Management of cerebrospinal fluid rhinorrhea as a rare complication of antiphospholipid syndrome.

Background: Antiphospholipid syndrome is a complex autoimmune condition associated with the formation of recurrent thrombosis in any vascular bed throughout the body. Jugular vein thrombosis is very rare with only a 0.9% occurrence and is not typically associated with cerebrospinal rhinorrhea as a result of raised intracranial pressure. Case Description: A 54-year-old patient presented with a 9-month history of cerebrospinal fluid (CSF) rhinorrhea and headache on a background of antiphospholipid syndrome. Investigations showed a superior vena cava (SVC) and right internal jugular vein (IJV) obstruction with moderately elevated intracranial venous pressures. Her magnetic resonance imaging (MRI) brain was consistent with a CSF leak. The patient underwent successful endovascular stenting of her obstructed SVC and right IJV followed by surgical repair of a herniating meningocele in the posterior left ethmoid air cells. Conclusion: CSF rhinorrhea is uncommon and never previously reported associated with SVC thrombosis induced by antiphospholipid syndrome. A combination of endovascular techniques and surgical repair is recommended for this challenging presentation.

Pore size estimation in axon-mimicking microfibers with diffusion-relaxation MRI.

PURPOSE: This study aims to evaluate two distinct approaches for fiber radius estimation using diffusion-relaxation MRI data acquired in biomimetic microfiber phantoms that mimic hollow axons. The methods considered are the spherical mean power-law approach and a T2-based pore size estimation technique. THEORY AND METHODS: A general diffusion-relaxation theoretical model for the spherical mean signal from water molecules within a distribution of cylinders with varying radii was introduced, encompassing the evaluated models as particular cases. Additionally, a new numerical approach was presented for estimating effective radii (i.e., MRI-visible mean radii) from the ground truth radii distributions, not reliant on previous theoretical approximations and adaptable to various acquisition sequences. The ground truth radii were obtained from scanning electron microscope images. RESULTS: Both methods show a linear relationship between effective radii estimated from MRI data and ground-truth radii distributions, although some discrepancies were observed. The spherical mean power-law method overestimated fiber radii. Conversely, the T2-based method exhibited higher sensitivity to smaller fiber radii, but faced limitations in accurately estimating the radius in one particular phantom, possibly because of material-specific relaxation changes. CONCLUSION: The study demonstrates the feasibility of both techniques to predict pore sizes of hollow microfibers. The T2-based technique, unlike the spherical mean power-law method, does not demand ultra-high diffusion gradients, but requires calibration with known radius distributions. This research contributes to the ongoing development and evaluation of neuroimaging techniques for fiber radius estimation, highlights the advantages and limitations of both methods, and provides datasets for reproducible research.

An efficient semi-supervised quality control system trained using physics-based MRI-artefact generators and adversarial training.

Large medical imaging data sets are becoming increasingly available. A common challenge in these data sets is to ensure that each sample meets minimum quality requirements devoid of significant artefacts. Despite a wide range of existing automatic methods having been developed to identify imperfections and artefacts in medical imaging, they mostly rely on data-hungry methods. In particular, the scarcity of artefact-containing scans available for training has been a major obstacle in the development and implementation of machine learning in clinical research. To tackle this problem, we propose a novel framework having four main components: (1) a set of artefact generators inspired by magnetic resonance physics to corrupt brain MRI scans and augment a training dataset, (2) a set of abstract and engineered features to represent images compactly, (3) a feature selection process that depends on the class of artefact to improve classification performance, and (4) a set of Support Vector Machine (SVM) classifiers trained to identify artefacts. Our novel contributions are threefold: first, we use the novel physics-based artefact generators to generate synthetic brain MRI scans with controlled artefacts as a data augmentation technique. This will avoid the labour-intensive collection and labelling process of scans with rare artefacts. Second, we propose a large pool of abstract and engineered image features developed to identify 9 different artefacts for structural MRI. Finally, we use an artefact-based feature selection block that, for each class of artefacts, finds the set of features that provide the best classification performance. We performed validation experiments on a large data set of scans with artificially-generated artefacts, and in a multiple sclerosis clinical trial where real artefacts were identified by experts, showing that the proposed pipeline outperforms traditional methods. In particular, our data augmentation increases performance by up to 12.5 percentage points on the accuracy, F1, F2, precision and recall. At the same time, the computation cost of our pipeline remains low - less than a second to process a single scan - with the potential for real-time deployment. Our artefact simulators obtained using adversarial learning enable the training of a quality control system for brain MRI that otherwise would have required a much larger number of scans in both supervised and unsupervised settings. We believe that systems for quality control will enable a wide range of high-throughput clinical applications based on the use of automatic image-processing pipelines.

