Simulation of a virtual liver iron overload model and R2 * estimation using multispectral fat-water models for GRE and UTE acquisitions at 1.5 T and 3 T.

R2 *-MRI has emerged as a noninvasive alternative to liver biopsy for assessment of hepatic iron content (HIC). Multispectral fat-water R2 * modeling techniques such as the nonlinear least squares (NLSQ) fitting and autoregressive moving average (ARMA) models have been proposed for the accurate assessment of iron overload by also considering fat, which can otherwise confound R2 *-based HIC measurements in conditions of coexisting iron overload and steatosis. However, the R2 * estimation by these multispectral models has not been systematically investigated for various acquisition methods in iron overload only conditions and across the full clinically relevant range of HICs (0-40 mg Fe/g dry liver weight). The purpose of this study is to evaluate the R2 * accuracy and precision of multispectral models for various multiecho gradient echo (GRE) and ultrashort echo time (UTE) imaging acquisitions by constructing virtual iron overload models based on true histology and synthesizing MRI signals via Monte Carlo simulations at 1.5 T and 3 T, and comparing their results with monoexponential model and published in vivo R2 *-HIC calibrations. The signals were synthesized with TE1 = 1.0 ms for GRE and TE1 = 0.1 ms for UTE acquisition for varying echo spacing, ΔTE (0.1, 0.5, 1, 2 ms), and maximum echo time, TEmax (2, 4, 6, 10 ms). An iron-doped phantom study is also conducted to validate the simulation results in experimental GRE (TE1 = 1.2 ms, ΔTE = 0.72 ms, TEmax = 6.24 ms) and UTE (TE1 = 0.1 ms, ΔTE = 0.5 ms, TEmax = 6.1 ms) acquisitions. For GRE acquisitions, the multispectral ARMA and NLSQ models produced higher slopes (0.032-0.035) compared with the monoexponential model and published in vivo R2 *-HIC calibrations (0.025-0.028). However, for UTE acquisition for shorter echo spacing (≤0.5 ms) and longer maximum echo time, TEmax (≥6 ms), the multispectral and monoexponential signal models produced similar R2 *-HIC slopes (1.5 T, 0.028-0.032; 3 T, 0.014-0.016) and precision values (coefficient of variation < 25%) across the full clinical spectrum of HICs at both 1.5 T and 3 T. The phantom analysis also showed that all signal models demonstrated a significant improvement in R2 * estimation for UTE acquisition compared with GRE, confirming our simulation findings. Future work should investigate the performance of multispectral fat-water models by simulating liver models in coexisting conditions of iron overload and steatosis for accurate R2 * and fat quantification.

Systemic thrombolysis with newer thrombolytics vs anticoagulation in acute intermediate risk pulmonary embolism: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCTs) comparing systemic thrombolysis to anticoagulation in intermediate risk pulmonary embolism (PE) have yielded mixed results. A prior meta-analysis on this topic had included studies that used lower than standard dose of thrombolytics and included thrombolytic agents that are no longer available. Hence, interpreting the findings of that paper is not valid in contemporary practice. OBJECTIVES: We undertook a systematic review and meta-analysis of randomized controlled trials of systemic thrombolysis with newer thrombolytic agents vs anticoagulation in intermediate risk PE. METHODS: This systematic review and meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. RESULTS: Nine randomized controlled trials were included in the study. We did not find any difference in in-hospital mortality (RR: 0.79; 95% CI: 0.42-1.50; I2: 0) or risk of major bleeding (RR:2.08;95% CI: 0.98-4.42; I2: 23.9%) between systemic thrombolysis and anticoagulation. Systemic thrombolysis was associated with lower risks for vasopressor use (RR: 0.27; 95% CI: 0.11-0.64, I2: 0) and secondary/rescue thrombolysis (RR: 0.25; 95% CI: 0.14-0.45; I2: 0). But systemic thrombolysis was found to have an increased risk of intracranial hemorrhage (RR: 4.55; 95% CI: 1.30-15.91; I2:0). There was no difference in mechanical ventilation between the two groups (RR: 0.61; 95% CI: 0.31-1.19, I2:0). CONCLUSION: In our meta-analysis of randomized controlled trials of systemic thrombolysis vs anticoagulation in intermediate risk PE, we did not find any difference in in-hospital mortality or overall risk of major bleeding. With systemic thrombolysis, we found lower risks for vasopressor use and need for secondary/ rescue thrombolysis and an increased risk of intracranial hemorrhage.

