Computed Tomography and Magnetic Resonance Imaging in Neonates With Congenital Cardiovascular Disease

Computed Tomography and Magnetic Resonance Imaging in Neonates With Congenital Cardiovascular Disease

Computed Tomography and Magnetic Resonance Imaging in Neonates With Congenital Cardiovascular Disease Frandics P. Chan, MD, PhD, and Kate Hanneman, MD...

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Computed Tomography and Magnetic Resonance Imaging in Neonates With Congenital Cardiovascular Disease Frandics P. Chan, MD, PhD, and Kate Hanneman, MD Most cardiac diseases in the newborn are caused by structural abnormalities developed in utero. With few exceptions, palliative and definitive treatments require cardiac surgery. The diagnosis and management decisions regarding uncomplicated lesions, such as atrial septal defect, ventricular septal defect, patent ductus arteriosus, and tetralogy of Fallot, can be accomplished by echocardiography alone. Abnormalities beyond the sonographic window, complex 3-dimensional lesions, and detailed functional information require additional imaging. In the past, this was fulfilled by catheter angiography, but today much of the information can be obtained from noninvasive computed tomography angiography and magnetic resonance imaging. This article discusses the design and application of these imaging techniques to the newborn, with emphasis on safety, efficacy, and image quality. Understanding the capabilities and limitations of these techniques is crucial for making rational choices among imaging options based on sound risk and benefit considerations. Important examples of congenital heart lesions have been illustrated with 3-dimensional reconstruction from computed tomography and magnetic resonance images. Semin Ultrasound CT MRI ]:]]]-]]] C 2015 Published by Elsevier Inc.



he utilities of computed tomography (CT) angiography (CTA) and magnetic resonance imaging (MRI) in the diagnosis and management of congenital heart disease have been well established.1 However, their applications in neonates present special challenges.2,3 The small size of newborn cardiovascular structures requires exquisite spatial resolution to delineate. High neonatal heart rates challenge the temporal resolution of both techniques while their small weight severely limits the amount of contrast agent and even the total volume of fluid that can be administered in each study. Neonates are physically fragile, and those afflicted with cardiac disease are often hemodynamically unstable. Care for their well-being must be accorded the highest priority throughout the study. In the case of CT, the radiation dose must be carefully managed. Low-dose studies in the millisievert range, at a fraction of annual background radiation, are possible with modern scanners. In the case of MRI, imaging protocols must be

Department of Radiology, Lucile Packard Childrenʼs Hospital, Stanford University, Stanford, CA. Address reprint requests to Frandics P. Chan, MD, Department of Radiology, Stanford University, 300 Pasteur Dr, S-066, Stanford, CA 94305-5105. E-mail: [email protected] 0887-2171/& 2015 Published by Elsevier Inc.

carefully prescribed to minimize study duration, which in turn reduces anesthesia time and the risk of related complications. In this article, we consider the technical approaches to imaging congenital heart disease in the neonates, defined as children in their first month of life. Specifically, we emphasize changes to the general CTA and MRI techniques needed for this group of patients. In the neonatal period, echocardiography is the first-line imaging tool for the evaluation of cardiac function and flow. CTA and MRI principally supplement information from anatomical regions not accessible by echocardiography and may better characterize the 3dimensional (3D) anatomical relationships of cardiovascular abnormalities. Many congenital anomalies, such as aortic coarctation and tetralogy of Fallot (TOF), can be evaluated with echocardiography alone. Lesions that require CTA or MRI tend to be complex anomalies of the aorta, pulmonary artery stenoses, anomalous pulmonary venous connections, and anomalous coronary arteries. Representative imaging examples have been given.

CTA Techniques Performance of an optimal CTA requires careful consideration of scan parameters that can be grouped into 4 categories: 1

2 geometric factors, contrast injection, cardiac synchronization, and radiation control.

Geometric Factors Geometric factors of a scan concern the field of view and the scan length necessary to cover the relevant anatomy, the slice thickness and the in-plane resolution required to resolve the anatomical lesion, and the gantry rotation rate and the pitch factor that determine the scan time. The in-plane resolving power of a CT scanner is commonly specified by the number of line pairs resolvable per centimeter.4 For a typical reconstruction kernel and signal-to-noise level of a CTA, the resolvable line pairs per centimeter for a typical scanner is approximately 6-8, corresponding to an in-plane resolution of approximately 0.7 mm. This is approximately the same size as the thinnest slice thickness. Thus, the overall spatial resolution for CTA is approximately 0.7 mm for most current scanners. In typical CTA protocols, a short scan time is desirable, as it minimizes motion artifacts and the contrast dose. As a result, the gantry rotation rate and the pitch factor are set to the maximum values available to the scanner. To illustrate how these parameters are related, consider a 64-slice single-source multi-detector CT scanner with a detector thickness of 0.625 mm, a pitch factor of 1.5, and a gantry rotation rate of 3 cycles per second, which has a scan speed of 18 cm/s. For a neonatal chest of 10-cm length, the scan time is only 0.6 second. At this speed, artifacts from respiratory motion are often negligible and breath-holding by anesthesia-induced apnea may be unnecessary. In contrast, the pitch factor for cardiac-gated CTA can be as low as 0.2. Using the same scanner parameters with this pitch factor yields a scan time of more than 4 seconds and in this setting breath-holding may be necessary. In general, scan time in a CTA may be reduced by increasing the number of detector rows, the gantry rotation rate, the change from a single-source to a dual-source scanner, and the change from a cardiac-gated study to a nongated study.

Contrast Injection Contrast injection concerns the intravenous injection site, caliber of the intravenous catheter, choice of contrast agent, volume and dilution of the contrast agent, injection rate, and injection duration. If a scan is triggered by bolus tracking technique, then the monitoring site and the timing of the monitoring scans must be specified. Of these parameters, the injection duration is of primary importance, as it ensures that all the vascular territories of interest are consistently opacified through the entire scan duration. This duration includes the time to build up contrast opacification in all vascular territories of interest, the delay time from the trigger of the scan to the start of the scan, and the actual time scanning over the region of interest. For most neonatal CTA studies, these factors require an injection time of 15-25 seconds. The injection rate must be sufficiently high to quickly fill the dead space in the injection line, the intravenous catheter, and the systemic veins to maintain a high concentration of the contrast bolus.

