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

NCT04221594 | Completed DMC

• 2 other identifiers: IRB001071511R01HL143350-01
• Study Type: observational
• Target: 68
• Locations: 2 countries
• Sites: 6

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.

Conditions

Coronary Artery Disease

Keywords

Fractional flow reserve; Myocardial blood flow; Relative flow reserve; Non-invasive measure; Cardiac catheterization; CT coronary angiography; Dynamic PET; Invasive coronary angiography; 3D fusion dPET/CTA; FFRCT

Outcome Measures

Primary Outcomes (2)

• Myocardial blood flow (MBF) measurement comparing non-invasive to the traditional approaches

  Myocardial blood flow (MBF) measured in milliliters per minute per gram of tissue is providing unique pathophysiologic and diagnostic information on the function of the coronary macro- and microcirculation.

  Up to 3 months

• Vessel-specific quantification of myocardial blood flow RFR

  Ratio of absolute hyperemic MBFs (abnormal / normal) measured in mL/min/g.

  Up to 3 months

Secondary Outcomes (6)

• Absolute myocardial blood flow (MBF) measurement comparing non-invasive to the traditional approaches

  Up to 3 months

• Myocardial flow reserve (MFR) measurement comparing non-invasive to the traditional approaches

  Up to 3 months

• Fractional Flow Reserve (FFR) measurement comparing non-invasive to the traditional approaches

  Up to 3 months

• Stress myocardial blood flow (sMBF)/Regional myocardial blood flow (rMBF) ratio

  Up to 3 months

• Distal/proximal pressure ratio

  Up to 3 months

Study Arms (1)

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.

Procedure: Invasive Cardiac Catheterization (ICA); Procedure: Coronary Computed Tomographic Angiogram (CCTA); Procedure: Dynamic Cardiac Positron Emission Tomography (dPET)

Interventions

Invasive Cardiac Catheterization (ICA) 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.

CAD detection/risk assessment

Coronary Computed Tomographic Angiogram (CCTA) 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.

CAD detection/risk assessment

Dynamic Cardiac Positron Emission Tomography (dPET) 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.

CAD detection/risk assessment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with angina referred to an initial imaging test for the assessment of CAD will be screened and considered for inclusion in the study. Different hospital policies and guidelines determine which initial test is commonly requested: at Emory University Hospital patients who underwent a dPET will be considered for enrollment; at the South Korean centers patients who received a CTA will be screened. Depending on test results, patients who are referred to undergo a cardiac catheterization, will be invited to participate in the study.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead
• Samsung Medical Center: collaborator
• Seoul National University: collaborator
• Chonnam National University Hospital: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

Emory Clinic

Atlanta, Georgia, 30322, United States

Location

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Saint Francis Hospital & Heart Center

Roslyn, New York, 11576, United States

Location

Chonnam National University

Gwangju, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Related Publications (1)

• 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.

  PMID: 32026327 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Study Officials

• Marina Piccinelli, PhD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 9, 2020
• Study Start: November 1, 2019
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: October 2, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Processed anonymized data and extracted measurements are available now to co-investigators as each evaluable case is completed. All raw data described above is also available to co-investigators now on demand and will be accessible to the co-investigators remotely as soon as the imaging database is operational expected to be online, password protected on May 1, 2020. The same data described in the above paragraph will be available to all others (non-co-investigators) two years after termination of this grant cycle, August 1, 2024.
• Access Criteria: All data is available to all co-investigators now and all others on 8/1/2024.Co-investigators will analyze and test the hypotheses listed in the R01 proposal. Priority for testing the scientific/technical hypotheses will be given to the Emory investigators and those for testing the clinical hypotheses to the external investigators. Other project sub-analysis will be prioritized on a first come first served basis when approved by each of the grant site principal investigators. All others can analyze the data for any purpose starting on 8/1/2024. All shared anonymized data will be available from password protected imaging databases and databases of extracted measurements and clinical demographics databases via a Gmail/Gdrive account being constructed.

Locations

KR (3); US (3)