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1.
Neuroinflammation and immunoregulation in glioblastoma and brain metastases: Recent developments in imaging approaches.
Roesler, R, Dini, SA, Isolan, GR
Clinical and experimental immunology. 2021;(3):314-324
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Abstract
Brain tumors and brain metastases induce changes in brain tissue remodeling that lead to immunosuppression and trigger an inflammatory response within the tumor microenvironment. These immune and inflammatory changes can influence invasion and metastasis. Other neuroinflammatory and necrotic lesions may occur in patients with brain cancer or brain metastases as sequelae from treatment with radiotherapy. Glioblastoma (GBM) is the most aggressive primary malignant brain cancer in adults. Imaging methods such as positron emission tomography (PET) and different magnetic resonance imaging (MRI) techniques are highly valuable for the diagnosis and therapeutic evaluation of GBM and other malignant brain tumors. However, differentiating between tumor tissue and inflamed brain tissue with imaging protocols remains a challenge. Here, we review recent advances in imaging methods that have helped to improve the specificity of primary tumor diagnosis versus evaluation of inflamed and necrotic brain lesions. We also comment on advances in differentiating metastasis from neuroinflammation processes. Recent advances include the radiosynthesis of 18 F-FIMP, an L-type amino acid transporter 1 (LAT1)-specific PET probe that allows clearer differentiation between tumor tissue and inflammation compared to previous probes, and the combination of different advanced imaging protocols with the inclusion of radiomics and machine learning algorithms.
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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.
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USPIO-Enhanced MRI Neuroimaging: A Review.
Gkagkanasiou, M, Ploussi, A, Gazouli, M, Efstathopoulos, EP
Journal of neuroimaging : official journal of the American Society of Neuroimaging. 2016;(2):161-8
Abstract
MRI is a powerful tool for the diagnosis and management for a variety of central nervous system (CNS) diseases. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are a novel category of MRI contrast agents that seem to play a crucial role in the imaging of CNS. Due to their physical properties, USPIOs act as blood pool agents. USPIOs improve visualization of tumor vasculature and relative cerebral blood volume measurements, tumor-associated inflammation, inflammatory-immune mediated disorders, stroke and vascular malformations. Ferumoxytol, a new type of USPIO agent, appears to have ideal characteristics for the imaging of CNS. The last few years, ferumoxytol has been successfully used to image CNS neoplasms, CNS inflammations and cerebral malformations offering useful information on cellular and molecular level. In addition, ferumoxytol studies focused on the pathophysiology of other CNS disorders like multiple sclerosis and epilepsy are already in progress. Aim of this review article is to provide the potential role of USPIO-enhanced MRI and the latest clinical applications of ferumoxytol agent in CNS imaging.
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Visualization of inflammation using (19) F-magnetic resonance imaging and perfluorocarbons.
Stoll, G, Basse-Lüsebrink, T, Weise, G, Jakob, P
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology. 2012;(4):438-47
Abstract
Inflammation plays a central pathophysiological role in a large number of diseases. While conventional magnetic resonance imaging (MRI) can depict gross tissue alterations due to proton changes, specific visualization of inflammation is an unmet task in clinical medicine. (19) F/(1) H MRI is a novel technology that allows tracking of stem and immune cells in experimental disease models after labelling with perfluorocarbon (PFC) emulsions. (19) F markers such as PFC compounds provide a unique signal in vivo due to the negligible (19) F background signal of the body. Concomitant acquisition of (1) H images places the labelled cells into their anatomical context. This novel imaging technique has been applied to monitor immune cell responses in myocardial infarction, pneumonia, bacterial abscess formation, peripheral nerve injury, and rejection of donor organs after transplantation. Upon systemic application PFC nanoparticles are preferentially phagozytosed by circulating monocytes/macrophages and, thus, the fluorine signal in inflamed organs mainly reflects macrophage infiltration. Moreover, attenuation of the inflammatory response after immunosuppressive or antibiotic treatments could be depicted based on (19) F/(1) H-MRI. Compared to other organ systems (19) F-MRI of neuroinflammation is still challenging, mainly because of lack in sensitivity. In focal cerebral ischemia early application of PFCs revealed ongoing thrombotic vessel occlusion rather than cell migration indicating that timing of contrast agent application is critical. Current restrictions of (19) F/(1) H-MRI in sensitivity may be overcome by improved imaging hardware, imaging sequences and reconstruction techniques, as well as improved label development and cell labelling procedures in the future.