F.P. Chan and K. Hanneman Empirically, a 1-mL/s injection consistently delivered by a mechanical injector produces good results for neonates. A 24gauge peripheral intravenous catheter and a maximum injector pressure setting of 200 psi are generally adequate. Contrast injection through a foot intravenous catheter is preferred over an arm injection. This avoids the artifact created by dense contrast in the superior vena cava (SVC), which can obscure important mediastinal vessels. The choice of iodinated contrast agent is principally governed by the expected renal function. In term babies with normally developed kidneys and collecting system, nonionic low-osmolality contrast agents used in adults, such as iopamidol (Isovue), iohexol (Omnipaque), ioproide (Ultravist) and others, are acceptable. The iodine concentration should be greater than 300 mgI/mL. Contrast agent with a higher concentration produces better vascular contrast and allows a greater degree of volume dilution if necessary. For a premature newborn or one with known renal pathology, if the renal function is adequate for contrast use, an iso-osmolar agent such as iodixanol (Visipaque) may be safer. However, the isoosmolality agent is more viscous and can be difficult to inject through a small intravenous catheter at the accepted injection pressure. The small weight of a neonate imposes certain constraints that are not usually important in a larger patient. For example, given the usual contrast dose of 2 mL/kg for common iodinated contrast agents, the total contrast volume may be as small 8 mL for a 4-kg baby. Meeting the requirements for injection time and rate may require a contrast volume larger than the weight-based dosage allows. In this case, the total contrast volume may be augmented by saline dilution. The total fluid volume that can be administered in a single study is also limited to 10 mL/kg or less, depending on the fluid volume status of the patient. For example, consider a nongated CTA ordered to evaluate the pulmonary vasculature and the aorta in a 3.5-kg newborn baby. If it takes 5 seconds to opacify the pulmonary arteries and the aorta equally, 5 seconds to move the table to the starting position and initiate breath-hold, and 5 seconds to scan through the region of interest, then the injection time should be at least 15 seconds. At an injection rate of 1 mL/s, the injection volume should be 15 mL. At a 2-mL/kg dose, the contrast dose is limited to 7 mL for a 3.5-kg baby. Therefore, 8 mL of saline should be added to augment the injection volume to 15 mL. The total bolus volume is less than the 35-mL limit. The choice of monitoring location for bolus tracking can be challenging, because the precise vascular anatomy may not be known before the scan. Additionally, the order of vessel enhancement may not be as expected owing to shunted blood flow or blood vessels that are abnormally connected. For example, in pulmonary atresia (PA) with major aortopulmonary collateral arteries, the pulmonary arterial supply comes from the aorta exclusively. Therefore, the aorta enhances before the pulmonary vessels. In general, the scan should be triggered when the last diagnostically important structure begins to enhance. The aorta is best monitored at its descending portion along the spine, while the pulmonary vessels are best monitored in the lungs. Therefore, in the case of PA, the scan

CT and MRI in neonates with congenital cardiovascular disease should be manually triggered when the pulmonary vessels in the lung enhance.

Cardiac Gating Cardiac gating is a special scanning technique used in conjunction with conventional CTA to produce (1) a volume of axial images all synchronized at one cardiac phase and (2) each image with the least amount of degradation from cardiac motion. The first requirement is accomplished by either prospective electrocardiogram (ECG) triggering or retrospective ECG-gating.5 Prospectively triggered acquisition, also known as the “step-and-shoot” method, irradiates the patient starting at a predetermined delay time from the R wave, lasting just long enough to allow acquiring the necessary projections for image reconstruction. This method produces images only for a single cardiac phase or for cardiac phases of a limited duration. Therefore, cardiac cine is not possible using this method. However, when compared with retrospective gating, use of prospective triggered acquisition can result in a radiation dose 3-5 times lower, at a level close to nongated CTA. For a scan length covering the chest of the neonate (approximately 10 cm), it is possible for a scanner with sufficient total detector width to cover the whole chest in a single gantry rotation. For example, the total detector width for a 240-slice scanner with a 0.5-mm single detector width is 12 cm. In this case, a prospectively triggered scan can be done in a single heartbeat, with the advantage that beat-to-beat variation from arrhythmia becomes irrelevant.6 In retrospective gating, the patient is irradiated and projections are acquired throughout the entire cardiac cycle. Images can be reconstructed at any cardiac phase, and it is possible to produce cines to inspect cardiac motion or to adjust for the cardiac phase that yields the least amount of motion artifact. Central to the operation of retrospective gating is that each table location of the chest must be viewed at multiple cardiac phases by different detectors. To satisfy this requirement, the pitch factor for retrospective gating must be significantly less than 1, typically 0.2-0.3. This can incur a radiation dose 5 times higher than a nongated CTA at a pitch factor of 1.5. This dose can be somewhat reduced by ECG modulation of the x-ray output, concentrating the highest dose at the cardiac phase most likely to yield the best images. Prospective triggering and retrospective gating are means of cardiac synchronization but by themselves, they do not eliminate motion artifact from cardiac motion. The severity of cardiac motion is determined by temporal resolution, defined by the time it takes to capture an axial image. It must be sufficiently short to freeze the cardiac motion of an anatomical structure needed for diagnostic evaluation. Cardiac structures in a neonatal heart can move quite fast as the heart rate can be as high as 150 beats per minute. Temporal resolution is determined by the gantry rotation rate and the rotation angle required for image reconstruction. It is always desirable to choose the fastest gantry rotation rate possible. For a single-source scanner rotating at a rate of 3 cycles per second, the temporal resolution for a nongated CTA scan that requires 3601 projections is 333 ms. For cardiac-gated scans that

3 employ 1801 projections, the temporal resolution is 167 ms. For a heart rate of 120 beats per minute, this temporal resolution is 33% of the cardiac cycle and artifacts related to cardiac motion can be expected. A dual-source scanner reduces the required rotation angle to 901. For the same gantry rotation rate, the temporal resolution is reduced to 84 ms or 17% of the cardiac cycle, with resulting improvement of motion artifact. Finally, a 2-sector reconstruction from a retrospectively gated CTA can shorten temporal resolution up to half that of a single-sector reconstruction. This technique can be applied to single- or dual-source scanners, but it must be used in conjunction with retrospective gating at the cost of a higher radiation dose.

