Franz Von Ziegler, MD

Cardiac CT's promise awaits aid of outcomes studies

Advances in spatial, temporal resolution should help CT provide better functional, anatomic information 

Multislice CT scanners used in cardiac imaging are 16- to 64-slice systems that provide for a slice collimation of 0.5 to 0.75 mm (high spatial resolution) and rotation times of 330 to 420 msec (high temporal resolution). Therefore, a high-resolution data set of the beating heart can be achieved in a single breath-hold period.

The use of retrospective ECG triggering makes possible depiction of the heart in every cardiac phase and cross-sectional image reconstruction, leading to motion-free 2D and 3D images, usually in diastole, or at 65% of the cardiac cycle. ECG-correlated images require a regular heart rate, however, and most experienced centers recommend the use of beta blockers to lower the heart rate below a threshold of 60 to 65 bpm. This step provides for more stable and predictable image quality and also serves to lower radiation exposure. The introduction of technology such as dual-source CT (DSCT) scanners, which work with two radiation tubes and therefore improve temporal resolution to 83 msec, might overcome these limitations.

CT permits exact morphologic imaging of the heart and can document intracardiac calcification well. After injection of contrast agents, anatomic relationships and the dimension and configuration of cardiac chambers can be clearly assessed. Reconstruction of systolic and diastolic images permits assessment of global and regional ventricular function (see figure).1,2

With the exception of cardiac calcification, however, CT plays a very limited clinical role with respect to cardiac function and morphology, as echocardiography in most cases provides all clinically relevant information. If further need for clarification arises, MRI is the next step. But CT can be an alternative in cases in which ECG provides unsatisfactory results and MRI is impossible to perform because of metallic implants or claustrophobia, to provide detailed information on cardiac morphology and function.

The assessment of coronary calcification, which correlates well with atherosclerotic plaque burden and its quantification by various methods (Agatston score, volume, or mass), is now widely accepted for the purpose of risk stratification because its predictive value is significantly higher than that of traditional risk factors.3-6 It remains unclear, however, which patients require such refined risk stratification and benefit from performing calcium scoring.

Most likely, calcium scoring will be useful in those patients who are considered to be at intermediate risk following traditional risk assessment. Neither calcium scoring in patients who are clearly at high risk nor unselected screening of the general population is reasonable. Also inappropriate is repeated or follow-up coronary calcium scanning. It is important to note that in asymptomatic individuals, the demonstration of even very large amounts of calcium is no reason by itself to perform invasive coronary angiography, because even pronounced coronary calcium, though a sign of high plaque burden, is not necessarily associated with the presence of significant coronary stenosis.

The beneficial utilization of high-resolution contrast-enhanced CT angiography of the entire coronary artery tree is attracting considerable interest. One of the central rationales for this application has been the noninvasive detection and grading of coronary artery stenosis. It must not be forgotten, however, that visualization of the small, tortuous, and rapidly moving coronary arteries stretches the temporal and spatial resolution of CT to its limits. Preselection by sinus rhythm, preparation of patients through heart rate control with beta blockers if needed and nitrates to dilate the coronary arteries, and very careful image acquisition are mandatory to achieve reliable results. The image quality of MSCT, for which a maximum spatial resolution of 0.4 x 0.4 x 0.4 mm is assumed under optimal conditions, does not equal that of conventional invasive coronary angiography.

In experienced hands, nevertheless, a high sensitivity (82% to 95%) and specificity (95% to 96%) for the detection of hemodynamically relevant coronary artery stenosis can be achieved. The percentage of unevaluable coronary artery segments is generally lower than 12%. Moreover, all studies, even with the use of 16-slice CT, consistently report a very high negative predictive value (96% to 99%).7,8 Although these results may be influenced by the relatively low prevalence of coronary stenoses in most studies, they nonetheless indicate that MSCT may be a reliable technology to noninvasively rule out the presence of significant coronary stenosis in such patient populations if performed with the latest generation of CT scanners.

Congenital coronary anomalies are infrequent but sometimes clinically significant. Assessment of atypical origin and course of anomalous coronary arteries can be difficult and time-consuming by invasive angiography, whereas several studies have shown that MSCT offers the possibility to reliably investigate the exact anatomic relationship.9,10

MSCT angiography, despite its encouraging results, has a number of limitations and cannot be expected to widely replace invasive cardiac catheterization in the near future. Pronounced coronary calcification and, especially in patients with high heart rates, motion artifacts can render images difficult or even impossible to interpret. Patients with atrial fibrillation or other arrhythmias cannot be evaluated. New and faster scanner generations such as DSCT may overcome these restrictions.

