scholarly journals MR Susceptibility Imaging for Detection of Tumor-Associated Macrophages in Glioblastoma

2021 ◽  
Author(s):  
Amir Nazem ◽  
Samantha Guiry ◽  
Mehrdad Pourfathi ◽  
Jeffrey B. Ware ◽  
Hannah Anderson ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Imaging Biomarker ◽  
Tumor Associated Macrophages ◽  
Intracellular Iron ◽  
Positive Correlation ◽  
Non Invasive ◽  
Cell Counts ◽  
Susceptibility Maps ◽  
Invasive Method ◽  
M1 Phenotype

Abstract Purpose Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, we investigated MRI to quantify iron as an imaging biomarker for TAMs in GBM patients. Methods 21 adult patients with GBM underwent a 3D single echo gradient echo MRI sequence and quantitative susceptibility maps were generated. In 3 subjects, ex vivo imaging of surgical specimens was performed on a 9.4 Tesla MRI using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated. Each specimen was stained with hematoxylin and eosin, as well as CD68, CD86, CD206, and L-Ferritin. Results Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). The mean susceptibility significantly correlated with positivity percent for CD68 (ρ = 0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ = 0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). Conclusion MR quantitative susceptibility mapping can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.

NIMG-12. MR SUSCEPTIBILITY IMAGING FOR DETECTION OF TUMOR-ASSOCIATED MACROPHAGES IN GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi130-vi130
Author(s):  
Amir Nazem ◽  
Samantha Guiry ◽  
Mehrdad Pourfathi ◽  
Jeffrey B Ware ◽  
Hannah Anderson ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Ex Vivo ◽  
Necrotic Core ◽  
Adult Patients ◽  
Imaging Biomarkers ◽  
Tumor Associated Macrophages ◽  
Intracellular Iron ◽  
Positive Correlation ◽  
Non Invasive ◽  
Cell Counts

Abstract BACKGROUND Tumor-associated macrophages (TAMs) are a key component of glioblastoma (GBM) tumor microenvironment. Considering the differential role of different TAM phenotypes in iron metabolism with the M1 phenotype storing intracellular iron, and M2 phenotype releasing iron in the tumor microenvironment, here we investigated non-invasive quantitative susceptibility mapping (QSM) and T2* MRI relaxometry to quantify iron as imaging biomarkers for TAMs in adult patients with GBM. METHODS In this prospective study, 21 adult patients with GBM were enrolled between 2016 to 2019. Patients underwent a 3D single echo gradient echo sequence in addition to standard anatomical sequences on a 3 Tesla MRI. QSM images were reconstructed using the morphology-enabled dipole inversion (MEDI) algorithm. In 3 subjects, ex vivo imaging of surgical specimens was performed on a Bruker 9.4 Tesla 8.9 cm vertical bore MR using 3D multi-echo GRE scans, and R2* (1/T2*) maps were generated by a pixel-wise monoexponential fitting. Each specimen was stained with hematoxylin and eosin, as well as with CD68, CD86, CD206, and L-Ferritin. RESULTS Significant positive correlation was observed between mean susceptibility for the tumor enhancing zone and the L-ferritin positivity percent (r =0.56, p=0.018) and the combination of tumor’s enhancing zone and necrotic core and the L-Ferritin positivity percent (r=0.72; p=0.001). Moreover, the mean susceptibility significantly correlated with positivity percent for CD68 (ρ=0.52, p=0.034) and CD86 (r=0.7 p=0.001), but not for CD206 (ρ=0.09; p=0.7). There was a positive correlation between mean R2* values and CD68 positive cell counts (r =0.6, p=0.016). Similarly, mean R2* values significantly correlated with CD86 (r=0.54, p=0.03) but not with CD206 (r=0.15, p=0.5). High mean susceptibility in the necrotic core was associated with inferior PFS (hazard ratio,4.5, p=0.016). CONCLUSION MR Susceptibility Imaging can quantify the iron content of GBM and provide a non-invasive method for TAM quantification and phenotyping.