Radiation Control CT employs penetrating x-rays as the primary means of investigating the interior structures of a patient. Inherent to this modality is the risk of cancer, as ionizing radiation may disrupt genes controlling cell divisions. This is a particular concern for young children as their rapid somatic growth may make them more vulnerable to radiation damage. When compared with adults, neonates also have a longer expected lifetime to express cancer after a given radiation exposure. A recent study suggests that the expected lifetime attributable cancer risk for solid tumors per equivalent dose from a chest CTA is 60% higher for children younger than 5 years compared with ages 10-14 years.7 It should be noted that estimated risks for CT-induced cancer are low, at approximately 0.05%/mSv for girls and 0.02%/mSv for boys younger than 5 years. For a single CT study that incurs 3 mSv, about the same amount as can be expected from annual background radiation, the estimated cancer risk is at most 0.15%. If the CT information is needed for surgical planning, this risk compares favorably to surgical mortality rates of 5% for neonatal operations, 1% for coarctation repair, and 3% for TOF repair.8 Although the cancer risk from a CT study cannot be avoided completely, it can be reduced by using protocols and techniques that limit radiation dose. The most important means of radiation dose reduction for neonates is the use of low tube voltage, adjusted to 80 kVp or less. Radiation dose is a strong function of tube voltage such that a moderate reduction of the tube voltage leads to a substantial reduction in radiation dose. However, a tube-voltage reduction also increases image noise, which may require an increase in tube current to compensate. Without further consideration, it is unclear whether this strategy can yield any dose savings. Fortunately, the image quality of a CTA study is dominated by the attenuation difference between vessels filled with iodinated contrast agent and nonenhancing soft tissues and spaces. A lower tube voltage is a closer match to the k-edge of iodine of 33.2 keV. Therefore, at lower tube voltages, the attenuation of iodine increases and the image contrast between vessels and nonvessels also increases. By adjusting the tube current to keep the contrast-to-noise ratio constant, it can be shown that a drop from 120-80 kVp results in a 40% decrease in radiation dose, as measured by CT dose index.9 Using a low voltage technique and careful adjustment of tube current appropriate to the

F.P. Chan and K. Hanneman

4 patient size, a nongated CTA for a neonate can be performed with a resulting dose of 1 mSv or less.10 A second consideration for radiation control is whether to use retrospective gating. Among various scanning methods, retrospective gating with dual-sector reconstruction yields the highest temporal resolution, followed by prospective triggering with 1801-degree projections, and then nongated CTA with 3601 projections. Owing to its low pitch factor, retrospective gating incurs a significantly higher radiation dose than other techniques. A further consideration against retrospective gating is that it may lengthen scan time long enough such that breathholding is required to eliminate respiratory motion. For neonates, breath-holding requires anesthesia-induced apnea, possibly with intubation. Therefore, it is reasonable to reserve the use of retrospective gating for imaging small, moving cardiac structures, such as valve leaflets, septal defects, and coronary arteries. For the great arteries and veins, nongated CTA or prospectively triggered CTA is usually sufficient. Recently, various iterative reconstruction algorithms have been developed to reduce image noise. The goal of these postprocessing techniques is to enable a further reduction of tube current and radiation dose by recovering diagnostic images from low-dose scans. Different implementations of iterative reconstruction are generally compromises between the complexity of the prediction model, which affects realism and effectiveness of noise reduction, and computational cost, which affects the waiting time for image reconstruction.11 A comprehensive model may take into account the geometry of a specific scanner, such as the x-ray tube output, the cone beam behavior, the detector response, and other aspects of x-ray physics. As implementation of iterative reconstruction is tied to the specific architecture of a scanner, which is proprietary, there is no consensus as to which method is the most effective. Published preliminary clinical results are limited to iterative reconstruction algorithms implemented for specific scanner platforms. Although radiation dose reduction is expected,12,13 the lowest possible radiation dose remains unknown.

Anesthesia for CT A CTA study for a neonate may require anesthesia for the purposes of (1) controlling pain during intravenous catheter placement, (2) immobilizing the body during the scan, (3) breath-holding if necessary, and (4) reducing stimulation from contrast administration. Anesthesiologists also ensure patient safety by monitoring the hemodynamic status of the patient and intervening if necessary. As scanner performance improves, the requirement for anesthesia, and the depth of anesthesia, has lessened. For example, a dual-source scanner operating at a high pitch factor of 3 can scan a neonatal chest in less than half a second, during which respiratory motion is negligible even at a rate of 60 breaths per minute.10 Similarly, a small degree of body motion may be tolerated. This allows the use of soft restraints in lieu of anesthetic intervention. In summary, the protocol for a neonatal CTA should take into account the scanner capability and anesthesia needs, as much as the imaging objectives and radiation dose considerations.

CMRI Techniques Protocols for cardiovascular MRI are built on cardiac and vascular MR sequences acquired in prescribed 2-dimensional image planes or 3D image volumes. The specific combination and order of acquired sequences depends on the diagnostic objectives. In neonates, MRI is technically challenging because the high spatial resolution required may be limited by a low signal-to-noise ratio. Neonatal MRI is also clinically challenging as the required imaging time to complete a study is longer and the patient is less accessible for monitoring and intervention than with CT.

Pulse Sequences for Neonates For imaging structural heart diseases, 4 general categories of MR sequences are commonly used: (1) black-blood sequences, (2) bright-blood cine sequences, (3) MR angiography (MRA), and (4) phase-contrast (PC) sequences.2,14 Specialized cardiac sequences have been developed for myocardial tissue characterization, such as delayed enhancement, perfusion, and T1 mapping, but they are seldom used in neonatal studies and have not been discussed here. Cardiac synchronized k-space acquisition is achieved through the use of a segmented k-space technique.15 In this scheme, a fixed number of k-space readout lines or “views per segment” are acquired per cardiac cycle. The higher this number is, the shorter the total scan time and the lower the temporal resolution would be. For neonates with high heart rates, the number of views per segment should be kept low to maintain adequate temporal resolution to image rapidly moving parts. Although neonatal respiratory rates are higher than those of older children, their lung tidal volumes and diaphragmatic displacements are relatively small. Respiratory artifacts are often tolerable and breath-holding is generally unnecessary. Phase ghosting from respiratory motion can be further reduced by averaging, by respiratory compensation, and by respiratory triggering. Black-blood sequences usually produce images at a single cardiac phase. In each image, moving blood in the cardiac chambers and the vessel lumens is dark, whereas muscles, fat, and immobile blood are bright. In the past, black-blood imaging was implemented using a cardiac-gated, T1weighted spin echo sequence, but today it is typically implemented using a double-inversion recovery sequence. Images must be taken without or before contrast administration. In neonatal imaging, this sequence is important as it typically yields a higher signal-to-noise ratio that can support greater spatial resolution in a smaller field of view. It is particularly useful for evaluation of morphology and the connections of cardiovascular structures. The disadvantage is that it provides no temporal information regarding cardiac motion or blood flow. Bright-blood cine sequences produce a series of images that can be looped as a movie to demonstrate cardiac motion. Each image demonstrates mixed T2 weighting where both blood and fat are bright. In the past, bright-blood cine imaging was implemented using cardiac-gated gradientrecalled–type sequences. Today, bright-blood cine imaging

