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1
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Nitz A, Giraldez Chavez JH, Eliason ZG, Payne SH. Are We There Yet? Assessing the Readiness of Single-Cell Proteomics to Answer Biological Hypotheses. J Proteome Res 2025; 24:1482-1492. [PMID: 38981598 PMCID: PMC11976870 DOI: 10.1021/acs.jproteome.4c00091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 05/02/2024] [Accepted: 06/13/2024] [Indexed: 07/11/2024]
Abstract
Single-cell analysis is an active area of research in many fields of biology. Measurements at single-cell resolution allow researchers to study diverse populations without losing biologically meaningful information to sample averages. Many technologies have been used to study single cells, including mass spectrometry-based single-cell proteomics (SCP). SCP has seen a lot of growth over the past couple of years through improvements in data acquisition and analysis, leading to greater proteomic depth. Because method development has been the main focus in SCP, biological applications have been sprinkled in only as proof-of-concept. However, SCP methods now provide significant coverage of the proteome and have been implemented in many laboratories. Thus, a primary question to address in our community is whether the current state of technology is ready for widespread adoption for biological inquiry. In this Perspective, we examine the potential for SCP in three thematic areas of biological investigation: cell annotation, developmental trajectories, and spatial mapping. We identify that the primary limitation of SCP is sample throughput. As proteome depth has been the primary target for method development to date, we advocate for a change in focus to facilitate measuring tens of thousands of single-cell proteomes to enable biological applications beyond proof-of-concept.
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Affiliation(s)
- Alyssa
A. Nitz
- Biology Department, Brigham Young University, Provo, Utah 84602, United States
| | | | - Zachary G. Eliason
- Biology Department, Brigham Young University, Provo, Utah 84602, United States
| | - Samuel H. Payne
- Biology Department, Brigham Young University, Provo, Utah 84602, United States
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2
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Spangenberg P, Bessler S, Widera L, Bottek J, Richter M, Thiebes S, Siemes D, Krauß SD, Migas LG, Kasarla SS, Phapale P, Kleesiek J, Führer D, Moeller LC, Heuer H, Van de Plas R, Gunzer M, Soehnlein O, Soltwisch J, Shevchuk O, Dreisewerd K, Engel DR. msiFlow: automated workflows for reproducible and scalable multimodal mass spectrometry imaging and microscopy data analysis. Nat Commun 2025; 16:1065. [PMID: 39870624 PMCID: PMC11772593 DOI: 10.1038/s41467-024-55306-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Accepted: 12/08/2024] [Indexed: 01/29/2025] Open
Abstract
Multimodal imaging by matrix-assisted laser desorption ionisation mass spectrometry imaging (MALDI MSI) and microscopy holds potential for understanding pathological mechanisms by mapping molecular signatures from the tissue microenvironment to specific cell populations. However, existing software solutions for MALDI MSI data analysis are incomplete, require programming skills and contain laborious manual steps, hindering broadly applicable, reproducible, and high-throughput analysis to generate impactful biological discoveries. Here, we present msiFlow, an accessible open-source, platform-independent and vendor-neutral software for end-to-end, high-throughput, transparent and reproducible analysis of multimodal imaging data. msiFlow integrates all necessary steps from raw data import to analytical visualisation along with state-of-the-art and self-developed algorithms into automated workflows. Using msiFlow, we unravel the molecular heterogeneity of leukocytes in infected tissues by spatial regulation of ether-linked phospholipids containing arachidonic acid. We anticipate that msiFlow will facilitate the broad applicability of MSI in multimodal imaging to uncover context-dependent cellular regulations in disease states.
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Affiliation(s)
- Philippa Spangenberg
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | | | - Lars Widera
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | - Jenny Bottek
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | - Mathis Richter
- Institute of Experimental Pathology (ExPat), Center of Molecular Biology of Inflammation (ZMBE), University of Münster, Münster, Germany
| | - Stephanie Thiebes
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | - Devon Siemes
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | - Sascha D Krauß
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | - Lukasz G Migas
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA
- Delft Center for Systems and Control, Delft University of Technology, Delft, The Netherlands
| | - Siva Swapna Kasarla
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany
| | - Prasad Phapale
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany
| | - Jens Kleesiek
- Institute for AI in Medicine (IKIM), University Hospital Essen, Essen, Germany
| | - Dagmar Führer
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, Essen, Germany
| | - Lars C Moeller
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, Essen, Germany
| | - Heike Heuer
- Department of Endocrinology, Diabetes and Metabolism, University Hospital Essen, Essen, Germany
| | - Raf Van de Plas
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA
- Delft Center for Systems and Control, Delft University of Technology, Delft, The Netherlands
- Department of Biochemistry, Vanderbilt University, Nashville, TN, USA
| | - Matthias Gunzer
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
- Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V., Dortmund, Germany
| | - Oliver Soehnlein
- Institute of Experimental Pathology (ExPat), Center of Molecular Biology of Inflammation (ZMBE), University of Münster, Münster, Germany
| | - Jens Soltwisch
- Institute of Hygiene, University of Münster, Münster, Germany
| | - Olga Shevchuk
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany
| | | | - Daniel R Engel
- Institute for Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany.
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3
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Good CJ, Butrico CE, Colley ME, Emmerson LN, Gibson-Corley KN, Cassat JE, Spraggins JM, Caprioli RM. Uncovering lipid dynamics in Staphylococcus aureus osteomyelitis using multimodal imaging mass spectrometry. Cell Chem Biol 2024; 31:1852-1868.e5. [PMID: 39389064 PMCID: PMC11977171 DOI: 10.1016/j.chembiol.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Revised: 06/20/2024] [Accepted: 09/18/2024] [Indexed: 10/12/2024]
Abstract
Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are tools that can be employed to interrogate the lipidome of S. aureus-infected murine femurs and reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, suggesting a hypothesized dysregulation of lipid metabolism in a population of cells that cannot be discerned with traditional microscopy. These data provide insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages.
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Affiliation(s)
- Christopher J Good
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
| | - Casey E Butrico
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Madeline E Colley
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA
| | - Lauren N Emmerson
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA; Chemical and Physical Biology Program, Vanderbilt University, Nashville, TN 37235, USA
| | - Katherine N Gibson-Corley
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - James E Cassat
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jeffrey M Spraggins
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA.
| | - Richard M Caprioli
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA; Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA; Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA
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4
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Zhan L, Huang Y, Wang G. Multi-modal mass spectrometry imaging of a single tissue section. JOURNAL OF MASS SPECTROMETRY : JMS 2024; 59:e5074. [PMID: 39017393 DOI: 10.1002/jms.5074] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 06/10/2024] [Accepted: 06/21/2024] [Indexed: 07/18/2024]
Abstract
Mass spectrometry imaging (MSI) was developed to visualize spatial chemical information within tissues, thereby facilitating spatial multi-omic analysis. However, due to the limited spatial information provided by individual modal MSI, correlating various chemical data within tissues remains a significant challenge. In recent years, multimodal MSI has garnered considerable attention due to its ability to visualize the spatial distributions of multiple biomolecules within tissues. Among the strategies employed in this field, multimodal imaging on a single tissue section circumvents multiple issues introduced by integration of images of consecutive tissue sections. In this minireview, we provide an overview of multimodal MSI on a single tissue section, with a particular focus on the use of Matrix-Assisted Laser Desorption/Ionization-MSI for spatial multi-omic investigations that offer a comprehensive and in-depth elucidation of the biological state and activities, aiming to inspire the development of new approaches in this field.
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Affiliation(s)
- Lingpeng Zhan
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China
| | - Yanyi Huang
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China
- Biomedical Pioneering Innovation Center, Peking University, Beijing, China
- College of Chemistry and Molecular Engineering, Beijing National Laboratory for Molecular Sciences, Peking University, Beijing, China
- Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
| | - Guanbo Wang
- Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen, China
- Biomedical Pioneering Innovation Center, Peking University, Beijing, China
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5
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Wang J, Zhu Y, Ye B, Dun J, Yu X, Sui Q. Absorption and translocation of selected pharmaceuticals in Pistia stratiotes: Spatial distribution analysis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. JOURNAL OF HAZARDOUS MATERIALS 2024; 469:134028. [PMID: 38493630 DOI: 10.1016/j.jhazmat.2024.134028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 03/11/2024] [Accepted: 03/12/2024] [Indexed: 03/19/2024]
Abstract
Phytoremediation can eliminate pharmaceuticals from aquatic environments through absorption; however, understanding of absorption and transport processes in plants remains limited. In this study, a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-MSI) method was developed to explore the absorption and translocation mechanisms of seven common pharmaceuticals in Pistia stratiotes. Results showed that 2,3-dicyanohydroquinone, an infrequently used matrix, exhibited outstanding performance in MALDI-MSI analysis, producing the highest signal intensity for four of the seven pharmaceuticals. Region of Interest (ROI) analysis revealed that charge speciation of pharmaceuticals significantly influenced their ability to enter vascular bundle. Neutral and positively charged pharmaceuticals easily entered vascular bundle, while negatively charged pharmaceuticals faced difficulty. ROI results for neutral and negatively charged pharmaceuticals exhibited positive correlation with their transfer factor values, indicating that their translocation ability from root to shoot was related to their capacity to enter vascular bundle. However, no correlation was observed for positively charged pharmaceuticals, suggesting that these compounds, upon entering vascular bundle, encountered difficulties in upward translocation through the xylem. This study introduces an innovative approach and offers novel insights into the retention and migration of pharmaceuticals in plant tissues, aiming to enhance the understanding of pharmaceutical accumulation in plants. ENVIRONMENTAL IMPLICATION: Pharmaceuticals in aquatic environment can inflict detrimental effects on both human health and ecosystem. Phytoremediation can remove pharmaceuticals from aquatic environments through absorption. However, our understanding of absorption and transportation of pharmaceuticals in plants remains limited. This study developed a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry imaging (MALDI-MSI) method for pharmaceuticals in plant roots, and to explore the absorption and translocation mechanisms of pharmaceuticals. The study offers direct evidence of differences in accumulation behavior of pharmaceuticals in plants, providing valuable insights for targeted and effective strategies in using plants for remediating the aquatic ecosystem from pharmaceuticals.
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Affiliation(s)
- Jiaxi Wang
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Yiwen Zhu
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Beibei Ye
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Junling Dun
- Analytical Applications Center, Shimadzu (China) Co., Ltd., Shanghai 200233, China
| | - Xia Yu
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China
| | - Qian Sui
- State Environmental Protection Key Laboratory of Environmental Risk Assessment and Control on Chemical Process, School of Resources and Environmental Engineering, East China University of Science and Technology, Shanghai 200237, China; Shanghai Institute of Pollution Control and Ecological Security, Shanghai 200092, China.
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6
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Gorman BL, Taylor MJ, Tesfay L, Lukowski JK, Hegde P, Eder JG, Bloodsworth KJ, Kyle JE, Torti S, Anderton CR. Applying Multimodal Mass Spectrometry to Image Tumors Undergoing Ferroptosis Following In Vivo Treatment with a Ferroptosis Inducer. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2024; 35:5-12. [PMID: 38079508 DOI: 10.1021/jasms.3c00193] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2024]
Abstract
Epithelial ovarian cancer (EOC) is the most common form of ovarian cancer. The poor prognosis generally associated with this disease has led to the search for improved therapies such as ferroptosis-inducing agents. Ferroptosis is a form of regulated cell death that is dependent on iron and is characterized by lipid peroxidation. Precise mapping of lipids and iron within tumors exposed to ferroptosis-inducing agents may provide insight into processes of ferroptosis in vivo and ultimately assist in the optimal deployment of ferroptosis inducers in cancer therapy. In this work, we present a method for combining matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) with secondary ion mass spectrometry (SIMS) to analyze changes in spatial lipidomics and metal composition, respectively, in ovarian tumors following exposure to a ferroptosis inducer. Tumors were obtained by injecting human ovarian cancer tumor-initiating cells into mice, followed by treatment with the ferroptosis inducer erastin. SIMS imaging detected iron accumulation in the tumor tissue, and sequential MALDI-MS imaging of the same tissue section displayed two chemically distinct regions of lipids. One region was associated with the iron-rich area detected with SIMS, and the other region encompassed the remainder of the tissue section. Bulk lipidomics confirmed the lipid assignments putatively assigned from the MALDI-MS data. Overall, we demonstrate the ability of multimodal MSI to identify the spatial locations of iron and lipids in the same tissue section and associate these regions with clinical pathology.
