Quantification of Myocardial Blood Flow Using Dynamic PET/CTA Fused Imagery

NCT ID: NCT04221594

Last Updated: 2023-10-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 68 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-11-01
• Study Completion Date: 2023-06-30

Brief Summary

This observational prospective clinical study is to develop software tools to fuse coronary anatomy data obtained from CT coronary angiography with dynamic PET data to noninvasively measure absolute myocardial blood flow, flow reserve and relative flow reserve across specific coronary lesions. Results will be compared to those obtained invasively in the catheterization laboratory.

Detailed Description

This observational prospective clinical study is to develop software tools to fuse coronary anatomy data obtained from CT coronary angiography with dynamic PET data to noninvasively measure absolute myocardial blood flow, flow reserve and relative flow reserve across specific coronary lesions. These results will be compared to those obtained invasively in the catheterization laboratory. The long-term objective of the study is to improve the care of cardiac patients by developing, validating and implementing clinically computer-based methods to noninvasively determine the physiological significance of specific coronary lesions using methods to fuse and quantify multi-modality cardiac imagery.

Conditions

Coronary Artery Disease

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

CAD detection/risk assessment

Patients with angina referred for the assessment of CAD will undergo imaging studies to develop tools to fuse coronary anatomic data obtained from CCTA with dPET data to non-invasively measure absolute MBF, MFR and RFR along vessels centerlines and across coronary lesions.

Invasive Cardiac Catheterization (ICA)

Intervention Type: PROCEDURE

Invasive functional measurements will be performed to assess the functional significance of specific lesions by means of FFR and CFR, and to test the presence of microvascular disease by means of IMR in all vessels for which the procedures are feasible. In summary, a 5- to 7-F guide catheter without side holes is used to engage the coronary artery and a pressure-temperature sensor-tipped guidewire introduced. The pressure sensor is positioned at the distal segment of a target vessel, and intracoronary nitroglycerine (100-200 mg) administered before each measurement. The best systolic and diastolic phase (located between 30-50%, and 60-75% of the cardiac cycle) will be selected for successive processing as it allows a relative motion free visualization of the main vessels and the myocardium.

Coronary Computed Tomographic Angiogram (CCTA)

Intervention Type: PROCEDURE

Fasting patients will undergo a test for coronary calcium by CT; calcium scoring analysis will be done post image data acquisition using the manufacturer's software. Nitroglycerine will be administered in all patients (sublingual administration prior to CCTA initiation). CT acquisitions will be prospectively ECG-gated (30-80% of the cardiac cycle). The acquisition begins with a scout scan to identify the borders of the heart to minimize the field of view and exposure to the patient. A bolus of 60 mL nonionic contrast agent is then injected followed by 60 mL of saline at a rate of 4 mL/s to enhance signal from coronary arteries and blood chambers. In case of irregular heart rate, beta-blockers can be provided to keep optimal heart rate \~65-70 bpm. Trans-axial images are reconstructed by means of a filtered back-projection algorithm.

Dynamic Cardiac Positron Emission Tomography (dPET)

Intervention Type: PROCEDURE

Patients will be asked to fast for 24 hours prior to the test. Before the resting perfusion phase, a single low-dose CT-based transmission scan is acquired for attenuation correction (AC) of all subsequent acquisitions. AC-CT images are automatically registered to the perfusion images, visually verified and manually corrected if necessary. Resting perfusion imaging started with the intravenous injection of a single bolus of 82Rb. Pharmacological stress imaging is obtained after adenosine infusion (140 μg/kg/min) through a peripheral vein, followed by a second dose of 82Rb. Image reconstruction is achieved by means of ordered subset expectation maximization (OSEM) iterative method. The hemodynamic responses to rest/stress tests are collected in terms of mean heart rate, mean blood systolic pressures and diastolic at rest and stress. Dynamic, gated and ungated trans-axial reconstructions are saved in DICOM format for further analysis and processing.

Interventions

Invasive Cardiac Catheterization (ICA)

Invasive functional measurements will be performed to assess the functional significance of specific lesions by means of FFR and CFR, and to test the presence of microvascular disease by means of IMR in all vessels for which the procedures are feasible. In summary, a 5- to 7-F guide catheter without side holes is used to engage the coronary artery and a pressure-temperature sensor-tipped guidewire introduced. The pressure sensor is positioned at the distal segment of a target vessel, and intracoronary nitroglycerine (100-200 mg) administered before each measurement. The best systolic and diastolic phase (located between 30-50%, and 60-75% of the cardiac cycle) will be selected for successive processing as it allows a relative motion free visualization of the main vessels and the myocardium.