CT and MRI in neonates with congenital cardiovascular disease is typically implemented using a steady-state free precession (SSFP) sequence that produces images that are relatively free of signal fluctuation caused by inflow effect. Contrast administration is usually not necessary for SSFP sequences. Using a contiguous stack of SSFP-cine bright-blood images, both right and left ventricular volumes can be segmented and quantified. SSFP-cine sequences are commonly used in cardiac MRI protocols for adults and older children. However, this sequence performs poorly in the setting of neonatal imaging, principally because the spatial resolution is limited, especially when compared with a dark-blood sequence. At a given image matrix size, an SSFP image tends to degrade markedly at a small field of view, which is necessary for the small neonatal chest. This behavior forces the use of a large field of view and thick image section often too large for the neonatal heart. In a 3-T scanner, SSFP images are further degraded because of increased band artifacts from off-resonance effects. For these reasons, SSFP-based bright-blood imaging tends to be less useful in neonates than in adults. Contrast-enhanced MRA produces high-resolution 3D images that render the contrast-filled cardiovascular lumens bright. Similar to CTA, first-pass contrast-enhanced MRA can be done if the timing of contrast arrival to a region of interest can be measured or calculated. This can be achieved using a bolus tracking technique. Alternatively, time-resolved MRA can generate multiple image volumes taken at different time points as the contrast bolus progresses.16 Precise contrast timing becomes unnecessary using this technique. If first-pass contrast enhancement is not required, MRA may be obtained at the contrast equilibrium phase, using a fixed time delay after contrast administration. Most of the time, MRA is performed without cardiac gating. However, cardiac gating or triggering can be used to improve vessel wall definition and to reduce phase-ghosting artifact from cardiac motion, at the cost of a longer scan time. Contrast-enhanced MRA benefits from higher signal-to-noise ratio at 3 T compared with 1.5 T.17 This signal-to-noise gain can be traded for higher spatial resolution, larger field-of-view coverage, or shorter scan time with use of parallel imaging and a higher acceleration factor. Contrast-enhanced MRA is particularly important for neonatal imaging as it can provide information about vascular structures that are inaccessible by echocardiography. PC sequences generate quantitative velocity information that is functionally similar to information obtained using duplex Doppler sonography. A PC sequence produces 2 types of images: a magnitude image demonstrating anatomy and one or more phase images encoding the components of the velocity vectors of motion, such as blood flow. Similar to bright-blood SSFP-cine imaging, cardiac PC sequences are cardiac gated and result in movies of the magnitude and phase images. Phasecontrast data acquisition can be 2D-PC with arbitrary orientation of the image plane, or it can be 3D with a volume that captures the entire chest. The latter approach has been termed 4D-flow or 4D-PC.18 With either 2D-PC or 4D-flow acquisition, velocity vectors within a vessel lumen can be summed to measure flow, such as cardiac output, valvular regurgitation, and shunt ratio.

5 Although 4D-flow techniques have been investigated for many years, they are only now becoming available on clinical scanners. 4D-flow imaging is typically implemented based on variations of gradient-recalled echo sequences. Administration of an intravascular contrast agent helps to increase signal strength within flow lumens and to increase contrast between blood and soft tissue. The former improves the signal-to-noise ratio of velocity data, and the latter improves delineation of the ventricular and vascular boundaries and helps with segmentation. 4D-data acquisition is typically accelerated by parallel imaging and temporally accelerated algorithms. Even so, a 4D-flow acquisition for a moderate matrix size usually takes several minutes at least. Therefore, breath-holding is not practical, and some degree of respiratory motion artifact is inevitable, although this can be reduced using various respiration correction techniques. A 4D-flow scan produces a large number of images. For example, a study with 64 slices, 20 cardiac phases, 1 magnitude image, and 3 velocity component images generates 5120 images. Manual inspection of these images is impractical and special postprocessing software is needed for visualization and flow quantification.19 Similar to contrast-enhanced MRA, 4D-flow imaging performance improves when scanning at higher field strengths. This technique is especially promising for neonatal cardiovascular imaging. As a cine sequence, it eliminates the need for 2D-SSFP bright-blood cine imaging. By acquiring flow data everywhere in a 3D space, it eliminates the need to perform multiple 2D phase-contrast scans, and the time-consuming task of positioning these planes precisely while the patient is under anesthesia. Owing to the fact that no breath-holding is required, the depth of anesthesia can be lightened in comparison with that used for conventional cardiac MRI scans. Deferring the prescription of oblique planes to postprocessing results in shorter study duration and anesthesia time. After proper eddy-current correction, flow quantification from 4Dflow scans has been shown to be consistent and accurate.20,21 Current challenges with respect to 4D-flow imaging are mainly related to workflow, such as long reconstruction times, large data sets to archive and to transfer, and complicated software that is required for postprocessing. With improvement in computational, data storage, and network resources, these challenges can be overcome in time.

