Comprehensive Assessment of Interconnection Between Brain Emotional Activity and Coronary Plaque Instability

Biological Interconnection Between Stress-associated Neurobiological Activity and Atherosclerotic Plaque Instability: A Prospective Cohort Study With OCT-FLIM Dual-modal Intravascular Imaging and Serial 18F-FDG-PET/CT Assessment

Emotional stress is associated with future cardiovascular events. However, the biological interconnection between brain emotional neural activity and acute plaque instability is not fully understood. Optical coherence tomography-Fluorescence Lifetime (OCT-FLIM) dual modal intravascular imaging is a novel technique that enables comprehensive assessment of structural and biochemical characteristics of coronary atheroma and estimates the level of plaque instability. 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) enables simultaneous estimation of multi-system activities including emotional stress, arterial inflammation, and hematopoiesis. The present study aims to prospectively investigate mechanistic linkage between coronary plaque instability, stress-associated neurobiological activity, and macrophage hematopoiesis using OCT-FLIM and 18F-FDG PET/CT imaging assessment.

Study Overview

• Status: Recruiting
• Conditions: Inflammation; Atherosclerosis; Acute Coronary Syndrome; Emotional Stress; Atherosclerosis, Coronary; Hematopoiesis; Atherosclerosis Coronary Artery With Angina Pectoris; Atheroma; Heart
• Intervention / Treatment: Device: OCT-FLIM (optical coherence tomography-fluorescence life time)

Detailed Description

Thirty two patients with multivessel coronary artery disease (including both stable angina and acute coronary syndrome), who have at least one severe obstructive lesion (>70% diameter stenosis) that is considered suitable for percutaneous coronary intervention (PCI), will be included in the study.

Structural/biochemical characteristics of coronary culprit plaque (with or without mild to moderate stenotic non-culprit plaque) will be assessed comprehensively using OCT-FLIM dual modal intravascular imaging.

After coronary revascularization with PCI, subjects will undergo serial 18F-FDG-PET/CT molecular imaging at baseline admission and 6-month follow-up to measure PET signal activities at target tissues including amygdala, carotid artery, aorta, bone marrow, and spleen.

Correlation between OCT-FLIM parameters and baseline PET signals will be assessed to provide insight into the mechanistic linkage between multi-system metabolic activities and coronary plaque instability. Serial PET/CT imaging after 6 month will enable estimation of natural course of multi-system PET signal activities according to different levels of coronary plaque instability.

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

• Study Contact: Name: Jin Won Kim, MD, PhD; Phone Number: +82-2-2626-3006; Email: kjwmm@korea.ac.kr
• Study Contact Backup: Name: Dong Oh Kang, MD, PhD; Phone Number: +82-2-2626-3184; Email: gelly9@naver.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 08308
    • Recruiting
    • Korea University Guro Hospital
    • Contact: Dong Oh Kang, MD, PhD; Phone Number: +82-2-2626-3184; Email: gelly9@naver.com
    • Principal Investigator: JIN WON KIM, MD, PhD
    • Sub-Investigator: Dong Oh Kang, MD, PhD
    • Sub-Investigator: Sunwon Kim, MD, PhD
    • Sub-Investigator: Hongki Yoo, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects are planned to undergo percutaneous coronary intervention with utilization of OCT-FLIM dual modal intravascular imaging for culprit plaque assessment and stent optimization. After PCI, subjects will undergo serial 18F-FDG-PET/CT molecular imaging at baseline and 6-month follow-up.

Description

Inclusion Criteria:

• Age: greater than 20, less than 75
• Patients with severe coronary atherosclerosis (diameter stenosis >70%) requiring coronary revascularization
• Reference vessel diameter: between 2.5 and 4.0 mm
• Obtained informed consent from voluntary participants before study enrollment

Exclusion Criteria:

• Complex coronary lesion (ostial lesion, unprotected left main lesion, chronic total occlusion, grafted vessels, etc)
• Reference vessel diameter: less than 2.5 mm, greater than 4.0 mm
• Coronary lesion with heavy calcification
• Hemodynamic instability during coronary intervention
• Contraindication to antithrombotic therapy
• Chronic renal insufficiency (Serum creatinine >2.0mg/dL)
• Severe liver dysfunction (aspartate transaminase or alanine transferase > 5 times of upper normal limit)
• Pregnancy or potential pregnancy
• Life expectancy less than 1 year
• Patient refused to sign the informed consent at enrollment

