Magnetic Resonance Angiography of Aortic Diseases in Children

Magnetic resonance angiography (MRA), a non-invasive, radiation-free imaging technique dependent on the body’s natural magnetic properties in blood vessels, investigates abnormalities within the aorta. MRA is generally divided into Gadolinium (Gd) based contrast enhanced MRA (CE-MRA) and non-contrast enhanced MRA (NCE-MRA), used for both qualitative and quantitative assessment of the aorta. These sequences can be exemplified with a variety of aortic abnormalities including aortic dissection, coarctation of the aorta, genetic disorders with aortic pathologies (e.g., Marfan’s syndrome, Loeys-Dietz syndrome), ascending and descending aortic aneurysms, Takayasu Arteritis, and various anomalies concerning the aortic arch as well as the aortic valve. While MRA can be applied to nearly any vessel in the body, the primary objective of this chapter is to focus on the role of MRA in the accurate quantitative and qualitative assessment of congenital and acquired aortic diseases. In many hospitals, a significant number of patients who are referred to MRA imaging is comprised of patients with aortic diseases, especially coarctation of aorta [Taylor, 2008]. The diagnostic utility of MRA is illustrated by a variety of pediatric aortic abnormalities.


Introduction
Magnetic resonance angiography (MRA), a non-invasive, radiation-free imaging technique dependent on the body's natural magnetic properties in blood vessels, investigates abnormalities within the aorta.MRA is generally divided into Gadolinium (Gd) based contrast enhanced MRA (CE-MRA) and non-contrast enhanced MRA (NCE-MRA), used for both qualitative and quantitative assessment of the aorta.These sequences can be exemplified with a variety of aortic abnormalities including aortic dissection, coarctation of the aorta, genetic disorders with aortic pathologies (e.g., Marfan's syndrome, Loeys-Dietz syndrome), ascending and descending aortic aneurysms, Takayasu Arteritis, and various anomalies concerning the aortic arch as well as the aortic valve.While MRA can be applied to nearly any vessel in the body, the primary objective of this chapter is to focus on the role of MRA in the accurate quantitative and qualitative assessment of congenital and acquired aortic diseases.In many hospitals, a significant number of patients who are referred to MRA imaging is comprised of patients with aortic diseases, especially coarctation of aorta [Taylor, 2008].The diagnostic utility of MRA is illustrated by a variety of pediatric aortic abnormalities.

Magnetic resonance angiography sequences
Examination of the aorta can be classified under purely qualitative imaging and both qualitative and quantitative imaging.

Qualitative aortic angiography
The first basic sequence employed is the non-electrocardiographic (ECG) gated steady-state free precision (SSFP) localizers in the coronal, axial and sagittal planes to visualize the entire chest and upper abdomen, providing a basic overview of cardiac and visceral situs and cardiovascular anatomy (Figure 1A-C).The localizers serve as the starting point for further disease-specific multiplanar image acquisition of the aorta for morphological, functional, and hemodynamic evaluation.Black-blood imaging, where the flowing blood appears dark and general aortic anatomy can be assessed, is exclusively used for qualitative analysis of the aortic morphology in multiple planes (Figure 1D-F).Black blood imaging includes a T1weighted spin echo sequence (which allows for rapid aortic morphological assessment at low spatial resolution) followed by a double inversion recovery spin echo sequence (which allows for high spatial resolution and improved blood-myocardium contrast) in order to characterize cardiovascular tissue and assess airway obstruction.

Quantitative & qualitative aortic angiography
In assessing the aorta both qualitatively and quantitatively, the cardiac imager may have two intentions in the quantitative measurement of vessels.On one hand, the imager can measure hemodynamic parameters such as blood flow, which would be accomplished more thoroughly by sequences which are concerned with functional assessment.On the other hand, more static measurements, such as assessing aortic root dilatation, would be accomplished more readily with sequences dedicated to morphological assessment.The following qualitative and quantitative sequences are discussed below.

Functional Assessment
A popular sequence used for functional assessment is the SSFP cine white blood imaging sequence, which provides superior quantitative imaging of the aorta and its branch vessels [Finn et al., 2006] without the use of contrast agents with high temporal resolution in multiple planes (Figure 2).SSFP imaging is very useful in qualitative assessment of aortic valve for regurgitation and stenosis.This technique requires breath-hold which is necessary to improve image quality by avoiding motion artifacts.Post processing of SSFP images includes assessment of 3D computational fluid dynamics (CFD).CFD simulation of hemodynamics in aortic arch models allows for quantification of high resolution internal flow fields (e.g.velocity, pressure) as well as useful flow derived parameter such as time resolved wall shear stress, energy dissipation and power loss (Figure 3).Flow derived parameters have application in surgical planning and post-operative assessment of hemodynamic efficiency in surgical anastomosis or venous flow confluences [Lara et al., 2011].CFD is a powerful tool for simulation of altered hemodynamics in pathological anatomies and may be used to assess aortic arch abnormalities, severity of coarctation (via assessment of pressure gradients, collateral flow, and velocity across the coarctation), and flow in arch anomalies (e.g.hypoplastic arch).