1.5-T vs 3-T MRI Scanner At body temperature, the magnetic spins in the body are in constant motion in thermal equilibrium. The net magnetization, that is the vector sum of all magnetic spins, is zero. By putting the body in an MRI scanner, a small fraction of the spins align with the main magnetic field. The execution of an MRI sequence manipulates these aligned spins to produce the signal in an image. By increasing the field strength from 1.5- T, the number of aligned spins double, which can potentially be used to increase the image signal. The signal gain is a complex function of the sequence and of the changes in the relaxation constants T1, T2, and T2*. The increase in signal strength can be used to increase spatial resolution or to shorten scan time by

F.P. Chan and K. Hanneman


Figure 1 A 5-day-old male infant with type A interrupted aortic arch (IAA). The aorta is interrupted distal to the origin of the left subclavian artery, consistent with type A IAA (A, volume-rendered CTA). The descending aorta is small and is supplied by a large patent ductus arteriosus (PDA), arrow (B, sagittal oblique CTA). There were no other major collateral arteries. (Color version of figure is available online.)

increasing the acceleration factor. Imaging of the brain and the joints has taken advantage of these gains. However, improvements with respect to cardiac imaging are less certain. As discussed previously, the SSFP-cine sequence, which is a workhorse for cardiac imaging, has worsening off-resonance–related band artifacts and inflow artifacts at 3-T field strength. In contrast, the signal gain from 3-T scanner benefits contrast-enhanced MRA and 4D-Flow imaging by permitting greater spatial resolution. Therefore, if cine imaging is important and the SSFP-cine sequence is necessary, then imaging at 1.5 T may be a better choice. If imaging the extracardiac vasculature is the principal objective of a study, then contrastenhanced MRA performed at 3 T may be preferred.

Contrast Considerations Idiosyncratic allergic reactions to gadolinium-based MRI contrast agents are rare in the neonatal population. Their effects on patients with inadequate renal function are of greater concern. When given at a volume that is comparable to iodinated contrast agents, typical gadolinium agents such as gadopentetate (Magnevist) and gadodiamide (Omniscan) are more nephrotoxic than their iodinated counterparts are. Therefore, great care must be given to the dosage administered. For a 4-kg neonate, a single dose of 0.2 mL/kg of gadopentetate yields a contrast volume of 0.8 mL only. For first-pass MRA, the contrast volume is diluted with saline to a total volume of 10 mL, and injected at a slow rate of 1 mL/s, followed by a saline chase at a volume large enough to flush through the infusion line and the systemic veins. For this amount of dilution, it may be advantageous to use a high relaxivity agent, such as gadobenate (MultiHance),22 where the degree of T1 shortening is greater for the same amount of gadolinium atoms. For venous or blood pool imaging, gadofosveset (Ablavar) is an important option.23 This contrast agent stays in the

blood pool by binding reversibly to human serum albumin. In patients with impaired renal clearance (less than 30 mL/ min), gadolinium-associated nephrogenic systemic fibrosis is a concern, although no cases have been reported for neonates. In this setting, gadolinium agents are best avoided.

Anesthesia for MRI The anesthesia requirements for MRI studies are generally greater than those for CTA studies. All anesthesia equipment, such as infusion pumps, ventilators, gas tanks, tools, and monitoring equipment, must be MRI compatible. Otherwise, they may fail to function properly near the strong magnetic field, or worse, become projectiles. Should it be necessary to call a code, the patient must be transported out of the scanner suite first before resuscitation and intervention. MRI studies generally take longer than CTA studies. Although breath-holding is rarely necessary for neonates, enough anesthesia must be maintained to keep the patient still and the airways must be secured for the entire study duration. One aspect of the MRI environment that differs greatly from the CT environment is that a neonate is completely encased within the magnet out of visual or tactile contact for the entire study. Monitoring to ensure patient safety relies on instrument readings, such as heart rate, blood pressure, ECG tracing, and pulse oximetry. Anesthesia complications during MRI or CT studies are uncommon, but understandably, MRI studies often provoke greater concern from anesthesiologists.

CTA vs MRI Cardiac MRI and CT each have unique strengths and weaknesses. The choice between both the modalities depends on the diagnostic questions, the capabilities of each modality

CT and MRI in neonates with congenital cardiovascular disease


Figure 2 An 8-week-old male infant with double aortic arch. A dominant and intact right arch (thick arrow) gives rise to the right common carotid artery and right subclavian artery, and a smaller left arch (thin arrow) gives rise to the left common carotid artery and left subclavian artery (A, coronal MRA). There was moderate compression of the distal trachea (B, axial MRA). (Color version of figure is available online.)

to answer these questions, safety considerations, equipment and expertise available, and the condition of the patient. Both MRI and CTA are capable of evaluating anomalous anatomy found in cases of neonatal cardiovascular disease. CT is the modality of choice for imaging the lung parenchyma, the pulmonary vessels, and the coronary arteries. MRI is the modality of choice if flow and cine imaging are necessary. For critically ill patients, the speed of CT imaging and the accessibility of the patient during scanning make CT a safer choice. The greatest advantage of MRI over CT is that it uses no ionizing radiation and has no known cancer risks. The cumulative radiation dose from CT can be substantial in patients who need multiple scans. In these cases, efforts should be made to use MRI wherever feasible.

Applications Structural cardiovascular disease typically presents in the neonatal period either because a diagnosis is made by fetal ultrasound during prenatal care or because early symptoms uncover the disease. In the neonatal period, the strengths of MRI and CT lie in the evaluation of vascular structures, rather than intracardiac anatomy, which in most cases is well delineated by echocardiography. In the neonatal period, echocardiography has often been performed before CTA or MRI is requested. The imager should review the echocardiographic data before constructing an appropriate protocol to address the diagnostic questions. At this early age, assessment of the cardiovascular anatomy is simpler as it has not been altered by surgery. Careful application of segmental analysis should yield the proper diagnosis. The following sections give examples of structural cardiovascular diseases often seen in the neonatal period, grouped into anomalies of the aorta, pulmonary arteries, systemic veins, pulmonary veins, and coronary arteries.

Aortic Anomalies Interrupted Aortic Arch Interrupted aortic arch (IAA) is a rare cardiovascular defect, affecting approximately 3 per million live births. IAA is characterized by a complete lack of anatomical continuity between the aortic arch and the descending thoracic aorta (Fig. 1). Differential considerations include atresia of the aortic arch where continuity between the arch and descending aortic is maintained by a nonpatent fibrous connection. Classification of IAA is based on the site of interruption in relation to the arch vessels: type A is distal to the left subclavian artery, type B is between the left common carotid artery and the left subclavian artery, and type C is between the innominate artery and the left common carotid artery. The right subclavian artery may arise normally or abnormally in any of the 3 types. IAA is associated with DiGeorge syndrome with 22q11 microdeletion. Among patients with IAA, approximately 50% have DiGeorge syndrome, while 5%–20% of patients with DiGeorge syndrome have IAA, most commonly type B. IAA and complete common atrioventricular canal may be seen in the setting of CHARGE syndrome, characterized by Coloboma, Heart disease, choanal Atresia, Retarded growth and development or central nervous system anomalies, Genital hypoplasia, and Ear anomalies, usually caused by mutations in CHD7 (chromosome 8q12.1).24 IAA usually occurs in association with a nonrestrictive ventricular septal defect (VSD) and patent ductus arteriosus (PDA), but it may occur less commonly with a large aortopulmonary window or truncus arteriosus (TA).25 In patients with PDA, acute cardiovascular collapse or heart failure occurs after spontaneous closure of the ductus arteriosus in the first few days of life. However, treatment with prostaglandin E1 allows for resuscitation of neonates in anticipation of surgical therapy. Hypoplasia of the subaortic