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
OCT-FLIM dual modal intravascular imaging with serial 18F-FDG-PET/CT assessment; Group of patients undergoing PCI with comprehensive assessment of coronary plaque with OCT-FLIM dual modal intravascular imaging followed by serial 18F-FDG-PET/CT imaging	Device: OCT-FLIM (optical coherence tomography-fluorescence life time); comprehensive assessment of coronary plaque with OCT-FLIM dual modal intravascular catheter imaging followed by serial 18F-FDG-PET/CT imaging; Other Names: 18F-FDG-PET/CT (positron emission tomography-computed tomography)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline amygdalar activity (Stress-associated neurobiological activity)	Amygdalar target-to-background ratio (TBR) = Amygdalar standardized uptake value (SUV) / Temporal lobe SUV	Baseline (within index admission)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline carotid inflammation (arterial atherosclerotic inflammation)	Carotid TBR = Carotid SUV / Jugular vein SUV	Baseline (within index admission)
Baseline aortic inflammation (arterial atherosclerotic inflammation)	Aorta TBR = Aorta SUV / Jugular vein SUV	Baseline (within index admission)
Baseline bone marrow hematopoiesis (hematopoietic activity)	Bone marrow TBR = Bone marrow SUV / Jugular vein SUV	Baseline (within index admission)
Baseline splenic hematopoiesis (hematopoietic activity)	Spleen TBR = Spleen SUV / Jugular vein SUV	Baseline (within index admission)
Coronary plaque composition estimated by OCT-FLIM	Fluorescence Lifetime values that predicts detailed coronary plaque composition	Baseline (day 1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Follow-up amygdalar activity (Stress-associated neurobiological activity)	Amygdalar TBR = Amygdalar SUV / Temporal lobe SUV	6-month follow-up
Follow-up carotid inflammation (arterial atherosclerotic inflammation)	Carotid TBR = Carotid SUV / Jugular vein SUV	6-month follow-up
Follow-up aortic inflammation (arterial atherosclerotic inflammation)	Aorta TBR = Aorta SUV / Jugular vein SUV	6-month follow-up
Follow-up bone marrow hematopoiesis (hematopoietic activity)	Bone marrow TBR = Bone marrow SUV / Jugular vein SUV	6-month follow-up
Follow-up splenic hematopoiesis (hematopoietic activity)	Spleen TBR = Spleen SUV / Jugular vein SUV	6-month follow-up

Collaborators and Investigators

• Sponsor: Korea University Guro Hospital
• Investigators: Principal Investigator: Jin Won Kim, MD, PhD, Korea University Guro Hospital; Study Director: Dong Oh Kang, MD, PhD, Korea University Guro Hospital; Study Director: Sun Won Kim, MD, PhD, Korea University; Study Director: Hongki Yoo, PhD, Korea Advanced Institute of Science and Technology

Publications and helpful links

General Publications

• Tawakol A, Ishai A, Takx RA, Figueroa AL, Ali A, Kaiser Y, Truong QA, Solomon CJ, Calcagno C, Mani V, Tang CY, Mulder WJ, Murrough JW, Hoffmann U, Nahrendorf M, Shin LM, Fayad ZA, Pitman RK. Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. Lancet. 2017 Feb 25;389(10071):834-845. doi: 10.1016/S0140-6736(16)31714-7. Epub 2017 Jan 12. Erratum In: Lancet. 2017 Feb 25;389(10071):804. Lancet. 2017 Feb 25;389(10071):804.
• Lee MW, Song JW, Kang WJ, Nam HS, Kim TS, Kim S, Oh WY, Kim JW, Yoo H. Comprehensive intravascular imaging of atherosclerotic plaque in vivo using optical coherence tomography and fluorescence lifetime imaging. Sci Rep. 2018 Sep 28;8(1):14561. doi: 10.1038/s41598-018-32951-9.
• Kim S, Yoo H, Kim JW. Long Journey of Intravascular Imaging: What and How to Look at the Atheroma in Coronary Artery. JACC Cardiovasc Imaging. 2021 Sep;14(9):1843-1845. doi: 10.1016/j.jcmg.2020.11.015. Epub 2020 Dec 16. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: April 5, 2021
• First Submitted That Met QC Criteria: April 18, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2022
• Last Update Submitted That Met QC Criteria: August 22, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Optical coherence tomography; PET-CT; Arterial Inflammation; Fluorescence lifetime imaging; High-risk plaque; Amygdalar activity; Hematopoietic activity; Biochemical imaging
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Pathological Conditions, Anatomical; Coronary Disease; Chest Pain; Coronary Artery Disease; Myocardial Ischemia; Inflammation; Atherosclerosis; Acute Coronary Syndrome; Angina Pectoris; Plaque, Atherosclerotic; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Fluorodeoxyglucose F18
• Other Study ID Numbers: SRFC-IT1501-05_a

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Due to patient confidentiality, individual participant data (IPD) will not be shared to other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No