Magnetic Resonance Evaluation of Coronary Anatomy, First-Pass Myocardial Perfusion and Late Gadolinium Enhancement in children and Young Adults with Acquired and Congenital Heart Disease

there are few studies evaluating the role of resonance the of along with assessment of The purpose this is to evaluate the extensive use evaluating and and ECG gated acquisition was performed to obtain T2 prep whole heart coronary images. Majority of the studies were performed without any sedation but few children younger than 9 years of age were sedated. Studies were post-processed on a satellite workstation and reviewed by experienced cardiologist in charge of the clinical MRI reporting. Late gadolinium enhancement imaging: Inversion recovery Gadolinium enhanced MR imaging was performed after intravenous injection of gadopentetate dimeglumine by using T1 weighted imaging technique in the cardiac short axis, four chamber view, and left ventricular two chamber. The inversion time was obtained by look-locker technique for optimal suppression of normal myocardial signal.


Introduction
The assessment and evaluation of patients with congenital and acquired heart disease requires a thorough clinical investigation with the support of different imaging modalities [1]. Echocardiography has invariably become the rst line imaging study for the vast majority of these patients, both pre and post operatively, as it provides diagnostic anatomical and functional images, while being portable and noninvasive at the same time. However, some of its limitations include less accurate information in those patients with poor acoustic window as well as limited thoracic vasculature and coronary artery evaluation, among others [2,3].
Cardiac magnetic resonance (CMR) has expanded its role in the diagnosis and management of congenital and acquired heart disease in children and young adults for the past 20 years [4][5][6][7]. It provides high quality images that help outline complex thoracic vasculature, cardiac anatomy, coronary arteries (including vessel wall), cardiac function and viability assessment, as well as cardiac perfusion, with the bene t of obviating the risks from invasive catheterization, iodinated contrast agent use and ionizing radiation exposure [8][9][10].
Anomalous coronary arteries may be assessed through magnetic resonance angiography (MRA), often with superior reconstruction and results compared to x-ray angiography [11,12]. It is the preferred test for younger patients with both suspected and/or known anomalous coronary artery origin as well as for those with other concomitant cardiac pathologies (13).
Clinically accepted indications of coronary MRA are limited to the assessment of coronary artery anomalies (class I indication) such as aneurysms (i.e. Kawasaki disease) and aorto-coronary bypass grafts (class II indication). Respiratory motion artifacts, usually regarded as a known CMR limitation, can be decreased through prospective real-time navigator gating and correction techniques [14][15][16].
Coronary aneurysmal disease or ectasia in children is mainly caused by Kawasaki disease, followed by congenital causes. In ammatory and other connective tissue disorders such as Takayasu's arteritis, lupus, rheumatoid arthritis, Marfan syndrome, among others, have also been described to cause them [17,18]. Mavrogeni et al demonstrated that MRI can effectively identify coronary disease in patients with Kawasaki disease and other autoimmune diseases, and that in fact MRA is equal to quantitative coronary angiography, with the additional advantage of being a noninvasive study [19][20][21].
Preliminary data in the past suggested that MRI coronary angiography could be used as a screening test to exclude clinically important stenosis in patients who would have been referred for diagnostic contrast angiography [22]. Nowadays, comparisons between CMR and computerized tomography (CT) angiography have demonstrated to similarly identify signi cant coronary stenosis in patients with suspected or known coronary artery disease [23].
Cardiac magnetic resonance imaging has been demonstrated to detect magnitude of infarcted myocardium along with delineation of origin and proximal course of coronary arteries [24][25][26][27]. In their multicenter trial, Kato et al found that whole-heart coronary MRA can noninvasively detect signi cant coronary artery stenosis with a sensitivity of 88% and speci city of 72% [28].
Contrast enhancement in coronary MRA may help to decrease the T1 relaxation time for blood, which in turn allows for an increased contrast-to-noise ratio for coronary MRA [29].
CMR has also signi cantly evolved in regards to perfusion imaging techniques to detect blood ow inside the myocardium. While single photon emission computed tomography (SPECT) has been regarded to be the clinical standard of myocardial perfusion, it does not come without some disadvantages such as ionizing radiation usage, poor spatial resolution, and artifacts secondary to soft tissue attenuation, among others. Myocardial perfusion imaging by rst-pass contrast enhanced CMR measures the amount of contrast agent owing within the myocardium during the rst pass after a bolus injection of contrast is given. Myocardial areas with lesser local blood ow will look hypointense and may be detected provided there is acceptable image quality. First-pass contrast enhanced CMR myocardial perfusion can also provide quantitative measurements of blood ow, give estimates of myocardial ow reserve, and evaluate regions with prior myocardial ischemia [30][31][32].
Though there are multiple studies that evaluate the role of CMR in describing and assessing cardiac anatomy, ventricular function and major vessel anatomy [11,12,16,[33][34][35], there are very few that describe the anatomy of coronary arteries in different congenital and acquired cardiac pathologies along with assessment of rst pass myocardial perfusion in children and young adults. In this study we discuss the extensive use of CMR for delineating coronary artery anatomy, evaluating rst pass myocardial perfusion and late gadolinium enhancement in children and young adults with acquired and congenital heart disease.