F.P. Chan and K. Hanneman


Figure 3 A 3-day-old male infant with complete transposition of the great arteries (TGA). Axial (A) and sagittal oblique (B) MRA images. It should be noted that the position of the ascending aorta is anterior and to the right of the main PA (the MPA is normally anterior and to left of ascending aorta). The PDA is occluded at the PA end.

outflow tract often accompanies IAA, potentially complicating the surgical approach.26 Vascular Ring Vascular rings are rare congenital anomalies accounting for less than 1% of congenital cardiac defects. These are characterized by early developmental aberrations of the aortic arch resulting in a complete or incomplete ring surrounding the trachea or esophagus, potentially resulting in compression (Fig. 2). Most patients with a vascular ring present with symptoms related to airway or esophageal compression in infancy or very early in childhood. The 2 most common types of complete vascular rings are double aortic arch and right aortic arch with aberrant left subclavian artery and left ligamentum arteriosum, accounting for approximately 90% of cases. Less common complete rings include right aortic arch with mirror-image branching and left liagamentum arteriosum and left aortic arch with retroesophageal right subclavian artery, right-sided descending aorta, and right ligamentum arteriosum. Vascular rings result from abnormal or incomplete regression of 1 of the 6 embryonic branchial arches. A double aortic arch develops when involution of the distal right fourth arch does not take place. The fourth right and left arches persist, joining the left-sided descending thoracic aorta. A right aortic arch is present if the left fourth branchial arch involutes and the right remains. A mirror-image right aortic arch (without left ligamentum) is associated with other congenital cardiac anomalies, most commonly TOF. Band 22q11 deletion is also associated with aortic arch anomalies including vascular rings.27 Transposition of the Great Arteries Transposition of the great arteries (TGA) is the most common cyanotic congenital heart lesion presenting in neonates, accounting for 5%-7% of all congenital cardiac defects, with an

incidence of approximately 1 in 2000 to 5000 live births.28 There is a male predominance with a male to female sex ratio reported between 1.5:1 and 3:1. Postulated risk factors include gestational diabetes mellitus, exposure to herbicides, and antiepileptic drugs. The diagnosis is typically made by echocardiography; however, CT and MRI may provide complementary information, including assessment of associated cardiac defects. TGA is characterized by ventriculoarterial discordance, with the aorta arising from the morphologic right ventricle and the pulmonary artery arising from the morphologic left ventricle (Fig. 3). The clinical presentation is dominated by cyanosis with or without congestive heart failure. ventriculoarterial discordance is an isolated finding in 50% of cases. In 10% of cases, TGA is associated with noncardiac malformations. TGA may be associated with other cardiac malformations, including VSD and left ventricular outflow tract obstruction, which may influence the severity and onset of symptoms. Patent Ductus Arteriosus PDA is a common congenital heart defect with an estimated incidence between 0.02% and 0.006% of live births, accounting for approximately 5%-10% of congenital heart defects. The incidence is higher in infants born prematurely, with low birth weight and with a history of perinatal asphyxia. There is a female predominance with a female to male sex ratio of approximately 2:1. PDA is characterized by a persistent communication between the descending thoracic aorta and the pulmonary artery resulting from failure of normal physiological closure of the fetal ductus arteriosus (Fig. 4). Isolated PDA results in left to right shunting in infants. The shunt volume is determined by the size of the communication and pulmonary vascular resistance. PDA may also exist with other cardiac anomalies, which must be considered at the time of diagnosis. In some cases, such as TGA and IAA, PDA is critical for survival and needs to remain open to allow oxygenated blood to mix with

CT and MRI in neonates with congenital cardiovascular disease


Figure 4 A 1-day-old female infant with patent ductus arteriosus (PDA) (thick arrows). Sagittal oblique magnitude (A) and color (B) 4D-flow MRA images. Asc. aorta, ascending aorta; D. aorta, descending aorta; MPA, main pulmonary artery. (Color version of figure is available online.)

deoxygenated blood. In this setting, treatment with prostaglandins is used to keep the ductus arteriosus open.

Pulmonary Artery Anomalies Alagille Syndrome Alagille syndrome is an autosomal dominant disorder with variable expression associated with a characteristic facial appearance and abnormalities of the liver, heart, skeleton, eye, and kidneys.29 The incidence is approximately 1 in every 100,000 live births. Patients with Alagille syndrome may have mutations in either JAG1 or NOTCH2 genes. JAG1 encodes a ligand critical

to the notch gene-signaling cascade, which is important in fetal development.30 Most children present by 6 months of age with either neonatal jaundice related to biliary hypoplasia or cardiac-related symptoms, most commonly pulmonary artery stenosis (Fig. 5). Most patients have cardiac murmurs. Other associated cardiac lesions include atrial septal defects (ASDs), VSDs, TOF, PDA, and PA. TOF With Absent Pulmonary Valve TOF is the most common cyanotic congenital heart defect characterized by malaligned VSD; valvular, subvalvular, and supravalvular pulmonary stenoses; overriding aorta; and right ventricular hypertrophy.31 TOF with absent pulmonary valve

Figure 5 A male infant with Alagille syndrome and long-segment stenosis of the left main pulmonary artery (arrows), which measured 2.5 mm compared with the right main pulmonary artery which measured 7 m (A, axial CT image; B, oblique volume-rendered image [view from above]). Multiple segmental pulmonary artery dilations and focal stenoses were also noted. (Color version of figure is available online.)