scholarly journals Ex vivo 18F-fluoride uptake and hydroxyapatite deposition in human coronary atherosclerosis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alastair J. Moss ◽  
Alisia M. Sim ◽  
Philip D. Adamson ◽  
Michael A. Seidman ◽  
Jack P. M. Andrews ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Signal To Noise Ratio ◽  
Imaging Study ◽  
Coronary Plaque ◽  
Osteoblastic Differentiation ◽  
Imaging Biomarker ◽  
High Signal ◽  
Fluoride Uptake ◽  
Non Invasive ◽  
Related Transcription Factor

AbstractEarly microcalcification is a feature of coronary plaques with an increased propensity to rupture and to cause acute coronary syndromes. In this ex vivo imaging study of coronary artery specimens, the non-invasive imaging radiotracer, 18F-fluoride, was highly selective for hydroxyapatite deposition in atherosclerotic coronary plaque. Specifically, coronary 18F-fluoride uptake had a high signal to noise ratio compared with surrounding myocardium that makes it feasible to identify coronary mineralisation activity. Areas of 18F-fluoride uptake are associated with osteopontin, an inflammation-associated glycophosphoprotein that mediates tissue mineralisation, and Runt-related transcription factor 2, a nuclear protein involved in osteoblastic differentiation. These results suggest that 18F-fluoride is a non-invasive imaging biomarker of active coronary atherosclerotic mineralisation.

scholarly journals #17: Disease and Immunoprophylaxis Model of Human Nose Organoids to Study SARS-CoV-2 and RSV Infection

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S8-S8
Author(s):  
Anubama Rajan ◽  
Gina Marie Aloisio ◽  
Ashley Morgan Weaver ◽  
Joseph Jelinski ◽  
Hannah Johnson ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Unmet Need ◽  
Infection Model ◽  
Dependent Manner ◽  
Non Invasive ◽  
Apical Side ◽  
Neutralizing Capacity ◽  
Rsv Infection ◽  
Invasive Method ◽  
Human Nose

Abstract Background There is a significant and unmet need for pre-clinical models to predict responsiveness of immunotherapies to both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and respiratory syncytial virus (RSV) infection. Airway organoid models have been recently developed to study respiratory viruses; however, the current methods rely on invasive or biopsy derived samples to generate lung or airway organoids. Objective To establish human nose organoids (HNOs) as a model to study SARS-CoV-2 and RSV pathogenesis and test therapeutics. Methods We developed a non-invasive method to establish HNOs using stem cells isolated from nasal-wash and mid-turbinate samples. We made air liquid interface (ALI) cultures from undifferentiated 3-dimensional HNOs and differentiated for 21 days to form differentiated nasal epithelium. We inoculated the apical epithelium and assessed SARS-CoV-2 and RSV infection on the apical compartment using real time-polymerase chain reaction, plaque assays and immunofluorescence techniques. We then evaluated the feasibility of HNO-ALI model system to test the efficacy of serum antibodies to prevent SARS-CoV-2 infection and palivizumab monoclonal antibodies to prevent infection using palivizumab sensitive and resistant RSV strains. We introduced the antibodies in the basolateral compartment and monitored its neutralizing capacity on the apical side mimicking the neutralizing effects of antibodies in circulation. Results Our HNO-ALI cultures consist of well-differentiated, pseudostratified, ciliated, and mucosal respiratory epithelial cells and are susceptible to SARS-CoV-2, RSV A and B infection. SARS-CoV-2 and RSV replicates in the apical ciliated cells of the HNO-ALI cultures, peaks at 4 days, and plateaus at 8 days post infection. Infected HNO-ALI recapitulates aspects of SARS-CoV-2 and RSV disease, including viral shedding, asynchronous cilia beating/ciliary damage, and mucus hyper-secretion. Our model effectively showed protection to infection in a concentration dependent manner of the antibodies used. Conclusion We established a non-invasive method to generate HNO-ALI epithelial model as an authentic and an alternative model to 1-D cell culture systems. Our ex-vivo HNO-ALI infection model provides a novel approach for testing therapeutic interventions.