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Affiliation(s)
- Brittney L Gorman
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
| | - Michael J Taylor
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
| | - Lia Tesfay
- Department of Molecular Biology and Biophysics, University of Connecticut Health, Farmington, Connecticut 06030, United States
| | - Jessica K Lukowski
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
- School of Medicine, Washington University in St. Louis, St. Louis, Missouri 63110, United States
| | - Poornima Hegde
- Department of Pathology and Laboratory Medicine, University of Connecticut Health, Farmington, 06030, Connecticut United States
| | - Josie G Eder
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
| | - Kent J Bloodsworth
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
| | - Jennifer E Kyle
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
| | - Suzy Torti
- Department of Molecular Biology and Biophysics, University of Connecticut Health, Farmington, Connecticut 06030, United States
| | - Christopher R Anderton
- Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, Washington 99352, United States
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7
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Krestensen KK, Heeren RMA, Balluff B. State-of-the-art mass spectrometry imaging applications in biomedical research. Analyst 2023; 148:6161-6187. [PMID: 37947390 DOI: 10.1039/d3an01495a] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2023]
Abstract
Mass spectrometry imaging has advanced from a niche technique to a widely applied spatial biology tool operating at the forefront of numerous fields, most notably making a significant impact in biomedical pharmacological research. The growth of the field has gone hand in hand with an increase in publications and usage of the technique by new laboratories, and consequently this has led to a shift from general MSI reviews to topic-specific reviews. Given this development, we see the need to recapitulate the strengths of MSI by providing a more holistic overview of state-of-the-art MSI studies to provide the new generation of researchers with an up-to-date reference framework. Here we review scientific advances for the six largest biomedical fields of MSI application (oncology, pharmacology, neurology, cardiovascular diseases, endocrinology, and rheumatology). These publications thereby give examples for at least one of the following categories: they provide novel mechanistic insights, use an exceptionally large cohort size, establish a workflow that has the potential to become a high-impact methodology, or are highly cited in their field. We finally have a look into new emerging fields and trends in MSI (immunology, microbiology, infectious diseases, and aging), as applied MSI is continuously broadening as a result of technological breakthroughs.
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Affiliation(s)
- Kasper K Krestensen
- The Maastricht MultiModal Molecular Imaging (M4I) Institute, Maastricht University, 6229 ER Maastricht, The Netherlands.
| | - Ron M A Heeren
- The Maastricht MultiModal Molecular Imaging (M4I) Institute, Maastricht University, 6229 ER Maastricht, The Netherlands.
| | - Benjamin Balluff
- The Maastricht MultiModal Molecular Imaging (M4I) Institute, Maastricht University, 6229 ER Maastricht, The Netherlands.
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8
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Good CJ, Butrico CE, Colley ME, Gibson-Corley KN, Cassat JE, Spraggins JM, Caprioli RM. In situ lipidomics of Staphylococcus aureus osteomyelitis using imaging mass spectrometry. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.12.01.569690. [PMID: 38077019 PMCID: PMC10705574 DOI: 10.1101/2023.12.01.569690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are invaluable tools that can be employed to interrogate the lipidome of S. aureus-infected murine femurs to reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were significantly altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, indicating dysregulated lipid metabolism in a subpopulation of leukocytes that cannot be discerned with traditional microscopy. These data provide chemical insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages.
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Affiliation(s)
- Christopher J. Good
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA
- Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
| | - Casey E. Butrico
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Madeline E. Colley
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA
- Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA
| | - Katherine N. Gibson-Corley
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - James E. Cassat
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37235, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Jeffrey M. Spraggins
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA
- Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA
- Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37235, USA
| | - Richard M. Caprioli
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN 37235, USA
- Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA
- Department of Biochemistry, Vanderbilt University, Nashville, TN 37235, USA
- Department of Medicine, Vanderbilt University, Nashville, TN 37235, USA
- Department of Pharmacology, Vanderbilt University, Nashville, TN 37235, USA
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9
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Ikegawa M, Kakuda N, Miyasaka T, Toyama Y, Nirasawa T, Minta K, Hanrieder J. Mass Spectrometry Imaging in Alzheimer's Disease. Brain Connect 2023; 13:319-333. [PMID: 36905365 PMCID: PMC10494909 DOI: 10.1089/brain.2022.0057] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023] Open
Abstract
Introduction: Amyloid-beta (Aβ) pathology is the precipitating histopathological characteristic of Alzheimer's disease (AD). Although the formation of amyloid plaques in human brains is suggested to be a key factor in initiating AD pathogenesis, it is still not fully understood the upstream events that lead to Aβ plaque formation and its metabolism inside the brains. Methods: Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been successfully introduced to study AD pathology in brain tissue both in AD mouse models and human samples. By using MALDI-MSI, a highly selective deposition of Aβ peptides in AD brains with a variety of cerebral amyloid angiopathy (CAA) involvement was observed. Results: MALDI-MSI visualized depositions of shorter peptides in AD brains; Aβ1-36 to Aβ1-39 were quite similarly distributed with Aβ1-40 as a vascular pattern, and deposition of Aβ1-42 and Aβ1-43 was visualized with a distinct senile plaque pattern distributed in parenchyma. Moreover, how MALDI-MSI covered in situ lipidomics of plaque pathology has been reviewed, which is of interest as aberrations in neuronal lipid biochemistry have been implicated in AD pathogenesis. Discussion: In this study, we introduce the methodological concepts and challenges of MALDI-MSI for the studies of AD pathogenesis. Diverse Aβ isoforms including various C- and N-terminal truncations in AD and CAA brain tissues will be visualized. Despite the close relationship between vascular and plaque Aβ deposition, the current strategy will define cross talk between neurodegenerative and cerebrovascular processes at the level of Aβ metabolism.
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Affiliation(s)
- Masaya Ikegawa
- Department of Life and Medical Systems, Doshisha University, Kyotanabe, Kyoto, Japan
| | - Nobuto Kakuda
- Department of Life and Medical Systems, Doshisha University, Kyotanabe, Kyoto, Japan
| | - Tomohiro Miyasaka
- Department of Life and Medical Systems, Doshisha University, Kyotanabe, Kyoto, Japan
| | - Yumiko Toyama
- Department of Life and Medical Systems, Doshisha University, Kyotanabe, Kyoto, Japan
| | | | - Karolina Minta
- Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, United Kingdom
| | - Jörg Hanrieder
- Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
- Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, United Kingdom
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10
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Dekker J, Larson T, Tzvetkov J, Harvey VL, Dowle A, Hagan R, Genever P, Schrader S, Soressi M, Hendy J. Spatial analysis of the ancient proteome of archeological teeth using mass spectrometry imaging. RAPID COMMUNICATIONS IN MASS SPECTROMETRY : RCM 2023; 37:e9486. [PMID: 36735645 DOI: 10.1002/rcm.9486] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 01/28/2023] [Accepted: 01/29/2023] [Indexed: 06/18/2023]
Abstract
RATIONALE Proteins extracted from archaeological bone and teeth are utilised for investigating the phylogeny of extinct and extant species, the biological sex and age of past individuals, as well as ancient health and physiology. However, variable preservation of proteins in archaeological materials represents a major challenge. METHODS To better understand the spatial distribution of ancient proteins preserved within teeth, we applied matrix assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) for the first time to bioarchaeological samples to visualise the intensity of proteins in archaeological teeth thin sections. We specifically explored the spatial distribution of four proteins (collagen type I, of which the chains alpha-1 and alpha-2, alpha-2-HS-glycoprotein, haemoglobin subunit alpha and myosin light polypeptide 6). RESULTS We successfully identified ancient proteins in archaeological teeth thin sections using mass spectrometry imaging. The data are available via ProteomeXchange with identifier PXD038114. However, we observed that peptides did not always follow our hypotheses for their spatial distribution, with distinct differences observed in the spatial distribution of several proteins, and occasionally between peptides of the same protein. CONCLUSIONS While it remains unclear what causes these differences in protein intensity distribution within teeth, as revealed by MALDI-MSI in this study, we have demonstrated that MALDI-MSI can be successfully applied to mineralised bioarchaeological tissues to detect ancient peptides. In future applications, this technique could be particularly fruitful not just for understanding the preservation of proteins in a range of archaeological materials, but making informed decisions on sampling strategies and the targeting of key proteins of archaeological and biological interest.
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Affiliation(s)
- Joannes Dekker
- BioArCh, Department of Archaeology, University of York, York, UK
- Section for GeoBiology, Globe Institute, University of Copenhagen, Copenhagen, Denmark
- Faculty of Archaeology, Leiden University, Leiden, the Netherlands
| | - Tony Larson
- Metabolomics & Proteomics Laboratory, Bioscience Technology Facility, Department of Biology, University of York, York, UK
| | | | - Virginia L Harvey
- BioArCh, Department of Archaeology, University of York, York, UK
- Department of Biological Sciences, University of Chester, Chester, UK
| | - Adam Dowle
- Metabolomics & Proteomics Laboratory, Bioscience Technology Facility, Department of Biology, University of York, York, UK
| | - Richard Hagan
- BioArCh, Department of Archaeology, University of York, York, UK
| | - Paul Genever
- Department of Biology, University of York, York, UK
| | - Sarah Schrader
- Faculty of Archaeology, Leiden University, Leiden, the Netherlands
| | - Marie Soressi
- Faculty of Archaeology, Leiden University, Leiden, the Netherlands
| | - Jessica Hendy
- BioArCh, Department of Archaeology, University of York, York, UK
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11
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Wang X, Zhang L, Xiang Y, Ye N, Liu K. Systematic study of tissue section thickness for MALDI MS profiling and imaging. Analyst 2023; 148:888-897. [PMID: 36661109 DOI: 10.1039/d2an01739c] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) has become a powerful method for studying the spatial distribution of molecules. Preparation of tissue sections is a critical step for obtaining high-quality imaging data. The thickness of the slice of tissue affects the feature quality of MALDI MSI. However, few studies involved in-depth and systematic examination of slice thickness. Herein, we investigate the effect of tissue slice thickness on MALDI MSI detection. We found that the thicker the slice, the worse the results obtained by MALDI MS, which we attributed to the charging effect. The optimal slice thickness of brain tissue obtained in this work is 2-6 μm. Comparisons of the effects of slice thickness on atmospheric pressure and vacuum MALDI assays indicated that the ion signals and imaging quality of vacuum MALDI were more seriously affected by the thickness, with atmospheric pressure (AP) MALDI having a greater tolerance for slice thickness than vacuum MALDI. The MALDI MSI of peptides after enzymatic digestion of tissue sections of different thicknesses was also studied, revealing that the most suitable tissue thickness for enzyme digestion is about 10 μm. Finally, we optimized the slice thicknesses of six tissues in mice to provide a reference for MALDI MSI studies. It is worth mentioning that in our study the values of slice thickness range from the nanometer level (400 nm) at the minimum to 150 μm at the maximum, values which were unprecedented. Detailed in-depth and systematic studies of slice thickness will promote the development of sample preparation technology of AP and vacuum MALDI MSI, which will provide important references for the selection of tissue section thickness.
