Alison Knauth Meadows and Michael W. Dae
Echocardiography (ECG) has been and remains a mainstay of imaging in congenital heart disease. Despite its importance in rapid diagnosis and follow-up, it has limitations. The presence of postoperative scar, chest wall deformities, overlying lung tissue, and large body size as the patient ages often results in suboptimal transthoracic echocardiographic windows. Transesophageal echocardiography provides improved acoustic windows, but is limited by its small field of view and more invasive nature.
Cardiac catheterization, employing x-ray fluoroscopy and contrast angiography, has an expanding role in minimally invasive interventions, but its role as a diagnostic procedure is rapidly diminishing. This is in part due to its limitation as a 2-dimensional projection imaging technique with poor soft tissue contrast and the substantial ionizing radiation exposure involved and in part because both diagnostic and functional analyses are often better performed with noninvasive imaging techniques.
This chapter focuses on the evolving and expanding roles of other imaging modalities in diagnosing and monitoring patients with congenital heart disease, including cardiac magnetic resonance imaging (MRI), cardiac computed tomography (CT), and radionucleotide scintigraphy.
Cardiac magnetic resonance imaging (MRI) has emerged over the past few decades as an alternative, complementary, and frequently superior imaging modality for investigating the anatomy and function in the patient with congenital heart disease. It has many advantages over other imaging modalities. It does not require the use of iodinated contrast agents and does not involve exposure to ionizing radiation. This is particularly important in a population of patients who have been, and continue to be, exposed to large doses of contrast agent and radiation during hemodynamic and interventional catheterization. Additionally, many of these patients are children who are more susceptible to the adverse effects of radiation. Major advances in MRI hardware and software, including advanced coil design, faster gradients, new pulse sequences, and faster image reconstruction techniques, allow rapid, high-resolution imaging of complex anatomy and accurate, quantitative assessment of physiology and function.
CARDIAC MRI TECHNIQUES
There are a number of MRI techniques useful in examining the anatomy and physiology of the congenital heart disease patient.
ECG-gated gradient-echo sequences provide multiple images throughout the cardiac cycle in prescribed anatomic locations. Display of these images in a cine mode allows visualization of the dynamic motion of the heart and vessels.1-3 Cine MRI techniques, at a minimum, allow assessment of anatomy. More importantly, they allow qualitative and quantitative assessment of physiology and function. Specifically, cine MRI allows quantification of chamber volumes, myocardial mass, and ventricular function. furthermore, cine MRI allows qualitative assessment of focal and global wall motion abnormalities; qualitative and quantitative assessment of valve pathology, including the mechanism and severity of valve regurgitation and the location and severity of valve stenoses; identification and quantification of intra- and extracardiac shunts; and visualization of other areas of flow turbulence.
Briefly, evaluation of function begins with obtaining a series of contiguous slices (cines) along the short axis of the ventricles, extending from base to apex. These images are played back in a cine loop, and the end-systolic and end-diastolic phases are chosen. The endocar-dial borders are traced at both time points, and the epicardial borders are traced at one of the 2 time points (Fig. 494-1). Ventricular volumes are then calculated as the sum of the traced volumes (area times slice thickness). Myocardial mass is calculated as the myocardial muscle volume times 1.05 g/mm3 (density of myocardium). From these data, ventricular end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, myocardial mass, and mass/volume ratio can be calculated for both the right and left ventricles.
Spin-echo (Black Blood) Imaging
ECG-gated spin-echo sequences, or black blood imaging allows assessment of anatomy with thin slices, high spatial resolution, and excellent blood-myocardium and blood-vessel wall contrast (Fig. 494-2). Black blood techniques are superb for evaluating the spatial relationship between cardiovascular and other intrathoracic structures such as the chest wall and the tracheo-bronchial tree. These features hold particular relevance when delineating complicated native and postsurgical cardiac anatomy. Such techniques are also less susceptible to artifact from metallic implanted devices such as stents, coils, occluder devices, clips, and sternal wires.
Cardiac-gated gradient-echo sequences with flow-encoding gradients are used to quantify the velocity and flow of blood (Fig. 494-3).11 These sequences are referred to as velocity-encoded cine MRI or phase-contrast MRI. Two-dimensional velocity-encoded cine MRI sequences are the most commonly used in clinical practice. They can be used to quantify cardiac output, pulmonary to systemic flow ratio (shunt), valvular regurgitation, differential lung perfusion, coronary flow reserve, and to observe the location and severity of flow obstruction.