Quantitative MRI of diffuse liver diseases: techniques and tissue-mimicking phantoms.

Quantitative magnetic resonance imaging (MRI) techniques are emerging as non-invasive alternatives to biopsy for assessment of diffuse liver diseases of iron overload, steatosis and fibrosis. For testing and validating the accuracy of these techniques, phantoms are often used as stand-ins to human tissue to mimic diffuse liver pathologies. However, currently, there is no standardization in the preparation of MRI-based liver phantoms for mimicking iron overload, steatosis, fibrosis or a combination of these pathologies as various sizes and types of materials are used to mimic the same liver disease. Liver phantoms that mimic specific MR features of diffuse liver diseases observed in vivo are important for testing and calibrating new MRI techniques and for evaluating signal models to accurately quantify these features. In this study, we review the liver morphology associated with these diffuse diseases, discuss the quantitative MR techniques for assessing these liver pathologies, and comprehensively examine published liver phantom studies and discuss their benefits and limitations.

Hepatic Iron Quantification Using a Free-Breathing 3D Radial Gradient Echo Technique and Validation With a 2D Biopsy-Calibrated R2* Relaxometry Method.

BACKGROUND: Hepatic iron content (HIC) is an important parameter for the management of iron overload. Non-invasive HIC assessment is often performed using biopsy-calibrated two-dimensional breath-hold Cartesian gradient echo (2D BH GRE) R2* -MRI. However, breath-holding is not possible in most pediatric patients or those with respiratory problems, and three-dimensional free-breathing radial GRE (3D FB rGRE) has emerged as a viable alternative. PURPOSE: To evaluate the performance of a 3D FB rGRE and validate its R2* and fat fraction (FF) quantification with 3D breath-hold Cartesian GRE (3D BH cGRE) and biopsy-calibrated 2D BH GRE across a wide range of HICs. STUDY TYPE: Retrospective. SUBJECTS: Twenty-nine patients with hepatic iron overload (22 females, median age: 15 [5-25] years). FIELD STRENGTH/SEQUENCE: Three-dimensional radial and 2D and 3D Cartesian multi-echo GRE at 1.5 T. ASSESSMENT: R2* and FF maps were computed for 3D GREs using a multi-spectral fat model and 2D GRE R2* maps were calculated using a mono-exponential model. Mean R2* and FF values were calculated via whole-liver contouring and T2* -thresholding by three operators. STATISTICAL TESTS: Inter- and intra-observer reproducibility was assessed using Bland-Altman and intraclass correlation coefficient (ICC). Linear regression and Bland-Altman analysis were performed to compare R2* and FF values among the three acquisitions. One-way repeated-measures ANOVA and Wilcoxon signed-rank tests, respectively, were used to test for significant differences between R2* and FF values obtained with different acquisitions. Statistical significance was assumed at P < 0.05. RESULTS: The mean biases and ICC for inter- and intra-observer reproducibility were close to 0% and >0.99, respectively for both R2* and FF. The 3D FB rGRE R2* and FF values were not significantly different (P > 0.44) and highly correlated (R2 ≥ 0.98) with breath-hold Cartesian GREs, with mean biases ≤ ±2.5% and slopes 0.90-1.12. In non-breath-holding patients, Cartesian GREs showed motion artifacts, whereas 3D FB rGRE exhibited only minimal streaking artifacts. DATA CONCLUSION: Free-breathing 3D radial GRE is a viable alternative in non-breath-hold patients for accurate HIC estimation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Morphological characterization of hepatic steatosis and Monte Carlo modeling of MRI signal for accurate quantification of fat fraction and relaxivity.

