scholarly journals Integration of Mass Spectrometry Imaging and Machine Learning Visualizes Region-Specific Age-Induced and Drug-Target Metabolic Perturbations in the Brain

2021 ◽  
Author(s):  
Theodosia Vallianatou ◽  
Reza Shariatgorji ◽  
Anna Nilsson ◽  
Maria Karlgren ◽  
Heather Hulme ◽  
...  
Keyword(s):  
Machine Learning ◽  
Mass Spectrometry ◽  
Drug Target ◽  
Mass Spectrometry Imaging ◽  
The Brain

scholarly journals Transcriptomic, peptidomic and mass spectrometry imaging analysis of the brain in the ant Cataglyphis nodus

2021 ◽  
Author(s):  
Jens Habenstein ◽  
Franziska Schmitt ◽  
Sander Liessem ◽  
Alice Ly ◽  
Dennis Trede ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Imaging Analysis ◽  
The Brain

scholarly journals Imaging Sterols and Oxysterols in Mouse Brain Reveals Distinct Spatial Cholesterol Metabolism

2018 ◽  
Author(s):  
Eylan Yutuc ◽  
Roberto Angelini ◽  
Mark Baumert ◽  
Natalia Mast ◽  
Irina Pikuleva ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mouse Brain ◽  
Brain Function ◽  
Mass Spectrometry Imaging ◽  
Cholesterol Metabolism ◽  
Biologically Active ◽  
Wild Type ◽  
Tissue Slices ◽  
The Brain

AbstractDysregulated cholesterol metabolism is implicated in a number of neurological disorders. Many sterols, including cholesterol and its precursors and metabolites, are biologically active and important for proper brain function. However, spatial cholesterol metabolism in brain and the resulting sterol distributions are poorly defined. To better understand cholesterol metabolism in situ across the complex functional regions of brain, we have developed on-tissue enzyme-assisted derivatisation in combination with micro-liquid-extraction for surface analysis and liquid chromatography - mass spectrometry to image sterols in tissue slices (10 µm) of mouse brain. The method provides sterolomic analysis at 400 µm spot diameter with a limit of quantification of 0.01 ng/mm2. It overcomes the limitations of previous mass spectrometry imaging techniques in analysis of low abundance and difficult to ionise sterol molecules, allowing isomer differentiation and structure identification. Here we demonstrate the spatial distribution and quantification of multiple sterols involved in cholesterol metabolic pathways in wild type and cholesterol 24S-hydroxylase knock-out mouse brain. The technology described provides a powerful tool for future studies of spatial cholesterol metabolism in healthy and diseased tissues.SignificanceThe brain is a remarkably complex organ and cholesterol homeostasis underpins brain function. It is known that cholesterol is not evenly distributed across different brain regions, however, the precise map of cholesterol metabolism in the brain remains unclear. If cholesterol metabolism is to be correlated with brain function it is essential to generate such a map. Here we describe an advanced mass spectrometry imaging platform to reveal spatial cholesterol metabolism in situ at 400 µm resolution on 10 µm tissue slices from mouse brain. We mapped, not only cholesterol, but also other biologically active sterols arising from cholesterol turnover in both wild type and mice lacking cholesterol 24-hydroxylase (Cyp46a1), the major cholesterol metabolising enzyme.

scholarly journals Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5388
Author(s):  
Paul Mittal ◽  
Mark R. Condina ◽  
Manuela Klingler-Hoffmann ◽  
Gurjeet Kaur ◽  
Martin K. Oehler ◽  
...  
Keyword(s):  
Machine Learning ◽  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Histopathological Examination ◽  
Supervised Machine Learning ◽  
Charge Ratio ◽  
Cancer Tissue ◽  
Ionization Mass ◽  
Colorectal Tumour ◽  
Cancer Diagnostic

Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.

scholarly journals Toward nanoscale molecular mass spectrometry imaging via physically constrained machine learning on co-registered multimodal data

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolay Borodinov ◽  
Matthias Lorenz ◽  
Steven T. King ◽  
Anton V. Ievlev ◽  
Olga S. Ovchinnikova
Keyword(s):  
Machine Learning ◽  
Mass Spectrometry ◽  
Molecular Mass ◽  
Mass Spectrometry Imaging ◽  
Multimodal Data ◽  
Molecular Mass Spectrometry

scholarly journals Mass Spectrometry Imaging Reveals Heterogeneous Efavirenz Distribution within Putative HIV Reservoirs

2015 ◽  
Vol 59 (5) ◽  
pp. 2944-2948 ◽  
Author(s):  
Corbin G. Thompson ◽  
Mark T. Bokhart ◽  
Craig Sykes ◽  
Lourdes Adamson ◽  
Yuri Fedoriw ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Desorption Electrospray Ionization ◽  
Laser Desorption ◽  
Imaging Data ◽  
Hiv Replication ◽  
Viral Reservoirs ◽  
Antiretroviral Drug ◽  
The Brain ◽  
Matrix Assisted Laser

ABSTRACTPersistent HIV replication within active viral reservoirs may be caused by inadequate antiretroviral penetration. Here, we used mass spectrometry imaging with infrared matrix-assisted laser desorption–electrospray ionization to quantify the distribution of efavirenz within tissues from a macaque dosed orally to a steady state. Intratissue efavirenz distribution was heterogeneous, with the drug concentrating in the lamina propria of the colon, the primary follicles of lymph nodes, and the brain gray matter. These are the first imaging data of an antiretroviral drug in active viral reservoirs.

scholarly journals Mass spectrometry imaging identifies abnormally elevated brain l-DOPA levels and extrastriatal monoaminergic dysregulation in l-DOPA–induced dyskinesia

2021 ◽  
Vol 7 (2) ◽  
pp. eabe5948
Author(s):  
Elva Fridjonsdottir ◽  
Reza Shariatgorji ◽  
Anna Nilsson ◽  
Theodosia Vallianatou ◽  
Luke R. Odell ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Side Effects ◽  
Mass Spectrometry Imaging ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Brain Areas ◽  
Bed Nucleus ◽  
Neuronal Signaling ◽  
Cortical Areas ◽  
The Brain

l-DOPA treatment for Parkinson’s disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA–induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.

scholarly journals Visualizing Cholesterol in the Brain by On-Tissue Derivatization and Quantitative Mass Spectrometry Imaging

2021 ◽  
Author(s):  
Roberto Angelini ◽  
Eylan Yutuc ◽  
Mark F. Wyatt ◽  
Jillian Newton ◽  
Fowzi A. Yusuf ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Mass Spectrometry Imaging ◽  
Quantitative Mass Spectrometry ◽  
The Brain
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