Coronary CTA is also a purely diagnostic tool. Unlike invasive catheter-based angiography, it offers no possibility for an immediate coronary intervention. Therefore, patients who, on the basis of their clinical presentation, have a very high likelihood of significant stenosis-those with absolutely typical chest pain and an unambiguously positive stress test-will not benefit from noninvasive angiography of any kind.

The high negative predictive value of coronary MSCT angiography, however, may make its clinical application in place of an invasive procedure quite useful in patients who are symptomatic but do not have a high pretest likelihood of coronary stenosis. If CTA can clearly rule out coronary heart disease, invasive angiography is not necessary. But unselected screening of asymptomatic individuals is not justified.

Unlike catheter angiography, CTA's cross-sectional nature enables assessment of the vessel wall as well. This offers a potential strength for noninvasive identification and characterization of atherosclerotic disease and is currently being evaluated. Several recent publications have shown that MSCT also permits visualization and characterization of fibrous, lipid-rich noncalcified plaque components by measuring CT attenuation within the lesion.11,12 But clinical applications are not supported by any prospective or outcome data. Performing contrast-enhanced CT studies in asymptomatic individuals with the purpose of plaque detection in a setting of risk stratification is therefore currently not justified. Before any clinical conclusion can be drawn from such observations, further corroboration is required.

Bypass vessels are somewhat larger than the native coronary arteries, and they move less rapidly. Thus, their visualization with CT is relatively straightforward. Occlusions and stenoses of bypass grafts can be detected with very high accuracy.13 Clinically, however, it is not be sufficient in most cases simply to assess the graft vessels themselves if a patient with previous bypass surgery presents with symptoms. It would also be necessary to depict the status of the native coronary arteries distal to the bypass anastomosis and of those branches that did not receive a graft. So far, it has not been shown conclusively that CT imaging permits assessment of the bypass grafts, the anastomotic site, and the native vessels. Coronary arteries in this special case may be challenging, because they tend to calcify heavily.

Visualization of intracoronary stents is theoretically possible, especially with later CT scanners, but image quality is often impaired by artifacts because of the stents' high-density metallic nature. Some initial studies in small patient populations have shown encouraging results, but even larger stents may be impossible to evaluate with regard to in-stent restenosis.14,15 More data are needed before any clinical recommendation can be made concerning the use of MSCT for follow-up after stent placement.

Dr. von Ziegler is a research fellow in cardiovascular imaging at the University of Florida at Jacksonville.

1. Halliburton SS, Petersilka M, Schvartzman PR, et al. Evaluation of left ventricular dysfunction using multiphasic reconstructions of coronary multi-slice computed tomography data in patients with chronic ischemic heart disease: validation against cine magnetic resonance imaging. Int J Cardiovasc Imaging 2003;19:73-78.

2. Grude M, Juergens KU, Wichter T, et. al. Evaluation of global left ventricular myocardial function with electrocardiogram-gated multidetector computed tomography: comparison with magnetic resonance imaging. Invest Radiol 2003;38:653-661.

3. Agatston AS, Janowitz WR, Hildner FJ, et al. Quantification of coronary artery calcium using ultra-fast computed tomography. J Am Coll Cardiol 1990;15:827-832.

4. Arad Y, Goodman KJ, Roth M, et al. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol 2005;46:158-165.

5. Shaw LJ, Raggi P, Schisterman E, et al. Prognostic value of cardiac risk factors and coronary artery calcium screening for all-cause mortality. Radiology 2003;228:826-833.

6. Greenland P, Smith SC, Grundy SM. Improving coronary heart disease risk assessment in asymptomatic people: role of traditional risk factors and non-invasive cardiovascular tests. Circulation 2001;104:1863-1867.

7. Achenbach S, Ropers D, Pohle FK, et al. Detection of coronary artery stenosis using multi-detector CT with 16x0.75 mm collimation and 375 ms rotation. Eur Heart J 2005;26:1978-1986.

8. Leber AW, Knez A, von Ziegler F, et al. Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography. A comparative study with quantitative coronary angiography and intravascular ultrasound. J Am Coll Cardiol 2005;46:147-154.

9. Ropers D, Moshage W, Daniel WG, et al. Visualization of coronary artery anomalies and their course by contrast-enhanced electron beam tomography and three-dimensional reconstruction. Am J Cardiol 2001;87:193-197.

10. Datta J, White CS, Gilkeson RC, et al. Anomalous coronary arteries in adults: depiction at multi-detector row CT angiography. Radiology 2005;235-812-818.

11. Becker CR, Knez A, Ohnesorge B, et al. Imaging of noncalcified coronary plaques using helical CT with retrospective ECG gating. AJR 2000;175:423-424.