A B
Fig. 3. Cine MRI based surface model reconstructions of a normal neonatal arch [Pekkan et al. 2008] were used to conduct 3D CFD and assess vascular flow.(A) Streamlines colored by inlet normalized velocity magnitude, |V|, for a mean steady aortic root velocity of 0.33 m/s; B) Wall shear strain rate, with an observed stain rate is within normal ranges for neonatal flow.
Another functional imaging sequence is velocity-encoded cine phase contrast imaging (Figure 4).Phase contrast imaging is a method of obtaining quantitative information on blood flow, in addition to providing anatomic imaging of vessels.Its mechanics depend on magnetic moments, or spins, which ultimately shift in their phase of rotation, allowing for a voxel specific velocity to be calculated and an image to be formed [Lotz et al., 2002;Sena 2008].Quantification of flow at multiple levels of the aorta can be performed with and without breath holding using this technique.Determination of collateral flow, velocity, and pressure gradient across the coarctation in patients with coarctation of aorta can be preformed using this MR technique.14D later in the chapter.

Morphological Assessment
Traditional imaging of MRA includes both Gd-based CE-MRA as well as NCE-MRA using 3D SSFP, both of which serve as the source images for further post-processing which allows for static measurements and the creation of 3D models.
Gd-based CE-MRA has certain technical advantages over non-contrast enhanced MRA including superior visualization of vasculature, shorter acquisition times, and being less prone to alteration by motion artifacts [Hartung et al., 2011].CE-MRA is considered the most quick and efficient way of illustrating the entire thoracic vasculature (Figure 5A); high resolution spatial techniques within this sequence are especially beneficial in imaging the small vasculature of newborns with specific aortic malformations like truncus arteriosus [Sena et al., 2008].The ability to reconstruct maximum intensified projection (MIP) images (Figure 5B), volume rendered (VR) images (Figure 5C), and curved planar reformatted images allows for accurate measurements of vascular dimensions and aortic anatomy in patients with congenital and acquired aortic diseases.Limitations of CE-MRA techniques include the presence of motion artifacts in patients unable to breath-hold and patients with history of contrast agent allergies.A long-term complication of Nephrogenic Systemic Fibrosis in patients with poor renal function is another limitation of CE-MRA.Patients with metabolic syndromes, diabetes, and renal disease are especially at high risk and complications in these patients have spurred research with more diluted doses of contrast agents [Perazella et al., 2009].
With recent technical advancements in aortic imaging, NCE-MRA using 3D SSFP with and without breath hold imaging aids in the qualitative and quantitative assessment of the aorta with excellent spatial resolution without the need for Gd based contrast agents (Figure 5D).This advanced cardiovascular MRA sequence is especially useful in patients with a contraindication to contrast agents or who are unable to hold their breath.Measurements of the aorta and its branch vessels along with 3D and MIP image reconstructions in multiple planes are also possible with high accuracy using this sequence.A type of NCE-MRA, which will not be discussed in this chapter, is time of flight (TOF) MRA, which is based off of inflow effects, is a technique which is limited by longer acquisition time and a higher incidence of artifacts.
Additionally, late gadolinium enhancement (LGE) is a method by which regions of inflammation and fibrosis in the wall of aorta and its branch vessels can be identified.LGE, As mentioned, MRA can be utilized to image nearly any vessel in the body.The following table is a concise summary of current MRA techniques used for imaging of various vessels in the body, with sequences like black blood, phase contrast, SSFP, and ECG-gated fast spin echo (which is a variation of SSFP which we have not discussed in the chapter due to its irregular and sparse use), which are specifically used for aortic imaging [Morita et al., 2011].

Diseases of the aorta
Various diseases of the aorta, primarily highlighted in the pediatric population due to the large volume of pediatric cases in our institution as well as the congenital presentation of most of the diseases, are illustrated with the sequences discussed above.In general, almost all aortic diseases will be imaged via black-blood, CE-MRA, SSFP, phase contrast, and postprocessed to MIP and VR images as necessary for a comprehensive assessment available for the cardiac imager, cardiologist, or the surgeon.

