant heterogeneity in second-line treatment and underline the urgent need for clinical trials and registry analyses on rare entities with high mortality like progressive onset type and lung involvement of cGVHD. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life-threatening complication that can develop after hematopoietic cell transplantation. Clinically, SOS/VOD is characterized by hepatomegaly, right upper quadrant pain, jaundice and ascites, most often occurring within the first 3 wk after hematopoietic cell transplantation. Early therapeutic intervention is pivotal for survival in SOS/VOD. Thus, a rapid and reliable diagnosis has to be made. Diagnosis of SOS/VOD is based on clinical criteria, such as the Seattle, Baltimore or recently issued European Society for Blood and Marrow Transplantation criteria, to which hemodynamic and/or ultrasound evidence of SOS were added for the first time. However, to rule out major differential diagnoses and to verify the diagnosis, a reliable imaging method is needed. Ultrasound techniques have been proposed in SOS/VOD. Nevertheless, the sensitivity and specificity of transabdominal ultrasound and Doppler techniques need to be improved. Innovative ultrasound methods such as a combination of Doppler ultrasound with shear wave elastography and contrast-enhanced ultrasound techniques should be evaluated for diagnosis and follow-up of SOS/VOD. The goals of this review are to discuss currently available ultrasound techniques and to identify areas for future studies in SOS/VOD. [ABSTRACT FROM AUTHOR]

Abstract With aging, the brain undergoes several structural changes. These changes reflect the normal aging process and are therefore not necessarily pathologic. In fact, better understanding of these normal changes is an important cornerstone to also disentangle pathologic changes. Several studies have investigated normal brain aging, both cross-sectional and longitudinal, and focused on a broad range of magnetic resonance imaging (MRI) markers. This study aims to comprise the different aspects in brain aging, by performing a comprehensive longitudinal assessment of brain aging, providing trajectories of volumetric (global and lobar; subcortical and cortical), microstructural, and focal (presence of microbleeds, lacunar or cortical infarcts) brain imaging markers in aging and the sequence in which these markers change in aging. Trajectories were calculated on 10,755 MRI scans that were acquired between 2005 and 2016 among 5286 persons aged 45 years and older from the population-based Rotterdam Study. The average number of MRI scans per participant was 2 scans (ranging from 1 to 4 scans), with a mean interval between MRI scans of 3.3 years (ranging from 0.2 to 9.5 years) and an average follow-up time of 5.2 years (ranging from 0.3 to 9.8 years). We found that trajectories of the different volumetric, microstructural, and focal markers show nonlinear curves, with accelerating change with advancing age. We found earlier acceleration of change in global and lobar volumetric and microstructural markers in men compared with women. For subcortical and cortical volumes, results show a mix of more linear and nonlinear trajectories, either increasing, decreasing, or stable over age for the subcortical and cortical volume and thickness. Differences between men and women are visible in several parcellations; however, the direction of these differences is mixed. The presence of focal markers show a nonlinear increase with age, with men having a higher probability for cortical or lacunar infarcts. The data presented in this study provide insight into the normal aging process in the brain, and its variability. [ABSTRACT FROM AUTHOR]