12. Leber AW, Knez A, Becker A, et al. Accuracy of multidetector spiral computed tomography in identifiying and differentiating the composition of coronary atherosclerotic plaques: a comparative study with intracoronary ultrasound. J Am Coll Cardiol 2004;43:1241-1247.

13. Nieman K, Pattynama PMT, Rensing BJ, et al. Evaluation of patients after coronary artery bypass surgery: CT angiographic assessment of grafts and coronary arteries. Radiology 2003;229:749-756.

14. Gilard M, Comly JC, Rioufol G, et al. Noninvasive assessment of left main coronary stent patency with 16-slice computed tomography. Am J Cardiol 2005;95:110-112.

15. Schuijf JD, Bax JJ, Jukema JW, et al. Feasibility of assessment of coronary stent patency using 16-slice computed tomography. Am J Cardiol 2004;94:427-430.

Articles

Advances in spatial, temporal resolution should help CT provide better functional, anatomic information

Quantitative analysis of myocardial defects could move into routine clinical use with advances 

At the University of Florida, we use multiple modalities, including echocardiography, nuclear stress perfusion, coronary CT angiography, and MR first-pass perfusion, for initial noninvasive detection of coronary artery disease. CTA routinely evaluates low to intermediate risk patients. The CT data are evaluated for extent and location of significant CAD through multiplanar reconstruction and 3D volume rendering. Once CAD is detected, further evaluation with additional noninvasive tests or coronary angiography is appropriate if significant stenoses have been noted on CT.

MR first-pass perfusion (MRFPP) imaging often follows coronary CTA to determine the physiologic effects and extent of decreased myocardial blood flow due to stenosis. Our approach to MR perfusion imaging uses software solutions developed from years of research in this area. Input data are the first-pass signal intensity curves from both the left ventricle blood pool and the myocardium. Output data are absolute myocardial blood flows and myocardial perfusion reserves.

A typical scenario involves a patient with a prior coronary CTA that either detected or failed to determine a stenosis. Often in the latter case, the patient has severe calcium. Any approach to cardiac imaging must take account of the global picture of the heart, using all the elements of a standard cardiac examination, including cine wall motion, wall thickness, and viability.

The presence of coronary stenosis is detected on MRFPP by determining diminished blood flow to the myocardium. Blood flow is imaged by using an injection of gadolinium contrast agents, which have yet to achieve FDA approval for cardiac use. The following synopsis represents an off-label use of Magnevist. Gadopentetate dimeglumine (Magnevist, Berlex) is injected via power injector (MedRad) at a dose of 0.1 mol/kg at a rate of 9 mL/sec followed by a normal saline flush. The scan is started immediately before injection to capture the first pass of contrast through the myocardium and continues another 50 to 70 seconds. Typically, the stress portion is acquired before the rest examination to maximize contrast enhancement and to eliminate the effect of early delayed hyperenhancement. The second contrast injection typically has persisting contrast in the blood pool and myocardium, depending on pathology, that may interfere with image interpretation and analysis.

Adenosine used for the stress portion of the examination is infused for four minutes at a dose of 140 mcg/kg/min. It causes dilation of the coronary smooth muscle cells through its effects on the A2a receptor. Adenosine in the normal heart increases blood flow to approximately four times that at rest. It has a half-life of less than four to 10 seconds, so its effects rapidly dissipate.

Wilson et al have shown that coronary stenosis of 50%, 70%, or 80% decreases blood flow by 33%, 55%, or 67%, respectively. Hence, MRI perfusion imaging must detect about a 50% decrement in blood flow to determine stenosis greater than 70%. Compensatory vasodilation distal to the stenosis may be able to maintain blood flow during resting conditions. But introducing a pharmacologic agent such as adenosine or dipyridamole that causes dilation of the distal vessels may exceed the capacity of this physiologic response.

The ratio of myocardial blood flow at stress and at rest is defined as the myocardial perfusion reserve. This ratio decreases with increasing stenosis severity. Using the vasodilator adenosine as the stress agent, the expected perfusion reserve is greater than 3.5 in normal volunteers. Significant stenosis ( > 75% luminal stenosis) decreases the myocardial perfusion reserve to less than 1.5.

Although a number of sequences are used for perfusion imaging, the two most common are saturation recovery fast low-angle single-shot (SR-FLASH) and saturation recovery echo-planar imaging (SR-EPI). Requirements of a perfusion sequence are fast acquisition, high signal to noise ratio, minimal artifacts, and high enough resolution to distinguish the subendocardium. Our group uses SR-FLASH sequences to image the first pass of contrast through the heart. Depending on heart rate, three to four slices are obtained, typically three short-axis images and one long-axis image.

