Differentiation between normal and metastatic lymph nodes in patients with skin melanoma: Preliminary findings using a DIXON-based whole-body MRI approach.

Purpose: Metastatic melanoma lymph nodes (MMLns) might be challenging to detect on MR-WBI, as both MMLns and normal lymph nodes (NLns) can show restricted water diffusion. Our purpose is to assess the potential contribution of the DIXON sequence in differentiating MMLns from NLns. Material and methods: We followed a cohort of 107 patients with stage IIIb/c and IV skin melanoma for 32 months using MR-WBI with DIXON, STIR, and DWI/ADC sequences. We compared signal intensity (SI) values of MMLns and NLns in the four series of the DIXON sequence (in/out-of-phase, fat_only, and water_only series). The fat fraction (SIfat_only/SIin) and the long:short axis ratio of MMLns were calculated. The fat fraction was also calculated in the fatty hila of NLns. Results: All MMLns (8 from 7 patients) showed SIout>SIin with a mean fat fraction of 10%. In 40 normal fatty hila (25 patients), the proportion of SIout>SIin was 100% and mean fat fraction was 89% (p<0.001 for fat fraction, Mann-Whitney U-test). In the cortex of NLns, a SIout>SIin pattern was identified in 41/113 cases from 19/40 patients. The median long:short axis ratio in MMLns was 1.13 (range 1.03-1.25). Conclusion: The combination of three features of MMLns (SIout>SIin, low-fat fraction and rounded shape) might hold promise in differentiating NLns from MMLns in patients with skin melanoma. Further research is warranted due to the small number of MMLns in our cohort.

Ketogenic propensity is differentially related to lipid-induced hepatic and peripheral insulin resistance.

AIM: Determine the ketogenic response (ß-hydroxybutyrate, a surrogate of hepatic ketogenesis) to a controlled lipid overload in humans. METHODS: In total, nineteen young, healthy adults (age: 28.4 ± 1.7 years; BMI: 22.7 ± 0.3 kg/m2 ) received either a 12 h overnight lipid infusion or saline in a randomized, crossover design. Plasma ketones and inflammatory markers were quantified by colorimetric and multiplex assays. Hepatic and peripheral insulin sensitivity was assessed by the hyperinsulinemic-euglycemic clamp. Skeletal muscle biopsies were obtained to quantify gene expression related to ketone body metabolism and inflammation. RESULTS: By design, the lipid overload-induced hepatic (50%, p < 0.001) and peripheral insulin resistance (73%, p < 0.01) in healthy adults. Ketones increased with hyperlipidemia and were subsequently reduced with hyperinsulinemia during the clamp procedure (Saline: Basal = 0.22 mM, Insulin = 0.07 mM; Lipid: Basal = 0.78 mM, Insulin = 0.51 mM; 2-way ANOVA: Lipid p < 0.001, Insulin p < 0.001, Interaction p = 0.07). In the saline control condition, ketones did not correlate with hepatic or peripheral insulin sensitivity. Conversely, in the lipid condition, ketones were positively correlated with hepatic insulin sensitivity (r = 0.59, p < 0.01), but inversely related to peripheral insulin sensitivity (r = -0.64, p < 0.01). Hyperlipidemia increased plasma inflammatory markers, but did not impact skeletal muscle inflammatory gene expression. Gene expression related to ketone and fatty acid metabolism in skeletal muscle increased in response to hyperlipidemia. CONCLUSION: This work provides important insight into the role of ketones in human health and suggests that ketone body metabolism is altered at the onset of lipid-induced insulin resistance.

Preclinical validation of the advection diffusion flow estimation method using computational patient specific coronary tree phantoms.

Coronary computed tomography angiography (CCTA) does not allow the quantification of reduced blood flow due to coronary artery disease (CAD). In response, numerical methods based on the CCTA image have been developed to compute coronary blood flow and assess the impact of disease. However to compute blood flow in the coronary arteries, numerical methods require specification of boundary conditions that are difficult to estimate accurately in a patient-specific manner. We describe herein a new noninvasive flow estimation method, called Advection Diffusion Flow Estimation (ADFE), to compute coronary artery flow from CCTA to use as boundary conditions for numerical models of coronary blood flow. ADFE uses image contrast variation along the tree-like structure to estimate flow in each vessel. For validating this method we used patient specific software phantoms on which the transport of contrast was simulated. This controlled validation setting enables a direct comparison between estimated flow and actual flow and a detailed investigation of factors affecting accuracy. A total of 10 CCTA image data sets were processed to extract all necessary information for simulating contrast transport. A spectral element method solver was used for computing the ground truth simulations with high accuracy. On this data set, the ADFE method showed a high correlation coefficient of 0.998 between estimated flow and the ground truth flow together with an average relative error of only 1 % . Comparing the ADFE method with the best method currently available (TAFE) for image-based blood flow estimation, which showed a correlation coefficient of 0.752 and average error of 20 % , it can be concluded that the ADFE method has the potential to significantly improve the quantification of coronary artery blood flow derived from contrast gradients in CCTA images.

