Dynamic Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease

Summary

Coronary artery computed tomographic angiography (CTA) is a widely used, highly accurate technique for the detection of coronary artery disease (CAD), with sensitivity and negative predictive values of over 90% (1-4). Patients with normal CTA findings have an excellent prognosis and do not require further testing for CAD (5). However, like invasive coronary angiography (QCA), CTA is an anatomic test and, unless lesions are very severe (\>90% stenosis), cannot reliably predict the impairment of flow (functional significance) of intermediate grade stenoses.

For this reason, in approximately 15-25% of patients, additional functional testing may be required after CTA, usually in the form of stress testing (6-8). Stress testing is commonly done by exercise or pharmacologic stress with electrocardiographic monitoring and often, imaging of myocardial perfusion by nuclear scintigraphy (MPI) or detection of abnormal contraction by echocardiography. This requires a separate procedure, entailing time, expense and limited risk. Furthermore, in patients with previously known CAD, CTA alone is not an adequate test, because in most cases there are multiple lesions that are possible sources of ischemia.

Over the last 10 years, these investigators and others around the world have developed a method of imaging myocardial perfusion by CT (CTP). This test is an adjunct to the usual Cardiac Computed Tomography Angiography (CCTA) procedure and can be done immediately thereafter, using conventional pharmacologic stress agents. It has demonstrated accuracy in many single center trials, and in this large multicenter study, the CORE320 trial (9,10) which showed a high accuracy in predicting the combined results of QCA plus MPI testing and a second multicenter trial established non-inferiority of myocardial CTP compared with nuclear stress testing (11,12). Additionally, this investigator group has published a direct comparison of diagnostic performance of myocardial CTP imaging and SPECT myocardial perfusion imaging and demonstrated superior diagnostic performance of CTP imaging compared with SPECT for the diagnosis of significant disease on invasive angiography (13).

CTP images can be acquired with two different approaches: static or dynamic. In the CORE320 study, the CTP protocol used static acquisition method. The static CTP method, samples a snapshot of the iodine distribution in the blood pool and the myocardium over a short period of time, targeting either the upslope or the peak of contrast bolus. The notion behind this is that, at the upslope of the contrast, the difference in attenuation value of the ischemic and remote myocardium is at the maximum which enables for qualitative and semi-quantitative assessment of myocardial perfusion defects. The static CTP, however, does not allow for direct quantification of the myocardial blood flow (MBF). One of the drawbacks of static CTP lies in the acquirement of only one sample of data and the possibility of mistiming of the contrast bolus that results in poor contrast-to-tissue ratios by missing the peak attenuation (14). Output and flow rate of the contrast material may affect bolus timing. In addition, the acquisition of data from sequential heartbeats affects the attenuation gradient and may result in a heterogeneous iodine distribution, mimicking perfusion defects (15). Furthermore, the static CTP is limited in detection of balanced ischemia, where the perfusion of the entire myocardium is impaired and therefore there is no reference remote myocardium for comparison for semi-quantitative or qualitative static methods of CTP interpretation.

Dynamic CT perfusion imaging uses serial imaging over time to record the kinetics of iodinated contrast in the arterial blood pool and myocardium. This technique allows for multiple sampling of the myocardium and the blood pool and creating time attenuation curves (TAC) by measuring the change in CT attenuation over time. Mathematical modelling of TACs permits for direct quantification of MBF. Despite its advantages, the use of dynamic CTP were limited in the past. A high temporal resolution and high number of detectors are required for dynamic CTP to allow for entire myocardial coverage, and in order to obtain multiple consecutive images at high heart rates(16,17). But the main challenge of dynamic CTP acquisition was the high radiation dose associated with this technique. Nevertheless, with the introduction of the cutting-edge 320 detector CT scanning systems with fast gantry rotation the issue of the cardiac coverage is eliminated(17). The second-generation 320-row scanners also permit the quantification of the MBF with dynamic CTP acquisition with relatively low-dose of radiation(18,19).

In this study the investigators aim to evaluate the feasibility, safety and accuracy of the low-radiation dose dynamic myocardial CT perfusion compared to static CTP approach to detect hemodynamically significant coronary artery disease.

Conditions

• Coronary Artery Disease
• Ischemia

Interventions

DIAGNOSTIC_TEST

Computed Tomography Angiography

This will be a prospective study comparing the low-dose dynamic vs. static CTP combined with the CTA for detecting hemodynamically significant coronary artery stenosis. Patients will have two 18-20 gauge intravenous lines placed for contrast administration. The following image sequences will be completed: coronary calcium scan (non-contrast), rest coronary arterial imaging (with 4-5 mL/sec intravenous ISOVUE-370 infusion), stress myocardial perfusion imaging 20 minutes after rest acquisition imaging (blood pressure will be checked then an infusion of adenosine will be started for a total of 5 minutes; after 5 minutes of adenosine infusion, CT perfusion imaging will be performed during a 4-5 mL/sec ISOVUE-370 infusion). Total estimated radiation dose: 10.551 mSv.

Sponsors & Collaborators

• Toshiba Medical Systems Corporation, Japan

  collaborator INDUSTRY

• Johns Hopkins University

  lead OTHER

Principal Investigators

• Joao AC Lima, MD · Johns Hopkins School of Medicine

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

45 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-30

Primary Completion

2022-05-08

Completion

2022-05-08

FDA Device

Yes

Countries

• United States

Study Locations