Chemical-shift-based fat-water MRI signal models with single- or dual-R2 * correction have been proposed for quantification of fat fraction (FF) and assessment of hepatic steatosis. However, there is a void in our understanding of which model truly mimics the underlying biophysical mechanism of steatosis on MRI signal relaxation. The purpose of this study is to morphologically characterize and build realistic steatosis models from histology and synthesize MRI signal using Monte Carlo simulations to investigate the accuracy of single- and dual-R2 * models in quantifying FF and R2 *. Fat morphology was characterized by performing automatic segmentation on 16 mouse liver histology images and extracting the radius, nearest neighbor (NN) distance, and regional anisotropy of fat droplets. A gamma distribution function (GDF) was used to generalize extracted features, and regression analysis was performed to derive relationships between FF and GDF parameters. Virtual steatosis models were created based on derived morphological and statistical descriptors, and the MRI signal was synthesized at 1.5 T and 3 T. R2 * and FF values were calculated using single- and dual-R2 * models and compared with in vivo R2 *-FF calibrations and simulated FFs. The steatosis models generated with regional anisotropy and NN distribution closely mimicked the true in vivo fat morphology. For both R2 * models, predicted R2 * values showed positive correlation with FFs, with slopes similar to those of the in vivo calibrations (P > 0.05), and predicted FFs showed excellent agreement with true FFs (R2 > 0.99), with slopes close to unity. Our study, hence, demonstrates the proof of concept for generating steatosis models from histologic data and synthesizing MRI signal to show the expected signal relaxation under conditions of steatosis. Our results suggest that a single R2 * is sufficient to accurately estimate R2 * and FF values for lower FFs, which agrees with in vivo studies. Future work involves characterizing and building steatosis models at higher FFs and testing single- and dual-R2 * models for accurate assessment of steatosis.

Hepatic steatosis modeling and MRI signal simulations for comparison of single- and dual-R2* models and estimation of fat fraction at 1.5T and 3T.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has emerged as a noninvasive clinical tool for assessment of hepatic steatosis. Multi-spectral fat-water MRI models, incorporating single or dual transverse relaxation decay rate(s) (R2*) have been proposed for accurate fat fraction (FF) estimation. However, it is still unclear whether single- or dual-R2* model accurately mimics in vivo signal decay for precise FF estimation and the impact of signal-to-noise ratio (SNR) on each model performance. Hence, this study aims to construct virtual steatosis models and synthesize MRI signals with different SNRs to systematically evaluate the accuracy of single- and dual-R2* models for FF and R2* estimations at 1.5T and 3.0T. METHODS: Realistic hepatic steatosis models encompassing clinical FF range (0-60 %) were created using morphological features of fat droplets (FDs) extracted from human liver biopsy samples. MRI signals were synthesized using Monte Carlo simulations for noise-free (SNRideal) and varying SNR conditions (5-100). Fat-water phantoms were scanned with different SNRs to validate simulation results. Fat water toolbox was used to calculate R2* and FF for both single- and dual-R2* models. The model accuracies in R2* and FF estimates were analyzed using linear regression, bias plot and heatmap analysis. RESULTS: The virtual steatosis model closely mimicked in vivo fat morphology and Monte Carlo simulation produced realistic MRI signals. For SNRideal and moderate-high SNRs, water R2* (R2*W) by dual-R2* and common R2* (R2*com) by single-R2* model showed an excellent agreement with slope close to unity (0.95-1.01) and R2 > 0.98 at both 1.5T and 3.0T. In simulations, the R2*com-FF and R2*W-FF relationships exhibited slopes similar to in vivo calibrations, confirming the accuracy of our virtual models. For SNRideal, fat R2* (R2*F) was similar to R2*W and dual-R2* model showed slightly higher accuracy in FF estimation. However, in the presence of noise, dual-R2* produced higher FF bias with decreasing SNR, while leading to only marginal improvement for high SNRs and in regions dominated by fat and water. In contrast, single-R2* model was robust and produced accurate FF estimations in simulations and phantom scans with clinical SNRs. CONCLUSION: Our study demonstrates the feasibility of creating virtual steatosis models and generating MRI signals that mimic in vivo morphology and signal behavior. The single-R2* model consistently produced lower FF bias for clinical SNRs across entire FF range compared to dual-R2* model, hence signifying that single-R2* model is optimal for assessing hepatic steatosis.

Impact of sleep apnoea on 30 day hospital readmission rate and cost in heart failure with reduced ejection fraction.