This paper presents a novel image analysis strategy that increases the potential of macular Optical Coherence Tomography (OCT) by using speckle features as biomarkers in different stages of glaucoma. A large pool of features (480) were computed for a subset of macular OCT volumes of the Leuven eye study cohort. The dataset contained 258 subjects that were divided into four groups based on their glaucoma severity: Healthy (56), Mild (94), Moderate (48), and Severe (60). The OCT speckle features were categorized as statistical properties, statistical distributions, contrast, spatial gray-level dependence matrices, and frequency domain features. The averaged thicknesses of ten retinal layers were also collected. Kruskal–Wallis H test and multivariable regression models were used to infer the most significant features related to glaucoma severity classification and to the correlation with visual field mean deviation. Four features were selected as being the most relevant: the ganglion cell layer (GCL) and the inner plexiform layer (IPL) thicknesses, and two OCT speckle features, the data skewness computed on the retinal nerve fiber layer (RNFL) and the scale parameter (a) of the generalized gamma distribution fitted to the GCL data. Based on a significance level of 0.05, the regression models revealed that RNFL skewness exhibited the highest significance among the features considered for glaucoma severity staging (p-values of 8. 6 × 1 0 − 6 for the logistic model and 2. 8 × 1 0 − 7 for the linear model). Furthermore, it demonstrated a strong negative correlation with the visual field mean deviation (ρ = − 0. 64). The post hoc analysis revealed that, when distinguishing healthy controls from glaucoma subjects, GCL thickness is the most relevant feature (p -value of 8. 7 × 1 0 − 5 ). Conversely, when comparing the Mild versus Moderate stages of glaucoma, RNFL skewness emerged as the only feature exhibiting statistical significance (p -value = 0.001). This work shows that macular OCT speckle contains information that is currently not used in clinical practice, and not only complements structural measurements (thickness) but also has a potential for glaucoma staging. [ABSTRACT FROM AUTHOR]

Successful collection of peripheral blood stem cells (PBSCs) depends on the optimal orchestration of mobilization chemotherapy, granulocyte colony stimulating factor (G-CSF) application, and CD34 + cell number assessment in the peripheral blood (PB). However, determining the optimal timing in accordance to the applied chemomobilization regimen can be challenging. Although most centers apply their own local timing schedules, a reliable timetable including the currently most often used mobilization regimens is lacking. We present a comprehensive analysis of the timing modalities for 11 of the most commonly used chemomobilization regimens. A retrospective analysis was performed on the clinical and PBSC collection parameters (including duration of G-CSF application, time point of CD34 + assessment, PB CD34 + cell count, number of leukapheresis [LP] sessions, processed blood volume, and CD34 + collection results) of 91 representatively selected patients who had undergone stem cell mobilization at 2 collection centers. Six to 10 patients were analyzed per regimen with a variety of diagnoses, including multiple myeloma, malignant lymphoma, and sarcoma. No collection failures (<2 × 10 6 CD34 + cells/kg body weight) were observed. All analyzed patients successfully reached their individual collection goal in adherence to the given schedule of chemotherapy, application of G-CSF, measurement of CD34 + cells, and subsequent LP. The presented data on the timing of chemomobilization, G-CSF application, and stem cell collection may be helpful in clinical decision making and contribute to a more transparent and predictable treatment process. [ABSTRACT FROM AUTHOR]

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) is considered to be the only treatment providing long-term disease control. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy before HSCT in patients with r/r AML. Here, we report the long-term follow-up of this phase II multicenter trial and exploratory analyses on the impact of comorbidity on outcome. Eighty-four patients with a median age of 61 years (range, 40 to 75) were enrolled. Patients were scheduled for at least 1 cycle of salvage therapy with CLARA (clofarabine 30 mg/m 2 ; cytarabine 1 g/m 2 , days 1 to 5). Chemo-responsive patients with a donor received HSCT after first CLARA. The conditioning regimen consisted of clofarabine 30 mg/m 2 , day −6 to −3, and melphalan 140 mg/m 2 day −2. The Eastern Cooperative Oncology Group (ECOG) score, the hematopoietic cell transplantation–specific comorbidity index (HCT-CI), and the Cumulative Illness Rating Scale were obtained at study enrollment as well as before HSCT. Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40 months, the estimated 3-year overall survival (OS) for all enrolled patients and those with HSCT within the trial was 40% and 55%, respectively. Relapse-free survival for patients who underwent transplantation with a complete remission afterwards (n = 50) was 48%, calculated from the day of transplantation. In multivariate analysis, both the HCT-CI and ECOG score had a statistically significant impact on OS with a hazard ratio of 1.22 ( P  = .025)and 1.72 ( P  = .001), respectively. Using a clofarabine-based salvage therapy combined with early allogeneic HSCT, we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG scores gave prognostic information on OS, showing the feasibility and clinical relevance of comorbidity evaluation at the time of diagnosis of r/r AML patients. [ABSTRACT FROM AUTHOR]

