scholarly journals Spatial Chemometrics and Comprehensive Chemical Imaging based Molecular Histopathology Delineates Anatomical Heterogeneity at Single Pixel Resolution

Author(s):  
Patrick Wehrli ◽  
Wojciech Michno ◽  
Laurent Guerard ◽  
Julia Fernandez-Rodriguez ◽  
Anders Bergh ◽  
...  

<p>Imaging mass spectrometry (IMS) is a powerful tool for spatially-resolved chemical analysis and thereby offers novel perspectives for applications in biology and medicine. The understanding of chemically complex systems, such as biological tissues, benefits from the combination of multiple imaging modalities contributing with complementary molecular information. Effective analysis and interpretation of multimodal IMS data is challenging and requires both, precise alignment and combination of the imaging data as well as suitable statistical analysis methods to identify cross-modal correlations. Commonly applied IMS data analysis methods include qualitative comparative analysis where cross-modal interpretation is subject to human judgement; Workflows that incorporate image registration procedures are usually applied for co-representing data rather than to mine data across modalities. </p><p>Here, we present an IMS-based, histology-driven strategy for comprehensive interrogation of biological tissues by spatial chemometrics. Our workflow implements a 1+1-evolutionary image registration method enabling direct correlation of chemical information across multiple modalities at single pixel resolution. Comprehensive multimodal imaging data were evaluated using a novel approach based on orthogonal multiblock component analysis (OnPLS). Finally, we present a novel image fusion method by implementing consecutively acquired pathological staining data to enhance histological interpretation.</p><p>We demonstrate the method’s potential in two biomedical applications where trimodal matrix-assisted laser desorption/ionization (MALDI) IMS delineates pathology associated co-localization patterns of lipids and proteins in (1) a transgenic Alzheimer’s disease (AD) mouse model, and in (2) a human xenograft rat model of prostate cancer. The presented image analysis paradigm allows to comprehensively interrogate complex biological systems with single pixel resolution at cellular length scales.</p>

2020 ◽  
Author(s):  
Patrick Wehrli ◽  
Wojciech Michno ◽  
Laurent Guerard ◽  
Julia Fernandez-Rodriguez ◽  
Anders Bergh ◽  
...  

<p>Imaging mass spectrometry (IMS) is a powerful tool for spatially-resolved chemical analysis and thereby offers novel perspectives for applications in biology and medicine. The understanding of chemically complex systems, such as biological tissues, benefits from the combination of multiple imaging modalities contributing with complementary molecular information. Effective analysis and interpretation of multimodal IMS data is challenging and requires both, precise alignment and combination of the imaging data as well as suitable statistical analysis methods to identify cross-modal correlations. Commonly applied IMS data analysis methods include qualitative comparative analysis where cross-modal interpretation is subject to human judgement; Workflows that incorporate image registration procedures are usually applied for co-representing data rather than to mine data across modalities. </p><p>Here, we present an IMS-based, histology-driven strategy for comprehensive interrogation of biological tissues by spatial chemometrics. Our workflow implements a 1+1-evolutionary image registration method enabling direct correlation of chemical information across multiple modalities at single pixel resolution. Comprehensive multimodal imaging data were evaluated using a novel approach based on orthogonal multiblock component analysis (OnPLS). Finally, we present a novel image fusion method by implementing consecutively acquired pathological staining data to enhance histological interpretation.</p><p>We demonstrate the method’s potential in two biomedical applications where trimodal matrix-assisted laser desorption/ionization (MALDI) IMS delineates pathology associated co-localization patterns of lipids and proteins in (1) a transgenic Alzheimer’s disease (AD) mouse model, and in (2) a human xenograft rat model of prostate cancer. The presented image analysis paradigm allows to comprehensively interrogate complex biological systems with single pixel resolution at cellular length scales.</p>


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ghazal Azarfar ◽  
Ebrahim Aboualizadeh ◽  
Simona Ratti ◽  
Camilla Olivieri ◽  
Alessandra Norici ◽  
...  