Gadolinium-enhanced 3-Dimensional Angiography
Three-dimensional angiography (3D-MRA) sequences are typically not cardiac gated and thus do not allow assessment of intracardiac structures. Regardless, they provide excellent depiction of arterial and venous vascular structures (Fig. 494-4). In the congenital heart disease patient, 3D-MRA fills a significant diagnostic role. It can be used to diagnose systemic arterial anomalies such as aortopulmonary collaterals, shunts, vascular rings, and coarctation. It is useful in diagnosing pulmonary arterial abnormalities such as focal and diffuse stenoses and abnormal distal arborization patterns. Using 3D-MRA methods is also useful for investigating systemic and pulmonary venous abnormalities, both congenital and postoperative. Also, 3D-MRA is useful for evaluating the relation between vascular and other thoracic structures. With faster techniques and navigator pulses, time-resolved 3D-MRA as well as noncontrast 3D-MRA are becoming alternatives.12
Coronary Artery Imaging, Perfusion Imaging, and Myocardial Viability
Coronary artery abnormalities and ischemia are important issues to be investigated in postoperative congenital heart disease patients. Not only is this patient population aging sufficiently to develop atherosclerotic coronary artery disease, they also commonly have congenitally abnormal or postoperatively acquired coronary artery lesions. It is not uncommon to find an anomalous origin or course of the left or right coronary artery, postsurgical coronary obstruction (ie, after arterial switch for transposition of the great arteries), coronary artery thrombus, and abnormal fistulous connections (ie, pulmonary atresia with intact ventricular septum and right ventricular-dependent coronary circulation). Identifying such abnormalities is often critical to planning reintervention and medical management. There is growing evidence to support the concept that myocardial delayed enhancement in a number of subsets of postoperative congenital heart disease patients predicts poor outcome.13-16 In summary, although still not as robust as routine coronary artery angiography with x-ray fluoroscopy or cardiac-gated CT angiography at investigating distal coronary artery lesions, MRI can image proximal coronary arteries well,17-20 evaluate myocardial perfusion and viability,21-24 and allow stress testing,25,26 all noninvasively without exposure to contrast agents and ionizing radiation.
FIGURE 494-1. (A) To obtain a stack of short-axis cine images, a 2-chamber view is prescribed from an axial cine, then a 4-chamber view is prescribed from the 2-chamber cine, then a short-axis stack is prescribed from the 4-chamber cine at end diastole. Single image from a stack of short-axis cine images at end-diastole (B) and end-systole (C). Right and left ventricular endocardial contours are drawn at end systole, and endocardial and epicardial contours are drawn at end diastole. It is from these data that chamber volumes, myocardial mass, and ventricular function are derived.
GENERAL CLINICAL APPLICATIONS OF CARDIAC MRI
In general, MRI is indicated when transthoracic echocardiography does not provide adequate diagnostic information (eg, postoperative patients; adult with congenital heart disease), as an alternative to invasive and costly diagnostic catheterization, and when the unique capabilities of MRI can be exploited. Cardiac MRI is quite effective in the segmental description of complex anatomy and it is unrivaled in the quantitative evaluation biventricular function, particularly the right ventricle, which is so often at risk in patients with CHD. It is useful in evaluating arterial and venous anomalies and detecting and quantifying shunts, valvular and vascular stenoses, and regurgitant lesions. Cardiac MRI is also excellent for characterizing coronary arterial anatomy and myocardial perfusion and viability.
CARDIAC COMPUTED TOMOGRAPHY
The advent of high resolution CT and cardiac gating has emerged as a useful tool for assessing intracardiac anatomy, coronary anatomy, and myocardial function. Multislice CT has advanced significantly over the past decade, Although such technology is proving invaluable in cardiovascular imaging in adults, its use in the pediatric population in the assessment of congenital heart disease has just begun to be explored.27-29
The strengths of CT imaging include excellent spatial resolution (submillimeter isotropic resolution) and rapid acquisition times, often precluding the need for anesthesia. It is unparalleled in its ability to provide spatial relationships of intrathoracic structures, including the vasculature and the airways. Some argue that CT provides equal or even better image quality of the epicardial coronary vessels than does coronary angiography. It can also be used in congenital heart disease patients who have pacemakers or defibrillators.
