scholarly journals Structural Amyloid Plaque Polymorphism is Associated with Distinct Lipid Accumulations Revealed by Trapped Ion Mobility Mass Spectrometry Imaging (TIMS MSI)

2021 ◽  
Author(s):  
Wojciech Michno ◽  
Patrick M. Wehrli ◽  
Srinivas Koutarapu ◽  
Christian Marsching ◽  
Karolina Minta ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Mass Spectrometry Imaging ◽  
Amyloid Plaque ◽  
Ion Mobility Mass Spectrometry ◽  
Trapped Ion

scholarly journals Amyloid Plaque Polymorphism is Associated with Distinct Lipid Accumulations Revealed by Trapped Ion Mobility Mass Spectrometry Imaging (TIMS MSI)

2021 ◽  
Author(s):  
Wojciech Michno ◽  
Patrick Wehrli ◽  
Srinivas Koutarapu ◽  
Christian Marsching ◽  
Karolina Minta ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ion Mobility ◽  
Multimodal Imaging ◽  
Mass Spectrometry Imaging ◽  
Amyloid Plaque ◽  
Trapped Ion ◽  
Plaque Pathology ◽  
Lipid Species

Understanding of Alzheimer’s disease (AD) pathophysiology, requires molecular assessment of how key pathological factors, specifically amyloid β (Aβ) plaques, influence the surrounding microenvironment. Here, neuronal lipids are particularly of interest as these are implicated in pathological- and neurodegenerative processes in AD. The exact molecular characteristics of the cellular environment in direct proximity to Aβ plaques are however still not known, not in the least due to high molecular complexity of lipid species but also due to the lacking spatial resolution, sensitivity, and specificity of analytical approaches. Likewise, how such micro environmental changes differ, across structurally polymorphic Aβ features - such as diffuse, immature and mature, fibrillary structures - has been a challenge, requiring complemental, multimodal imaging approaches. Herein, we used matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) trapped ion mobility spectrometry Time-of-Flight (TIMS TOF) in combination with hyperspectral microscopy to probe lipidomic microenvironment associated with structural polymorphism of Aβ plaque in transgenic mouse model of Alzheimer’s disease (tgAPPSWE).Integrated multivariate imaging data analysis revealed alteration of multiple lipid species showing a general, Aβ associated enrichment/depletion patterns. The hyperspectral imaging strategy further delineated unique distribution of PA, PE-Cer and PI lipids to more/less aggregated Aβ fibrillary structures present within individual Aβ plaques at different timepoints of progressing plaque pathology. Using an elaborate on tissue and ex situ validation approach, the unique possibility to obtain gas-phase isobar and isomer separations through TIMS TOF, facilitated unambiguous identification of lipid isomers that showed plaque pathology associated localizations. Finally, we followed AD pathology associated lipid changes over time, identifying plaque growth and maturation to be characterized by peripheral accumulation of PI (40:6). Together, these data demonstrate the potential of multimodal imaging approaches to overcome limitations associated with conventional advanced MS imaging applications. This allowed for differentiation of both distinct lipid components in a complex micro environment, as well as their correlation to disease relevant amyloid plaque polymorphs.

Trends in trapped ion mobility – Mass spectrometry instrumentation

2019 ◽  
Vol 116 ◽  
pp. 324-331 ◽  
Author(s):  
Mark E. Ridgeway ◽  
Christian Bleiholder ◽  
Matthias Mann ◽  
Melvin A. Park
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Ion Mobility Mass Spectrometry ◽  
Trapped Ion

scholarly journals Ion Mobility-Mass Spectrometry Imaging Workflow

2020 ◽  
Vol 31 (12) ◽  
pp. 2437-2442 ◽  
Author(s):  
Daniela Mesa Sanchez ◽  
Steve Creger ◽  
Veerupaksh Singla ◽  
Ruwan T. Kurulugama ◽  
John Fjeldsted ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Mass Spectrometry Imaging ◽  
Ion Mobility Mass Spectrometry

scholarly journals An Ion Mobility-Mass Spectrometry Imaging Workflow

2020 ◽  
Author(s):  
Daniela Mesa Sanchez ◽  
Steve Creger ◽  
Veerupaksh Singla ◽  
Ruwan T. Kurulugama ◽  
John Fjeldsted ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Mass Spectrometry Imaging ◽  
Feature Detection ◽  
Drift Time ◽  
Biological Tissues ◽  
Ion Mobility Mass Spectrometry ◽  
Label Free ◽  
User Input ◽  
Spatially Resolved

<p>Mass spectrometry imaging (MSI) is a powerful technique for the label-free spatially-resolved analysis of biological tissues. Coupling ion mobility (IM) separation with MSI allows separation of isobars in the mobility dimension and increases confidence of peak assignments. Recently, imaging experiments have been implemented on the Agilent 6560 Ion Mobility Quadrupole Time of Flight Mass Spectrometer, making MSI experiments more broadly accessible to the MS community. However, the absence of data analysis software for this system presents a bottleneck. Herein, we present a vendor-specific imaging workflow to visualize IM-MSI data produced on the Agilent IM-MS system. Specifically, we have developed a Python script, the ion mobility-mass spectrometry image creation script (IM-MSIC), which interfaces Agilent’s Mass Hunter Mass Profiler software with the MacCoss lab’s Skyline software and generates drift time and mass-to-charge selected ion images. In the workflow, Mass Profiler is used for an untargeted feature detection. The IM-MSIC script mediates user input of data and extracts ion chronograms utilizing Skyline’s command-line interface, then proceeds towards ion image generation within a single user interface. Ion image post-processing is subsequently performed using different tools implemented in accompanying scripts.</p>

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