Intervention Type: PROCEDURE

Coronary Computed Tomographic Angiogram (CCTA)

Fasting patients will undergo a test for coronary calcium by CT; calcium scoring analysis will be done post image data acquisition using the manufacturer's software. Nitroglycerine will be administered in all patients (sublingual administration prior to CCTA initiation). CT acquisitions will be prospectively ECG-gated (30-80% of the cardiac cycle). The acquisition begins with a scout scan to identify the borders of the heart to minimize the field of view and exposure to the patient. A bolus of 60 mL nonionic contrast agent is then injected followed by 60 mL of saline at a rate of 4 mL/s to enhance signal from coronary arteries and blood chambers. In case of irregular heart rate, beta-blockers can be provided to keep optimal heart rate \~65-70 bpm. Trans-axial images are reconstructed by means of a filtered back-projection algorithm.

Intervention Type: PROCEDURE

Dynamic Cardiac Positron Emission Tomography (dPET)

Patients will be asked to fast for 24 hours prior to the test. Before the resting perfusion phase, a single low-dose CT-based transmission scan is acquired for attenuation correction (AC) of all subsequent acquisitions. AC-CT images are automatically registered to the perfusion images, visually verified and manually corrected if necessary. Resting perfusion imaging started with the intravenous injection of a single bolus of 82Rb. Pharmacological stress imaging is obtained after adenosine infusion (140 μg/kg/min) through a peripheral vein, followed by a second dose of 82Rb. Image reconstruction is achieved by means of ordered subset expectation maximization (OSEM) iterative method. The hemodynamic responses to rest/stress tests are collected in terms of mean heart rate, mean blood systolic pressures and diastolic at rest and stress. Dynamic, gated and ungated trans-axial reconstructions are saved in DICOM format for further analysis and processing.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Adult (≥18 years of age) - as the research topic to be studied is irrelevant to children
• Written consent form
• Patients with prior dynamic PET or CCTA or ICA for any indications

Exclusion Criteria

• Previous history of allergy to iodinated contrast
• Previous CABG
• Serum creatinine levels >1.8 mg/dl unless patient has end stage kidney disease, not producing any urine and dialysis
• History of claustrophobia (CT tunnel length of more than 100 cm)
• Significant arrhythmias or tachycardia
• History of frequent asthma attacks or acting wheezing
• Second- and third-degree heart block
• Systolic blood pressure of < 90 mmHg
• Heart failure with NYHA class III-IV at the time of the CCTA procedure. If it is deemed that, the heart failure has been resolved or the patient was incorrectly labeled as having heart failure the radiology physician in charge will verify the absence of Heart Failure at the time of CCTA and perform the procedure.
• Recent myocardial infarction
• If the patient has been diagnosed with unstable angina within 24 hours prior to CCTA, the patient will not be consented. If the patient does not have the diagnosis of unstable angina and is consented, the radiology physician in charge will verify the absence of unstable angina at the time of CCTA.
• Patients enrolled and consented for the invasive measurements that at the time of catheterization exhibit severe vessel disease and/or obstructions that prevent the operator from safely conducting the measurements will be removed from the study; further research imaging sessions - if planned - will be canceled and patients indicated as "screen failure" in our enrollment log.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Samsung Medical Center

OTHER

Sponsor Role: collaborator

Seoul National University

OTHER

Sponsor Role: collaborator

Chonnam National University Hospital

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Marina Piccinelli

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marina Piccinelli, PhD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Emory Clinic

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Saint Francis Hospital & Heart Center

Roslyn, New York, United States

Chonnam National University

Gwangju, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Countries

United States; South Korea

References

AlBadri A, Piccinelli M, Cho SG, Lee JM, Jaber W, De Cecco CN, Samady H, Koo BK, Bom HS, Garcia EV. Rationale and design of the quantification of myocardial blood flow using dynamic PET/CTA-fused imagery (DEMYSTIFY) to determine physiological significance of specific coronary lesions. J Nucl Cardiol. 2020 Jun;27(3):1030-1039. doi: 10.1007/s12350-020-02052-0. Epub 2020 Feb 5.

Reference Type: DERIVED

PMID: 32026327 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01HL143350-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00107151

Identifier Type: -

Identifier Source: org_study_id