The characteristics of tumour development and metastasis relate not only to genomic heterogeneity but also to spatial heterogeneity,associated with variations in the intratumoural arrangement of cell populations,vascu...The characteristics of tumour development and metastasis relate not only to genomic heterogeneity but also to spatial heterogeneity,associated with variations in the intratumoural arrangement of cell populations,vascular morphology and oxygen and nutrient supply.While optical(photonic)microscopy is commonly employed to visualize the tumour microenvironment,it assesses only a few hundred cubic microns of tissue.Therefore,it is not suitable for investigating biological processes at the level of the entire tumour,which can be at least four orders of magnitude larger.In this study,we aimed to extend optical visualization and resolve spatial heterogeneity throughout the entire tumour volume.We developed an optoacoustic(photoacoustic)mesoscope adapted to solid tumour imaging and,in a pilot study,offer the first insights into cancer optical contrast heterogeneity in vivo at an unprecedented resolution of<50μm throughout the entire tumour mass.Using spectral methods,we resolve unknown patterns of oxygenation,vasculature and perfusion in three types of breast cancer and showcase different levels of structural and functional organization.To our knowledge,these results are the most detailed insights of optical signatures reported throughout entire tumours in vivo,and they position optoacoustic mesoscopy as a unique investigational tool linking microscopic and macroscopic observations.展开更多
基金funding from the Deutsche Forschungsgemeinschaft(DFG),Germany[Gottfried Wilhelm Leibniz Prize 2013,NT 3/10–1]funding from the European Research Council(ERC)under the European Union’s Horizon 2020 research and innovation programme under grant agreement 694968(PREMSOT)+2 种基金funded by the National Natural Science Foundation of China(81771880,81401453)the support of a China Scholarship Council grant(201506255001)support from the Alexander von Humboldt Postdoctoral Fellowship Program.
文摘The characteristics of tumour development and metastasis relate not only to genomic heterogeneity but also to spatial heterogeneity,associated with variations in the intratumoural arrangement of cell populations,vascular morphology and oxygen and nutrient supply.While optical(photonic)microscopy is commonly employed to visualize the tumour microenvironment,it assesses only a few hundred cubic microns of tissue.Therefore,it is not suitable for investigating biological processes at the level of the entire tumour,which can be at least four orders of magnitude larger.In this study,we aimed to extend optical visualization and resolve spatial heterogeneity throughout the entire tumour volume.We developed an optoacoustic(photoacoustic)mesoscope adapted to solid tumour imaging and,in a pilot study,offer the first insights into cancer optical contrast heterogeneity in vivo at an unprecedented resolution of<50μm throughout the entire tumour mass.Using spectral methods,we resolve unknown patterns of oxygenation,vasculature and perfusion in three types of breast cancer and showcase different levels of structural and functional organization.To our knowledge,these results are the most detailed insights of optical signatures reported throughout entire tumours in vivo,and they position optoacoustic mesoscopy as a unique investigational tool linking microscopic and macroscopic observations.