Longitudinal changes in global structural brain connectivity and cognitive performance in former hospitalized COVID-19 survivors: an exploratory study.

BACKGROUND: Long-term sequelae of COVID-19 can result in reduced functionality of the central nervous system and substandard quality of life. Gaining insight into the recovery trajectory of admitted COVID-19 patients on their cognitive performance and global structural brain connectivity may allow a better understanding of the diseases' relevance. OBJECTIVES: To assess whole-brain structural connectivity in former non-intensive-care unit (ICU)- and ICU-admitted COVID-19 survivors over 2 months following hospital discharge and correlate structural connectivity measures to cognitive performance. METHODS: Participants underwent Magnetic Resonance Imaging brain scans and a cognitive test battery after hospital discharge to evaluate structural connectivity and cognitive performance. Multilevel models were constructed for each graph measure and cognitive test, assessing the groups' influence, time since discharge, and interactions. Linear regression models estimated whether the graph measurements affected cognitive measures and whether they differed between ICU and non-ICU patients. RESULTS: Six former ICU and six non-ICU patients completed the study. Across the various graph measures, the characteristic path length decreased over time (ß = 0.97, p = 0.006). We detected no group-level effects (ß = 1.07, p = 0.442) nor interaction effects (ß = 1.02, p = 0.220). Cognitive performance improved for both non-ICU and ICU COVID-19 survivors on four out of seven cognitive tests 2 months later (p < 0.05). CONCLUSION: Adverse effects of COVID-19 on brain functioning and structure abate over time. These results should be supported by future research including larger sample sizes, matched control groups of healthy non-infected individuals, and more extended follow-up periods.

Rationale and study design for lifestyle intervention in preparation for pregnancy (LIPP): A randomized controlled trial.

INTRODUCTION: Maternal obesity increases neonatal risk for obesity and metabolic syndrome later in life. Prior attempts to break this intergenerational obesity cycle by limiting excessive gestational weight gain have failed to reduce neonatal adiposity. Alternatively, pre-conception lifestyle interventions may improve the in utero metabolic milieu during early pregnancy leading to improved fetal outcomes. This randomized controlled trial (RCT) is evaluating whether a lifestyle intervention to reduce weight and improve maternal metabolism in preparation for pregnancy (LIPP) attenuates neonatal adiposity, compared to standard medical advice. MATERIAL AND METHODS: Overweight/class 1 obese women after a previous pregnancy, ~12 weeks postpartum, preparing for a subsequent pregnancy, will be block randomized (1:1) to either LIPP or standard of care in a parallel design. Randomization is stratified by lactation status and overweight vs. class 1 obesity. The LIPP program consists of intensive short-term weight loss followed by weight maintenance until conception using supervised exercise and a low glycemic Mediterranean diet. PRIMARY OUTCOMES: Group differences in neonatal adiposity at birth assessed by PEA POD and placental mitochondrial lipid metabolism. SECONDARY OUTCOMES: Group differences in maternal pregravid and gestational body composition, insulin sensitivity, ß-cell function, fasting metabolic and inflammatory biomarkers, and overall quality of life. Exploratory outcomes include umbilical cord blood insulin resistance, lipid profile and inflammation. DISCUSSION: This RCT will determine the efficacy of maternal weight loss prior to pregnancy on reducing neonatal adiposity. Findings may change standard obstetrical care by providing Level 1 evidence on lifestyle interventions improving neonatal outcomes for women planning for pregnancy. CLINICAL TRIAL REGISTRATION: NCT03146156.

Why do anti-inflammatory signals of bone marrow-derived stromal cells improve neurodegenerative conditions where anti-inflammatory drugs fail?