Progressive loss of hearing and balance in superficial siderosis due to occult spinal dural defects.

PURPOSE: Superficial siderosis, a progressive, debilitating, neurological disease, often presents with bilateral impairment of auditory and vestibular function. We highlight that superficial siderosis is often due to a repairable spinal dural defect of the type that can also cause spontaneous intracranial hypotension. METHODS: Retrospective chart review of five patients presenting with moderate to severe, progressive bilateral sensorineural hearing loss as well as vestibular loss. All patients had developed superficial siderosis from spinal dural defects: three after trauma, one after spinal surgery and one from a thoracic discogenic microspur. RESULTS: The diagnosis was made late in all five patients; despite surgical repair in four, hearing and vestibular loss failed to improve. CONCLUSIONS: In patients presenting with progressive bilateral sensorineural hearing loss, superficial siderosis should be considered as a possible cause. If these patients also have bilateral vestibular loss, cerebellar impairment and anosmia, then the diagnosis is likely and the inevitable disease progress might be halted by finding and repairing the spinal dural defect.

An Ocular Chameleon.

Patients presenting with transient visual loss is common in emergency departments. Neurologists, ophthalmologists and emergency care physicians may be called upon to evaluate such patients. Monocular visual loss should be differentiated from the binocular involvement as the oetologies, investigations and management of such patients differ considerably. We report a case of monocular visual loss that involved predominantly one eye but affected the other side independently, albeit less frequently. A meticulous history, thorough general, neurological and ophthalmological examinations are necessary in such patients to identify the cause and to treat appropriately. Ocular ischemic syndrome (OIS) is due to chronic hypoperfusion of the structures supplied by ophthalmic artery leading to monocular visual loss. Stenosis of the ipsilateral internal carotid artery from a variety of causes is the main underlying mechanism. The first case of OIS was reported by Hedges in 1963 and the term was coined later by Barry and Magargal. Ocular ischemic syndrome is an important differential diagnosis to consider especially in older people and those with vascular risk factors. An overview of important differential diagnosis, clinical features and treatment of OIC are discussed in this article. A multidisciplinary team is optimal for the management of ocular ischemic syndrome.

Evaluation of Dynamic Contrast-Enhanced MRI Measures of Lung Congestion and Endothelial Permeability in Heart Failure: A Prospective Method Validation Study.

BACKGROUND: Methods for accurate quantification of lung fluid in heart failure (HF) are needed. Dynamic contrast-enhanced (DCE)-MRI may be an appropriate modality. PURPOSE: DCE-MRI evaluation of fraction of fluid volume in the interstitial lung space (ve ) and vascular permeability (Ktrans ). STUDY TYPE: Prospective, single-center method validation. POPULATION: Seventeen evaluable healthy volunteers (HVs), 12 participants with HF, and 3 with acute decompensated HF (ADHF). FIELD STRENGTH/SEQUENCE: T1 mapping (spoiled gradient echo variable flip angle acquisition) followed by dynamic series (three-dimensional spoiled gradient-recalled echo acquisitions [constant echo time, repetition time, and flip angle at 1.5 T]). ASSESSMENT: Three whole-chest scans were acquired: baseline (Session 1), 1-week later (Session 2), following exercise (Session 3). Extended Tofts model quantified ve and Ktrans (voxel-wise basis); total lung median measures were extracted and fitted via repeat measure analysis of variance (ANOVA) model. Patient tolerability of the scanning protocol was assessed. STATISTICAL TESTS: This was constructed as an experimental medicine study. PRIMARY ENDPOINTS: Ktrans and ve at baseline (HV vs. HF), change in Ktrans and ve following exercise, and following lung congestion resolution (ADHF). Ktrans and ve were fitted separately using ANOVA. Secondary endpoint: repeatability, that is, within-participant variability in ve and Ktrans between sessions (coefficient of variation estimated via mixed effects model). RESULTS: There was no significant difference in mean Ktrans between HF and HV (P ≤ 0.17): 0.2216 minutes-1 and 0.2353 minutes-1 (Session 1), 0.2044 minutes-1 and 0.2567 minutes-1 (Session 2), 0.1841 minutes-1 and 0.2108 minutes-1 (Session 3), respectively. ve was greater in the HF group (all scans, P ≤ 0.02). Results were repeatable between Sessions 1 and 2; mean values for HF and HV were 0.4946 and 0.3346 (Session 1), 0.4353 and 0.3205 (Session 2), respectively. There was minimal difference in Ktrans or ve between scans for participants with ADHF (small population precluded significance testing). Scanning was well tolerated. DATA CONCLUSION: While no differences were detected in Ktrans , ve was greater in chronic HF patients vs. HV, augmented beyond plasma and intracellular volume. DCE-MRI is a valuable diagnostic and physiologic tool to evaluate changes in fluid volume in the interstitial lung space associated with symptomatic HF. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Distribution of biomass dynamics in relation to tree size in forests across the world.