Cardiac CT does have its weaknesses. There is less temporal resolution than cardiac MRI or echocardiography and thus is limited in its ability to characterize ventricular function. There are no CT techniques to quantify flow. CT contrast, albeit improved and less toxic, still has renal toxicity. Most importantly, there is significant radiation exposure associated with CT. It is critical for the clinician to consider this when ordering a CT, particularly in the young patient and the patient who has been, and continues to be, exposed to large doses of contrast agent and radiation during hemodynamic and interventional catheterization. It must also be recognized that gated studies and higher-resolution studies come at a cost of higher radiation doses. (See the as low as reasonably achievable [ALARA] guidelines.30)
GENERAL CLINICAL APPLICATIONS OF CARDIAC CT
The clinical indications for cardiac CT in congenital heart disease patients are evolving and growing as technology advances. CT is particularly indicated in patients with pacemakers and defibrillators in whom cardiac MRI is precluded or in patients with metallic implants that create unmanageable artifacts on cardiac MRI (ie, steel coils). It also can take the place of cardiac MRI if the question being studied is strictly vascular anatomy and not intracardiac anatomy or cardiac function. CT can answer these questions with a rapid study, often without sedation. CT is quite useful in evaluating the coronary arteries, particularly if there is concern about distal coronary disease. Cardiac CT has the added benefit of accurately delineating the relationship of vascular structures and the airways.
FIGURE 494-2. A: Axial spin-echo black blood image of a sinus venous defect (SVD). It can be visualized that the SVD is in the tissue that separates the posterior wall of the superior vena cava (SVC) and the anterior wall of the right upper pulmonary vein (RUPV). This defect allows for an intra-atrial communication. The aorta (Ao) and right ventricular outflow tract (RVOT) are identified for orientation. B: Axial spin-echo black blood image through the base of the heart. The initial surgery in this patient included a right ventricle-to-pulmonary artery conduit that subsequently became stenotic. Unknown to this patient’s caregivers was the fact that the indication for a conduit rather than a transannular patch was the presence of an anomalous left coronary artery from the right that traversed the right ventricular outflow tract. This was important for the management of her conduit stenosis as a percutaneous stent placement may have caused coronary compression. The aorta (Ao), native pulmonary artery (PA), right ventricular-to-pulmonary artery conduit (conduit), and anomalous coronary artery (anomalous CA) are identified. C: Coronal oblique spin echo black blood image of a double aortic arch. The right (R arch) and left (L arch) arches are identified. The trachea is not narrowed. D: Axial spin-echo black blood image in D-transposition of the great arteries following arterial switch procedure. The main (MPA), right (RPA), and left (LPA) pulmonary arteries are identified. The LPA is narrowed as it is tented over the ascending aorta (Ao).
FIGURE 494-3. A: From an image in the plane of the right ventricular outflow tract (RVOT), an imaging plane is chosen to capture the cross-section of the main pulmonary artery. Velocity-encoded cine MRI is then performed in this plane to produce a magnitude (above right) and phase (below right) image. A region of interest encompassing the main pulmonary artery is chosen for each image in the cardiac cycle. From these data, a net flow is obtained. B: Flow is then displayed allowing the calculation of peak velocity, net forward flow, and regurgitant fraction.
FIGURE 494-4. A: Three-dimensional (3D) gadolinium-enhanced angiography (MRA) in a patient with Scimitar syndrome. Images are displayed as a 3D volume-rendered reconstruction. B: 3D gadolinium-enhanced MRA in a patient with coarctation of the aorta (CoA). Images are displayed as a maximum intensity projection image. The region of CoA and collaterals are identified with arrows.
Radionuclide imaging is used primarily for assessing cardiac physiology. Although rarely used today for the assessment of right and left ventricular function in pediatric patients, radionuclide studies continue to provide valuable information for the evaluation of intra and extracardiac shunts and assessment of myocardial perfusion.