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Affiliation(s)
- Xiaofei Wang
- Department of Chemistry, Capital Normal University, Beijing 100048, China.
| | - Lu Zhang
- Department of Chemistry, Capital Normal University, Beijing 100048, China.
| | - Yuhong Xiang
- Department of Chemistry, Capital Normal University, Beijing 100048, China.
| | - Nengsheng Ye
- Department of Chemistry, Capital Normal University, Beijing 100048, China.
| | - Kehui Liu
- State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China. .,Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101 Beijing, China.,University of Chinese Academy of Sciences, Beijing 100049, China
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12
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Djambazova KV, Dufresne M, Migas LG, Kruse ARS, Van de Plas R, Caprioli RM, Spraggins JM. MALDI TIMS IMS of Disialoganglioside Isomers─GD1a and GD1b in Murine Brain Tissue. Anal Chem 2023; 95:1176-1183. [PMID: 36574465 DOI: 10.1021/acs.analchem.2c03939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Gangliosides are acidic glycosphingolipids, containing ceramide moieties and oligosaccharide chains with one or more sialic acid residue(s) and are highly diverse isomeric structures with distinct biological roles. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) enables the untargeted spatial analysis of gangliosides, among other biomolecules, directly from tissue sections. Integrating trapped ion mobility spectrometry with MALDI IMS allows for the analysis of isomeric lipid structures in situ. Here, we demonstrate the gas-phase separation and identification of disialoganglioside isomers GD1a and GD1b that differ in the position of a sialic acid residue, in multiple samples, including a standard mixture of both isomers, a biological extract, and directly from thin tissue sections. The unique spatial distributions of GD1a/b (d36:1) and GD1a/b (d38:1) isomers were determined in rat hippocampus and spinal cord tissue sections, demonstrating the ability to structurally characterize and spatially map gangliosides based on both the carbohydrate chain and ceramide moieties.
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Affiliation(s)
- Katerina V Djambazova
- Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Station B 351822, Nashville, Tennessee 37235, United States
- Mass Spectrometry Research Center, Vanderbilt University, 465 21st Avenue S #9160, Nashville, Tennessee 37235, United States
| | - Martin Dufresne
- Mass Spectrometry Research Center, Vanderbilt University, 465 21st Avenue S #9160, Nashville, Tennessee 37235, United States
- Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, Tennessee 37205, United States
| | - Lukasz G Migas
- Delft Center for Systems and Control, Delft University of Technology, 2628 CD Delft, The Netherlands
| | - Angela R S Kruse
- Mass Spectrometry Research Center, Vanderbilt University, 465 21st Avenue S #9160, Nashville, Tennessee 37235, United States
- Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, Tennessee 37205, United States
| | - Raf Van de Plas
- Delft Center for Systems and Control, Delft University of Technology, 2628 CD Delft, The Netherlands
| | - Richard M Caprioli
- Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Station B 351822, Nashville, Tennessee 37235, United States
- Mass Spectrometry Research Center, Vanderbilt University, 465 21st Avenue S #9160, Nashville, Tennessee 37235, United States
- Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, Tennessee 37205, United States
- Department of Pharmacology, Vanderbilt University, 2220 Pierce Avenue, Nashville, Tennessee 37232, United States
- Department of Medicine, Vanderbilt University, 1161 21st Avenue S, Nashville, Tennessee 37232, United States
| | - Jeffrey M Spraggins
- Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Station B 351822, Nashville, Tennessee 37235, United States
- Mass Spectrometry Research Center, Vanderbilt University, 465 21st Avenue S #9160, Nashville, Tennessee 37235, United States
- Department of Biochemistry, Vanderbilt University, 607 Light Hall, Nashville, Tennessee 37205, United States
- Department of Cell and Developmental Biology, Vanderbilt University, 465 21st Avenue S #3218, Nashville, Tennessee 37232, United States
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13
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Pekov SI, Zhvansky ES, Eliferov VA, Sorokin AA, Ivanov DG, Nikolaev EN, Popov IA. Determination of Brain Tissue Samples Storage Conditions for Reproducible Intraoperative Lipid Profiling. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27082587. [PMID: 35458785 PMCID: PMC9029908 DOI: 10.3390/molecules27082587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 04/11/2022] [Accepted: 04/12/2022] [Indexed: 11/16/2022]
Abstract
Ex-vivo molecular profiling has recently emerged as a promising method for intraoperative tissue identification, especially in neurosurgery. The short-term storage of resected samples at room temperature is proposed to have negligible influence on the lipid molecular profiles. However, a detailed investigation of short-term molecular profile stability is required to implement molecular profiling in a clinic. This study evaluates the effect of storage media, temperature, and washing solution to determine conditions that provide stable and reproducible molecular profiles, with the help of ambient ionization mass spectrometry using rat cerebral cortex as model brain tissue samples. Utilizing normal saline for sample storage and washing media shows a positive effect on the reproducibility of the spectra; however, the refrigeration shows a negligible effect on the spectral similarity. Thus, it was demonstrated that up to hour-long storage in normal saline, even at room temperature, ensures the acquisition of representative molecular profiles using ambient ionization mass spectrometry.
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Affiliation(s)
- Stanislav I. Pekov
- Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
- Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; (E.S.Z.); (V.A.E.); (A.A.S.); (D.G.I.)
- Siberian State Medical University, 634050 Tomsk, Russia
- Correspondence: (S.I.P.); (E.N.N); (I.A.P.)
| | - Evgeny S. Zhvansky
- Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; (E.S.Z.); (V.A.E.); (A.A.S.); (D.G.I.)
| | - Vasily A. Eliferov
- Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; (E.S.Z.); (V.A.E.); (A.A.S.); (D.G.I.)
| | - Anatoly A. Sorokin
- Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; (E.S.Z.); (V.A.E.); (A.A.S.); (D.G.I.)
- Department of Biochemistry and Systems Biology, Faculty of Health and Life Sciences, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK
| | - Daniil G. Ivanov
- Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; (E.S.Z.); (V.A.E.); (A.A.S.); (D.G.I.)
| | - Eugene N. Nikolaev
- Skolkovo Institute of Science and Technology, 121205 Moscow, Russia
- Correspondence: (S.I.P.); (E.N.N); (I.A.P.)
| | - Igor A. Popov
- Moscow Institute of Physics and Technology, 141701 Dolgoprudny, Russia; (E.S.Z.); (V.A.E.); (A.A.S.); (D.G.I.)
- National Medical Research Center for Obstetrics, Gynecology and Perinatology Named after Academician V.I. Kulakov, 117997 Moscow, Russia
- Correspondence: (S.I.P.); (E.N.N); (I.A.P.)
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14
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Mapping the Lipids of Skin Sebaceous Glands and Hair Follicles by High Spatial Resolution MALDI Imaging Mass Spectrometry. Pharmaceuticals (Basel) 2022; 15:ph15040411. [PMID: 35455408 PMCID: PMC9031257 DOI: 10.3390/ph15040411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/20/2022] [Accepted: 03/24/2022] [Indexed: 11/16/2022] Open
Abstract
Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a technology that utilizes the high sensitivity and specificity of mass spectrometry, combined with a high spatial resolution to characterize the molecular species present in skin tissue. In this article, we use MALDI IMS to map specific lipids characteristic of two important skin appendages in minipig skin: the sebaceous glands and hair follicles. A set of specific lipid markers linked to the synthesis of sebum, stages of sebum production, and the secretion of sebum for two different sebaceous gland subzones, the peripheral and central necrotic, were identified. Furthermore, biochemical pathway analysis of the identified markers provides potential drug-targeting strategies to reduce sebum overproduction in pathological conditions. In addition, specific lipid markers characteristic of the different layers in the hair follicle bulge area, including the outer root sheath, the inner root sheath, and the medulla that are associated with the growth cycles of the hair, were determined. This research highlights the ability of MALDI IMS to link a molecular distribution not only to the morphological features in skin tissue but to the physiological state as well. Thus, this platform can provide a basis for the investigation of biochemical pathways as well as the mechanisms of disease and pharmacology in the skin, which will ultimately be critical for drug discovery and the development of dermatology-related illnesses.
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15
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Karashima S, Osaka I. Rapidity and Precision of Steroid Hormone Measurement. J Clin Med 2022; 11:jcm11040956. [PMID: 35207229 PMCID: PMC8879901 DOI: 10.3390/jcm11040956] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 02/07/2022] [Accepted: 02/09/2022] [Indexed: 11/16/2022] Open
Abstract
Steroids are present in all animals and plants, from mammals to prokaryotes. In the medical field, steroids are commonly classified as glucocorticoids, mineralocorticoids, and gonadal steroid hormones. Monitoring of hormones is useful in clinical and research fields for the assessment of physiological changes associated with aging, disease risk, and the diagnostic and therapeutic effects of various diseases. Since the discovery and isolation of steroid hormones, measurement methods for steroid hormones in biological samples have advanced substantially. Although immunoassays (IAs) are widely used in daily practice, mass spectrometry (MS)-based methods have been reported to be more specific. Steroid hormone measurement based on MS is desirable in clinical practice; however, there are several drawbacks, including the purchase and maintenance costs of the MS instrument and the need for specialized training of technicians. In this review, we discuss IA- and MS-based methods currently in use and briefly present the history of steroid hormone measurement. In addition, we describe recent advances in IA- and MS-based methods and future applications and considerations.
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Affiliation(s)
- Shigehiro Karashima
- Institute of Liberal Arts and Science, Kanazawa University, Kanazawa 921-1192, Japan
- Correspondence: (S.K.); (I.O.)
| | - Issey Osaka
- Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, Imizu 939-0398, Japan
- Correspondence: (S.K.); (I.O.)
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16
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Zhu X, Xu T, Peng C, Wu S. Advances in MALDI Mass Spectrometry Imaging Single Cell and Tissues. Front Chem 2022; 9:782432. [PMID: 35186891 PMCID: PMC8850921 DOI: 10.3389/fchem.2021.782432] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 11/17/2021] [Indexed: 12/26/2022] Open
Abstract
Compared with conventional optical microscopy techniques, mass spectrometry imaging (MSI) or imaging mass spectrometry (IMS) is a powerful, label-free analytical technique, which can sensitively and simultaneously detect, quantify, and map hundreds of biomolecules, such as peptides, proteins, lipid, and other organic compounds in cells and tissues. So far, although several soft ionization techniques, such as desorption electrospray ionization (DESI) and secondary ion mass spectrometry (SIMS) have been used for imaging biomolecules, matrix-assisted laser desorption/ionization (MALDI) is still the most widespread MSI scanning method. Here, we aim to provide a comprehensive review of MALDI-MSI with an emphasis on its advances of the instrumentation, methods, application, and future directions in single cell and biological tissues.