Tree size shapes forest carbon dynamics and determines how trees interact with their environment, including a changing climate. Here, we conduct the first global analysis of among-site differences in how aboveground biomass stocks and fluxes are distributed with tree size. We analyzed repeat tree censuses from 25 large-scale (4-52 ha) forest plots spanning a broad climatic range over five continents to characterize how aboveground biomass, woody productivity, and woody mortality vary with tree diameter. We examined how the median, dispersion, and skewness of these size-related distributions vary with mean annual temperature and precipitation. In warmer forests, aboveground biomass, woody productivity, and woody mortality were more broadly distributed with respect to tree size. In warmer and wetter forests, aboveground biomass and woody productivity were more right skewed, with a long tail towards large trees. Small trees (1-10 cm diameter) contributed more to productivity and mortality than to biomass, highlighting the importance of including these trees in analyses of forest dynamics. Our findings provide an improved characterization of climate-driven forest differences in the size structure of aboveground biomass and dynamics of that biomass, as well as refined benchmarks for capturing climate influences in vegetation demographic models.

Bias, Repeatability and Reproducibility of Liver T1 Mapping With Variable Flip Angles.

BACKGROUND: Three-dimensional variable flip angle (VFA) methods are commonly used for T1 mapping of the liver, but there is no data on the accuracy, repeatability, and reproducibility of this technique in this organ in a multivendor setting. PURPOSE: To measure bias, repeatability, and reproducibility of VFA T1 mapping in the liver. STUDY TYPE: Prospective observational. POPULATION: Eight healthy volunteers, four women, with no known liver disease. FIELD STRENGTH/SEQUENCE: 1.5-T and 3.0-T; three-dimensional steady-state spoiled gradient echo with VFAs; Look-Locker. ASSESSMENT: Traveling volunteers were scanned twice each (30 minutes to 3 months apart) on six MRI scanners from three vendors (GE Healthcare, Philips Medical Systems, and Siemens Healthineers) at two field strengths. The maximum period between the first and last scans among all volunteers was 9 months. Volunteers were instructed to abstain from alcohol intake for at least 72 hours prior to each scan and avoid high cholesterol foods on the day of the scan. STATISTICAL TESTS: Repeated measures ANOVA, Student t-test, Levene's test of variances, and 95% significance level. The percent error relative to literature liver T1 in healthy volunteers was used to assess bias. The relative error (RE) due to intrascanner and interscanner variation in T1 measurements was used to assess repeatability and reproducibility. RESULTS: The 95% confidence interval (CI) on the mean bias and mean repeatability RE of VFA T1 in the healthy liver was 34 ± 6% and 10 ± 3%, respectively. The 95% CI on the mean reproducibility RE at 1.5 T and 3.0 T was 29 ± 7% and 25 ± 4%, respectively. DATA CONCLUSION: Bias, repeatability, and reproducibility of VFA T1 mapping in the liver in a multivendor setting are similar to those reported for breast, prostate, and brain. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Demographic composition, not demographic diversity, predicts biomass and turnover across temperate and tropical forests.