F.P. Chan and K. Hanneman


In the early neonatal period, increased pulmonary vascular resistance results in a right to left shunt at the level of the VSD, thus causing cyanosis. However, after the fall in pulmonary vascular resistance, respiratory difficulties are the most prominent symptom, with net left to right shunting. This condition is associated with absence of the ductus arteriosus, and a pathogenic link between the lack of the ductus arteriosus and pulmonary artery dilatation has been proposed.33 In approximately 20% of cases, absent pulmonary valve is also associated with 22q11 microdeletion and DiGeorge syndrome, among other chromosomal abnormalities.32

Figure 6 A 2-day-old male infant with tetralogy of Fallot and absent pulmonary valve. The main pulmonary artery is enlarged with aneurysmal enlargement of the right pulmonary artery (RPA). Aberrant distal pulmonary artery branching with mild narrowing of the right lower lobe pulmonary artery branches (arrow). (Color version of figure is available online.)

is very rare, accounting for approximately 3% of cases of TOF, and is characterized by features of TOF with either rudimentary or complete absence of pulmonic valve tissue. Absence of significant pulmonary valve tissue results in severe pulmonary regurgitation, frequently associated with massive dilatation of the pulmonary arteries (Fig. 6). Aneurysmal pulmonary arteries may result in compression of the tracheobronchial tree. Prognosis is related to the degree of tracheobronchial obstruction secondary to pulmonary artery dilation. Airway compromise may result in hypoxemia, heart failure, and respiratory failure. Morbidity in cases with absent pulmonary valves far exceeds that in patients with typical features of TOF.32

PA With Major Aorticopulmonary Collaterals (MAPCAs) PA with major aorticopulmonary collaterals (MAPCAs) is a cyanotic congenital heart defect characterized by underdevelopment of the right ventricular outflow tract with atresia of the pulmonary valve. PA may be associated with an intact ventricular septum (PA-IVS) or with a VSD (PA-VSD). PA-VSD accounts for approximately 2%-4% of congenital cardiac defects and was previously referred to as pseudotruncus or TA type 4. Most patients present in the early neonatal period with cyanosis and hypoxia after closure of the ductus arteriosus. The VSD may be membranous or infundibular and is usually very large and unrestricted.34 Approximately half of patients with PA-VSD also have a secundumtype ASD or patent foramen ovale. In patients with PA, the PDA, systemic to pulmonary collaterals, or plexuses of bronchial and pleural arteries may contribute to pulmonary circulation. Collateral arteries arise most commonly from the thoracic aorta, but they may also arise from subclavian arteries, internal mammary arteries, intercostal arteries, the abdominal aorta, and rarely the coronary arteries (Fig. 7). In most cases, collateral arteries demonstrate stenoses, which can progress over time.

Figure 7 A 4-week-old infant with tetralogy of Fallot, pulmonary atresia, and multiple major aortopulmonary collateral arteries (MAPCAs). Tiny native pulmonary arteries (thick arrow) (A, axial CTA image). The patient has an aberrant right subclavian artery. MAPCA arising from the descending aorta supplies the right lower lobe, thin arrow (B, coronal CTA image). The tortuosity and variation in caliber of this vessel should be noted. (Color version of figure is available online.)

CT and MRI in neonates with congenital cardiovascular disease


Figure 8 A 6-day-old infant with truncus arteriosus and right-sided aortic arch (A, axial oblique CTA image; B, oblique volume-rendered CTA). The right and left pulmonary arteries have separate but proximate origins, arising from the posterolateral aspect of the common arterial trunk, consistent with Collett-Edwards type II and Van Praagh type A2 disease. (Color version of figure is available online.)

PA may be classified into 3 types depending on pulmonary blood flow. Pulmonary blood flow is provided by the native pulmonary arteries in type A, by native pulmonary arteries and MAPCAs in type B, and by MAPCAs alone in type C. PA-VSD has been considered to represent the most severe end of the spectrum of TOF. In patients with standard TOF, the pulmonary arteries are typically normal in size with normal peripheral arborization; however, peripheral pulmonary artery stenoses are relatively common. In PA-VSD, abnormal intrapulmonary arborization with stenoses of pulmonary arteries and pulmonary hypertension is especially frequent, particularly if there are multiple collateral vessels and the ductus is absent. Truncus Arteriosus TA is a rare congenital defect representing 1%-2% of congenital heart defects with an estimated incidence of approximately 5-15 of 100,000 live births. The embryonic TA fails to divide into the aorta and pulmonary artery. Therefore, TA is characterized by a single arterial trunk arising from the heart by means of a single semilunar valve, providing mixed blood to the coronary, pulmonary, and systemic circulation. The pulmonary arteries originate from the common arterial trunk distal to the coronary artery origins and proximal to the first aortic arch branch. The common trunk most commonly straddles the 2 ventricles, but it may be committed to either ventricle. A significant proportion of cases are associated with chromosome 22q11 deletion (DiGeorge syndrome). TA is classified based on the pattern of pulmonary arteries arising from the common trunk. The earliest classification was proposed by Collett and Edwards35 in 1949. Type I is characterized by a single pulmonary trunk arising from the left lateral aspect of the common trunk with branching of the left and right pulmonary arteries from the pulmonary trunk. Type II (Fig. 8) is characterized by separate but proximate

origins of the left and right pulmonary artery branches from the posterolateral aspect of the common arterial trunk. Type III is characterized by branch pulmonary arteries originating independently from the common truck or aortic arch. Type IV was originally proposed as a type of TA with neither pulmonary artery branch arising from the common trunk, but it is now recognized as a form of TOF (PA-VSD) (described previously). Another well-known classification was proposed by Van Praagh and Van Praagh36 in 1965, which also includes 4 primary types. Type A1 is identical to Collett and Edwards type I. Type A2 includes Collett and Edwards type II and many cases of type III (those with separate origins of the right and left pulmonary arteries from the lateral aspects of the common trunk). Type A3 is characterized by the origin of one branch pulmonary artery from the common trunk, with blood flow to the other lung by a pulmonary artery arising from the aortic arch or by systemic to pulmonary collaterals. Type A4 is characterized by the coexistence of an IAA. In any of the types, stenosis, hypoplasia, or both may be present in one or both branch pulmonary arteries. Common associated findings include structural abnormalities of the truncal valve, including dysplastic and supernumerary leaflets. Significant truncal valve regurgitation is not uncommon. The proximal coronary arteries may be abnormal, including single coronary artery or intramural course. IAA is a common association and almost always occurs between the left common carotid artery and left subclavian artery (type B).