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Affiliation(s)
- Xiaoping Zhu
- Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, China
- Research Center of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou, China
| | - Tianyi Xu
- Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, China
- Research Center of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou, China
| | - Chen Peng
- Research Center of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou, China
| | - Shihua Wu
- Joint Research Centre for Engineering Biology, Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, China
- Research Center of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zhejiang University, Hangzhou, China
- *Correspondence: Shihua Wu, ; Shihua Wu,
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17
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Noun M, Akoumeh R, Abbas I. Cell and Tissue Imaging by TOF-SIMS and MALDI-TOF: An Overview for Biological and Pharmaceutical Analysis. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2022; 28:1-26. [PMID: 34809729 DOI: 10.1017/s1431927621013593] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The potential of mass spectrometry imaging (MSI) has been demonstrated in cell and tissue research since 1970. MSI can reveal the spatial distribution of a wide range of atomic and molecular ions detected from biological sample surfaces, it is a powerful and valuable technique used to monitor and detect diverse chemical and biological compounds, such as drugs, lipids, proteins, and DNA. MSI techniques, notably matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and time of flight secondary ion mass spectrometry (TOF-SIMS), witnessed a dramatic upsurge in studying and investigating biological samples especially, cells and tissue sections. This advancement is attributed to the submicron lateral resolution, the high sensitivity, the good precision, and the accurate chemical specificity, which make these techniques suitable for decoding and understanding complex mechanisms of certain diseases, as well as monitoring the spatial distribution of specific elements, and compounds. While the application of both techniques for the analysis of cells and tissues is thoroughly discussed, a briefing of MALDI-TOF and TOF-SIMS basis and the adequate sampling before analysis are briefly covered. The importance of MALDI-TOF and TOF-SIMS as diagnostic tools and robust analytical techniques in the medicinal, pharmaceutical, and toxicology fields is highlighted through representative published studies.
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Affiliation(s)
- Manale Noun
- Lebanese Atomic Energy Commission - NCSR, Beirut, Lebanon
| | - Rayane Akoumeh
- Lebanese Atomic Energy Commission - NCSR, Beirut, Lebanon
| | - Imane Abbas
- Lebanese Atomic Energy Commission - NCSR, Beirut, Lebanon
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18
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Abdelmoula WM, Stopka SA, Randall EC, Regan M, Agar JN, Sarkaria JN, Wells WM, Kapur T, Agar NYR. massNet: integrated processing and classification of spatially resolved mass spectrometry data using deep learning for rapid tumor delineation. Bioinformatics 2022; 38:2015-2021. [PMID: 35040929 PMCID: PMC8963284 DOI: 10.1093/bioinformatics/btac032] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 01/04/2022] [Accepted: 01/13/2022] [Indexed: 01/21/2023] Open
Abstract
MOTIVATION Mass spectrometry imaging (MSI) provides rich biochemical information in a label-free manner and therefore holds promise to substantially impact current practice in disease diagnosis. However, the complex nature of MSI data poses computational challenges in its analysis. The complexity of the data arises from its large size, high-dimensionality and spectral nonlinearity. Preprocessing, including peak picking, has been used to reduce raw data complexity; however, peak picking is sensitive to parameter selection that, perhaps prematurely, shapes the downstream analysis for tissue classification and ensuing biological interpretation. RESULTS We propose a deep learning model, massNet, that provides the desired qualities of scalability, nonlinearity and speed in MSI data analysis. This deep learning model was used, without prior preprocessing and peak picking, to classify MSI data from a mouse brain harboring a patient-derived tumor. The massNet architecture established automatically learning of predictive features, and automated methods were incorporated to identify peaks with potential for tumor delineation. The model's performance was assessed using cross-validation, and the results demonstrate higher accuracy and a substantial gain in speed compared to the established classical machine learning method, support vector machine. AVAILABILITY AND IMPLEMENTATION https://github.com/wabdelmoula/massNet. The data underlying this article are available in the NIH Common Fund's National Metabolomics Data Repository (NMDR) Metabolomics Workbench under project id (PR001292) with http://dx.doi.org/10.21228/M8Q70T. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- Walid M Abdelmoula
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Invicro LLC, Boston, MA 02210, USA
| | - Sylwia A Stopka
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Elizabeth C Randall
- Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Michael Regan
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Jeffrey N Agar
- Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02111, USA
| | - Jann N Sarkaria
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55902, USA
| | - William M Wells
- Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Computer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA 02139, USA
| | - Tina Kapur
- Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Nathalie Y R Agar
- Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Department of Radiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA,Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA,To whom correspondence should be addressed.
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19
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Balluff B, Heeren RM, Race AM. An overview of image registration for aligning mass spectrometry imaging with clinically relevant imaging modalities. J Mass Spectrom Adv Clin Lab 2022; 23:26-38. [PMID: 35156074 PMCID: PMC8821033 DOI: 10.1016/j.jmsacl.2021.12.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Revised: 12/13/2021] [Accepted: 12/15/2021] [Indexed: 01/25/2023] Open
Abstract
Mass spectrometry imaging (MSI) is a powerful molecular imaging technique. Integration with other imaging modalities is essential in clinical MSI. Image integration is performed by image registration techniques. Technical potential of image registration in MSI has not been fully exploited. Roadmap proposed to improve registration accuracy. Mass spectrometry imaging (MSI) is used in many aspects of clinical research, including pharmacokinetics, toxicology, personalised medicine, and surgical decision-making. Maximising its potential requires the spatial integration of MSI images with imaging data from existing clinical imaging modalities, such as histology and MRI. To ensure that the information is properly integrated, all contributing images must be accurately aligned. This process is called image registration and is the focus of this review. In light of the ever-increasing spatial resolution of MSI instrumentation and a diversification of multi-modal MSI studies (e.g., spatial omics, 3D-MSI), the accuracy, versatility, and precision of image registration must increase accordingly. We review the application of image registration to align MSI data with different clinically relevant ex vivo and in vivo imaging techniques. Based on this, we identify steps in the current image registration processes where there is potential for improvement. Finally, we propose a roadmap for community efforts to address these challenges in order to increase registration quality and help MSI to fully exploit its multi-modal potential.
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20
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Abstract
Matrix-assisted laser desorption ionization (MALDI) remains the reference method to generate molecular images of proteins and lipids within thin tissue sections. However, traditional MALDI imaging mass spectrometry (IMS) suffers from low matrix homogeneity and high signal background in low mass range caused by matrix signals. To overcome these issues, alternative workflow and methods have been developed. Of these, metal-assisted laser desorption ionization (LDI) has become a reference technique to ionize low molecular weight compounds while allowing IMS at very high spatial resolutions with very low background signal in the low mass range. Silver and gold remain the two most used metals for the detection of neutral lipids including cholesterol, free fatty acids, and triglycerides. In this chapter, we demonstrate the potential of metal-assisted LDI IMS through the analysis of spinal cord and kidney thin tissue sections after silver and gold metal deposition. We also detail typical step-by-step workflows and discuss the strength of the methods.
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Affiliation(s)
| | - Pierre Chaurand
- Department of Chemistry, Université de Montréal, Montreal, QC, Canada.
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21
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Prentice BM. Gas-Phase Ion-Ion Reactions for Lipid Identification in Biological Tissue Sections. Methods Mol Biol 2022; 2437:3-19. [PMID: 34902137 PMCID: PMC9148664 DOI: 10.1007/978-1-0716-2030-4_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The unambiguous identification of isobaric (i.e., same nominal mass) and isomeric (i.e., same exact mass) lipids remains a challenging yet vital aspect of imaging mass spectrometry (IMS) workflows. This chapter presents a methodology for the preparation of biological tissue samples and the use of a hybrid mass spectrometer to perform gas-phase charge inversion ion/ion reactions for improved lipid identification. This gas-phase ion/ion reaction method provides lipid structural information beyond what can be obtained via conventional tandem mass spectrometry (MS/MS) experiments. While this procedure is described here for the identification of phosphatidylcholine (PC) analyte cations using 1,4-phenylenedipropionic acid reagent dianions, it can readily be generalized to perform a diverse array of ion/ion reaction chemistries.
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Affiliation(s)
- Boone M Prentice
- Department of Chemistry, University of Florida, Gainesville, FL, USA.
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22
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Molecular Histology Analysis of Cryopreserved Tissue Using Peptide/Protein MALDI-TOF Imaging Mass Spectrometry (MALDI-IMS). METHODS IN MOLECULAR BIOLOGY (CLIFTON, N.J.) 2021; 2420:177-190. [PMID: 34905174 DOI: 10.1007/978-1-0716-1936-0_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) has emerged as a powerful tool for analyzing the spatial distribution of peptides, small proteins, and other molecules within biological tissues. The obtained signals can be correlated with underlying tissue architecture, without any geometrical distortion, enabling the so-called molecular histology. Here, we analyzed cryopreserved tissue samples employing the MALDI-IMS for proteins and peptides. We used a nonstandard OCT-free cryo-slicing protocol, followed by Carnoy delipidation. Automated matrix spray was utilized to circumvent some of MALDI-IMS technology drawbacks in protein and peptide analysis.
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23
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Lee PY, Yeoh Y, Omar N, Pung YF, Lim LC, Low TY. Molecular tissue profiling by MALDI imaging: recent progress and applications in cancer research. Crit Rev Clin Lab Sci 2021; 58:513-529. [PMID: 34615421 DOI: 10.1080/10408363.2021.1942781] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Matrix-assisted laser desorption/ionization (MALDI) imaging is an emergent technology that has been increasingly adopted in cancer research. MALDI imaging is capable of providing global molecular mapping of the abundance and spatial information of biomolecules directly in the tissues without labeling. It enables the characterization of a wide spectrum of analytes, including proteins, peptides, glycans, lipids, drugs, and metabolites and is well suited for both discovery and targeted analysis. An advantage of MALDI imaging is that it maintains tissue integrity, which allows correlation with histological features. It has proven to be a valuable tool for probing tumor heterogeneity and has been increasingly applied to interrogate molecular events associated with cancer. It provides unique insights into both the molecular content and spatial details that are not accessible by other techniques, and it has allowed considerable progress in the field of cancer research. In this review, we first provide an overview of the MALDI imaging workflow and approach. We then highlight some useful applications in various niches of cancer research, followed by a discussion of the challenges, recent developments and future prospect of this technique in the field.
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Affiliation(s)
- Pey Yee Lee
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Yeelon Yeoh
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Nursyazwani Omar
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Yuh-Fen Pung
- Division of Biomedical Science, University of Nottingham Malaysia, Selangor, Malaysia
| | - Lay Cheng Lim
- Department of Life Sciences, School of Pharmacy, International Medical University (IMU), Kuala Lumpur, Malaysia
| | - Teck Yew Low
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
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24
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Hu Y, Wang Z, Liu L, Zhu J, Zhang D, Xu M, Zhang Y, Xu F, Chen Y. Mass spectrometry-based chemical mapping and profiling toward molecular understanding of diseases in precision medicine. Chem Sci 2021; 12:7993-8009. [PMID: 34257858 PMCID: PMC8230026 DOI: 10.1039/d1sc00271f] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/15/2021] [Indexed: 12/11/2022] Open
Abstract
Precision medicine has been strongly promoted in recent years. It is used in clinical management for classifying diseases at the molecular level and for selecting the most appropriate drugs or treatments to maximize efficacy and minimize adverse effects. In precision medicine, an in-depth molecular understanding of diseases is of great importance. Therefore, in the last few years, much attention has been given to translating data generated at the molecular level into clinically relevant information. However, current developments in this field lack orderly implementation. For example, high-quality chemical research is not well integrated into clinical practice, especially in the early phase, leading to a lack of understanding in the clinic of the chemistry underlying diseases. In recent years, mass spectrometry (MS) has enabled significant innovations and advances in chemical research. As reported, this technique has shown promise in chemical mapping and profiling for answering "what", "where", "how many" and "whose" chemicals underlie the clinical phenotypes, which are assessed by biochemical profiling, MS imaging, molecular targeting and probing, biomarker grading disease classification, etc. These features can potentially enhance the precision of disease diagnosis, monitoring and treatment and thus further transform medicine. For instance, comprehensive MS-based biochemical profiling of ovarian tumors was performed, and the results revealed a number of molecular insights into the pathways and processes that drive ovarian cancer biology and the ways that these pathways are altered in correspondence with clinical phenotypes. Another study demonstrated that quantitative biomarker mapping can be predictive of responses to immunotherapy and of survival in the supposedly homogeneous group of breast cancer patients, allowing for stratification of patients. In this context, our article attempts to provide an overview of MS-based chemical mapping and profiling, and a perspective on their clinical utility to improve the molecular understanding of diseases for advancing precision medicine.