An automated method for registering B-mode ultrasound (US) and magnetic resonance imaging (MRI) of the carotid arteries is proposed. The registration uses geometric features, namely, lumen centerlines and lumen segmentations, which are extracted fully automatically from the images after manual annotation of three seed points in US and MRI. The registration procedure starts with alignment of the lumen centerlines using a point-based registration algorithm. The resulting rigid transformation is used to initialize a rigid and subsequent non-rigid registration procedure that jointly aligns centerlines and segmentations by minimizing a weighted sum of the Euclidean distance between centerlines and the dissimilarity between segmentations. The method was evaluated in 28 carotid arteries from eight patients and six healthy volunteers. First, the automated US lumen segmentation method was validated and optimized in a cross-validation experiment. Next, the effect of the weighting parameter of the proposed registration dissimilarity metric and the control point spacing in the non-rigid registration was evaluated. Finally, the proposed registration method was evaluated in comparison to an existing intensity-and-point-based method, a registration using only the centerlines and a registration using manual US lumen segmentations. Registration accuracy was measured in terms of the mean surface distance between manual US segmentations and the registered MRI segmentations. The average mean surface distance was 0.78 ± 0.34 mm for all subjects, 0.65 ± 0.09 mm for healthy volunteers and 0.87 ± 0.42 mm for patients. The results for the complete set were significantly better (Wilcoxon test, p < 0.01) than the results for the intensity-and-point-based method and the centerline-based registration method. We conclude that the proposed method can robustly and accurately register US and MR images of the carotid artery, allowing multimodal analysis of the carotid plaque to improve plaque assessment. [ABSTRACT FROM AUTHOR]

To expand the current knowledge about azacitidine (Aza) and donor lymphocyte infusions (DLI) as salvage therapy for relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify predictors for response and survival, we retrospectively analyzed data of 154 patients with acute myeloid leukemia (AML, n = 124), myelodysplastic (MDS, n = 28), or myeloproliferative syndrome (n = 2). All patients received a median number of 4 courses of Aza (range, 4 to 14) and DLI were administered to 105 patients (68%; median number of DLI, 2; range, 1 to 7). Complete and partial remission rates were 27% and 6%, respectively, resulting in an overall response rate of 33%. Multivariate analysis identified molecular-only relapse (hazard ratio [HR], 9.4; 95% confidence interval [CI], 2.0 to 43.5; P = .004) and diagnosis of MDS (HR, 4.1; 95% CI, 1.4 to 12.2; P = .011) as predictors for complete remission. Overall survival (OS) at 2 years was 29% ± 4%. Molecular-only relapse (HR, .14; 95% CI, .03 to .59; P = .007), diagnosis of MDS (HR, .33; 95% CI, .16 to .67; P = .002), and bone marrow blasts <13% (HR, .54; 95% CI, .32 to .91; P = .021) were associated with better OS. Accordingly, 2-year OS rate was higher in MDS patients (66% ± 10%, P = .001) and correlated with disease burden in patients with AML. In summary, Aza and DLI is an effective and well-tolerated treatment option for patients with relapse after allo-HSCT, in particular those with MDS or AML and low disease burden. The latter finding emphasizes the importance of stringent disease monitoring and early intervention. [ABSTRACT FROM AUTHOR]

Carotid plaque segmentation in B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) is crucial to the assessment of plaque morphology and composition, which are linked to plaque vulnerability. Segmentation in BMUS is challenging because of noise, artifacts and echo-lucent plaques. CEUS allows better delineation of the lumen but contains artifacts and lacks tissue information. We describe a method that exploits the combined information from simultaneously acquired BMUS and CEUS images. Our method consists of non-rigid motion estimation, vessel detection, lumen–intima segmentation and media–adventitia segmentation. The evaluation was performed in training (n = 20 carotids) and test (n = 28) data sets by comparison with manually obtained ground truth. The average root-mean-square errors in the training and test data sets were comparable for media–adventitia (411 ± 224 and 393 ± 239 μm) and for lumen–intima (362 ± 192 and 388 ± 200 μm), and were comparable to inter-observer variability. To the best of our knowledge, this is the first method to perform fully automatic carotid plaque segmentation using combined BMUS and CEUS. [ABSTRACT FROM AUTHOR]