Anomalous Systemic Venous Drainage Left SVC A left-sided SVC is the most common congenital venous anomaly in the chest, seen in 0.3%-0.5% of the normal population and in approximately 5% of those with congenital

F.P. Chan and K. Hanneman


Figure 9 A 2-day-old male infant with Treacher Collins syndrome and heterotaxia, with dextrocardia and situs inversus. Coronal MRA image demonstrates bilateral superior vena cava (SVC). The right SVC (thick arrow) drains into the right-sided morphologic left atrium. The left IVC (thin arrow) drains into the left-sided morphologic right atrium. The interatrial septum was incomplete. No bridging innominate vein is present. IVC, inferior vena cava. (Color version of figure is available online.)

heart disease. Usually, it is accompanied by a normal rightsided SVC, and a bridging vein is identified in 25%-35% of cases 37 (Fig. 9). Associations include ASD most commonly, as well as VSD, TOF, aortic coarctation, and unroofed coronary sinus.

Figure 11 A 1-day-old male infant with mixed total anomalous pulmonary venous return (TAPVR). Oblique coronal CTA demonstrates pulmonary venous drainage from both right upper and lower pulmonary veins to the superior vena cava (thin arrows) and from the left lung to the main portal vein (thick arrow). (Color version of figure is available online.)

Drainage is to the coronary sinus in more than 90% of cases, which is functionally insignificant, and most patients are asymptomatic. Even in the minority of patients who have a right to left shunt due to drainage into the left atrium (o10%), the shunt is usually not large enough to cause cyanosis as it only drains the left upper limb and left side of the head and neck.

Figure 10 A 2-day-old male infant with heterotaxy, right isomerism, and total anomalous pulmonary venous return (TAPVR). All bilateral pulmonary veins (PV) drain into a venous confluence behind the left atrium (thin arrow, A, axial MRA image). This drains into a vertical vein that courses under the aortic arch and drains unobstructed into the left superior vena cava (LSVC), which drains into the left-sided (morphologic right) atrium (B, oblique sagittal MRA). Intracardiac anomalies included common AV canal and single double-outlet morphologic right ventricle. AV, atrioventricular. (Color version of figure is available online.)

CT and MRI in neonates with congenital cardiovascular disease

13 The 4 variants of TAPVR include supracardiac (Fig. 10), in which drainage is to one of the innominate veins or the SVC; cardiac, in which blood drains directly into the coronary sinus or right atrium; infracardiac, with drainage to the portal or hepatic veins, and a mixed variant (Fig. 11). Although transthoracic echocardiography is considered the first-line imaging modality in the setting of TAPVR, CT and MRI may provide additional noninvasive information if findings by echocardiography are uncertain.39

Anomalous Coronary Artery

Figure 12 Neonate with anomalous origin of the right coronary artery from the left cusp (arrow) with an interarterial course (oblique axial CT image). (Color version of figure is available online.)

Anomalous Pulmonary Venous Drainage Total Anomalous Pulmonary Venous Connection Total anomalous pulmonary venous return (TAPVR) is a rare condition in which all pulmonary veins make anomalous connections to the systemic venous circulation or right atrium. Oxygenated blood thus recirculates back through the lungs instead of supplying oxygen to the rest of the body, constituting a left to right shunt. An ASD or patent foramen ovale must be present to allow oxygenated blood to flow to the left side of the heart for an infant to survive with TAPVR. The severity of TAPVR depends on the level of drainage and whether veins are obstructed. Infants with obstructed TAPVR are frequently symptomatic and are often surgically corrected early in life, with long-term postsurgical survival rates more than 80%.38

Anomalous Coronary Origin From the Aorta Coronary artery anomalies are defined as variants of anatomy occurring in less than 1% of the general population. Variations in coronary artery anatomy may be associated with structural forms of congenital heart disease. Most coronary artery anomalies do not cause symptoms. However, a higher incidence of coronary artery anomalies has been reported in young adults who experienced sudden death compared with adults. A 5% incidence of coronary anomalies has been reported in adult patients undergoing angiographic investigation.40 Coronary anomalies include anomalous location of coronary ostia outside normal coronary aortic sinuses (including the pulmonary artery, below), anomalous origination of the coronary ostia from the opposite coronary sinus, and anomalies of coronary termination (including fistulae). The course of an anomalous coronary may be described as prepulmonic, retroaortic, transseptal, or interarterial. The anomalous origin of the left coronary artery from the right sinus of Valsalva with interarterial course is associated with sudden cardiac death and warrants surgical referral and evaluation. Sudden death is less commonly seen in association with anomalous origin of the right coronary artery from the left sinus of Valsalva, and management may be conservative

Figure 13 Neonate with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), arrows (A, oblique volume-rendered CTA and B, coronal oblique CTA). LPA, left pulmonary artery; MPA, main pulmonary artery; RPA, right pulmonary artery. (Color version of figure is available online.)

14 depending on the clinical presentation (Fig. 12). Particular note should be made of a pre-pulmonic course prior to midline sternotomy, and of a retro-aortic course prior to aortic valve surgery. Anomalous Left Coronary Artery From the Pulmonary Artery Anomalous origin of the left coronary artery arising from the pulmonary artery (ALCAPA), also known as Bland-WhiteGarland syndrome, is a rare but serious anomaly accounting for approximately 0.25-0.5% of all congenital heart diseases (Fig. 13). Anomalous left coronary artery from the pulmonary artery is usually an isolated anomaly, but it has been associated with other conditions in rare cases, including PDA, VSD, TOF, and aortic coarctation. Infants typically present within the first few months of life with symptoms related to myocardial ischemia and congestive heart failure.

Conclusions Neonatal cardiovascular CTA and MRI provide important diagnostic information that confirms and supplements echocardiography findings. The choice of modality and protocol should be based on evaluation of the risks and benefits to the patient. Finally, imagers should maintain a high level of competency toward the optimal use of scanners and their associated equipment.

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15 38. Yong MS, dʼUdekem Y, Robertson T, et al: Outcomes of surgery for simple total anomalous pulmonary venous drainage in neonates. Ann Thorac Surg 91:1921-1927, 2011 39. Robinson BL, Kwong RY, Varma PK, et al: Magnetic resonance imaging of complex partial anomalous pulmonary venous return in adults. Circulation 129:e1-e2, 2014 40. Angelini P: Coronary artery anomalies: An entity in search of an identity. Circulation 115:1296-1305, 2007