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Affiliation(s)
- Yechen Hu
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Zhongcheng Wang
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Liang Liu
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
- Department of Pharmacy, Zhongnan Hospital of Wuhan University Wuhan 430071 China
| | - Jianhua Zhu
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Dongxue Zhang
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Mengying Xu
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Yuanyuan Zhang
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Feifei Xu
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
| | - Yun Chen
- School of Pharmacy, Nanjing Medical University Nanjing 211166 China
- State Key Laboratory of Reproductive Medicine, Key Laboratory of Cardiovascular & Cerebrovascular Medicine Nanjing 210029 China
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25
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Pekov SI, Bormotov DS, Nikitin PV, Sorokin AA, Shurkhay VA, Eliferov VA, Zavorotnyuk DS, Potapov AA, Nikolaev EN, Popov IA. Rapid estimation of tumor cell percentage in brain tissue biopsy samples using inline cartridge extraction mass spectrometry. Anal Bioanal Chem 2021; 413:2913-2922. [PMID: 33751161 DOI: 10.1007/s00216-021-03220-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/28/2021] [Accepted: 02/03/2021] [Indexed: 10/21/2022]
Abstract
Tumor cell percentage (TCP) is an essential characteristic of biopsy samples that directly affects the sensitivity of molecular testing in clinical practice. Apart from clarifying diagnoses, rapid evaluation of TCP combined with various neuronavigation systems can be used to support decision making in neurosurgery. It is known that ambient mass spectrometry makes it possible to rapidly distinguish healthy from malignant tissues. In connection with this, here we demonstrate the possibility of using non-imaging ambient mass spectrometry to evaluate TCP in glial tumor tissues with a high degree of confidence. Molecular profiles of histologically annotated human glioblastoma tissue samples were obtained using the inline cartridge extraction ambient mass spectrometry approach. XGBoost regressors were trained to evaluate tumor cell percentage. Using cross-validation, it was estimated that the TCP was determined by the regressors with a precision of approximately 90% using only low-resolution data. This result demonstrates that ambient mass spectrometry provides an accurate method todetermine TCP in dissected tissues even without implementing mass spectrometry imaging. The application of such techniques offers the possibility to automate routine tissue screening and TCP evaluation to boost the throughput of pathology laboratories. Rapid estimation of tumor cell percentage during neurosurgery.
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Affiliation(s)
- Stanislav I Pekov
- Skolkovo Institute of Science and Technology, Skolkovo, Moscow region, 143026, Russian Federation.,Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Denis S Bormotov
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Pavel V Nikitin
- N.N. Burdenko National Scientific and Practical Center for Neurosurgery, Moscow, 125047, Russian Federation
| | - Anatoly A Sorokin
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Vsevolod A Shurkhay
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation.,N.N. Burdenko National Scientific and Practical Center for Neurosurgery, Moscow, 125047, Russian Federation
| | - Vasiliy A Eliferov
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Denis S Zavorotnyuk
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation
| | - Alexander A Potapov
- N.N. Burdenko National Scientific and Practical Center for Neurosurgery, Moscow, 125047, Russian Federation
| | - Eugene N Nikolaev
- Skolkovo Institute of Science and Technology, Skolkovo, Moscow region, 143026, Russian Federation
| | - Igor A Popov
- Moscow Institute of Physics and Technology, Dolgoprudny, Moscow Region, 141701, Russian Federation.
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26
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Race AM, Sutton D, Hamm G, Maglennon G, Morton JP, Strittmatter N, Campbell A, Sansom OJ, Wang Y, Barry ST, Takáts Z, Goodwin RJA, Bunch J. Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration. Anal Chem 2021; 93:3061-3071. [PMID: 33534548 DOI: 10.1021/acs.analchem.0c02726] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
An ever-increasing array of imaging technologies are being used in the study of complex biological samples, each of which provides complementary, occasionally overlapping information at different length scales and spatial resolutions. It is important to understand the information provided by one technique in the context of the other to achieve a more holistic overview of such complex samples. One way to achieve this is to use annotations from one modality to investigate additional modalities. For microscopy-based techniques, these annotations could be manually generated using digital pathology software or automatically generated by machine learning (including deep learning) methods. Here, we present a generic method for using annotations from one microscopy modality to extract information from complementary modalities. We also present a fast, general, multimodal registration workflow [evaluated on multiple mass spectrometry imaging (MSI) modalities, matrix-assisted laser desorption/ionization, desorption electrospray ionization, and rapid evaporative ionization mass spectrometry] for automatic alignment of complex data sets, demonstrating an order of magnitude speed-up compared to previously published work. To demonstrate the power of the annotation transfer and multimodal registration workflows, we combine MSI, histological staining (such as hematoxylin and eosin), and deep learning (automatic annotation of histology images) to investigate a pancreatic cancer mouse model. Neoplastic pancreatic tissue regions, which were histologically indistinguishable from one another, were observed to be metabolically different. We demonstrate the use of the proposed methods to better understand tumor heterogeneity and the tumor microenvironment by transferring machine learning results freely between the two modalities.
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Affiliation(s)
- Alan M Race
- Imaging and AI, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Daniel Sutton
- Imaging and AI, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Gregory Hamm
- Imaging and AI, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Gareth Maglennon
- Oncology Safety, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Jennifer P Morton
- Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K
- Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, U.K
| | - Nicole Strittmatter
- Imaging and AI, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Andrew Campbell
- Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K
| | - Owen J Sansom
- Cancer Research UK Beatson Institute, Garscube Estate, Switchback Road, Glasgow G61 1BD, U.K
- Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Glasgow G61 1QH, U.K
| | - Yinhai Wang
- Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Simon T Barry
- Bioscience, Early Oncology, AstraZeneca, Cambridge CB4 0WG, U.K
| | - Zoltan Takáts
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, U.K
| | - Richard J A Goodwin
- Imaging and AI, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, U.K
- Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, U.K
| | - Josephine Bunch
- Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, U.K
- National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory, Teddington TW11 0LW, U.K
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27
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Tuck M, Blanc L, Touti R, Patterson NH, Van Nuffel S, Villette S, Taveau JC, Römpp A, Brunelle A, Lecomte S, Desbenoit N. Multimodal Imaging Based on Vibrational Spectroscopies and Mass Spectrometry Imaging Applied to Biological Tissue: A Multiscale and Multiomics Review. Anal Chem 2020; 93:445-477. [PMID: 33253546 DOI: 10.1021/acs.analchem.0c04595] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Michael Tuck
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
| | - Landry Blanc
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
| | - Rita Touti
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
| | - Nathan Heath Patterson
- Mass Spectrometry Research Center, Department of Biochemistry, Vanderbilt University, Nashville, Tennessee 37232-8575, United States
| | - Sebastiaan Van Nuffel
- Materials Research Institute, The Pennsylvania State University, University Park, Pennsylvania 16802, United States
| | - Sandrine Villette
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
| | - Jean-Christophe Taveau
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
| | - Andreas Römpp
- Bioanalytical Sciences and Food Analysis, University of Bayreuth, Universitätsstraße 30, 95440 Bayreuth, Germany
| | - Alain Brunelle
- Laboratoire d'Archéologie Moléculaire et Structurale, LAMS UMR 8220, CNRS, Sorbonne Université, 4 Place Jussieu, 75005 Paris, France
| | - Sophie Lecomte
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
| | - Nicolas Desbenoit
- Institut de Chimie & Biologie des Membranes & des Nano-objets, CBMN UMR 5248, CNRS, Université de Bordeaux, 1 Allée Geoffroy Saint-Hilaire, 33600 Pessac, France
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28
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Ščupáková K, Dewez F, Walch AK, Heeren RMA, Balluff B. Morphometric Cell Classification for Single-Cell MALDI-Mass Spectrometry Imaging. Angew Chem Int Ed Engl 2020; 59:17447-17450. [PMID: 32668069 PMCID: PMC7540554 DOI: 10.1002/anie.202007315] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 07/04/2020] [Indexed: 12/14/2022]
Abstract
The large-scale and label-free molecular characterization of single cells in their natural tissue habitat remains a major challenge in molecular biology. We present a method that integrates morphometric image analysis to delineate and classify individual cells with their single-cell-specific molecular profiles. This approach provides a new means to study spatial biological processes such as cancer field effects and the relationship between morphometric and molecular features.
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Affiliation(s)
- Klára Ščupáková
- Maastricht MultiModal Molecular Imaging Institute (M4I)University of MaastrichtUniversiteitssingel 506200 MDMaastrichtThe Netherlands
| | - Frédéric Dewez
- Maastricht MultiModal Molecular Imaging Institute (M4I)University of MaastrichtUniversiteitssingel 506200 MDMaastrichtThe Netherlands
- Mass Spectrometry Laboratory (MSLab)University of LiègeBelgium
| | - Axel K. Walch
- Research Unit Analytical PathologyHelmholtz Zentrum MünchenOberschleißheimGermany
| | - Ron M. A. Heeren
- Maastricht MultiModal Molecular Imaging Institute (M4I)University of MaastrichtUniversiteitssingel 506200 MDMaastrichtThe Netherlands
| | - Benjamin Balluff
- Maastricht MultiModal Molecular Imaging Institute (M4I)University of MaastrichtUniversiteitssingel 506200 MDMaastrichtThe Netherlands
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29
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Ščupáková K, Dewez F, Walch AK, Heeren RMA, Balluff B. Morphometric Cell Classification for Single‐Cell MALDI‐Mass Spectrometry Imaging. Angew Chem Int Ed Engl 2020. [DOI: 10.1002/ange.202007315] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Affiliation(s)
- Klára Ščupáková
- Maastricht MultiModal Molecular Imaging Institute (M4I) University of Maastricht Universiteitssingel 50 6200 MD Maastricht The Netherlands
| | - Frédéric Dewez
- Maastricht MultiModal Molecular Imaging Institute (M4I) University of Maastricht Universiteitssingel 50 6200 MD Maastricht The Netherlands
- Mass Spectrometry Laboratory (MSLab) University of Liège Belgium
| | - Axel K. Walch
- Research Unit Analytical Pathology Helmholtz Zentrum München Oberschleißheim Germany
| | - Ron M. A. Heeren
- Maastricht MultiModal Molecular Imaging Institute (M4I) University of Maastricht Universiteitssingel 50 6200 MD Maastricht The Netherlands
| | - Benjamin Balluff
- Maastricht MultiModal Molecular Imaging Institute (M4I) University of Maastricht Universiteitssingel 50 6200 MD Maastricht The Netherlands
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30
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Denti V, Piga I, Guarnerio S, Clerici F, Ivanova M, Chinello C, Paglia G, Magni F, Smith A. Antigen Retrieval and Its Effect on the MALDI-MSI of Lipids in Formalin-Fixed Paraffin-Embedded Tissue. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2020; 31:1619-1624. [PMID: 32678590 PMCID: PMC8009503 DOI: 10.1021/jasms.0c00208] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Formalin-fixed paraffin-embedded (FFPE) tissue represents the primary source of clinical tissue and is routinely used in MALDI-MSI studies. However, it is not particularly suitable for lipidomics imaging given that many species are depleted during tissue processing. Irrespective, a number of solvent-resistant lipids remain, but their extraction may be hindered by the cross-link between proteins. Therefore, an antigen retrieval step could enable the extraction of a greater number of lipids and may provide information that is complementary to that which can be obtained from other biomolecules, such as proteins. In this short communication, we aim to address the effect of performing antigen retrieval prior to MALDI-MSI of lipids in FFPE tissue. As a result, an increased number of lipid signals could be detected and may have derived from lipid species that are known to be implicated in the lipid-protein cross-linking that is formed as a result of formalin fixation. Human renal cancer tissue was used as a proof of concept to determine whether using these detected lipid signals were also able to highlight the histopathological regions that were present. These preliminary findings may highlight the potential to enhance the clinical relevance of the lipidomic information obtained from FFPE tissue.