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Novel applications of magnetic resonance imaging to image tissue inflammation after stroke.
Nighoghossian, N, Wiart, M, Berthezene, Y
Journal of neuroimaging : official journal of the American Society of Neuroimaging. 2008;(4):349-52
Abstract
Experimental studies suggest that stroke-induced brain damage progresses during subacute stages. Cerebral ischemic injury is associated with the induction of a series of inflammatory events, including the infiltration of circulating immune cells and activation of resident cells. Local brain inflammation is spatiotemporally related to the occurrence of delayed apoptotic cell death. Therefore, ischemia-associated inflammation may not only play a major role in the pathogenesis of neurodegeneration associated with stroke, but may also mediate beneficial effects such as lesion demarcation, wound healing, and tissue regeneration especially via secretion of nerve growth factors. In this context, noninvasive imaging of inflammation associated with ischemic stroke lesions could have a predictive value and may be helpful for the development of cytoprotective drugs.
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Automatic detection of regional heart rejection in USPIO-enhanced MRI.
Chang, HH, Moura, JM, Wu, YL, Ho, C
IEEE transactions on medical imaging. 2008;(8):1095-106
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Abstract
Contrast-enhanced magnetic resonance imaging (MRI) is useful to study the infiltration of cells in vivo. This research adopts ultrasmall superparamagnetic iron oxide (USPIO) particles as contrast agents. USPIO particles administered intravenously can be endocytosed by circulating immune cells, in particular, macrophages. Hence, macrophages are labeled with USPIO particles. When a transplanted heart undergoes rejection, immune cells will infiltrate the allograft. Imaged by T(2)(*)-weighted MRI, USPIO-labeled macrophages display dark pixel intensities. Detecting these labeled cells in the image facilitates the identification of acute heart rejection. This paper develops a classifier to detect the presence of USPIO-labeled macrophages in the myocardium in the framework of spectral graph theory. First, we describe a USPIO-enhanced heart image with a graph. Classification becomes equivalent to partitioning the graph into two disjoint subgraphs. We use the Cheeger constant of the graph as an objective functional to derive the classifier. We represent the classifier as a linear combination of basis functions given from the spectral analysis of the graph Laplacian. Minimization of the Cheeger constant based functional leads to the optimal classifier. Experimental results and comparisons with other methods suggest the feasibility of our approach to study the rejection of hearts imaged by USPIO-enhanced MRI.
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MR imaging in abdominal emergencies.
Pedrosa, I, Rofsky, NM
Radiologic clinics of North America. 2003;(6):1243-73
Abstract
The use of MR imaging in the emergency setting is evolving. Clear indications include situations in need of contrast media when iodinated contrast cannot be administered or to facilitate assessments in pregnant patients and children when exposure to ionizing radiation is considered unacceptable. The availability of rapid, motion-immune sequences now makes MR imaging a feasible study in less cooperative patients extending the range of patients for whom a diagnostic study can be achieved. Capitalizing on the unique benefits of MR imaging there is optimism that MR imaging can eliminate test redundancy and impact patient care in a cost-effective manner. Further investigations are needed to identify the diagnostic algorithms for which this favorable use holds true.
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Water content profiles with a 1D centric SPRITE acquisition.
Mastikhin, IV, Mullally, H, MacMillan, B, Balcom, BJ
Journal of magnetic resonance (San Diego, Calif. : 1997). 2002;(1):122-30
Abstract
The purpose of this work is to develop a rapid MRI method amenable to profiling with minimal or no T(1) relaxation weighting. The behavior of a signal during a centric SPRITE acquisition is analyzed. It is shown that the technique can be made immune to a broad range of T(1) changes. In a properly executed measurement, only T(2)* and proton density parameters define the image intensity. A T(2)* mapping technique can be easily applied, separating T(2)* and proton density contributions to the image. A drying soil sample with low initial water content is experimentally studied as a demonstration of the technique. A characteristic baseline artifact is easily removed from the profiles by a simple operation.