Formation of multiple ion types during MALDI imaging mass spectrometry analysis of Mitragyna speciosa alkaloids in dosed rat brain tissue

Liang, Zhongling; Guo, Yingchan; Ellin, Nicholas; King, Tamara I.; Berthold, Erin C.; Mukhopadhyay, Sushobhan; Sharma, Abhisheak; McCurdy, Christopher R.; Prentice, Boone M.

doi:10.1016/j.talanta.2024.125923

Cited by 3 publications

(5 citation statements)

References 49 publications

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“…While this can complicate spectral and imaging analyses, the improved alkaloid limit of detection enabled by DCTB here is necessary for high-spatial resolution imaging and enables this proof-ofconcept image fusion demonstration. 49 In negative ion mode, a DAN MALDI matrix enables detection of GABA and glutamine on a serial tissue section, which are localized to the molecular layer (Supporting Information, Figure S2b,c). Kratom is known to treat pain and opioid withdrawal symptoms, 10,11 and the alkaloidal components of kratom are the main contributors to the analgesic effects of kratom.…”

Section: ■ Resultsmentioning

confidence: 99%

“…We have previously noted that dehydrogenated [M – H] + and [M – 3H] + alkaloid ion types can be formed under certain MALDI analysis conditions (e.g., employing DCTB as a MALDI matrix). While this can complicate spectral and imaging analyses, the improved alkaloid limit of detection enabled by DCTB here is necessary for high-spatial resolution imaging and enables this proof-of-concept image fusion demonstration . In negative ion mode, a DAN MALDI matrix enables detection of GABA and glutamine on a serial tissue section, which are localized to the molecular layer (Supporting Information, Figure S2b,c).…”

Section: Resultsmentioning

confidence: 99%

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Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds

Liang,

Guo,

Sharma

et al. 2024

Anal. Chem.

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Multimodal imaging analyses of dosed tissue samples can provide more comprehensive insights into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multimodal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging. Imaging mass spectrometry enables direct mapping of pharmaceutical compounds and metabolites, IHC fluorescence imaging can visualize large proteins, and brightfield microscopy imaging provides tissue morphology information. Single-cell resolution images are generally difficult to acquire using imaging mass spectrometry but are readily acquired with IHC fluorescence and brightfield microscopy imaging. Spatial sharpening of mass spectrometry images would thus allow for higher fidelity coregistration with other higher-resolution microscopy images. Imaging mass spectrometry spatial resolution can be predicted to a finer value via a computational image fusion workflow, which models the relationship between the intensity values in the mass spectrometry image and the features of a high-spatial resolution microscopy image. As a proof of concept, our multimodal workflow was applied to brain tissue extracted from a Sprague-Dawley rat dosed with a kratom alkaloid, corynantheidine. Four candidate mathematical models, including linear regression, partial least-squares regression, random forest regression, and twodimensional convolutional neural network (2-D CNN), were tested. The random forest and 2-D CNN models most accurately predicted the intensity values at each pixel as well as the overall patterns of the mass spectrometry images, while also providing the best spatial resolution enhancements. Herein, image fusion enabled predicted mass spectrometry images of corynantheidine, GABA, and glutamine to approximately 2.5 μm spatial resolutions, a significant improvement compared to the original images acquired at 25 μm spatial resolution. The predicted mass spectrometry images were then coregistered with an H&E image and IHC fluorescence image of the μ-opioid receptor to assess colocalization of corynantheidine with brain cells. Our study also provides insights into the different evaluation parameters to consider when utilizing image fusion for biological applications.

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Section: ■ Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds

Liang,

Guo,

Sharma

et al. 2024

Anal. Chem.

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“…Imaging mass spectrometry allows for the direct mapping of a wide variety of analytes in thin tissue sections. − However, the separation and identification of isobaric (i.e., same nominal mass) and isomeric (i.e., same exact mass) compounds can be challenging for small-molecule lipid and metabolite analyses. − Failure to resolve these compounds results in inaccurate molecular identifications and composite images that distort the spatial distributions of analytes of interest. Many chromatographic techniques commonly used to effect separations in lipidomics and metabolomics studies, such as liquid and gas chromatography, are incompatible with pixel-by-pixel imaging mass spectrometry experiments. , High resolving power instruments such as those equipped with Fourier transform ion cyclotron resonance (FT-ICR) or orbital trapping (e.g., Orbitrap) mass analyzers allow for the separation of isobaric compounds but are expensive, require long transient times, and do not resolve isomeric compounds. − Tandem mass spectrometry (MS/MS or MS n ) experiments that utilize collision-induced dissociation (CID) provide additional specificity by fragmenting the target compounds and subsequently analyzing the product masses. − The use of CID in pixel-by-pixel imaging mass spectrometry experiments can resolve these overlapping compounds so long as unique fragment ions are produced for each compound. ,,,− However, CID alone is often unable to fully differentiate all isobaric and isomeric compounds, necessitating alternative approaches.…”