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Affiliation(s)
- Vanna Denti
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Isabella Piga
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Sonia Guarnerio
- Biomolecular
Sciences Research Centre, Sheffield-Hallam
University, City Campus, Howard Street, Sheffield S1 1WB, United Kingdom
| | - Francesca Clerici
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Mariia Ivanova
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Clizia Chinello
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Giuseppe Paglia
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Fulvio Magni
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
| | - Andrew Smith
- Clinical
Proteomics and Metabolomics Unit, Department of Medicine and Surgery, University of Milano-Bicocca, Vedano al Lambro 20854, Italy
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31
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Guo C, Baluya DL, Thompson EA, Whitley EM, Cressman ENK. Correlation of molecular and morphologic effects of thermoembolization in a swine model using mass spectrometry imaging. JOURNAL OF MASS SPECTROMETRY : JMS 2020; 55:e4477. [PMID: 31804009 PMCID: PMC7145752 DOI: 10.1002/jms.4477] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 11/08/2019] [Accepted: 11/15/2019] [Indexed: 05/03/2023]
Abstract
Hepatocellular carcinoma is a growing worldwide problem with a high mortality rate. This malignancy does not respond well to chemotherapy, and most patients present late in their disease at which time surgery is no longer an option. Over the past three decades, minimally invasive methods have evolved to treat unresectable disease and prolong survival. Intra-arterial embolization techniques are used for large or multiple tumors but have distressingly high levels of local recurrence and can be costly to implement. A new method called thermoembolization was recently reported, which destroys target tissue by combining reactive exothermic chemistry with an extreme local change in pH and ischemia. Described herein are experiments performed using this technique in vivo in a swine model. A microcatheter was advanced under fluoroscopic guidance into a branch of the hepatic artery to deliver a targeted dose of dichloroacetyl chloride dissolved in ethiodized oil into the liver. The following day, the animals were imaged by computed tomography and euthanized. Assessing the reaction product distribution and establishing a correlation with the effects are important for understanding the effects. This presented a significant challenge, however, as the reagent used does not contain a chromophore and is not otherwise readily detectable. Mass spectrometry imaging was employed to determine spatial distribution in treated samples. Additional insights on the biology were obtained by correlating the results with histology, immunohistochemistry, and immunofluorescence. The results are encouraging and may lead to a therapy with less local recurrence and improved overall survival for patients with this disease.
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Affiliation(s)
- Chunxiao Guo
- Department of Interventional Radiology, UT MD Anderson Cancer Center, Houston, Texas, USA
| | - Dodge L Baluya
- Department of Interventional Radiology, UT MD Anderson Cancer Center, Houston, Texas, USA
| | - Emily A Thompson
- Department of Interventional Radiology, UT MD Anderson Cancer Center, Houston, Texas, USA
| | - Elizabeth M Whitley
- Department of Veterinary Medicine and Surgery, UT MD Anderson Cancer Center, Houston, Texas, USA
| | - Erik N K Cressman
- Department of Interventional Radiology, UT MD Anderson Cancer Center, Houston, Texas, USA
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32
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Fournelle F, Yang E, Dufresne M, Chaurand P. Minimizing Visceral Fat Delocalization on Tissue Sections with Porous Aluminum Oxide Slides for Imaging Mass Spectrometry. Anal Chem 2020; 92:5158-5167. [DOI: 10.1021/acs.analchem.9b05665] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Frédéric Fournelle
- Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada H2V 0B3
| | - Ethan Yang
- Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada H2V 0B3
| | - Martin Dufresne
- Mass Spectrometry Research Center, Vanderbilt University, Nashville, Tennessee 37205, United States
| | - Pierre Chaurand
- Department of Chemistry, Université de Montréal, Montreal, Quebec, Canada H2V 0B3
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33
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Tucker LH, Hamm GR, Sargeant RJE, Goodwin RJA, Mackay CL, Campbell CJ, Clarke DJ. Untargeted Metabolite Mapping in 3D Cell Culture Models Using High Spectral Resolution FT-ICR Mass Spectrometry Imaging. Anal Chem 2019; 91:9522-9529. [DOI: 10.1021/acs.analchem.9b00661] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Lulu H. Tucker
- EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom
| | - Gregory R. Hamm
- Pathology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, United Kingdom
| | - Rebecca J. E. Sargeant
- Pathology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, United Kingdom
| | - Richard J. A. Goodwin
- Pathology, Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0WG, United Kingdom
| | - C. Logan Mackay
- EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom
| | - Colin J. Campbell
- EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom
| | - David J. Clarke
- EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom
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34
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Nozaki K, Nakabayashi Y, Murakami T, Miyazato A, Osaka I. Novel approach to enhance sensitivity in surface-assisted laser desorption/ionization mass spectrometry imaging using deposited organic-inorganic hybrid matrices. JOURNAL OF MASS SPECTROMETRY : JMS 2019; 54:612-619. [PMID: 31070274 DOI: 10.1002/jms.4370] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Revised: 04/16/2019] [Accepted: 05/02/2019] [Indexed: 06/09/2023]
Abstract
Sample pretreatment is key to obtaining good data in matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). Although sublimation is one of the best methods for obtaining homogenously fine organic matrix crystals, its sensitivity can be low due to the lack of a solvent extraction effect. We investigated the effect of incorporating a thin film of metal formed by zirconium (Zr) sputtering into the sublimation process for MALDI matrix deposition for improving the detection sensitivity in mouse liver tissue sections treated with olanzapine. The matrix-enhanced surface-assisted laser desorption/ionization (ME-SALDI) method, where a matrix was formed by sputtering Zr to form a thin nanoparticle layer before depositing MALDI organic matrix comprising α-cyano-4-hydroxycinnamic acid (CHCA) by sublimation, resulted in a significant improvement in sensitivity, with the ion intensity of olanzapine being about 1800 times that observed using the MALDI method, comprising CHCA sublimation alone. When Zr sputtering was performed after CHCA deposition, however, no such enhancement in sensitivity was observed. The enhanced sensitivity due to Zr sputtering was also observed when the CHCA solution was applied by spraying, being about twice as high as that observed by CHCA spraying alone. In addition, the detection sensitivity of these various pretreatment methods was similar for endogenous glutathione. Given that sample preparation using the ME-SALDI-MSI method, which combines Zr sputtering with the sublimation method for depositing an organic matrix, does not involve a solvent, delocalization problems such as migration of analytes observed after matrix spraying and washing with aqueous solutions as sample pretreatment are not expected. Therefore, ME-Zr-SALDI-MSI is a novel sample pretreatment method that can improve the sensitivity of analytes while maintaining high spatial resolution in MALDI-MSI.
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Affiliation(s)
- Kazuyoshi Nozaki
- Bioimaging, Analysis & Pharmacokinetics Research Labs. Drug Discovery research, Astellas Pharma Inc, 21 Miyukigaoka, Tsukuba-shi, Ibaraki, 305-8585, Japan
| | - Yuji Nakabayashi
- Center for Nano Material and Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan
| | - Tatsuya Murakami
- Center for Nano Material and Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan
| | - Akio Miyazato
- Center for Nano Material and Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan
| | - Issey Osaka
- Department of Pharmaceutical Engineering, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu-City, Toyama, 939-0398, Japan
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35
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Han J, Permentier H, Bischoff R, Groothuis G, Casini A, Horvatovich P. Imaging of protein distribution in tissues using mass spectrometry: An interdisciplinary challenge. Trends Analyt Chem 2019. [DOI: 10.1016/j.trac.2018.12.016] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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36
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A patch-based super resolution algorithm for improving image resolution in clinical mass spectrometry. Sci Rep 2019; 9:2915. [PMID: 30814528 PMCID: PMC6393664 DOI: 10.1038/s41598-019-38914-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Accepted: 01/09/2019] [Indexed: 01/07/2023] Open
Abstract
Mass spectrometry imaging (MSI) and histology are complementary analytical tools. Integration of the two imaging modalities can enhance the spatial resolution of the MSI beyond its experimental limits. Patch-based super resolution (PBSR) is a method where high spatial resolution features from one image modality guide the reconstruction of a low resolution image from a second modality. The principle of PBSR lies in image redundancy and aims at finding similar pixels in the neighborhood of a central pixel that are then used to guide reconstruction of the central pixel. In this work, we employed PBSR to increase the resolution of MSI. We validated the proposed pipeline by using a phantom image (micro-dissected logo within a tissue) and mouse cerebellum samples. We compared the performance of the PBSR with other well-known methods: linear interpolation (LI) and image fusion (IF). Quantitative and qualitative assessment showed advantage over the former and comparability with the latter. Furthermore, we demonstrated the potential applicability of PBSR in a clinical setting by accurately integrating structural (i.e., histological) and molecular (i.e., MSI) information from a case study of a dog liver.
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37
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Assadsangabi A, Evans CA, Corfe BM, Lobo A. Application of Proteomics to Inflammatory Bowel Disease Research: Current Status and Future Perspectives. Gastroenterol Res Pract 2019; 2019:1426954. [PMID: 30774653 PMCID: PMC6350533 DOI: 10.1155/2019/1426954] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 10/08/2018] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic relapsing/remitting inflammatory illness of the gastrointestinal tract of unknown aetiology. Despite recent advances in decoding the pathophysiology of IBD, many questions regarding disease pathogenesis remain. Genome-wide association studies (GWAS) and knockout mouse models have significantly advanced our understanding of genetic susceptibility loci and inflammatory pathways involved in IBD pathogenesis. Despite their important contribution to a better delineation of the disease process in IBD, these genetic findings have had little clinical impact to date. This is because the presence of a given gene mutation does not automatically correspond to changes in its expression or final metabolic or structural effect(s). Furthermore, the existence of these gene susceptibility loci in the normal population suggests other driving prerequisites for the disease manifestation. Proteins can be considered the main functional units as almost all intracellular physiological functions as well as intercellular interactions are dependent on them. Proteomics provides methods for the large-scale study of the proteins encoded by the genome of an organism or a cell, to directly investigate the proteins and pathways involved. Understanding the proteome composition and alterations yields insights into IBD pathogenesis as well as identifying potential biomarkers of disease activity, mucosal healing, and cancer progression. This review describes the state of the art in the field with respect to the study of IBD and the potential for translation from biomarker discovery to clinical application.
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Affiliation(s)
- Arash Assadsangabi
- Gastroenterology Unit, Salford Royal Hospital, Salford, UK
- Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology and Insigneo Institute, University of Sheffield, Sheffield, UK
| | - Caroline A. Evans
- Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, UK
| | - Bernard M. Corfe
- Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology and Insigneo Institute, University of Sheffield, Sheffield, UK
| | - Alan Lobo
- Gastroenterology Unit, Salford Royal Hospital, Salford, UK
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38
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Vaysse PM, Heeren RMA, Porta T, Balluff B. Mass spectrometry imaging for clinical research - latest developments, applications, and current limitations. Analyst 2018. [PMID: 28642940 DOI: 10.1039/c7an00565b] [Citation(s) in RCA: 138] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Mass spectrometry is being used in many clinical research areas ranging from toxicology to personalized medicine. Of all the mass spectrometry techniques, mass spectrometry imaging (MSI), in particular, has continuously grown towards clinical acceptance. Significant technological and methodological improvements have contributed to enhance the performance of MSI recently, pushing the limits of throughput, spatial resolution, and sensitivity. This has stimulated the spread of MSI usage across various biomedical research areas such as oncology, neurological disorders, cardiology, and rheumatology, just to name a few. After highlighting the latest major developments and applications touching all aspects of translational research (i.e. from early pre-clinical to clinical research), we will discuss the present challenges in translational research performed with MSI: data management and analysis, molecular coverage and identification capabilities, and finally, reproducibility across multiple research centers, which is the largest remaining obstacle in moving MSI towards clinical routine.
