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Differentiation of benign and malignant lymph nodes in pediatric patients on ferumoxytol-enhanced PET/MRI.
Muehe, AM, Siedek, F, Theruvath, AJ, Seekins, J, Spunt, SL, Pribnow, A, Hazard, FK, Liang, T, Daldrup-Link, H
Theranostics. 2020;(8):3612-3621
Abstract
The composition of lymph nodes in pediatric patients is different from that in adults. Most notably, normal lymph nodes in children contain less macrophages. Therefore, previously described biodistributions of iron oxide nanoparticles in benign and malignant lymph nodes of adult patients may not apply to children. The purpose of our study was to evaluate if the iron supplement ferumoxytol improves the differentiation of benign and malignant lymph nodes in pediatric cancer patients on 18F-FDG PET/MRI. Methods: We conducted a prospective clinical trial from May 2015 to December 2018 to investigate the value of ferumoxytol nanoparticles for staging of children with cancer with 18F-FDG PET/MRI. Ferumoxytol is an FDA-approved iron supplement for the treatment of anemia and has been used "off-label" as an MRI contrast agent in this study. Forty-two children (7-18 years, 29 male, 13 female) received a 18F-FDG PET/MRI at 2 (n=20) or 24 hours (h) (n=22) after intravenous injection of ferumoxytol (dose 5 mg Fe/kg). The morphology of benign and malignant lymph nodes on ferumoxytol-enhanced T2-FSE sequences at 2 and 24 h were compared using a linear regression analysis. In addition, ADCmean-values, SUV-ratio (SUVmax lesion/SUVmean liver) and R2*-relaxation rate of benign and malignant lymph nodes were compared with a Mann-Whitney-U test. The accuracy of different criteria was assessed with a receiver operating characteristics (ROC) curve. Follow-up imaging for at least 6 months served as the standard of reference. Results: We examined a total of 613 lymph nodes, of which 464 (75.7%) were benign and 149 (24.3%) were malignant. On ferumoxytol-enhanced T2-FSE images, benign lymph nodes showed a hypointense hilum and hyperintense parenchyma, while malignant lymph nodes showed no discernible hilum. This pattern was not significantly different at 2 h and 24 h postcontrast (p=0.82). Benign and malignant lymph nodes showed significantly different ferumoxytol enhancement patterns, ADCmean values of 1578 and 852 x10-6 mm2/s, mean SUV-ratios of 0.5 and 2.8, and mean R2*-relaxation rate of 127.8 and 84.4 Hertz (Hz), respectively (all p<0.001). The accuracy of ADCmean, SUV-ratio and pattern (area under the curve (AUC): 0.99; 0.98; 0.97, respectively) was not significantly different (p=0.07). Compared to these three parameters, the accuracy of R2* was significantly lower (AUC: 0.93; p=0.001). Conclusion: Lymph nodes in children show different ferumoxytol-enhancement patterns on MRI than previously reported for adult patients. We found high accuracy (>90%) of ADCmean, SUV-ratio, pattern, and R2* measurements for the characterization of benign and malignant lymph nodes in children. Ferumoxytol nanoparticle accumulation at the hilum can be used to diagnose a benign lymph node. In the future, the delivery of clinically applicable nanoparticles to the hilum of benign lymph nodes could be harnessed to deliver theranostic drugs for immune cell priming.
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Nontraumatic Chylothorax: Nonenhanced MR Lymphography.
Cholet, C, Delalandre, C, Monnier-Cholley, L, Le Pimpec-Barthes, F, El Mouhadi, S, Arrivé, L
Radiographics : a review publication of the Radiological Society of North America, Inc. 2020;(6):1554-1573
Abstract
Chylothorax is a rare cause of pleural effusion, secondary to accumulation of lymph in the pleural space. Diagnosis is based on the triglyceride and cholesterol content of pleural fluid obtained with thoracentesis. Because the lymphatic system plays an essential role in fat absorption and immune response, lymphatic leak associated with chylothorax may cause life-threatening malnutrition and immunodeficiency. Chylothorax is usually described as traumatic or nontraumatic. The main cause of chylothorax is traumatic, typically postsurgical, secondary to iatrogenic direct puncture of the thoracic duct during thoracic surgery. Causes of nontraumatic chylothorax include a wide range of differential diagnoses. Lymphoma and thoracic malignancies are the most common causes and are responsible for chylothorax by extrinsic compression or invasion of the thoracic duct. Other rare causes include primary and secondary diffuse lymphatic diseases, responsible for chylothorax by lymphatic vessel wall dysfunction. Imaging the lymphatic system remains a challenge in the days of modern imaging. Nonenhanced MR lymphography is a noninvasive technique based on heavily T2-weighted sequences, thus enabling visualization of the lymphatic circulation. This technique allows diagnosis and differential diagnosis, evaluation of disease severity, and guidance of therapeutic management in nontraumatic chylothorax. Furthermore, it may offer radiologic classification of primary lymphatic diseases on the basis of morphologic features of lymphatic vessels. The authors describe the anatomy and physiology of the thoracic lymphatic system, present the technique of nonenhanced MR lymphography, and discuss pathophysiologic mechanisms and imaging features in different causes of nontraumatic chylothorax. ©RSNA, 2020.
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Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress.
Wang, H, Braun, C, Murphy, EF, Enck, P
The American journal of gastroenterology. 2019;(7):1152-1162
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Abstract
OBJECTIVES Accumulating evidence indicates that the gut microbiota communicates with the central nervous system, possibly through neural, endocrine, and immune pathways, and influences brain function. B. longum 1714™ has previously been shown to attenuate cortisol output and stress responses in healthy subjects exposed to an acute stressor. However, the ability of B. longum 1714™ to modulate brain function in humans is unclear. METHODS In a randomized, double-blinded, placebo-controlled trial, the effects of B. longum 1714™ on neural responses to social stress, induced by the "Cyberball game," a standardized social stress paradigm, were studied. Forty healthy volunteers received either B. longum 1714™ or placebo for 4 weeks at a dose of 1 × 10 cfu/d. Brain activity was measured using magnetoencephalography and health status using the 36-item short-form health survey. RESULTS B. longum 1714™ altered resting-state neural oscillations, with an increase in theta band power in the frontal and cingulate cortex (P < 0.05) and a decrease in beta-3 band in the hippocampus, fusiform, and temporal cortex (P < 0.05), both of which were associated with subjective vitality changes. All groups showed increased social stress after a 4-week intervention without an effect at behavioral level due to small sample numbers. However, only B. longum 1714™ altered neural oscillation after social stress, with increased theta and alpha band power in the frontal and cingulate cortex (P < 0.05) and supramarginal gyrus (P < 0.05). DISCUSSION B. longum 1714™ modulated resting neural activity that correlated with enhanced vitality and reduced mental fatigue. Furthermore, B. longum 1714™ modulated neural responses during social stress, which may be involved in the activation of brain coping centers to counter-regulate negative emotions.