Abstract: An accurate spatial relationship between 3D in-vivo carotid plaque and lumen imaging and histological cross sections is required to study the relationship between biomechanical parameters and atherosclerotic plaque components. We present and evaluate a fully three-dimensional approach for this registration problem, which accounts for deformations that occur during the processing of the specimens. By using additional imaging steps during tissue processing and semi-automated non-linear registration techniques, a 3D-reconstruction of the histology is obtained. The methodology was evaluated on five specimens obtained from patients, operated for severe atherosclerosis in the carotid bifurcation. In more than 80% of the histology slices, the quality of the semi-automated registration with computed tomography angiography (CTA) was equal to or better than the manual registration. The inter-observer variability was between one and two in-vivo CT voxels and was equal to the manual inter-observer variability. Our technique showed that the angles between the normals of the registered histology slices and the in-vivo CTA scan direction ranged 6–56°, indicating that proper 3D-registration is crucial for establishing a correct spatial relation with in-vivo imaging modalities. This new 3D-reconstruction technique of atherosclerotic plaque tissue opens new avenues in the field of biomechanics as well as in the field of image processing, where it can be used for validation purposes of segmentation algorithms. [ABSTRACT FROM AUTHOR]

Abstract: Atlas-based segmentation is a powerful generic technique for automatic delineation of structures in volumetric images. Several studies have shown that multi-atlas segmentation methods outperform schemes that use only a single atlas, but running multiple registrations on volumetric data is time-consuming. Moreover, for many scans or regions within scans, a large number of atlases may not be required to achieve good segmentation performance and may even deteriorate the results. It would therefore be worthwhile to include the decision which and how many atlases to use for a particular target scan in the segmentation process. To this end, we propose two generally applicable multi-atlas segmentation methods, adaptive multi-atlas segmentation (AMAS) and adaptive local multi-atlas segmentation (ALMAS). AMAS automatically selects the most appropriate atlases for a target image and automatically stops registering atlases when no further improvement is expected. ALMAS takes this concept one step further by locally deciding how many and which atlases are needed to segment a target image. The methods employ a computationally cheap atlas selection strategy, an automatic stopping criterion, and a technique to locally inspect registration results and determine how much improvement can be expected from further registrations. AMAS and ALMAS were applied to segmentation of the heart in computed tomography scans of the chest and compared to a conventional multi-atlas method (MAS). The results show that ALMAS achieves the same performance as MAS at a much lower computational cost. When the available segmentation time is fixed, both AMAS and ALMAS perform significantly better than MAS. In addition, AMAS was applied to an online segmentation challenge for delineation of the caudate nucleus in brain MRI scans where it achieved the best score of all results submitted to date. [Copyright &y& Elsevier]

Two issues of great interest in the field of lasers in artwork conservation are the so-called yellowing effect and the discoloration of pigments. We have viewed these issues from a comprehensive point of view, considering all our present experimental results as well as ongoing modeling and theoretical calculations. The first concern to be discussed is the yellowing effect in laser cleaning of marble or stone artifacts. Although, in most cases, a yellowish layer exists underneath the black encrustation, the so-called ‘patina’, it has become clear that there are situations where yellowing cannot be attributed to an existing layer. In the present study, a light scattering model that may account for the yellowing is presented. This model considers a thin absorbent layer and the surface roughness and/or created voids and accounts for the reflectance spectra measured by (i) hyper-spectral imaging and (ii) integrating sphere. Additional experimental data, such as the absence of yellowing when the third harmonic of a Q-swihed Nd:YAG laser is used, support this model. A thorough understanding of the quantitative characteristics of pigment discoloration, on the other hand, has been attempted by means of X-ray diffraction and theoretical studies. The model developed suggests a nucleation process for cinnabar resulting in a structural modification within the volume of a pigment’s crystal or particle close to the ‘ablation front’, which extends for a few nanometers from its surface. [Copyright &y& Elsevier]