The growth and survival of individual trees determine the physical structure of a forest with important consequences for forest function. However, given the diversity of tree species and forest biomes, quantifying the multitude of demographic strategies within and across forests and the way that they translate into forest structure and function remains a significant challenge. Here, we quantify the demographic rates of 1961 tree species from temperate and tropical forests and evaluate how demographic diversity (DD) and demographic composition (DC) differ across forests, and how these differences in demography relate to species richness, aboveground biomass (AGB), and carbon residence time. We find wide variation in DD and DC across forest plots, patterns that are not explained by species richness or climate variables alone. There is no evidence that DD has an effect on either AGB or carbon residence time. Rather, the DC of forests, specifically the relative abundance of large statured species, predicted both biomass and carbon residence time. Our results demonstrate the distinct DCs of globally distributed forests, reflecting biogeography, recent history, and current plot conditions. Linking the DC of forests to resilience or vulnerability to climate change, will improve the precision and accuracy of predictions of future forest composition, structure, and function.

Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study.

Perianal Crohn's Disease (pCD) is a common manifestation of Crohn's Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn's Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.

Race and Gender Disparity in the Surgical Management of Hepatocellular Cancer: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Program Registry.

BACKGROUND: The existence of race and gender disparity has been described in numerous areas of medicine. The management of hepatocellular cancer is no different, but in no other area of medicine, is the treatment algorithm more complicated by local, regional, and national health care distribution policy. METHODS: Multivariate logistic regression and Cox-regression were utilized to analyze the treatment of patients with hepatocellular cancer registered in SEER between 1999 and 2013 to determine the incidence and effects of racial and gender disparity. Odd ratios (OR) are relative to Caucasian males, SEER region, and tumor characteristics. RESULTS: The analysis of 57,449 patients identified the minority were female (25.31%) and African-American (16.26%). All tumor interventions were protective (p < 0.001) with respect to survival. The mean survival for all registered patients was 13.01 months with conditional analysis, confirming that African-American men were less likely to undergo ablation, resection, or transplantation (p < 0.001). Women were more likely to undergo resection (p < 0.001). African-American women had an equivalent OR for resection but had a significantly lower transplant rate (p < 0.001). CONCLUSIONS: Utilizing SEER data as a surrogate for patient navigation in the treatment of hepatocellular cancer, our study identified not only race but gender bias with African-American women suffering the greatest. This is underscored by the lack of navigation of African-Americans to any therapy and a significant bias to navigate female patients to resection potentially limiting subsequent access to definitive therapy namely transplantation.

Mycorrhizal type influences plant density dependence and species richness across 15 temperate forests.

Recent studies suggest that the mycorrhizal type associated with tree species is an important trait influencing ecological processes such as response to environmental conditions and conspecific negative density dependence (CNDD). However, we lack a general understanding of how tree mycorrhizal type influences CNDD strength and the resulting patterns of species abundance and richness at larger spatial scales. We assessed 305 species across 15 large, stem-mapped, temperate forest dynamics plots in Northeastern China and North America to explore the relationships between tree mycorrhizal type and CNDD, species abundance, and species richness at a regional scale. Tree species associated with arbuscular mycorrhizal (AM) fungi showed a stronger CNDD and a more positive relationship with species abundance than did tree species associated with ectomycorrhizal (ECM) fungi. For each plot, both basal area and stem abundance of AM tree species was lower than that of ECM tree species, suggesting that AM tree species were rarer than ECM tree species. Finally, ECM tree dominance showed a negative effect on plant richness across plots. These results provide evidence that tree mycorrhizal type plays an important role in influencing CNDD and species richness, highlighting this trait as an important factor in structuring plant communities in temperate forests.

Chemical novelty facilitates herbivore resistance and biological invasions in some introduced plant species.

Ecological release from herbivory due to chemical novelty is commonly predicted to facilitate biological invasions by plants, but has not been tested on a community scale. We used metabolomics based on mass spectrometry molecular networks to assess the novelty of foliar secondary chemistry of 15 invasive plant species compared to 46 native species at a site in eastern North America. Locally, invasive species were more chemically distinctive than natives. Among the 15 invasive species, the more chemically distinct were less preferred by insect herbivores and less browsed by deer. Finally, an assessment of invasion frequency in 2,505 forest plots in the Atlantic coastal plain revealed that, regionally, invasive species that were less preferred by insect herbivores, less browsed by white-tailed deer, and chemically distinct relative to the native plant community occurred more frequently in survey plots. Our results suggest that chemically mediated release from herbivores contributes to many successful invasions.

