Optical Windows for Imaging the Metastatic Tumour Microenvironment in vivo

Kitamura, Takanori; Pollard, Jeffrey W.; Vendrell, Marc

doi:10.1016/j.tibtech.2016.05.001

Cited by 25 publications

(19 citation statements)

References 12 publications

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“…1 A and B). With no exogenous markers or labels, the contrast of the multiphoton images originates from the intrinsic molecular properties of individual EVs with the intensity of 2PF and 3PF representing the cargo concentrations of FAD and NAD(P)H within the EVs (17)(18)(19), respectively, and the THG being generated from the lipid layers/structures of each EV (optical heterogeneity at the aqueous-lipid interface) (25). As expected, the multiphoton image of a negative control (just media centrifuged and collected) is dark in all of the channels (SI Appendix, Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The state of the art for EV visualization has been expanding mainly due to the rapid development of EV markers and labels (12)(13)(14)(15)(16)(17). However, as with other imaging applications, marker-based methods are fundamentally limited by the complex tissue distribution of the markers, unknown disturbance of physiological functions, and unavoidable artifacts of nonspecific falsepositive binding (18,19).…”

mentioning

confidence: 99%

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Label-free visualization and characterization of extracellular vesicles in breast cancer

You

Barkalifa

Chaney

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Despite extensive interest, extracellular vesicle (EV) research remains technically challenging. One of the unexplored gaps in EV research has been the inability to characterize the spatially and functionally heterogeneous populations of EVs based on their metabolic profile. In this paper, we utilize the intrinsic optical metabolic and structural contrast of EVs and demonstrate in vivo/in situ characterization of EVs in a variety of unprocessed (pre)clinical samples. With a pixel-level segmentation mask provided by the deep neural network, individual EVs can be analyzed in terms of their optical signature in the context of their spatial distribution. Quantitative analysis of living tumor-bearing animals and fresh excised human breast tissue revealed abundance of NAD(P)H-rich EVs within the tumor, near the tumor boundary, and around vessel structures. Furthermore, the percentage of NAD(P)H-rich EVs is highly correlated with human breast cancer diagnosis, which emphasizes the important role of metabolic imaging for EV characterization as well as its potential for clinical applications. In addition to the characterization of EV properties, we also demonstrate label-free monitoring of EV dynamics (uptake, release, and movement) in live cells and animals. The in situ metabolic profiling capacity of the proposed method together with the finding of increasing NAD(P)H-rich EV subpopulations in breast cancer have the potential for empowering applications in basic science and enhancing our understanding of the active metabolic roles that EVs play in cancer progression.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Label-free visualization and characterization of extracellular vesicles in breast cancer

You

Barkalifa

Chaney

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…One way to achieve this is by introducing an optical window in the chest wall to contact the lung. This has been technically achieved and allowed real-time investigation of lung microvasculature or inflammation in the context of metastasis or ILD with single-cell resolution up to several hours, but remains a terminal procedure due to its invasiveness [ 90 , 91 , 92 , 93 , 94 , 95 ].…”

Section: The Multimodal Toolbox For Biomedical Lung Disease Researmentioning

confidence: 99%

From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases

et al. 2020

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Lung diseases such as fibrosis, asthma, cystic fibrosis, infection and cancer are life-threatening conditions that slowly deteriorate quality of life and for which our diagnostic power is high, but our knowledge on etiology and/or effective treatment options still contains important gaps. In the context of day-to-day practice, clinical and preclinical studies, clinicians and basic researchers team up and continuously strive to increase insights into lung disease progression, diagnostic and treatment options. To unravel disease processes and to test novel therapeutic approaches, investigators typically rely on end-stage procedures such as serum analysis, cyto-/chemokine profiles and selective tissue histology from animal models. These techniques are useful but provide only a snapshot of disease processes that are essentially dynamic in time and space. Technology allowing evaluation of live animals repeatedly is indispensable to gain a better insight into the dynamics of lung disease progression and treatment effects. Computed tomography (CT) is a clinical diagnostic imaging technique that can have enormous benefits in a research context too. Yet, the implementation of imaging techniques in laboratories lags behind. In this review we want to showcase the integrated approaches and novel developments in imaging, lung functional testing and pathological techniques that are used to assess, diagnose, quantify and treat lung disease and that may be employed in research on patients and animals. Imaging approaches result in often novel anatomical and functional biomarkers, resulting in many advantages, such as better insight in disease progression and a reduction in the numbers of animals necessary. We here showcase integrated assessment of lung disease with imaging and histopathological technologies, applied to the example of lung fibrosis. Better integration of clinical and preclinical imaging technologies with pathology will ultimately result in improved clinical translation of (therapy) study results.

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“…Enormous efforts have been devoted to developing molecular markers to be used for intravital imaging to visualize cells and structures of interest in vivo 2 , 4 , 5 . Although the growing library of markers (i.e., fluorescent molecules, nanoparticles, genetically expressed fluorescent proteins) has enabled biologists to scrutinize various components in the microenvironment, marker-based methods are fundamentally limited by the complicated and sometimes unpredictable tissue distribution of the exogenous markers, unexpected or unknown disturbance of biological or physiological functions, and unavoidable artifacts of non-specific labeling 6 . Label-free nonlinear optical microscopy, which produces high-resolution images with rich functional and structural information based on intrinsic molecular contrast, has demonstrated significant potential to overcome these problems by leveraging its non-perturbative nature and intrinsic molecular profiling capability.…”

Section: Introductionmentioning

confidence: 99%

Intravital imaging by simultaneous label-free autofluorescence-multiharmonic microscopy

et al. 2018

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Intravital microscopy (IVM) emerged and matured as a powerful tool for elucidating pathways in biological processes. Although label-free multiphoton IVM is attractive for its non-perturbative nature, its wide application has been hindered, mostly due to the limited contrast of each imaging modality and the challenge to integrate them. Here we introduce simultaneous label-free autofluorescence-multiharmonic (SLAM) microscopy, a single-excitation source nonlinear imaging platform that uses a custom-designed excitation window at 1110 nm and shaped ultrafast pulses at 10 MHz to enable fast (2-orders-of-magnitude improvement), simultaneous, and efficient acquisition of autofluorescence (FAD and NADH) and second/third harmonic generation from a wide array of cellular and extracellular components (e.g., tumor cells, immune cells, vesicles, and vessels) in living tissue using only 14 mW for extended time-lapse investigations. Our work demonstrates the versatility and efficiency of SLAM microscopy for tracking cellular events in vivo, and is a major enabling advance in label-free IVM.

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Optical Windows for Imaging the Metastatic Tumour Microenvironment in vivo

Cited by 25 publications

References 12 publications

Label-free visualization and characterization of extracellular vesicles in breast cancer

Label-free visualization and characterization of extracellular vesicles in breast cancer

From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases

Intravital imaging by simultaneous label-free autofluorescence-multiharmonic microscopy

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