AbstractAlgae are the main primary producers in aquatic environments and therefore of fundamental importance for the global ecosystem. Mid-infrared (IR) microspectroscopy is a non-invasive tool that allows in principle studying chemical composition on a single-cell level. For a long time, however, mid-infrared (IR) imaging of living algal cells in an aqueous environment has been a challenge due to the strong IR absorption of water. In this study, we employed multi-beam synchrotron radiation to measure time-resolved IR hyperspectral images of individual Thalassiosira weissflogii cells in water in the course of acclimation to an abrupt change of CO2 availability (from 390 to 5000 ppm and vice versa) over 75 min. We used a previously developed algorithm to correct sinusoidal interference fringes from IR hyperspectral imaging data. After preprocessing and fringe correction of the hyperspectral data, principal component analysis (PCA) was performed to assess the spatial distribution of organic pools within the algal cells. Through the analysis of 200,000 spectra, we were able to identify compositional modifications associated with CO2 treatment. PCA revealed changes in the carbohydrate pool (1200–950 cm$$^{-1}$$ - 1 ), lipids (1740, 2852, 2922 cm$$^{-1}$$ - 1 ), and nucleic acid (1160 and 1201 cm$$^{-1}$$ - 1 ) as the major response of exposure to elevated CO2 concentrations. Our results show a local metabolism response to this external perturbation.


2021 ◽  
Vol 12 (11) ◽  
pp. 4111-4118
Author(s):  
Qi Zhang ◽  
Yunlong Shao ◽  
Boye Li ◽  
Yuanyuan Wu ◽  
Jingying Dong ◽  
...  

We achieved the low-damage spatial puncture of single cells at specific visual points with an accuracy of <65 nm.


2021 ◽  
pp. 000370282110133
Author(s):  
Rohit Bhargava ◽  
Yamuna Dilip Phal ◽  
Kevin Yeh

Discrete frequency infrared (DFIR) chemical imaging is transforming the practice of microspectroscopy by enabling a diversity of instrumentation and new measurement capabilities. While a variety of hardware implementations have been realized, considerations in the design of all-IR microscopes have not yet been compiled. Here we describe the evolution of IR microscopes, provide rationales for design choices, and the major considerations for each optical component that together comprise an imaging system. We analyze design choices in illustrative examples that use these components to optimize performance, under their particular constraints. We then summarize a framework to assess the factors that determine an instrument’s performance mathematically. Finally, we summarize the design and analysis approach by enumerating performance figures of merit for spectroscopic imaging data that can be used to evaluate the capabilities of imaging systems or suitability for specific intended applications. Together, the presented concepts and examples should aid in understanding available instrument configurations, while guiding innovations in design of the next generation of IR chemical imaging spectrometers.


Author(s):  
Katharina Halbach ◽  
Timothy Holbrook ◽  
Thorsten Reemtsma ◽  
Stephan Wagner

AbstractA workflow was developed and implemented in a software tool for the automated combination of spatially resolved laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) data and data on the morphology of the biological tissue. Making use of a recently published biological annotation software, FishImager automatically assigns the biological feature as regions of interest (ROIs) and overlays them with the quantitative LA-ICP-MS data. Furthermore, statistical tools including cluster algorithms can be applied to the elemental intensity data and directly compared with the ROIs. This is effectively visualized in heatmaps. This allows gaining statistical significance on distribution and co-localization patterns. Finally, the biological functions of the assigned ROIs can then be easily linked with elemental distributions. We demonstrate the versatility of FishImager with quantitative LA-ICP-MS data of the zebrafish embryo tissue. The distribution of natural elements and xenobiotics is analyzed and discussed. With the help of FishImager, it was possible to identify compartments affected by toxicity effects or biological mechanisms to eliminate the xenobiotic. The presented workflow can be used for clinical and ecotoxicological testing, for example. Ultimately, it is a tool to simplify and reproduce interpretations of imaging LA-ICP-MS data in many applications. Graphical abstract


2012 ◽  
Author(s):  
Takahiro Kawamura ◽  
Norihiro Omae ◽  
Masahiko Yamada ◽  
Wataru Ito ◽  
Kiyosumi Kawamoto ◽  
...  

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