scholarly journals Correlation of in vivo imaging to morphomolecular pathology in translational research: challenge accepted

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simone Ballke ◽  
Irina Heid ◽  
Carolin Mogler ◽  
Rickmer Braren ◽  
Markus Schwaiger ◽  
...  

AbstractCorrelation of in vivo imaging to histomorphological pathology in animal models requires comparative interdisciplinary expertise of different fields of medicine. From the morphological point of view, there is an urgent need to improve histopathological evaluation in animal model-based research to expedite translation into clinical applications. While different other fields of translational science were standardized over the last years, little was done to improve the pipeline of experimental pathology to ensure reproducibility based on pathological expertise in experimental animal models with respect to defined guidelines and classifications. Additionally, longitudinal analyses of preclinical models often use a variety of imaging methods and much more attention should be drawn to enable for proper co-registration of in vivo imaging methods with the ex vivo morphological read-outs. Here we present the development of the Comparative Experimental Pathology (CEP) unit embedded in the Institute of Pathology of the Technical University of Munich during the Collaborative Research Center 824 (CRC824) funding period together with selected approaches of histomorphological techniques for correlation of in vivo imaging to morphomolecular pathology.

2021 ◽  
Author(s):  
Simone Ballke ◽  
Irina Heid ◽  
Carolin Mogler ◽  
Rickmer Braren ◽  
Markus Schwaiger ◽  
...  

Abstract Correlation of in vivo imaging to histomorphological pathology in animal models requires comparative interdisciplinary expertise of different fields of medicine. From the morphological point of view, there is an urgent need to improve histopathological evaluation in animal model based research to expedite translation into clinical applications. While different other fields of translational science were standardized over the last years, little was done to improve the pipeline of experimental pathology to ensure reproducibility based on pathological expertise in experimental animal models with respect to defined guidelines and classifications. Additionally, longitudinal analyses of preclinical models often use a variety of imaging methods and much more attention should be drawn to enable for proper co-registration of in vivo imaging methods with the ex vivo morphological read-outs. Here we present the development of the Comparative Experimental Pathology (CEP) unit embedded in the Institute of Pathology of the Technical University of Munich during the Collaborative Research Center 824 (CRC824) funding period together with selected approaches of histomorphological techniques for correlation of in vivo imaging to morphomolecular pathology.


2016 ◽  
Vol 23 (6) ◽  
pp. 738-745 ◽  
Author(s):  
Paloma Navas-Navarro ◽  
Jonathan Rojo-Ruiz ◽  
Macarena Rodriguez-Prados ◽  
María Dolores Ganfornina ◽  
Loren L. Looger ◽  
...  

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149387 ◽  
Author(s):  
David Kryza ◽  
Frédéric Debordeaux ◽  
Laurent Azéma ◽  
Aref Hassan ◽  
Olivier Paurelle ◽  
...  

2000 ◽  
Vol 18 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Hitoshi Togashi ◽  
Taku Matsuo ◽  
Haruhide Shinzawa ◽  
Yoshio Takeda ◽  
Li Shao ◽  
...  

2005 ◽  
Vol 4 (4) ◽  
pp. 7290.2005.05133 ◽  
Author(s):  
Matthew J. Hardwick ◽  
Ming-Kai Chen ◽  
Kwamena Baidoo ◽  
Martin G. Pomper ◽  
Tomás R. Guilarte

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.


2017 ◽  
Vol 71 (0) ◽  
pp. 0-0
Author(s):  
Agnieszka Szczygieł ◽  
Elżbieta Pajtasz-Piasecka

Dendritic cells (DCs), as a link between innate and adaptive immunity, play a pivotal role in maintaining homeostasis of the immune system. The DC population is characterized by heterogeneity; it consists of many subpopulations which, despite their phenotypic and localization differences, play an essential function – they are professional antigen presenting cells. Due to their role, DCs can be utilized in a new cancer treatment strategy. Their main purpose is to generate an anticancer response leading to the elimination of cancer cells. The tumor microenvironment, abundant in immunosuppressive factors (e.g. IL-10, TGF-β, Arg1, IDO), impairs the proper function of DCs. For this reason, various strategies are necessary for ex vivo preparation of DC-based vaccines and for the support of in vivo DCs to fight against tumors. DC-based vaccines are combined with other forms of immunotherapy (e.g. blockade of immune checkpoint molecules, e.g. PD-1 or CTLA-4) or conventional types of therapies (e.g. chemotherapy). Despite the enormous progress that has been made in anticancer therapy in the past two decades, there are still many unresolved issues regarding the effectiveness of the DCs usage. In this paper we described, in both a mouse and a human subject, a series of DC subpopulations, differentiating in normal conditions or under the influence of cancer microenvironment. We listed factors affecting the quality of the in vivo and ex vivo generations of antitumoral responses, significant from a therapeutic point of view. Moreover, the most important strategies for the use of DCs in anticancer therapies, as well as further developments on this field, have been discussed.


Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 609
Author(s):  
Louise von Gersdorff Jørgensen

The use of zebrafish as a model for human conditions is widely recognized. Within the last couple of decades, the zebrafish has furthermore increasingly been utilized as a model for diseases in aquacultured fish species. The unique tools available in zebrafish present advantages compared to other animal models and unprecedented in vivo imaging and the use of transgenic zebrafish lines have contributed with novel knowledge to this field. In this review, investigations conducted in zebrafish on economically important diseases in aquacultured fish species are included. Studies are summarized on bacterial, viral and parasitic diseases and described in relation to prophylactic approaches, immunology and infection biology. Considerable attention has been assigned to innate and adaptive immunological responses. Finally, advantages and drawbacks of using the zebrafish as a model for aquacultured fish species are discussed.


2018 ◽  
Vol 27 (9) ◽  
pp. 1375-1389 ◽  
Author(s):  
Mehmet H. Kural ◽  
Guohao Dai ◽  
Laura E. Niklason ◽  
Liqiong Gui

Objective: Invasive coronary interventions can fail due to intimal hyperplasia and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating re-endothelialization, or local release of mTOR pathway inhibitors have helped reduce intimal hyperplasia after vessel injury. While animal models are powerful tools, they are complex and expensive, and not always reflective of human physiology. Therefore, we developed an in vitro 3D vascular model validating previous in vivo animal models and utilizing isolated human arteries to study vascular remodeling after injury. Approach: We utilized a bioreactor that enables the control of intramural pressure and shear stress in vessel conduits to investigate the vascular response in both rat and human arteries to intraluminal injury. Results: Culturing rat aorta segments in vitro, we show that vigorous removal of luminal ECs results in vessel injury, causing medial proliferation by Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when endothelial-denuded rat aortae and human umbilical arteries were subjected to arterial shear stress, pre-seeding with human umbilical ECs decreased the number and proliferation of smooth muscle cell (SMC) significantly in the media of both rat and human vessels. Conclusion: Our bioreactor system provides a novel platform for correlating ex vivo findings with vascular outcomes in vivo. The present in vitro human arterial injury model can be helpful in the study of EC-SMC interactions and vascular remodeling, by allowing for the separation of mechanical, cellular, and soluble factors.


2020 ◽  
Vol 117 (40) ◽  
pp. 25138-25149
Author(s):  
Kevin M. Anderson ◽  
Meghan A. Collins ◽  
Ru Kong ◽  
Kacey Fang ◽  
Jingwei Li ◽  
...  

Major depressive disorder emerges from the complex interactions of biological systems that span genes and molecules through cells, networks, and behavior. Establishing how neurobiological processes coalesce to contribute to depression requires a multiscale approach, encompassing measures of brain structure and function as well as genetic and cell-specific transcriptional data. Here, we examine anatomical (cortical thickness) and functional (functional variability, global brain connectivity) correlates of depression and negative affect across three population-imaging datasets: UK Biobank, Brain Genomics Superstruct Project, and Enhancing NeuroImaging through Meta Analysis (ENIGMA; combined n ≥ 23,723). Integrative analyses incorporate measures of cortical gene expression, postmortem patient transcriptional data, depression genome-wide association study (GWAS), and single-cell gene transcription. Neuroimaging correlates of depression and negative affect were consistent across three independent datasets. Linking ex vivo gene down-regulation with in vivo neuroimaging, we find that transcriptional correlates of depression imaging phenotypes track gene down-regulation in postmortem cortical samples of patients with depression. Integrated analysis of single-cell and Allen Human Brain Atlas expression data reveal somatostatin interneurons and astrocytes to be consistent cell associates of depression, through both in vivo imaging and ex vivo cortical gene dysregulation. Providing converging evidence for these observations, GWAS-derived polygenic risk for depression was enriched for genes expressed in interneurons, but not glia. Underscoring the translational potential of multiscale approaches, the transcriptional correlates of depression-linked brain function and structure were enriched for disorder-relevant molecular pathways. These findings bridge levels to connect specific genes, cell classes, and biological pathways to in vivo imaging correlates of depression.


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