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Affiliation(s)
- Pierre-Maxence Vaysse
- Maastricht MultiModal Molecular Imaging (M4I) institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
| | - Ron M A Heeren
- Maastricht MultiModal Molecular Imaging (M4I) institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
| | - Tiffany Porta
- Maastricht MultiModal Molecular Imaging (M4I) institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
| | - Benjamin Balluff
- Maastricht MultiModal Molecular Imaging (M4I) institute, Division of Imaging Mass Spectrometry, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
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39
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Maganti RJ, Hronowski XL, Dunstan RW, Wipke BT, Zhang X, Jandreski L, Hamann S, Juhasz P. Defining Changes in the Spatial Distribution and Composition of Brain Lipids in the Shiverer and Cuprizone Mouse Models of Myelin Disease. J Histochem Cytochem 2018; 67:203-219. [PMID: 30501365 PMCID: PMC6393840 DOI: 10.1369/0022155418815860] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Myelin is composed primarily of lipids and diseases affecting myelin are associated with alterations in its lipid composition. However, correlation of the spatial (in situ) distribution of lipids with the disease-associated compositional and morphological changes is not well defined. Herein we applied high resolution matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS), immunohistochemistry (IHC), and liquid chromatography–electrospray ionization–mass spectrometry (LC-ESI-MS) to evaluate brain lipid alterations in the dysmyelinating shiverer (Shi) mouse and cuprizone (Cz) mouse model of reversible demyelination. MALDI-IMS revealed a decrease in the spatial distribution of sulfatide (SHexCer) species, SHexCer (d42:2), and a phosphatidylcholine (PC) species, PC (36:1), in white matter regions like corpus callosum (CC) both in the Shi mouse and Cz mouse model. Changes in these lipid species were restored albeit not entirely upon spontaneous remyelination after demyelination in the Cz mouse model. Lipid distribution changes correlated with the local morphological changes as confirmed by IHC. LC-ESI-MS analyses of CC extracts confirmed the MALDI-IMS derived reductions in SHexCer and PC species. These findings highlight the role of SHexCer and PC in preserving the normal myelin architecture and our experimental approaches provide a morphological basis to define lipid abnormalities relevant to myelin diseases.
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Affiliation(s)
| | | | - Robert W Dunstan
- Biogen, Cambridge, Massachusetts.,AbbVie, Worcester, Massachusetts
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40
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Michno W, Wehrli PM, Blennow K, Zetterberg H, Hanrieder J. Molecular imaging mass spectrometry for probing protein dynamics in neurodegenerative disease pathology. J Neurochem 2018; 151:488-506. [PMID: 30040875 DOI: 10.1111/jnc.14559] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 07/03/2018] [Accepted: 07/12/2018] [Indexed: 12/14/2022]
Abstract
Recent advances in the understanding of basic pathological mechanisms in various neurological diseases depend directly on the development of novel bioanalytical technologies that allow sensitive and specific chemical imaging at high resolution in cells and tissues. Mass spectrometry-based molecular imaging (IMS) has gained increasing popularity in biomedical research for mapping the spatial distribution of molecular species in situ. The technology allows for comprehensive, untargeted delineation of in situ distribution profiles of metabolites, lipids, peptides and proteins. A major advantage of IMS over conventional histochemical techniques is its superior molecular specificity. Imaging mass spectrometry has therefore great potential for probing molecular regulations in CNS-derived tissues and cells for understanding neurodegenerative disease mechanism. The goal of this review is to familiarize the reader with the experimental workflow, instrumental developments and methodological challenges as well as to give a concise overview of the major advances and recent developments and applications of IMS-based protein and peptide profiling with particular focus on neurodegenerative diseases. This article is part of the Special Issue "Proteomics".
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Affiliation(s)
- Wojciech Michno
- Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
| | - Patrick M Wehrli
- Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
| | - Kaj Blennow
- Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
| | - Henrik Zetterberg
- Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.,Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.,Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.,UK Dementia Research Institute at UCL, London, UK
| | - Jörg Hanrieder
- Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.,Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, London, UK.,Department of Chemistry and Chemical Engineering, Chalmers University of Technology, Gothenburg, Sweden
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41
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Patterson NH, Tuck M, Van de Plas R, Caprioli RM. Advanced Registration and Analysis of MALDI Imaging Mass Spectrometry Measurements through Autofluorescence Microscopy. Anal Chem 2018; 90:12395-12403. [PMID: 30272960 DOI: 10.1021/acs.analchem.8b02884] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
The correlation of imaging mass spectrometry (IMS) with histopathology can help relate novel molecular findings obtained through IMS to the well-characterized and validated histopathology knowledge base. The quality of correlation between these two modalities is limited by the quality of the spatial mapping that is obtained by registration of the two image types. In this work, we develop novel workflows for MALDI IMS-to-microscopy data registration and analysis using nondestructive IMS-compatible wide field autofluorescence (AF) microscopy combined with computational image registration. First, a substantially automated procedure for high-accuracy registration between IMS and microscopy data of the same section is described that explicitly links the MALDI laser ablation pattern imaged by microscopy to its corresponding IMS pixel. Subsequent examination of the registered data allows for high-confidence colocalization of image features between the two modalities, down to single-cell scales within tissue. Building on this IMS-microscopy spatial mapping, we furthermore demonstrate the automated spatial correlation between IMS measurements from serial sections. This AF-registration-driven inter-section analysis, using a combination of nonlinear AF-to-AF and IMS-to-AF image registrations, can be applied to tissue sections that are prepared and imaged with different sample preparations (e.g., lipids vs proteins) and/or that are measured using different spatial resolutions. Importantly, all registrations, whether within a single section or across serial sections, are entirely independent of the IMS intensity signal content and thus unbiased by it.
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Affiliation(s)
| | | | - Raf Van de Plas
- Delft Center for Systems and Control (DCSC) , Delft University of Technology , 2628 CD Delft , The Netherlands
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42
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Patterson NH, Tuck M, Lewis A, Kaushansky A, Norris JL, Van de Plas R, Caprioli RM. Next Generation Histology-Directed Imaging Mass Spectrometry Driven by Autofluorescence Microscopy. Anal Chem 2018; 90:12404-12413. [PMID: 30274514 DOI: 10.1021/acs.analchem.8b02885] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Histology-directed imaging mass spectrometry (IMS) is a spatially targeted IMS acquisition method informed by expert annotation that provides rapid molecular characterization of select tissue structures. The expert annotations are usually determined on digital whole slide images of histological stains where the staining preparation is incompatible with optimal IMS preparation, necessitating serial sections: one for annotation, one for IMS. Registration is then used to align staining annotations onto the IMS tissue section. Herein, we report a next-generation histology-directed platform implementing IMS-compatible autofluorescence (AF) microscopy taken prior to any staining or IMS. The platform enables two histology-directed workflows, one that improves the registration process between two separate tissue sections using automated, computational monomodal AF-to-AF microscopy image registration, and a registration-free approach that utilizes AF directly to identify ROIs and acquire IMS on the same section. The registration approach is fully automated and delivers state of the art accuracy in histology-directed workflows for transfer of annotations (∼3-10 μm based on 4 organs from 2 species) while the direct AF approach is registration-free, allowing targeting of the finest structures visible by AF microscopy. We demonstrate the platform in biologically relevant case studies of liver stage malaria and human kidney disease with spatially targeted acquisition of sparsely distributed (composing less than one tenth of 1% of the tissue section area) malaria infected mouse hepatocytes and glomeruli in the human kidney case study.
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Affiliation(s)
| | | | - Adam Lewis
- Center for Infectious Disease Research , formerly Seattle Biomedical Research Institute, Seattle , Washington 98109 , United States.,Department of Global Health , University of Washington , Seattle , Washington 98195 , United States
| | - Alexis Kaushansky
- Center for Infectious Disease Research , formerly Seattle Biomedical Research Institute, Seattle , Washington 98109 , United States.,Department of Global Health , University of Washington , Seattle , Washington 98195 , United States
| | | | - Raf Van de Plas
- Delft Center for Systems and Control (DCSC) , Delft University of Technology , 2628 CD , Delft , The Netherlands
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43
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Tobias F, Olson MT, Cologna SM. Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1. J Lipid Res 2018; 59:2446-2455. [PMID: 30266834 DOI: 10.1194/jlr.d086090] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Revised: 09/24/2018] [Indexed: 12/12/2022] Open
Abstract
Mass spectrometry imaging (MSI) is a tool to rapidly map the spatial location of analytes without the need for tagging or a reporter system. Niemann-Pick disease type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder characterized by accumulation of unesterified cholesterol and sphingolipids in the endo-lysosomal system. Here, we use MSI to visualize lipids including cholesterol in cerebellar brain tissue from the NPC1 symptomatic mouse model and unaffected controls. To complement the imaging studies, a data-processing pipeline was developed to generate consensus mass spectra, thereby using both technical and biological image replicates to assess differences. The consensus spectra are used to determine true differences in lipid relative abundance; lipid distributions can be determined in an unbiased fashion without prior knowledge of location. We show the cerebellar distribution of gangliosides GM1, GM2, and GM3, including variants of lipid chain length. We also performed MALDI-MSI of cholesterol. Further analysis of lobules IV/V and X of the cerebellum gangliosides indicates regional differences. The specificity achieved highlights the power of MSI, and this new workflow demonstrates a universal approach for addressing reproducibility in imaging experiments applied to NPC1.
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Affiliation(s)
- Fernando Tobias
- Department of Chemistry University of Illinois at Chicago, Chicago, IL 60607
| | - Matthew T Olson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL 32224
| | - Stephanie M Cologna
- Department of Chemistry University of Illinois at Chicago, Chicago, IL 60607 .,Laboratory of Integrative Neuroscience, University of Illinois at Chicago, Chicago, IL 60607
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44
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Unveiling the olfactory proteostatic disarrangement in Parkinson's disease by proteome-wide profiling. Neurobiol Aging 2018; 73:123-134. [PMID: 30342273 DOI: 10.1016/j.neurobiolaging.2018.09.018] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 09/03/2018] [Accepted: 09/14/2018] [Indexed: 01/07/2023]
Abstract
Olfactory dysfunction is one of the earliest features in Lewy-type alpha-synucleinopathies (LTSs) such as Parkinson's disease (PD). However, the underlying molecular mechanisms associated to smell impairment are poorly understood. Applying mass spectrometry-based quantitative proteomics in postmortem olfactory bulbs across limbic, early-neocortical, and neocortical LTS stages of parkinsonian patients, a proteostasis impairment, was observed, identifying 268 differentially expressed proteins between controls and PD phenotypes. In addition, network-driven proteomics revealed a modulation in ERK1/2, MKK3/6, and PDK1/PKC signaling axes. Moreover, a cross-disease study of selected olfactory molecules in sporadic Alzheimer's disease (AD) cases revealed different protein derangements in the modulation of secretagogin (SCGN), calcyclin-binding protein (CACYBP), and glucosamine 6 phosphate isomerase 2 (GNPDA2) between PD and AD. An inverse correlation between GNPDA2 and α-synuclein protein levels was also reflected in PD cerebrospinal fluid. Interestingly, PD patients exhibited significantly lower serum GNPDA2 levels than controls (n = 82/group). Our study provides important avenues for understanding the olfactory bulb proteostasis imbalance in PD, deciphering mechanistic clues to the equivalent smell deficits observed in AD and PD pathologies.
