Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context
Summary: Background: Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in th...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-08-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642300292X |
| _version_ | 1797746009402507264 |
|---|---|
| author | Oscar Demeulenaere Philippe Mateo René Ferrera Paul-Mathieu Chiaroni Alain Bizé Jianping Dai Lucien Sambin Romain Gallet Mickaël Tanter Clément Papadacci Bijan Ghaleh Mathieu Pernot |
| author_facet | Oscar Demeulenaere Philippe Mateo René Ferrera Paul-Mathieu Chiaroni Alain Bizé Jianping Dai Lucien Sambin Romain Gallet Mickaël Tanter Clément Papadacci Bijan Ghaleh Mathieu Pernot |
| author_sort | Oscar Demeulenaere |
| collection | DOAJ |
| description | Summary: Background: Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in the clinics that can image directly the coronary microvascular vessels. Ultrasound Localization Microscopy (ULM) imaging was recently introduced to map microvascular flows at high spatial resolution (∼10 μm). In this study, we developed an approach to image alterations of the microvascular coronary flow in ex vivo perfused swine hearts. Methods: A porcine model of myocardial ischemia-reperfusion was used to obtain microvascular coronary alterations and no-reflow. Four female hearts with myocardial infarction in addition to 6 controls were explanted and placed immediately in a dedicated preservation and perfusion box manufactured for ultrasound imaging. Microbubbles (MB) were injected into the vasculature to perform Ultrasound Localization Microscopy (ULM) imaging and a linear ultrasound probe mounted on a motorized device was used to scan the heart on multiple slices. The coronary microvascular anatomy and flow velocity was reconstructed using dedicated ULM algorithms and analyzed quantitatively. Findings: We were able to image the coronary microcirculation of ex vivo swine hearts at a resolution of tens of microns and measure flow velocities ranging from 10 mm/s in arterioles up to more than 200 mm/s in epicardial arteries. Under different aortic perfusion pressures, we measured in large arteries of a subset of control hearts an increase of flow velocity from 31 ± 11 mm/s at 87 mmHg to 47 ± 17 mm/s at 132 mmHg (N = 3 hearts, P < 0.05). This increase was compared with a control measurement with a flowmeter in the aorta. We also compared 6 control hearts to 4 hearts in which no-reflow was induced by the occlusion and reperfusion of a coronary artery. Using average MB velocity and average density of MB per unit of surface as two ULM quantitative markers of perfusion, we were able to detect areas of coronary no-reflow in good agreement with a control anatomical pathology analysis of the cardiac tissue. In the no-reflow zone, we measured an average perfusion of 204 ± 305 MB/mm2 compared to 3182 ± 1302 MB/mm2 in the surrounding re-perfused area. Interpretation: We demonstrated this approach can directly image and quantify coronary microvascular obstruction and no-reflow on large mammal perfused hearts. This is a first step for noninvasive, quantitative and affordable assessment of the coronary microcirculation function and particularly coronary microvascular anatomy in the infarcted heart. This approach has the potential to be extended to other clinical situations characterized by microvascular dysfunction. Funding: This study was supported by the French National Research Agency (ANR) under ANR-21-CE19-0002 grant agreement. |
| first_indexed | 2024-03-12T15:30:59Z |
| format | Article |
| id | doaj.art-e7022e9b177d4139acf7e74e533ebbc4 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-03-12T15:30:59Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-e7022e9b177d4139acf7e74e533ebbc42023-08-10T04:34:36ZengElsevierEBioMedicine2352-39642023-08-0194104727Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in contextOscar Demeulenaere0Philippe Mateo1René Ferrera2Paul-Mathieu Chiaroni3Alain Bizé4Jianping Dai5Lucien Sambin6Romain Gallet7Mickaël Tanter8Clément Papadacci9Bijan Ghaleh10Mathieu Pernot11Physics for Medicine, ESPCI, INSERM U1273, CNRS UMR 8063, PSL University, Paris, FrancePhysics for Medicine, ESPCI, INSERM U1273, CNRS UMR 8063, PSL University, Paris, FranceCarMeN, 27102 INSERM U1060, INRA U1397, INSA de Lyon, Université Claude Bernard Lyon 1, Université de Lyon, Villeurbanne, FranceInserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94700, Créteil, France; APHP, Hôpitaux Universitaires Henri Mondor, Service de Cardiologie, F-94000, Créteil, FranceInserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94700, Créteil, FranceInserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94700, Créteil, FranceInserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94700, Créteil, FranceInserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94700, Créteil, France; APHP, Hôpitaux Universitaires Henri Mondor, Service de Cardiologie, F-94000, Créteil, FrancePhysics for Medicine, ESPCI, INSERM U1273, CNRS UMR 8063, PSL University, Paris, FrancePhysics for Medicine, ESPCI, INSERM U1273, CNRS UMR 8063, PSL University, Paris, France; Corresponding author. Physics for Medicine, ESPCI, CNRS, PSL, PariSante Campus, 2-10 rue d'Oradour-sur-Glane, 75015, Paris, France.Inserm U955-IMRB, UPEC, Ecole Nationale Vétérinaire