A radiologist or cardiologist eyeballs the images, looking at the first pass of contrast through the myocardium. The qualitative approach is enhanced by using it systematically with specific criteria in mind. Our criteria are the following: the perfusion defect should not fluctuate in signal intensity during the first pass; the defect is located in the distribution of a coronary artery; and the defect is seen only during stress imaging or is present during rest, stress, and delayed contrast imaging.

Applying the converse of all these criteria aids in the detection of artifacts in the study. The converse would be signal intensity that fluctuates during the first pass, is present during rest but not stress, or is not present consistently in all studies.

We also apply quantitative analysis to the first-pass signal intensity curves. Using a software solution developed and validated for the quantitative analysis of myocardial perfusion studies, we derive absolute myocardial blood flow as well as the myocardial perfusion reserve. The first step in quantitative analysis is using a program to contour the myocardium. We use several programs, including Medis (Leidin, the Netherlands) and Pie Medical (Maastricht, the Netherlands). Contours are placed around the regions of interest by outlining the endocardial and epicardial surfaces. The short axis is then radially segmented by placing a reference point at the anterior intersection of the right and left ventricles. The standard segmentation of the myocardium is typically used to divide the myocardium into six radial sectors, although it may be divided into more sectors for research. The program then calculates the average signal intensity in each radial sector and outputs this in either numerical or graphic form.

The most significant limitation of quantitative methods is the need to accurately and consistently draw all the myocardial contours for all the time points in the first-pass perfusion sequence manually. Automated computer detection of myocardial contours continues to be an active area of research, and its implementation is widely anticipated in cardiac imaging.

The second step is to use a custom software program developed in C++ code. This technique has previously been derived and validated in animals using radioactive microspheres. Our program takes the signal intensity curves and calculates myocardial blood flow and perfusion reserve using a Fermi function deconvolution method (see figure). The files for the signal intensity curves are specified for rest and stress, and the program calculates a least squares fit to the data on the order of milliseconds. Having fit the data, the program derives the absolute myocardial blood flows and perfusion reserves. This information is then displayed graphically and also in a numerical table.

Quantitative analysis is useful for a number of different clinical senarios. In patients with CAD, this analysis can help differentiate which coronary territories are affected. Cutoff values for myocardial perfusion reserve can be developed and applied that can assist in determining the severity of CAD stenosis. This analysis can be used for more accurate follow-up in comparing repeat studies in the same patient and can also be applied to microvascular obstruction. Wu has demonstrated that the presence of microvascular obstruction following myocardial infarction has prognostic information. Quantitative analysis can be used to assess arteriopathy in heart transplant patients.

In addition to fully quantitative measures, other semiquantitative indices can be derived from the signal intensity curves. These include the slope of signal intensity rise, peak of the signal intensity curve, and time to peak of the signal intensity curve. A decrease in slope of the signal intensity curves could indicate a decrease in myocardial blood flow. A myocardial perfusion reserve index, but not absolute blood flows, can be calculated using these techniques.

If a perfusion defect is detected, the next question is which artery is supplying that territory. We divide the short-axis perfusion myocardium into six to eight radial sectors and assign each sector to an artery on an anatomic distribution. In general, the anterior and anterior septal sectors are assigned to the left anterior descending artery, the lateral sectors to the left circumflex, and the inferior and inferior septal sectors to the right coronary artery. If the patient has had prior CTA or interventional catheterization reports and images, these are also reviewed.

Cardiac imaging has progressed immensely in recent years, in large part from postprocessing software and hardware solutions. MR perfusion imaging with sophisticated automated edge detection could move quantitative analysis into a routine clinical application in the future.

Dr. Klassen is a resident, Dr. Nguyen is a resident, Dr. von Ziegler is a research fellow, Mr. Siuciak is an imaging systems specialist, and Dr. Wilke is director of cardiovascular MR and CT, all at the University of Florida at Jacksonville.

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13. Cerqueira MD. The future of pharmacologic stress: selective A2A adenosine receptor agonists. Am J Cardiol 2004;94:33D-40D, discussion 40D-2D.

14. Zhang H, Shea SM, Park V, et al. Accurate myocardial T1 measurements: toward quantification of myocardial blood flow with arterial spin labeling. Magn Reson Med 2005;53:1135-1142.

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Quantitative analysis of myocardial defects could move into routine clinical use with advances

Franz Von Ziegler, MD

Articles

Cardiac CT's promise awaits aid of outcomes studies

Software analyzes MR first-pass perfusion data