Neurodegenerative disorders share the final degenerative pathway, the inflammation-induced apoptosis and/or necrosis, irrespective of their etiology, be it of acute and chronic traumatic, vascular and idiopathic origin. Although disease-modifying strategies are an unmet need in these disorders, lately, (pre)clinical studies suggested favorable effects after an intervention with bone marrow-derived stromal cells (bm-SC). Recent interventions with intrathecal transplantation of these cells in preclinical rodent models improved the functional outcome and reduced the inflammation, but not anti-inflammatory drugs. The benefit of bm-SCs was demonstrated in rats with an acute (traumatic spinal cord injury, tSCI) and in mice with a chronic [amyotrophic lateral sclerosis (ALS)-like FUS 1-358 or SOD1-G93-A mutation] neurodegenerative process. Bm-SCs, were found to modify underlying disease processes, to reduce final clinical SCI-related outcome, and to slow down ALS-like clinical progression. After double-blind interventions with bm-SC transplantations, Vehicle (placebo), and (non)steroidal anti-inflammatory drugs (Methylprednisolone, Riluzole, Celecoxib), clinical, histological and histochemical findings, serum/spinal cytokines, markers for spinal microglial activation inclusive, evidenced the cell-to-cell action of bm-SCs in both otherwise healthy and immune-deficient tSCI-rats, as well as wild-type and FUS/SOD1-transgenic ALS-like mice. The multi-pathway hypothesis of the cell-to-cell action of bmSCs, presumably using extracellular vesicles (EVs) as carriers of messages in the form of RNAs, DNA, proteins, and lipids rather than influencing a single inflammatory pathway, could be justified by the reported differences of cytokines and other chemokines in the serum and spinal tissue. The mode of action of bm-SCs is hypothesized to be associated with its dedicated adjustment of the pro-apoptotic glycogen synthase kinase-3ß level towards an anti-apoptotic level whereas their multi-pathway hypothesis seems to be confirmed by the decreased levels of the pro-inflammatory interleukin (IL)-1ß and tumor necrosis factor (TNF) as well as the level of the marker of activated microglia, ionized calcium binding adapter (Iba)-1 level.

Synthetic MRI of Preterm Infants at Term-Equivalent Age: Evaluation of Diagnostic Image Quality and Automated Brain Volume Segmentation.

BACKGROUND AND PURPOSE: Neonatal MR imaging brain volume measurements can be used as biomarkers for long-term neurodevelopmental outcome, but quantitative volumetric MR imaging data are not usually available during routine radiologic evaluation. In the current study, the feasibility of automated quantitative brain volumetry and image reconstruction via synthetic MR imaging in very preterm infants was investigated. MATERIALS AND METHODS: Conventional and synthetic T1WIs and T2WIs from 111 very preterm infants were acquired at term-equivalent age. Overall image quality and artifacts of the conventional and synthetic images were rated on a 4-point scale. Legibility of anatomic structures and lesion conspicuity were assessed on a binary scale. Synthetic MR volumetry was compared with that generated via MANTiS, which is a neonatal tissue segmentation toolbox based on T2WI. RESULTS: Image quality was good or excellent for most conventional and synthetic images. The 2 methods did not differ significantly regarding image quality or diagnostic performance for focal and cystic WM lesions. Dice similarity coefficients had excellent overlap for intracranial volume (97.3%) and brain parenchymal volume (94.3%), and moderate overlap for CSF (75.6%). Bland-Altman plots demonstrated a small systematic bias in all cases (1.7%-5.9%) CONCLUSIONS: Synthetic T1WI and T2WI sequences may complement or replace conventional images in neonatal imaging, and robust synthetic volumetric results are accessible from a clinical workstation in less than 1 minute. Via the above-described methods, volume assessments could be routinely used in daily clinical practice.

Alterations in the fronto-limbic network and corpus callosum in borderline-personality disorder.

Neuroimaging research provides evidence of grey matter changes in the prefrontal-limbic network in borderline personality disorder (BPD), yet research scarcely examines the white matter (WM) within this circuitry. The present study aimed to explore WM in prefrontal-limbic brain networks within BPD. Quantitative diffusion tensor imaging (DTI-MRI) measures of fractional anisotropy (FA) and mean diffusion (MD) were used to analyze the neural pathways in fifteen individuals with BPD (M = 25, SD = 6.76), in comparison to thirteen healthy individuals (M = 27.92, SD = 8.41). Quantitative DTI-MRI measures of FA and MD were evaluated for the cingulum, the fornix, the corpus callosum (CC), the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF). Lower FA values for both the left and the right cingulum, the genu, body, and splenium of the CC, left ILF and right SLF were found in BPD, compared to healthy individuals. MD values were higher for the genu and splenium of the CC in BPD. The findings indicate that a large-scale emotional brain network is affected in BPD with alterations in MD and FA of WM prefrontal-limbic pathways of the heteromodal association cortex involved in emotion processing and emotion regulation.