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45
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Dilillo M, Heijs B, McDonnell LA. Mass spectrometry imaging: How will it affect clinical research in the future? Expert Rev Proteomics 2018; 15:709-716. [PMID: 30203995 DOI: 10.1080/14789450.2018.1521278] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Mass spectrometry imaging (MSI) is a label free, multiplex imaging technology able to simultaneously record the distributions of 100's to 1000's of species, and which may be configured to study metabolites, lipids, glycans, peptides, and proteins simply by changing the tissue preparation protocol. Areas covered: The capability of MSI to complement established histopathological practice through the identification of biomarkers for differential diagnosis, patient prognosis, and response to therapy; the capability of MSI to annotate tissues on the basis of each pixel's mass spectral signature; the development of reproducible MSI through multicenter studies. Expert commentary: We discuss how MSI can be combined with microsampling/microdissection technologies in order to investigate, with more depth of coverage, the molecular changes uncovered by MSI.
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Affiliation(s)
| | - Bram Heijs
- b Center for Proteomics and Metabolomics , Leiden University Medical Center , Leiden , The Netherlands
| | - Liam A McDonnell
- a Fondazione Pisana per la Scienza ONLUS , Pisa , Italy.,b Center for Proteomics and Metabolomics , Leiden University Medical Center , Leiden , The Netherlands
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46
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Neumann EK, Comi TJ, Spegazzini N, Mitchell JW, Rubakhin SS, Gillette MU, Bhargava R, Sweedler JV. Multimodal Chemical Analysis of the Brain by High Mass Resolution Mass Spectrometry and Infrared Spectroscopic Imaging. Anal Chem 2018; 90:11572-11580. [PMID: 30188687 DOI: 10.1021/acs.analchem.8b02913] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The brain functions through chemical interactions between many different cell types, including neurons and glia. Acquiring comprehensive information on complex, heterogeneous systems requires multiple analytical tools, each of which have unique chemical specificity and spatial resolution. Multimodal imaging generates complementary chemical information via spatially localized molecular maps, ideally from the same sample, but requires method enhancements that span from data acquisition to interpretation. We devised a protocol for performing matrix-assisted laser desorption/ionization (MALDI)-Fourier transform ion cyclotron resonance-mass spectrometry imaging (MSI), followed by infrared (IR) spectroscopic imaging on the same specimen. Multimodal measurements from the same tissue provide precise spatial alignment between modalities, enabling more advanced image processing such as image fusion and sharpening. Performing MSI first produces higher quality data from each technique compared to performing IR imaging before MSI. The difference is likely due to fixing the tissue section during MALDI matrix removal, thereby preventing analyte degradation occurring during IR imaging from an unfixed specimen. Leveraging the unique capabilities of each modality, we utilized pan sharpening of MS (mass spectrometry) ion images with selected bands from IR spectroscopy and midlevel data fusion. In comparison to sharpening with histological images, pan sharpening can employ a plethora of IR bands, producing sharpened MS images while retaining the fidelity of the initial ion images. Using Laplacian pyramid sharpening, we determine the localization of several lipids present within the hippocampus with high mass accuracy at 5 μm pixel widths. Further, through midlevel data fusion of the imaging data sets combined with k-means clustering, the combined data set discriminates between additional anatomical structures unrecognized by the individual imaging approaches. Significant differences between molecular ion abundances are detected between relevant structures within the hippocampus, such as the CA1 and CA3 regions. Our methodology provides high quality multiplex and multimodal chemical imaging of the same tissue sample, enabling more advanced data processing and analysis routines.
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47
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Su Y, Liu Y, Behrens CR, Bidlingmaier S, Lee NK, Aggarwal R, Sherbenou DW, Burlingame AL, Hann BC, Simko JP, Premasekharan G, Paris PL, Shuman MA, Seo Y, Small EJ, Liu B. Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer. JCI Insight 2018; 3:121497. [PMID: 30185663 DOI: 10.1172/jci.insight.121497] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 07/24/2018] [Indexed: 12/25/2022] Open
Abstract
Although initially responsive to androgen signaling inhibitors (ASIs), metastatic castration-resistant prostate cancer (mCRPC) inevitably develops and is incurable. In addition to adenocarcinoma (adeno), neuroendocrine prostate cancer (NEPC) emerges to confer ASI resistance. We have previously combined laser capture microdissection and phage antibody display library selection on human cancer specimens and identified novel internalizing antibodies binding to tumor cells residing in their tissue microenvironment. We identified the target antigen for one of these antibodies as CD46, a multifunctional protein that is best known for negatively regulating the innate immune system. CD46 is overexpressed in primary tumor tissue and CRPC (localized and metastatic; adeno and NEPC), but expressed at low levels on normal tissues except for placental trophoblasts and prostate epithelium. Abiraterone- and enzalutamide-treated mCRPC cells upregulate cell surface CD46 expression. Genomic analysis showed that the CD46 gene is gained in 45% abiraterone-resistant mCRPC patients. We conjugated a tubulin inhibitor to our macropinocytosing anti-CD46 antibody and showed that the resulting antibody-drug conjugate (ADC) potently and selectively kills both adeno and NEPC cell lines in vitro (sub-nM EC50) but not normal cells. CD46 ADC regressed and eliminated an mCRPC cell line xenograft in vivo in both subcutaneous and intrafemoral models. Exploratory toxicology studies of the CD46 ADC in non-human primates demonstrated an acceptable safety profile. Thus, CD46 is an excellent target for antibody-based therapy development, which has potential to be applicable to both adenocarcinoma and neuroendocrine types of mCRPC that are resistant to current treatment.
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Affiliation(s)
| | | | | | | | | | - Rahul Aggarwal
- Department of Medicine.,Helen Diller Family Comprehensive Cancer Center
| | | | | | | | - Jeffry P Simko
- Helen Diller Family Comprehensive Cancer Center.,Department of Pathology
| | | | - Pamela L Paris
- Helen Diller Family Comprehensive Cancer Center.,Department of Urology, and
| | | | - Youngho Seo
- Department of Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA
| | - Eric J Small
- Department of Medicine.,Helen Diller Family Comprehensive Cancer Center.,Department of Urology, and
| | - Bin Liu
- Department of Anesthesia.,Helen Diller Family Comprehensive Cancer Center
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Simultaneous cancer and tumor microenvironment subtyping using confocal infrared microscopy for all-digital molecular histopathology. Proc Natl Acad Sci U S A 2018; 115:E5651-E5660. [PMID: 29866827 PMCID: PMC6016804 DOI: 10.1073/pnas.1719551115] [Citation(s) in RCA: 89] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Cancer alters both the morphological and the biochemical properties of multiple cell types in a tissue. Generally, the morphology of epithelial cells is practical for routine disease diagnoses. Here, infrared spectroscopic imaging biochemically characterizes breast cancer, both epithelial cells and the tumor-associated microenvironment. Unfortunately, conventional spectral analyses are slow. Hence, we designed and built a laser confocal microscope that demonstrates a high signal-to-noise ratio for confident diagnoses. The instrument cuts down imaging time from days to minutes, making the technology feasible for research and clinical translation. Finally, automated human breast cancer biopsy imaging is reported in ∼1 hour, paving the way for routine research into the total tumor (epithelial plus microenvironment) properties and rapid, label-free diagnoses. Histopathology based on spatial patterns of epithelial cells is the gold standard for clinical diagnoses and research in carcinomas; although known to be important, the tissue microenvironment is not readily used due to complex and subjective interpretation with existing tools. Here, we demonstrate accurate subtyping from molecular properties of epithelial cells using emerging high-definition Fourier transform infrared (HD FT-IR) spectroscopic imaging combined with machine learning algorithms. In addition to detecting four epithelial subtypes, we simultaneously delineate three stromal subtypes that characterize breast tumors. While FT-IR imaging data enable fully digital pathology with rich information content, the long spectral scanning times required for signal averaging and processing make the technology impractical for routine research or clinical use. Hence, we developed a confocal design in which refractive IR optics are designed to provide high-definition, rapid spatial scanning and discrete spectral tuning using a quantum cascade laser (QCL) source. This instrument provides simultaneously high resolving power (2-μm pixel size) and high signal-to-noise ratio (SNR) (>1,300), providing a speed increase of ∼50-fold for obtaining classified results compared with present imaging spectrometers. We demonstrate spectral fidelity and interinstrument operability of our developed instrument by accurate analysis of a 100-case breast tissue set that was analyzed in a day, considerably speeding research. Clinical breast biopsies typical of a patients’ caseload are analyzed in ∼1 hour. This study paves the way for comprehensive tumor-microenvironment analyses in feasible time periods, presenting a critical step in practical label-free molecular histopathology.
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49
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Bandu R, Mok HJ, Kim KP. Phospholipids as cancer biomarkers: Mass spectrometry-based analysis. MASS SPECTROMETRY REVIEWS 2018; 37:107-138. [PMID: 27276657 DOI: 10.1002/mas.21510] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 05/19/2016] [Indexed: 05/02/2023]
Abstract
Lipids, particularly phospholipids (PLs), are key components of cellular membrane. PLs play important and diverse roles in cells such as chemical-energy storage, cellular signaling, cell membranes, and cell-cell interactions in tissues. All these cellular processes are pertinent to cells that undergo transformation, cancer progression, and metastasis. Thus, there is a strong possibility that some classes of PLs are expected to present in cancer cells and tissues in cellular physiology. The mass spectrometric soft-ionization techniques, electrospray ionization (ESI), and matrix-assisted laser desorption/ionization (MALDI) are well-established in the proteomics field, have been used for lipidomic analysis in cancer research. This review focused on the applications of mass spectrometry (MS) mainly on ESI-MS and MALDI-MS in the structural characterization, molecular composition and key roles of various PLs present in cancer cells, tissues, blood, and urine, and on their importance for cancer-related problems as well as challenges for development of novel PL-based biomarkers. The profiling of PLs helps to rationalize their functions in biological systems, and will also provide diagnostic information to elucidate mechanisms behind the control of cancer, diabetes, and neurodegenerative diseases. The investigation of cellular PLs with MS methods suggests new insights on various cancer diseases and clinical applications in the drug discovery and development of biomarkers for various PL-related different cancer diseases. PL profiling in tissues, cells and body fluids also reflect the general condition of the whole organism and can indicate the existence of cancer and other diseases. PL profiling with MS opens new prospects to assess alterations of PLs in cancer, screening specific biomarkers and provide a basis for the development of novel therapeutic strategies. © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:107-138, 2018.
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Affiliation(s)
- Raju Bandu
- Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yong-in City, 446-701, Korea
| | - Hyuck Jun Mok
- Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yong-in City, 446-701, Korea
| | - Kwang Pyo Kim
- Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yong-in City, 446-701, Korea
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Rae Buchberger A, DeLaney K, Johnson J, Li L. Mass Spectrometry Imaging: A Review of Emerging Advancements and Future Insights. Anal Chem 2018; 90:240-265. [PMID: 29155564 PMCID: PMC5959842 DOI: 10.1021/acs.analchem.7b04733] [Citation(s) in RCA: 637] [Impact Index Per Article: 91.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Amanda Rae Buchberger
- Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States
| | - Kellen DeLaney
- Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States
| | - Jillian Johnson
- School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, United States
| | - Lingjun Li
- Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States
- School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, United States
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