TY - JOUR
T1 - Multimodal Imaging Mass Spectrometry to Identify Markers of Pulmonary Arterial Hypertension in Human Lung Tissue Using MALDI-ToF, ToF-SIMS, and Hybrid SIMS
AU - Van Nuffel, Sebastiaan
AU - Quatredeniers, Marceau
AU - Pirkl, Alexander
AU - Zakel, Julia
AU - Le Caer, Jean-Pierre
AU - Elie, Nicolas
AU - Vanbellingen, Quentin P.
AU - Dumas, Sebastien Joel
AU - Nakhleh, Morad Kamel
AU - Ghigna, Maria-Rosa
AU - Fadel, Elie
AU - Humbert, Marc
AU - Chaurand, Pierre
AU - Touboul, David
AU - Cohen-Kaminsky, Sylvia
AU - Brunelle, Alain
N1 - Funding Information:
This work was financially supported by the Agence Nationale de la Recherche (France, Grants ANR-2015-CE29-0007-01 and-02 DEFIMAGE) and by the Idex Paris-Saclay Jean d’Alembert fellowship program (France). The work was supported by LabEx LERMIT, Laboratory of Excellence in Research on Medication and Innovative Therapeutics under the Investment for the Future program Agence Nationale de la Recherche (ANR)-11-IDEX-0003-01 within the ANR-10-LABX-0033 (to S.C.-K.), Département Hospitalo-Universitaire Thorax Innovation, and Assistance Publique-Hôpitaux de Paris. This work was also funded by Institut National de la Santé Et de la Recherche Médicale (INSERM), Université Paris-Sud, and Hôpital Marie Lannelongue. The authors would also like to thank the French Pulmonary Hypertension Registry facilities and the French National Referral Center for Severe Pulmonary Hypertension for providing clinical samples and data. In particular, the authors thank Pr. Olaf Mercier, Pr. Dominique Fabre, and Dr. Sasha Mussot, surgeons in the Service de Chirurgie Thoracique & Vasculaire from Hôpital Marie Lannelongue for providing quality human lung tissue samples, as well as Caroline Communaux in the Service d’Anatomopathologie for providing clinical data. The authors would also like to thank Dr. Alex Henderson for the insightful discussions regarding supervised machine learning.
Funding Information:
This work was financially supported by the Agence Nationale de la Recherche (France, Grants ANR-2015-CE29-0007-01 and-02 DEFIMAGE) and by the Idex Paris-Saclay Jean d?Alembert fellowship program (France). The work was supported by LabEx LERMIT, Laboratory of Excellence in Research on Medication and Innovative Therapeutics under the Investment for the Future program Agence Nationale de la Recherche (ANR)-11-IDEX-0003-01 within the ANR-10-LABX-0033 (to S.C.-K.) De?partement Hospitalo-Universitaire Thorax Innovation, and Assistance Publique-Ho?pitaux de Paris. This work was also funded by Institut National de la Sante? Et de la Recherche Me?dicale (INSERM), Universite? Paris-Sud, and Ho?pital Marie Lannelongue. The authors would also like to thank the French Pulmonary Hypertension Registry facilities and the French National Referral Center for Severe Pulmonary Hypertension for providing clinical samples and data. In particular, the authors thank Pr. Olaf Mercier, Pr. Dominique Fabre and Dr. Sasha Mussot, surgeons in the Service de Chirurgie Thoracique & Vasculaire from Ho?pital Marie Lannelongue for providing quality human lung tissue samples as well as Caroline Communaux in the Service d?Anatomopathologie for providing clinical data. The authors woul also like to thank Dr. Alex Henderson for the insightful discussions regarding supervised machine learning.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15-60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at m/z 885.6 as a marker of PAH in human lung tissue. The m/z 885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.
AB - Pulmonary arterial hypertension (PAH) is a rare and deadly disease affecting roughly 15-60 people per million in Europe with a poorly understood pathology. There are currently no diagnostic tools for early detection nor does a curative treatment exist. The lipid composition of arteries in lung samples from human PAH and control patients were investigated using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) combined with time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging. Using random forests as an IMS data analysis technique, it was possible to identify the ion at m/z 885.6 as a marker of PAH in human lung tissue. The m/z 885.6 ion intensity was shown to be significantly higher around diseased arteries and was confirmed to be a diacylglycerophosphoinositol PI(C18:0/C20:4) via MS/MS using a novel hybrid SIMS instrument. The discovery of a potential biomarker opens up new research avenues which may finally lead to a better understanding of the PAH pathology and highlights the vital role IMS can play in modern biomedical research.
KW - MULTIVARIATE-ANALYSIS
KW - RESOLUTION
KW - NANOPARTICLES
KW - SUBLIMATION
KW - IMAGES
KW - CYCLE
KW - PTEN
U2 - 10.1021/acs.analchem.0c02815
DO - 10.1021/acs.analchem.0c02815
M3 - Article
C2 - 32786503
SN - 0003-2700
VL - 92
SP - 12079
EP - 12087
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 17
ER -