ASSESSMENT OF LEFT-TO-RIGHT SHUNTS
Echocardiography with Doppler is the most widely used method for determining the presence and magnitude of left-to-right shunts in congenital heart disease, although its accuracy in quantification of multiple level shunts or shunts in the presence of valve insufficiency or multiple shunts is not optimal. The radionuclide technique for left-to-right shunt quantification was established and validated more than 30 years ago and is not affected by such considerations.31
Knowledge of the size of a left-to-right shunt, expressed as pulmonary-to-systemic flow ratio (Qp/Qs), is essential for decisions regarding corrective surgery. The scintigraphic technique involves the rapid injection of a bolus of radionuclide (usually technetium-99m–labeled diethylenetriamine pentaace-tate, or 99mTc-DTPA) into the circulation while monitoring the transit through the heart and lungs with the gamma camera. For small infants (ie, premature newborn infants), a butterfly needle can be used in a temporal scalp vein to deliver a compact bolus of activity to the central circulation. In older children and adults, either a butterfly needle or a small cannula can be inserted, preferably into an external jugular vein, although an antecubital vein may also be used. The delivery of a compact, nonfragmented bolus of activity is essential to allow accurate determination of the size of the shunt. With good technique, the success rate should be greater than 90%. It may be necessary to sedate infants and some children, because crying simulates a Valsalva maneuver that can impede bolus entry into the thorax and lead to fragmentation of the bolus. As mentioned, 99mTc-DTPA is most commonly used for shunt studies. Doses are 200 microcuries (µCi) per kilogram of body weight, with a minimum dose of 2 mCi. The advantage of 99mTc-DTPA over other technetium based agents is the fairly rapid renal excretion and thus prompt clearance of background activity. This becomes important if it is necessary to perform a second injection to improve the quality of the bolus. Generally, no more than 2 sequential injections are performed due to dosimetry limitations.
For quantification, time-versus-radioactivity curves are generated from regions of interest over the superior vena cava to assess the quality of the bolus and the periphery of the right lung, for shunt detection and magnitude (Fig. 494-5). A separate curve may be generated from a region over the left lung if differential shunting is expected (as may occur with a patent ductus arteriosus). The normal pulmonary arterial curve has an ascending limb, reflecting the arrival of tracer in the pulmonary circulation, and a symmetric descending limb, reflecting the tracer exiting the lungs and entering the left side of the heart. A late peak wsill appear, reflecting systemic recirculation. In a left-to-right shunt, a shoulder will be present on the downslope, indicating recirculation of activity back to the lungs across the shunt. For shunt quantification, the shape of the pulmonary portion of the curve is approximated by an algebraic expression called a gamma variate function (Fig. 494-6).31 In practice, the computer is given the coordinates of the upslope and initial downslope of the pulmonary curve, and a curve is generated that approximates the shape of the curve. The area under this pulmonary curve is proportional to pulmonary flow, Qp. This fitted curve is then subtracted from the initial time-versus-radioactivity curve, and another gamma variate fit is done on the remaining curve. The area under this second fitted curve is proportional to the shunt flow, Qsh. The difference between the two fitted curves is a measure of systemic flow, Qs. The resultant calculation of pulmonary to systemic flow, Qp/Qs, is performed as:
Qp/Qs = Qp/(Qp − Qsh)
FIGURE 494-5. A: Time-activity curve from a region over the superior vena cava. The bolus of radiotracer is adequate because it produced a single peak. B: Pulmonary time-activity curves. Normal (left). Left-to-right shunt (right).
Ratios less than 1.2:1 are consistent with the absence of left-to-right shunts. The Qp/Qs calculation, by the gamma variate method, has shown excellent correlation with shunt size determined at cardiac catheterization over a clinically significant range of 1.2:1 to 3.0:1.31 This relationship remains valid even in the presence of pulmonary hypertension, tricuspid regurgitation, and heart failure.31,32 In these conditions, extensive dilution and slow flow lead to a slow downslope to the pulmonary curve. However, the upslope should be proportionately slowed, and the curve fit method should generally apply, although caution should be exercised. Since the method depends on the full passage of the administered radionuclide through the lungs, left-to-right shunts will be overestimated in the presence of right-to-left shunts. Shunts greater than 3.0:1 are difficult to fit by the gamma variate method due to distortions in curve shape as a result of the large and torrential shunt flow. This is not a practical limitation, however, as any shunt greater than 3.0:1 is very large. In general, a shunt of 2.0 or greater is sufficient to warrant surgical correction.