Increasing evidence suggests that impaired cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) is a major cause of uncontrolled CMV reactivations and associated complications in hematopoietic stem cell transplantation (HSCT). No reliable test exists to predict patients at risk of primary and/or recurrent CMV reactivations following HSCT. Accurately assessing CMV-CMI might therefore improve the risk stratification of patients and allow optimizing and individualizing patient care. This study aimed to evaluate the suitability of a novel IFN-γ ELISpot assay (T-Track® CMV), based on the stimulation of peripheral blood mononuclear cells with T-activated® pp65 and IE-1 CMV proteins, to predict protection from recurrent CMV reactivation following the resolution of a treatment-requiring primary CMV reactivation. A prospective, longitudinal, observational, multicenter study was conducted in 175 intermediate- and high-risk (Donor (D)+/Recipient (R)+, D+/R-, D-/R+) HSCT recipients (ClinicalTrials.gov ID: NCT02156479). Patients underwent preemptive antiviral therapy per institutional guidelines. CMV DNAemia was analyzed by quantitative PCR. CMV-CMI was measured at day 45, 60, 80, 100 and 120 post-transplantation, as well as at onset and following the end of preemptive treatment. Occurrence of recurrent CMV reactivation was monitored up to 7.5 months post-transplantation. 154/175 patients fulfilling the inclusion/exclusion criteria and having at least one valid T-Track® CMV test result were included in the final analysis. 101/154 (66%) patients experienced at least one (treatment-requiring) CMV reactivation during the observational period. Out of 74 patients (24 D+/R+, 3 D+/R-, 47 D-/R+) who experienced a first CMV reactivation and had a valid ELISpot test result at the end of this primary reactivation, 30 (41%) faced a recurrent CMV reactivation during the observational period. Interestingly, 41/44 patients free of recurrent reactivation had a positive test result (i.e. positive for at least one of pp65- and/or IE-1-specific result) after resolution of the primary CMV reactivation, resulting in a 93% specificity in diagnostic accuracy. Accordingly, a time-to-event analysis indicated a significantly lower incidence of recurrent CMV reactivation in patients with a positive test result (Figure 1; Hazard ratio=5.68; Log-Rank Test, p<0.001). A ROC analysis also demonstrated that pp65-specific response measured following a primary CMV reactivation is a good negative predictor for future CMV reactivation (AUC=0.840 [95% CI 0.741-0.939]; p<0.001). Altogether, this novel standardized IFN-γ ELISpot assay allows an improved risk stratification of CMV-related clinical complications, and can support clinicians in the identification and management of patients with increased risk of recurrent CMV reactivation following HSCT. [ABSTRACT FROM AUTHOR]

Purpose: Diagnosing desmoid-type fibromatosis (DTF) requires an invasive tissue biopsy with β-catenin staining and CTNNB1 mutational analysis, and is challenging due to its rarity. The aim of this study was to evaluate radiomics for distinguishing DTF from soft tissue sarcomas (STS), and in DTF, for predicting the CTNNB1 mutation types.Methods: Patients with histologically confirmed extremity STS (non-DTF) or DTF and at least a pretreatment T1-weighted (T1w) MRI scan were retrospectively included. Tumors were semi-automatically annotated on the T1w scans, from which 411 features were extracted. Prediction models were created using a combination of various machine learning approaches. Evaluation was performed through a 100x random-split cross-validation. The model for DTF vs. non-DTF was compared to classification by two radiologists on a location matched subset.Results: The data included 203 patients (72 DTF, 131 STS). The T1w radiomics model showed a mean AUC of 0.79 on the full dataset. Addition of T2w or T1w post-contrast scans did not improve the performance. On the location matched cohort, the T1w model had a mean AUC of 0.88 while the radiologists had an AUC of 0.80 and 0.88, respectively. For the prediction of the CTNNB1 mutation types (S45 F, T41A and wild-type), the T1w model showed an AUC of 0.61, 0.56, and 0.74.Conclusions: Our radiomics model was able to distinguish DTF from STS with high accuracy similar to two radiologists, but was not able to predict the CTNNB1 mutation status. [ABSTRACT FROM AUTHOR]