Coarctation of aorta
Coarctation of aorta, a congenital condition characterized by aortic narrowing, is subtyped based on the location of the narrowing relative to the ductus arteriosus.The use of MRA in determining the severity of stenosis within aortic coarctation is well documented [Nielsen et al., 2005;Muzzarelli et al., 2011;Secchi et al., 2009].Coarctation of aorta requires comprehensive qualitative and quantitative evaluation for the assessment of severity of coarctation (e.g.velocity measurements at the level of coarctation as well as pre-and postcoarctation).Morphological evaluation of coarctation (Figure 6) and functional assessment (Figure 7) of collateral flow at various levels of the descending aorta is routinely performed.

Ascending & descending aortic aneurysm
Ascending and descending aortic aneurysms both arise from systemic and connective tissue diseases, including systemic hypertension, Marfan's syndrome, Loeys-Dietz syndrome, etc. (Figure 8).A weakness in the aortic wall causes distension leading to increased pressure and flow which may lead to other pathologies (e.g.aortic dissection as discussed later).Ascending and descending aneurysms are typically imaged quantitatively through CE-MRA along with overall qualitative assessment of bulging of the aortic wall.Loeys-Dietz syndrome is a genetic disorder which involves a high likelihood of ascending aortic aneurysms as well as aortic dissections (see below).A dilated aortic root is demonstrated in this patient with Loeys-Dietz using NCE-MRA; this technique is used frequently since regular follow-up of this disease is required and may minimize complications arising from contrast agents.

Aortic dissection
Aortic dissection, a malformation in which the inner aortic wall is torn and ultimately desecrated, is a life threatening condition.Generally, this defect is further subtyped according to the origin of the tear and to the extent certain areas of the aorta are involved.Within all these variations, MRA was considered the gold standard in detection and assessment of aortic dissections since the early 1990s due to nearly flawless sensitivity and specificity [Neinaber et al., 1993].More recently, however, it has been shown that aortic dissection is diagnosed with equivalent reliability in a number of imaging modalities including echocardiography and computed tomography (Litmanovich et. al, 2009;Shiga et. al, 2006).Aortic dissection is typically sequenced via CE-MRA, SSFP, and phase contrast MRA, followed by post-processing of VR and MIP images, helping in delineating the extent of dissection and the flow within the true and false (which results from tearing) lumen.

Aortic arch malformations & vascular rings
In contrast to more innocuous forms of alternative aortic arch anatomy (Figure 10B), aortic arch malformations occur as congenital defects in the development of the aortic arch and great vessels.An example is hypoplastic aortic arch (Figure 10A), where narrowing of the aorta possibly leads to further complications.Vascular rings, which involve abnormal encircling of the trachea and/or esophagus by the aorta or its branches, include interrupted, double, and right aortic arches (Figures 11 & 12).

Aortic valve malformations: bicuspid & quadricuspid aortic valve
Bicuspid aortic valve is a defect in the aortic valve in which two leaflets exist instead of the characteristic three found between the left atrium and left ventricle (Figure 13C-E).While it may be innocuous initially, the bicuspid aortic valve can lead to complications such as calcifications and stenosis later in life with varying degrees of severity.MRA is an appropriate imaging modality for the exploration of this valvular defect, considering that imaging modalities like echocardiography may miss certain variations of bicuspid aortic valve [Piccoli et al., 2010]; additionally, recent research has been directed toward understanding the implications of flow dynamics within bicuspid aortic valve patients, a feature which only MRA can offer [Hope et al., 2010].Similarly, a quadricuspid aortic valve is a defect in the aortic valve in which four leaflets exist instead of the characteristic three found between the left atrium and left ventricle (Figure 13A-B).It is typically imaged with a combination of modalities, with MRA being particularly useful in assessing regurgitation of the valve [Pouleur et al., 2009].

Aortic valve malformation: aortic stenosis & regurgitation
Aortic stenosis, or narrowing of the aortic valve, presents with a variety of problems dependent on the severity of valvular narrowing (Figure 14A-B).MRA has been shown to be a superior method, in terms of less intra-and inter-observer measurement variability, over echocardiography in the assessment of aortic stenosis severity [Garcia et al., 2011].Aortic valve regurgitation results when the aortic valve insufficiently closes and allows blood to leak back into the left ventricle instead of completely entering the aorta (Figure 14C-D).
While the aortic valve regurgitation is commonly first noticed by echocardiography, the assessment of the severity of aortic valve regurgitation and its effect on left ventricular function is done most sophisticatedly through MRA [Gabriel et al., 2011;Uretsky et al., 2010;].

Aortic inflammatory disease: Takayasu arteritis
Takayasu Arteritis, an inflammatory disease which causes various types of stenosis, occlusion, and/or dilatation in the aorta, carries a significant risk of premature death (Figure 15).While MRA overall is a good diagnostic tool for the functional aspects of this multifaceted disease (Keenan et al., 2009), the feature of LGE is particularly useful in demonstrating scarring in Takayusu Arteritis patients.