With the anatomic detail provided by echocardiography, the hemodynamic correlates from Doppler examination, and the precise quantitation available from a radionuclide shunt study, it is sometimes possible to proceed directly to surgery without preoperative cardiac catheterization. This is particularly true with uncomplicated patent ductus and secundum atrial septal defect. In anomalous pulmonary venous return, the radionuclide determination of shunt size may be more accurate than that determined at catheterization by oximetric methods due to the inability to obtain a good mixed venous blood sample at catheterization.33 The radionuclide method has also been used to measure changes in shunt magnitude in response to oxygen therapy, and to assess the reactivity of the pulmonary vascular bed in patients with pulmonary arterial hypertension and large shunts.34 This is a very important consideration in determining operability in patients with moderate to large ventricular septal defects.
One of the leading indications for radionuclide shunt studies is the postoperative assessment of residual shunt size in patients with murmurs and echo Doppler evidence of persistent shunting after surgical correction of septal defects. Doppler quantification of shunt size is often not very reliable after patch closure of defects due to the turbulence generated in the vicinity of the patch. In this situation, the radionuclide technique has been helpful for assessing the need for repeat catheterization and possibly reoperation.
The easiest and most commonly used method to assess right-to-left shunts is the intravenous injection of 99mTc-labeled macroaggregated albumin particles, similar to those used for the assessment of pulmonary perfusion.39 In the absence of right-to-left shunting, all of the particles are trapped in the lungs. When right-to-left shunting occurs at any level, particles will enter the systemic circulation in proportion to the shunt flow, lodging in the capillary and precapillary beds of systemic organs. A series of whole body images are taken to determine the percentage of right-to-left shunt as:
Pulmonary-to-systemic flow ratio can be calculated as:
Qp/Qs = lung counts/whole body counts
In spite of the general reluctance to administer particles to patients with known right-to-left shunts, the method has proven to be safe, accurate, and very easy to perform.39 The particle number should be kept below 50,000 in pediatric patients.
ASSESSMENT OF VENTRICULAR FUNCTION
Although radionuclide methods are well suited for the assessment of ventricular size and function in congenital heart lesions, these methods have been largely replaced by echocardiography in current clinical practice. Both first-pass and gated equilibrium methods for the determination of ejection fraction have been validated in the pediatric age group.43,44 Quantitative assessment of absolute ventricular volumes45and determination of regurgitant fraction have been reported in children as well.46,47 For infants, the imaging is optimized with the use of a converging collimator to improve spatial resolution and increase the sensitivity. It is feasible to measure ejection fraction even in tiny premature infants with the pinhole collimator.48 Ventricular size and function evaluation are useful at rest and with dynamic stress in a variety of congenital lesions, both before and after surgical correction.49,50 Residual structural and functional abnormalities are very common, and careful, long-term follow-up is important.
FIGURE 494-6. Calculation of pulmonary-to-systemic flow ratio (Qp:Qs) using pulmonary time-activity curves and the gamma variate model. A1, Area under the first pass of tracer through the lungs as defined by a gamma variate extrapolation; Qp, pulmonary flow; A2, area under the portion of the curve corresponding to radiolabeled blood returning prematurely to the lung by the left-to-right shunt; A1 − A2= Qs, = systemic flow; Qshunt, shunt flow.
ASSESSMENT OF MYOCARDIAL PERFUSION
Myocardial perfusion scintigraphy has been used for clinical assessment in children for a number of years.51,52 In the pediatric patient, perfusion imaging has been most widely used for the noninvasive identification of anomalous left coronary artery.53-56 The condition is often associated with Q-waves on the electrocardiogram. Echocardiography is sometimes able to identify the aberrant origin of the left coronary, but catheterization is required for confirmation. Multidetector CT has shown promise for the noninvasive detection of anomalous origins of coronary arteries.57,58
Another clinical condition for which perfusion scintigraphy may be useful is Kawasaki disease.61 Before the introduction of intravenous gamma globulin therapy, about 20% to 25% of these patients developed aneurysms of the coronary arteries. Treatment with gamma globulin within 10 days of the onset of the illness reduces the frequency of coronary aneurysms to about 4%. About 30% to 50% of such aneurysms will spontaneously regress within the first 2 years of illness. The remaining aneurysms may later thrombose and cause myocardial ischemia and infarction.62,63
Assessment of myocardial perfusion is important in the evaluation and follow-up of patients with transposition of the great vessels who have undergone the arterial switch procedure.65,66