Production and performance of bio-based mineral fertilizers from agricultural waste using ammonia (stripping-)scrubbing technology.

Development and optimization of nutrient recovery technologies for agricultural waste is on the rise. The full scale adoption of these technologies is however hindered by complex legal aspects that result from lack of science-based knowledge on characterization and fertilizer performance of recovered end-products. Ammonium sulfate (AS) and ammonium nitrate (AN), end-products of (stripping-)scrubbing technology, are currently listed by the European Commission as high priority products with the potential of replacing synthetic N fertilizers. The legal acceptance of AS and AN will be highly dependent on critical mass of scientific evidence. This study describes four different (stripping-)scrubbing pathways to recover ammonia with an aim to (i) assess product characteristics of ammonium nitrate (AN) and ammonium sulfate (AS) produced from different installations, (ii) evaluate fertilizer performance of recovered end-products in greenhouse (Lactuca sativa L.) and full field (Zea mays L.) scale settings and (iii) compare the observed performances with other published studies. Results have indicated that the recovered products might have a different legal status, as either mineral N fertilizer or yet as animal manure, depending on the used (stripping-)scrubbing process pathway. Nevertheless, no significant differences in respect to product characterization and fertilizer performance of AN and AS have been identified in this study as compared to the conventional use of synthetic N fertilizers. This indicates that recovered AS and AN are valuable N sources and therefore might be used as N fertilizers in crop cultivation.

Ultrasonographic evaluation of the distance between the flexor pollicis longus tendon and volar prominence of the plate as a function of volar plate positioning and pronator quadratus repair - A cadaver study.

Flexor tendon injury after volar plating of distal radius fractures is due to friction against the plate. To assess this risk, the distance between the flexor pollicis longus (FPL) and the volar prominence of the plate was measured with ultrasonography under various conditions: a standard plate fixed proximal or distal to the watershed line and a low-profile volar rim plate, with and without transection of the pronator quadratus (PQ). Distance from the FPL to the volar prominence of the plate decreased significantly when the PQ was cut and when a standard plate was placed distal to the watershed line, with the tendon often bulging over the plate. No statistical difference was measured between a volar rim plate and a standard plate distal to the watershed line. Our results confirm the importance of positioning the volar plate proximal to the watershed line and of repairing the PQ.

Radiography of the distal extremity of the manus in the donkey foal: Normal images and quantitative characterization from birth to 2 years of age: A pilot study.

This study describes a radiographic survey of the anatomical development of the distal extremity of the manus in the donkey from 0 to 2 years of age. The right distal limb of 10 donkey foals, born in the spring of 2012, underwent radiographs every month for the first 6 months of age and every 3 months during the following 18 months. Latero-medial radiographs with and without barium marker at the coronary band and dorso-palmar radiographs with both front feet in weight bearing were obtained. The distal physis of the third metacarpal bone and the proximal physis of the proximal phalanx (phalanx proximalis) were closed at the mean age of 18.6 months. The distal physis of the proximal phalanx appeared as a clear radiolucent line at 2 weeks of age and was still subtly visible in some donkeys at 24 months. The proximal physis of the middle phalanx (phalanx media) was closed at the mean age of 16.7 months. The distal physis of this phalanx was visible at birth, but closed at 4 days. The distal phalanx (phalanx distalis) was triangular at birth. At the age of 20-21 months, the palmar processes (processus palmares) were both developed. The navicular bone (os sesamoideum distalis) was developed at the mean age of 9 months. The proximal sesamoid bones (ossa sesamoidea proximalia) were seen in continuously development during the 24 months. It seems that the physes in the distal extremity of the manus in the donkey close at an older age than the physes in the horse.

The imaging findings of impingement syndromes of the lower limb.

In this article we provide an overview of impingement syndromes of the lower limb. At the level of the hip, femoroacetabular and ischiofemoral impingement are recognised. At the level of the knee, we discuss Hoffa's fat pad impingement, suprapatellar fat pad impingement, pericruciate impingement, and iliotibial band syndrome. The impingement syndromes associated with anterior cruciate ligament (ACL) repair and intercondylar osteophytes are also illustrated. Most impingement syndromes are described at the level of the ankle. These include, anterior, anterolateral, posterior, anteromedial, posterior, and posterolateral impingement. For these conditions, we describe the best technique and expected imaging findings. It should be kept in mind that many of these findings have been observed in the asymptomatic population. Impingement is essentially a clinical diagnosis and imaging findings should be considered as supportive elements for this clinical diagnosis.