Diagnosing occupational asthma: insight from induced sputumThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 1-4 ◽  
Author(s):  
Catherine Lemiere
Keyword(s):  
Airway Inflammation ◽  
Occupational Asthma ◽  
Induced Sputum ◽  
Special Issue ◽  
Non Invasive ◽  
Cell Counts ◽  
Occupational Agent ◽  
Invasive Method ◽  
Laboratory Exposure ◽  
Selection Of

The diagnosis of occupational asthma needs to be made objectively using as many criteria as possible. The latter include laboratory exposure tests with occupational agent(s), which are only available in specialized centers. Another approach is to monitor peak expiratory flow (PEF) and (or) methacholine airway responsiveness during periods at work and away from work. However, these measurements are open to misinterpretation when they are not optimally performed. Airway inflammation is one of the main characteristics of asthma. Induced sputum, a non-invasive method to assess airway inflammation, has been successfully used in the management of asthma. However, airway inflammation is seldom assessed during the investigation of occupational asthma. This article reviews the studies that have investigated and characterized the changes in sputum cell counts occurring in subjects with occupational asthma after exposure to occupational agents in the laboratory, or at the workplace to assess to place of induced sputum in the investigation of occupational asthma.

scholarly journals Sodium accumulation in breast cancer predicts malignancy and treatment response

2021 ◽  
Author(s):  
Andrew D James ◽  
Theresa K Leslie ◽  
Joshua D Kaggie ◽  
Laura Wiggins ◽  
Lewis Patten ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ex Vivo ◽  
Breast Tumour ◽  
Cytotoxic Chemotherapy ◽  
Tumour Tissue ◽  
Imaging Biomarker ◽  
Sodium Accumulation ◽  
Non Invasive ◽  
Significant Clinical Improvement ◽  
Breast Tumour Tissue

AbstractBreast cancer is the leading cause of cancer-related death in women worldwide. Development of novel noninvasive diagnostic and predictive pathophysiological biomarkers would represent a significant clinical improvement. Here, we explored the utility of non-invasive 23Na MRI to profile tumour physiology using preclinical mouse models of breast cancer. We establish that tissue Na+ concentration ([Na+]) is elevated vs non-tumour regions across multiple different tumour models. Ex vivo SBFI fluorescence imaging corroborated that this elevation in tumour [Na+] is due to increased intracellular [Na+]. Effective treatment with cytotoxic chemotherapy reduced tumour tissue [Na+], but was not detected by 1H diffusion-weighted imaging (DWI). Moreover, combining 23Na MRI and DWI measurements enabled superior classification accuracy of tumour vs non-tumour regions compared to either parameter alone. Quantification of breast tumour tissue [Na+] using 23Na MRI thus represents a novel, accurate, non-invasive diagnostic and predictive imaging biomarker.

Malfunctional Reorganization in the Developing Limbo-Prefrontal System in Animals: Implications for Human Psychoses?

2001 ◽  
Vol 12 (1) ◽  
pp. 8-14
Author(s):  
Gertraud Teuchert-Noodt ◽  
Ralf R. Dawirs
Keyword(s):  
Prefrontal Cortex ◽  
Mental Disorders ◽  
Dentate Gyrus ◽  
Cognitive Functions ◽  
Experimental Approach ◽  
Regulatory Mechanisms ◽  
Hippocampal Dentate Gyrus ◽  
Non Invasive ◽  
Invasive Method ◽  
Activity Dependent

Abstract: Neuroplasticity research in connection with mental disorders has recently bridged the gap between basic neurobiology and applied neuropsychology. A non-invasive method in the gerbil (Meriones unguiculus) - the restricted versus enriched breading and the systemically applied single methamphetamine dose - offers an experimental approach to investigate psychoses. Acts of intervening affirm an activity dependent malfunctional reorganization in the prefrontal cortex and in the hippocampal dentate gyrus and reveal the dopamine position as being critical for the disruption of interactions between the areas concerned. From the extent of plasticity effects the probability and risk of psycho-cognitive development may be derived. Advance may be expected from insights into regulatory mechanisms of neurogenesis in the hippocampal dentate gyrus which is obviously to meet the necessary requirements to promote psycho-cognitive functions/malfunctions via the limbo-prefrontal circuit.

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