Section: Introductionmentioning

confidence: 99%

Enhancing Spatial Resolution in Tandem Mass Spectrometry Ion/Ion Reaction Imaging Experiments through Image Fusion

Liang,

Guo,

Diao

et al. 2024

J. Am. Soc. Mass Spectrom.

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We have recently developed a charge inversion ion/ion reaction to selectively derivatize phosphatidylserine lipids via gas-phase Schiff base formation. This tandem mass spectrometry (MS/MS) workflow enables the separation and detection of isobaric lipids in imaging mass spectrometry, but the images acquired using this workflow are limited to relatively poor spatial resolutions due to the current time and limit of detection requirements for these ion/ion reaction imaging mass spectrometry experiments. This trade-off between chemical specificity and spatial resolution can be overcome by using computational image fusion, which combines complementary information from multiple images. Herein, we demonstrate a proof-of-concept workflow that fuses a low spatial resolution (i.e., 125 μm) ion/ion reaction product ion image with higher spatial resolution (i.e., 25 μm) ion images from a full scan experiment performed using the same tissue section, which results in a predicted ion/ion reaction product ion image with a 5fold improvement in spatial resolution. Linear regression, random forest regression, and two-dimensional convolutional neural network (2-D CNN) predictive models were tested for this workflow. Linear regression and 2D CNN models proved optimal for predicted ion/ion images of PS 40:6 and SHexCer d38:1, respectively.

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“…23 Although such spatial resolution can be achieved by these platforms, UV-MALDI approaches may utilize spatial resolutions anywhere from 10 to 200 μm depending on the application. 24,25 Achieving comparable levels of spatial resolution is less accessible for IR-based techniques and often requires modifications to the laser optical train or alternative sampling techniques. Laser spots can be controllably overlapped to produce smaller spot sizes, rendering enhanced spatial resolution.…”

Section: ■ Introductionmentioning

confidence: 99%

“…For instance, conventional analyses by IR-MALDESI demonstrate spot sizes near 150 μm. ,, However, UV-MALDI platforms have reported spatial resolutions as low as 1.4 μm under ambient conditions, and others have employed a transmission mode strategy to achieve 1 μm, as demonstrated with a cell model . Although such spatial resolution can be achieved by these platforms, UV-MALDI approaches may utilize spatial resolutions anywhere from 10 to 200 μm depending on the application. , …”

Section: Introductionmentioning

confidence: 99%

Oversampling for Enhanced Spatial Resolution of Zebrafish by Top-Hat IR-MALDESI-MSI

Sohn,

Bowman,

Barnes

et al. 2024

J. Am. Soc. Mass Spectrom.

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Mass spectrometry imaging (MSI) has become a significant tool for measuring chemical species in biological tissues, where much of the impact of these platforms lies in their capability to report the spatial distribution of analytes for correlation to sample morphology. As a result, enhancement of spatial resolution has become a frontier of innovation in the field, and necessary developments are dependent on the ionization source. More particularly, laser-based imaging sources may require modifications to the optical train or alternative sampling techniques. These challenges are heightened for systems with infrared (IR) lasers, as their operating wavelength generates spot sizes that are inherently larger than their ultraviolet counterparts. Recently, the infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) source has shown the utility of a diffractive optical element (DOE) to produce square ablation patterns, termed top-hat IR-MALDESI. If the DOE optic is combined with oversampling methods, smaller ablation volumes can be sampled to render higher spatial resolution imaging experiments. Further, this approach enables reproducible spot sizes and ablation volumes for better comparison between scans. Herein, we investigate the utility of oversampling with top-hat IR-MALDESI to enhance the spatial resolution of measured lipids localized within the head of sectioned zebrafish tissue. Four different spatial resolutions were evaluated for data quality (e.g., mass measurement accuracy, spectral accuracy) and quantity of annotations. Other experimental parameters to consider for high spatial resolution imaging are also discussed. Ultimately, 20 μm spatial resolution was achieved in this work and supports feasibility for use in future IR-MALDESI studies.

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Formation of multiple ion types during MALDI imaging mass spectrometry analysis of Mitragyna speciosa alkaloids in dosed rat brain tissue

Cited by 3 publications

References 49 publications

Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds

Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds

Enhancing Spatial Resolution in Tandem Mass Spectrometry Ion/Ion Reaction Imaging Experiments through Image Fusion

Oversampling for Enhanced Spatial Resolution of Zebrafish by Top-Hat IR-MALDESI-MSI

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