Magnetic resonance angiography of other vessels
While not the main focus of this chapter, use of MRA extends to the coronary arteries and peripheral vessels as well.In terms of arterial stenosis within the coronary arteries, overall vessel diagnostic accuracy with MRA is approximately 73% sensitive and 86% specific, which is significantly lower than the nearly perfect visualization (approximately 98%) of the aorta as demonstrated with all of the aforementioned malformations [Miller et al., 2009].
Studies have shown computed tomography angiography to be more sensitive and specific than MRA in the visualization of coronary artery stenosis and detection of coronary artery disease [Dewey et al., 2006;Schuijf et al., 2006;Scheutz et al., 2010;].In the case of peripheral arterial diseases, however, MRA has been shown to have superior diagnostic accuracy over computed tomography angiography in the visualization of peripheral vessels, such as those in the lower extremities [Menke et al., 2010].

Conclusion
As demonstrated by various qualitative and quantitative techniques, MRA has contributed to understanding features of aortic diseases within the pediatric population in particular.Through a range of sequencing which evaluates the morphological and functional aspects related to aortic malformations, MRA allows a comprehensive assessment of aortic disease in a sophisticated manner over other imaging modalities.MRA is a favorable imaging modality (as opposed to computed tomography) for the patient because of a lack of radiation and for the clinician due to its clinical applications with cardiovascular diseases and the ability to investigate both anatomy and function simultaneously with high resolution [Brenner et al., 2007;Finn et al., 2006]; however, there are some challenges with MRA in patients less than 8 years of age, where imaging requires children to be anesthetized in order to ensure appropriate breath-hold which is necessary to mitigate motion artifacts [Taylor, 2008].When it comes to examining congenital heart diseases, MRA is still considered a superior diagnostic tool, as it is able to quantify particular lesions using flow measurements, a fundamental limitation within computed tomography.

Fig. 4 .
Fig. 4. Phase contrast image of the aorta demonstrating flow in the ascending aorta (red arrow) and descending aorta (green arrow) which is quantifiable as demonstrated in Figure.14D later in the chapter.
Fig. 5. CE-MRA coronal image (A), MIP sagittal reconstruction of CE-MRA (B), VR sagittal reconstruction of CE-MRA (C), and axial NCE-MRA image using 3D SSFP (D) of the aorta.MIP and VR reconstructions are extremely useful for a qualitative overview of the vascular morphology for preoperative assessment.asequence that visualizes fibrotic or infarcted heart tissue, derives its name from the fact that there is a delay in the washout of gadolinium-based contrast because fibrotic regions are filled with collagen.It was first demonstrated in the late 1980s with animal models demonstrating enhancement of myocardial infarcts[van Dijkman et al., 1989].In recent decades, LGE has been shown to be particularly useful in pediatric diseases[Prakash et al.,  2003].However, the exact mechanism of contrast agent localization in infarcted tissue is a debated topic[Finn et al., 2006].

Fig. 6 .
Fig. 6.Black blood axial T1 weighted image of coarctation (A), double oblique measurement of CE-MRA at coarctation demonstrating 73% stenosis (B), calculated by the distal to coarctation (C) measurement; VR (D) and MIP (E) images demonstrating aggressive collateral vessels due to severe coarctation of aorta.
Fig. 8. (A) CE-MRA double oblique view of an ascending aortic aneurysm with an aortic diameter of ≈ 6 cm (normal is < 3.5 cm); (B) Black blood coronal image of ascending aortic aneurysm; (C) CE-MRA double oblique view of a descending thoracic aortic aneurysm with an aortic diameter of ≈ 2.8 cm; VR (D) and MIP (E) reconstructions of descending thoracic and abdominal aortic aneurysm.

Fig. 10 .
Fig. 10.(A) SSFP sagittal image demonstrating hypoplastic aortic arch; VR (B) and MIP (C) reconstructions demonstrating the common origin of neck vessels from the aortic arch.

Fig. 14
Fig. 14. (A) SSFP cine short axis and (B) left ventricular outflow tract view demonstrating an aortic stenotic jet with a velocity of 1.8m/s (normal being ≈ 1); (C) SSFP cine left ventricular outflow tract view demonstrating aortic regurgitation; (D) Quantification of aortic regurgitation fraction measuring 45%, a calculation made possible by phase contrast imaging at the level of the ascending aorta.

Fig. 15 .
Fig. 15.(A) LGE image of the aorta in a sagittal plane demonstrating aortic wall enhancement, a marker of active inflammatory disease; (B) CE-MRA axial view of aortic arch branches demonstrating severe narrowing of the left common carotid artery measuring 2.2 mm; (C) Wall thickening also involves the 3 branches of the aortic arch, the right brachiocephalic, left common carotid and left subclavian artery with (D) long segment stenosis of the left common carotid artery.