d'Alfort, F-94700, Créteil, FrancePhysics for Medicine, ESPCI, INSERM U1273, CNRS UMR 8063, PSL University, Paris, FranceSummary: Background: Coronary microvascular obstruction also known as no-reflow phenomenon is a major issue during myocardial infarction that bears important prognostic implications. Alterations of the microvascular network remains however challenging to assess as there is no imaging modality in the clinics that can image directly the coronary microvascular vessels. Ultrasound Localization Microscopy (ULM) imaging was recently introduced to map microvascular flows at high spatial resolution (∼10 μm). In this study, we developed an approach to image alterations of the microvascular coronary flow in ex vivo perfused swine hearts. Methods: A porcine model of myocardial ischemia-reperfusion was used to obtain microvascular coronary alterations and no-reflow. Four female hearts with myocardial infarction in addition to 6 controls were explanted and placed immediately in a dedicated preservation and perfusion box manufactured for ultrasound imaging. Microbubbles (MB) were injected into the vasculature to perform Ultrasound Localization Microscopy (ULM) imaging and a linear ultrasound probe mounted on a motorized device was used to scan the heart on multiple slices. The coronary microvascular anatomy and flow velocity was reconstructed using dedicated ULM algorithms and analyzed quantitatively. Findings: We were able to image the coronary microcirculation of ex vivo swine hearts at a resolution of tens of microns and measure flow velocities ranging from 10 mm/s in arterioles up to more than 200 mm/s in epicardial arteries. Under different aortic perfusion pressures, we measured in large arteries of a subset of control hearts an increase of flow velocity from 31 ± 11 mm/s at 87 mmHg to 47 ± 17 mm/s at 132 mmHg (N = 3 hearts, P < 0.05). This increase was compared with a control measurement with a flowmeter in the aorta. We also compared 6 control hearts to 4 hearts in which no-reflow was induced by the occlusion and reperfusion of a coronary artery. Using average MB velocity and average density of MB per unit of surface as two ULM quantitative markers of perfusion, we were able to detect areas of coronary no-reflow in good agreement with a control anatomical pathology analysis of the cardiac tissue. In the no-reflow zone, we measured an average perfusion of 204 ± 305 MB/mm2 compared to 3182 ± 1302 MB/mm2 in the surrounding re-perfused area. Interpretation: We demonstrated this approach can directly image and quantify coronary microvascular obstruction and no-reflow on large mammal perfused hearts. This is a first step for noninvasive, quantitative and affordable assessment of the coronary microcirculation function and particularly coronary microvascular anatomy in the infarcted heart. This approach has the potential to be extended to other clinical situations characterized by microvascular dysfunction. Funding: This study was supported by the French National Research Agency (ANR) under ANR-21-CE19-0002 grant agreement.http://www.sciencedirect.com/science/article/pii/S235239642300292XCoronary microcirculationNo-reflowMedical imagingUltrasoundULM |
| spellingShingle | Oscar Demeulenaere Philippe Mateo René Ferrera Paul-Mathieu Chiaroni Alain Bizé Jianping Dai Lucien Sambin Romain Gallet Mickaël Tanter Clément Papadacci Bijan Ghaleh Mathieu Pernot Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context EBioMedicine Coronary microcirculation No-reflow Medical imaging Ultrasound ULM |
| title | Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context |
| title_full | Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context |
| title_fullStr | Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context |
| title_full_unstemmed | Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context |
| title_short | Assessment of coronary microcirculation alterations in a porcine model of no-reflow using ultrasound localization microscopy: a proof of concept studyResearch in context |
| title_sort | assessment of coronary microcirculation alterations in a porcine model of no reflow using ultrasound localization microscopy a proof of concept studyresearch in context |
| topic | Coronary microcirculation No-reflow Medical imaging Ultrasound ULM |
| url | http://www.sciencedirect.com/science/article/pii/S235239642300292X |
| work_keys_str_mv | AT oscardemeulenaere assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT philippemateo assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT reneferrera assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT paulmathieuchiaroni assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT alainbize assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT jianpingdai assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT luciensambin assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT romaingallet assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT mickaeltanter assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT clementpapadacci assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT bijanghaleh assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext AT mathieupernot assessmentofcoronarymicrocirculationalterationsinaporcinemodelofnoreflowusingultrasoundlocalizationmicroscopyaproofofconceptstudyresearchincontext |