AIMS: In this study, we estimated the 30 day all-cause and heart failure-specific readmission rates, predictors, mortality, and hospitalization costs in patients with obstructive sleep apnoea admitted with acute decompensated heart failure with reduced ejection fraction. METHODS AND RESULTS: This is a retrospective cohort study using the Agency of Healthcare Research and Quality's National Readmission Database for the year 2019. The primary outcome was the 30 day all-cause hospital readmission rate. The secondary outcomes were (i) in-hospital mortality rate for index admissions; (ii) 30 day mortality rate for index hospitalizations; (iii) the five most common principal diagnosis for readmission; (iv) readmission in-hospital mortality rate; (v) length of hospital stay; (vi) independent risk factors for readmission; and (vii) hospitalization costs. We identified 6908 hospitalizations that met our study definition. The mean patient age was 62.8 years, and women comprised only 27.6% of patients. The 30 day all-cause readmission rate was 23.4%. 48.9% of readmissions were due to decompensated heart failure. The in-hospital mortality rate during readmissions was significantly higher than that of the index admission (5.6% vs. 2.4%; P < 0.05). The mean length of stay for patients during index admissions was 6.5 days (6.06-7.02), while during readmissions, it was 8.5 days (7.4-9.6; P < 0.05). The mean total hospitalization charges at index admissions were $78 438 (68 053-88 824), while during readmissions, they were higher at $124 282 (90 906-157 659; P < 0.05). The mean total cost of hospitalization during index admissions was $20 535 (18 311-22 758), while at readmissions, it was higher at $29 954 (24 041-35 867; P < 0.05). The total hospital charges for all 30 day readmissions were $195 million, and total hospital costs was $46.9 million. The variables found to be associated with increased rate of readmissions were patients with Medicaid insurance, higher Charlson co-morbidity Index, and longer length of stay. The variables associated with lower rate of readmissions were prior percutaneous coronary intervention and patients with private insurance. CONCLUSIONS: In patients with obstructive sleep apnoea admitted with heart failure with reduced ejection fraction, we found a substantial all-cause readmission rate of 23.4% with heart failure readmission constituting about 48.9% of readmissions. Readmissions were associated with higher mortality and resource use.

Mortality and bleeding associated with the management of sub-massive pulmonary embolism: a systematic review and Bayesian network meta-analysis.

Current guidelines recommend anticoagulation (AC) for low and intermediate-risk pulmonary embolism (PE) and systemic thrombolysis (tPA) for high risk (massive) PE. How these treatment options compare with other modalities of treatment such as catheter directed thrombolysis (CDT), ultrasound assisted catheter thrombolysis (USAT), and administering lower dose of thrombolytics (LDT) is unclear. There is no study that has compared all these treatment options. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials in patients with submassive (intermediate risk) PE. Fourteen randomized controlled trials were included, comprising 2132 patients. On Bayesian network meta-analysis, a significant decrease in mortality was noted in tPA versus AC. There was no significant difference between USAT versus CDT. For risk of major bleeding, there was no significant difference in relative risk of major bleeding between tPA versus AC and USAT versus CDT. tPA was found to have a significantly higher risk of minor bleeding and a lower risk of recurrent PE compared to AC. Systemic thrombolysis is associated with a significant reduction in mortality and recurrent PE compared to anticoagulation but an increased risk of minor bleeding. There was no difference in risk of major bleeding. Our study also shows that while the newer modalities of treatment for pulmonary embolism are promising, there is lack of data to comment on the purported advantages.

Automated Segmentation and Morphological Characterization of Hepatic Steatosis and Correlation with Histopathology.

Background/objectives: Prevalence of nonalcoholic fatty liver disease (NAFLD) has increased to 25% of the world population. Hepatic steatosis is a hallmark feature of NAFLD and is assessed histologically using visual and ordinal fat grading criteria (0-3) from the Nonalcoholic Steatohepatitis (NASH) Clinical Research Network (CRN) scoring system. The purpose of this study is to automatically segment and extract morphological characteristics and distributions of fat droplets (FDs) on liver histology images and find associations with severity of steatosis. Methods: A previously published human cohort of 68 NASH candidates was graded for steatosis by an experienced pathologist using the Fat CRN grading system. The automated segmentation algorithm quantified fat fraction (FF) and fat-affected hepatocyte ratio (FHR), extracted fat morphology by calculating radius and circularity of FDs, and examined FDs distribution and heterogeneity using nearest neighbor distance and regional isotropy. Results: Regression analysis and Spearman correlation (ρ) yielded high correlations for radius (R2 = 0.86, ρ = 0.72), nearest neighbor distance (R2 = 0.82, ρ = -0.82), regional isotropy (R2 = 0.84, ρ = 0.74), and FHR (R2 = 0.90, ρ = 0.85), and low correlation for circularity (R2 = 0.48, ρ = -0.32) with FF and pathologist grades, respectively. FHR showed a better distinction between pathologist Fat CRN grades compared to conventional FF measurements, making it a potential surrogate measure for Fat CRN scores. Our results showed variation in distribution of morphological features and steatosis heterogeneity within the same patient's biopsy sample as well as between patients of similar FF. Conclusions: The fat percentage measurements, specific morphological characteristics, and patterns of distribution quantified with the automated segmentation algorithm showed associations with steatosis severity; however, future studies are warranted to evaluate the clinical significance of these steatosis features in progression of NAFLD and NASH.