Evidence of increased axillary blood flow velocity without increased handgrip strength and endurance in persons with a fibromuscular axillary arch.

BACKGROUND: The purpose of this in vivo study was to compare axillary artery blood flow velocity, and maximal handgrip strength and endurance performance in young subjects with and without an axillary arch (AA). MATERIALS AND METHODS: One hundred and fifty-six young adults were screened for the presence of an AA on their dominant arm side. After physical examination subjects were checked using diagnostic echography for the presence of an AA. Sixteen subjects with an AA and 15 without an AA had their axillary artery peak systolic velocity quantified in 3 different arm positions using Doppler ultrasound. Maximal handgrip strength and endurance performance was quantified in the same positions using a functional rehabilitation system. RESULTS: Mean peak systolic velocity was significantly higher in the AA group compared to controls in abduction/external rotation of the arm during muscle relaxation (p = 0.003) and contraction (p = 0.01). No significant differences between groups were found for maximal handgrip strength and endurance performance. CONCLUSIONS: This study provides evidence for a transient axillary artery compression by the AA in a throwing position. This is not reinforced by additional contraction of the shoulder muscles along with the AA. Axillary artery compression does not influence maximal handgrip strength and endurance performance in symptom-free young adults.

REPORT OF A RARE ANATOMIC VARIANT: LEFT UPPER LOBE PARTIAL ANOMALOUS PULMONARY VENOUS RETURN.

We report the CT findings in a case of partial anomalous pulmonary venous return (PAPVR) from the left upper lobe in an adult. PAPVR is an anatomic variant in which one to three pulmonary veins drain into the right atrium or its tributaries, rather than into the left atrium. This results in a left-to-right shunt with varying clinical presentation. These can range from asymptomatic patients to advanced cardiac failure.

Comparison of ventilation-perfusion single-photon emission computed tomography (V/Q SPECT) versus dual-energy CT perfusion and angiography (DECT) after 6 months of pulmonary embolism (PE) treatment.

BACKGROUND: The natural evolution of treated symptomatic pulmonary embolism shows often incomplete resolution of pulmonary thrombi. The prevalence of perfusion defects depend on the image modality used. This study directly compares V/Q SPECT with DECT. METHODS: A single-center prospective observational cohort study of patients with intermediate risk PE, reassessed at the end of treatment with V/Q SPECT. Abnormal V/Q SPECT images were compared with DECT. RESULTS: We compared DECT en V/Q SPECT in 28 consecutive patients with persistent V/Q mismatch on V/Q SPECT, 13 men and 15 woman, mean age 60 (+17), range 23-82 year. One patient was excluded from the final analysis due to inferior quality DECT. In 18/27 (66.7%) the results were concordant between CTPA (persistent embolus visible), DECT (segmentary defects on iodine map) and V/Q SPECT (segmentary ventilation-perfusion mismatch). In 3/18 (11.1% of the total group) the partialy matched V/Q SPECT defect could be explained on DECT lung images by lung infarction. In 6/27 (22.1%) only hypoperfusion was seen on DECT iodine map. In 3/27 (11.1%) results were discordant between V/Q SPECT and DECT images. CONCLUSION: Six months after diagnosis of first or recurrent PE, residual pulmonary perfusion-defects encountered on V/Q-SPECT corresponds in the majority of patients with chronic thromboembolic disease seen on DECT. In 22.1% of patients V/Q SPECT mismatch only corresponds with hypoperfusion on iodine map DECT scan. Some (11.1%) of the chronic thromboembolic lesions seen on V/Q SPECT can not be explained by DECT results.

Fetuin-A: a novel link between obesity and related complications.

Fetuin-A (FetA) is a 64-kDa glycoprotein that is secreted from both the liver and adipose tissue. Circulating FetA is elevated in obesity and related disorders including type 2 diabetes mellitus, nonalcoholic fatty liver disease and the metabolic syndrome; and a FetA-related parameter, caliciprotein particle, is highly relevant to vascular calcification in overweight/obese patients with chronic kidney disease. FetA level is also associated with impaired insulin sensitivity and glucose tolerance. Accumulating evidence suggests that elevated FetA level causes impaired glycemic control, as FetA has been implicated in impairment of insulin receptor signaling, toll-like receptor 4 activation, macrophage migration and polarization, adipocyte dysfunction, hepatocyte triacylglycerol accumulation and liver inflammation and fibrosis. Weight loss, aerobic exercise, metformin and pioglitazone have each been shown to be effective for reducing FetA level.