Diffusion model comparison identifies distinct tumor sub-regions and tracks treatment response.

PURPOSE: MRI biomarkers of tumor response to treatment are typically obtained from parameters derived from a model applied to pre-treatment and post-treatment data. However, as tumors are spatially and temporally heterogeneous, different models may be necessary in different tumor regions, and model suitability may change over time. This work evaluates how the suitability of two diffusion-weighted (DW) MRI models varies spatially within tumors at the voxel level and in response to radiotherapy, potentially allowing inference of qualitatively different tumor microenvironments. METHODS: DW-MRI data were acquired in CT26 subcutaneous allografts before and after radiotherapy. Restricted and time-independent diffusion models were compared, with regions well-described by the former hypothesized to reflect cellular tissue, and those well-described by the latter expected to reflect necrosis or oedema. Technical and biological validation of the percentage of tissue described by the restricted diffusion microstructural model (termed %MM) was performed through simulations and histological comparison. RESULTS: Spatial and radiotherapy-related variation in model suitability was observed. %MM decreased from a mean of 64% at baseline to 44% 6 days post-radiotherapy in the treated group. %MM correlated negatively with the percentage of necrosis from histology, but overestimated it due to noise. Within MM regions, microstructural parameters were sensitive to radiotherapy-induced changes. CONCLUSIONS: There is spatial and radiotherapy-related variation in different models' suitability for describing diffusion in tumor tissue, suggesting the presence of different and changing tumor sub-regions. The biological and technical validation of the proposed %MM cancer imaging biomarker suggests it correlates with, but overestimates, the percentage of necrosis.

Bile Leak Reduction with Laparoscopic Versus Open Liver Resection: A Multi-institutional Propensity Score-Adjusted Multivariable Regression Analysis.

INTRODUCTION: The reported rate of postoperative bile leak is variable between 3 and 33%. Recent data would suggest a minimally invasive approach to liver surgery has decreased this incidence. METHODS: This multi-institutional case-control study utilized databases from three high-volume surgeons. All consecutive open and minimally invasive liver resection cases were analyzed in a propensity score-adjusted multivariable regression. A p value < 0.05 was considered significant. RESULTS: In 1388 consecutive liver resections, the average age was 56.9 ± 14.0 years, 730 (52.59%) were male gender, and 599 (43.16%) underwent minimally invasive liver resection. Thirty-nine (2.81%) in the series were identified with post-resection bile duct leaks. Leaks were associated with major resections and increased blood loss (p < 0.05). Propensity score-adjusted multivariable regression identified minimally invasive liver resection significantly and independently reduced the odds of bile duct leak (OR 0.48, p = 0.046) even controlling for BMI, ASA, cirrhosis, major resection, and resection year. CONCLUSIONS: Our data suggest the incidence of bile leaks in a large-volume center series is far less than previously reported and that a minimally invasive approach to liver resection reduces the incidence of postoperative bile leak.

Temporal population variability in local forest communities has mixed effects on tree species richness across a latitudinal gradient.

Among the local processes that determine species diversity in ecological communities, fluctuation-dependent mechanisms that are mediated by temporal variability in the abundances of species populations have received significant attention. Higher temporal variability in the abundances of species populations can increase the strength of temporal niche partitioning but can also increase the risk of species extinctions, such that the net effect on species coexistence is not clear. We quantified this temporal population variability for tree species in 21 large forest plots and found much greater variability for higher latitude plots with fewer tree species. A fitted mechanistic model showed that among the forest plots, the net effect of temporal population variability on tree species coexistence was usually negative, but sometimes positive or negligible. Therefore, our results suggest that temporal variability in the abundances of species populations has no clear negative or positive contribution to the latitudinal gradient in tree species richness.

Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease.

BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. METHODS: We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using 23Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. RESULTS: CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = -0.5 ± 1.0 L; p = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4-31.3] vs. HC = 18.4 mmol/L [16.6-21.3]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02). CONCLUSION: Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.