Functional Plasticity Coupled With Structural Predispositions in Auditory Cortex Shape Successful Music Category Learning.

Categorizing sounds into meaningful groups helps listeners more efficiently process the auditory scene and is a foundational skill for speech perception and language development. Yet, how auditory categories develop in the brain through learning, particularly for non-speech sounds (e.g., music), is not well understood. Here, we asked musically naïve listeners to complete a brief (∼20 min) training session where they learned to identify sounds from a musical interval continuum (minor-major 3rds). We used multichannel EEG to track behaviorally relevant neuroplastic changes in the auditory event-related potentials (ERPs) pre- to post-training. To rule out mere exposure-induced changes, neural effects were evaluated against a control group of 14 non-musicians who did not undergo training. We also compared individual categorization performance with structural volumetrics of bilateral Heschl's gyrus (HG) from MRI to evaluate neuroanatomical substrates of learning. Behavioral performance revealed steeper (i.e., more categorical) identification functions in the posttest that correlated with better training accuracy. At the neural level, improvement in learners' behavioral identification was characterized by smaller P2 amplitudes at posttest, particularly over right hemisphere. Critically, learning-related changes in the ERPs were not observed in control listeners, ruling out mere exposure effects. Learners also showed smaller and thinner HG bilaterally, indicating superior categorization was associated with structural differences in primary auditory brain regions. Collectively, our data suggest successful auditory categorical learning of music sounds is characterized by short-term functional changes (i.e., greater post-training efficiency) in sensory coding processes superimposed on preexisting structural differences in bilateral auditory cortex.

Evaluation of Quality Indicators of Breast Cancer Management at a Tertiary Cancer Center in Nepal.

PURPOSE: Breast cancer is the second commonest cancer among female in Nepal. This is our first attempt to audit breast cancer management in our institute and compare with standard quality indicators (QIs) available. METHODS: The retrospective study included 104 female patients with breast cancer who had taken treatment at Bhaktapur Cancer Hospital in 1 year. Participants were selected on the basis of convenience sampling. Of 33 QIs in breast cancer management according to European Society of Breast Cancer Specialists guidelines, 19 QIs were chosen relevant to our setup. These QIs were calculated for all patients and compared with the European Society of Breast Cancer Specialists standard target. Frequencies and percentages were calculated and presented in tables. Binomial 95% of the rates for QI adherence were also calculated for each QI. RESULTS: One hundred four patients had a median age of 47.5 years (range 24-70 years). Applicable QIs were in the range of 5-15 with a mean of 9.66 per patient. Of 19 evaluable QIs, very high adherence rates were observed in six QIs, high adherence in three Qis, and low adherences in 10 QIs. High adherence rates were for QI 5 and QI 10a, which were 88.46% and 94.73%, respectively. The low compliance was for QI 1, QI 4a, QI 8, QI 9d, QI 10b, QI 11a, QI 11b, QI 13b, QI 13e, and 14b, which were 53.84%, 78.21%, 0%, 83.16%, 76.92%, 36.0%, 33.33%, 4.76%, 30.55%, and 10.81%, respectively. CONCLUSION: There are several QIs that have low levels of adherence in our setting and suggest that there is significant room for improvement. We will be continuing auditing these QIs regularly to improve our quality of care.

Disseminated blastomycosis in coalworkers' pneumoconiosis.

Blastomyces dermatitidis is a thermally dimorphic fungus that can cause pulmonary, extrapulmonary, or disseminated infections. Though it can infect both immune-competent and immunocompromised hosts, the disease can be severe in immunocompromised hosts. Exposure to silica dust is associated with silicosis, and this is associated with impaired immunity and an increased risk of mycobacterial and fungal infections. The fungal infections commonly associated with pneumoconiosis are pulmonary aspergillosis, histoplasmosis, coccidioidomycosis, and cryptococcosis. However, there is a dearth of data on the association of pneumoconiosis and blastomycosis. Clinical deterioration and new cavitary lesions in patients with pneumoconiosis should alert clinicians of new pulmonary infection. Traditional sputum sampling may lead to poor diagnostic yield, because the organism is frequently surrounded by a fibrotic wall. Aggressive diagnostic testing with lung or skin biopsies may be warranted. We present the first reported case of disseminated blastomycosis in a patient with coalworkers' pneumoconiosis.