Methods
Patients: This is a retrospective review of 81 consecutive CMR Whole Heart T2 Prep coronary angiography studies of patients with congenital and acquired heart disease that were performed from December 2013 to May 2015. Results of rst pass myocardial perfusion study (at rest and with adenosine stress) and late Gadolinium enhancement imaging ndings were also reviewed. This study was approved by institutional review board of the hospital.
Magnetic Resonance acquisition: All CMR studies were performed on 1.5 Tesla Ingenia (Philips).
Respiratory navigated ECG gated acquisition was performed to obtain T2 prep whole heart coronary images. Majority of the studies were performed without any sedation but few children younger than 9 years of age were sedated. Studies were post-processed on a satellite workstation and reviewed by experienced cardiologist in charge of the clinical MRI reporting.
Late gadolinium enhancement imaging: Inversion recovery Gadolinium enhanced MR imaging was performed after intravenous injection of gadopentetate dimeglumine by using T1 weighted imaging technique in the cardiac short axis, four chamber view, and left ventricular two chamber. The inversion time was obtained by look-locker technique for optimal suppression of normal myocardial signal.

Results
The median age at the time of CMR was 14 years with range of 2 months to 35 years of age with 46 male and 35 female patients. Among the patient's pre-CMR diagnosis ( Table 1), tetralogy of Fallot was the most common averaging 30% of all subjects (24/81), followed by suspected coronary artery anomaly in about 19% of subjects (15/81) of all subjects.
First pass perfusion defects were identi ed in 2.5% (2/81) of subjects. Delayed myocardial enhancement study was performed in 83% of all patients (67/81), with an abnormal result identi ed in 28% of these subjects (19/67).
In our patients' coronary artery study (Table 2), the left coronary origin, proximal course and proximal branches were visualized in about 94% (76/81) of the subjects. For the right coronary, its origin, proximal course and branches were visualized in 89% (72/81) of subjects. We found good diagnostic quality images in 90% (73/81) of all the subjects.
The different coronary artery ndings can be observed in Table 3. The most common nding was clockwise rotation of coronary artery origin, seen in about 27% of subjects (20/81). A proximal conal branch arising from proximal right coronary artery (RCA) and coursing anteriorly around the right ventricular out ow tract (RVOT) was observed in 16% of all subjects (13/81). The left anterior descending (LAD) artery was found to run close to the posterior aspect of the RVOT and in close proximity behind the right ventricle to pulmonary artery (RV-PA) homograft in about 9% of subjects each (14/81 total). The RCA was found to be smaller than the left coronary artery (LCA) in 6% of the subjects (5/81). An abnormal coronary artery origin was observed in almost 9% of all subjects (7/81). Coronary aneurysmal malformations were identi ed in 6% of all subjects (5/81). We were unable to visualize either one of the coronary arteries in about 9% of subjects (7/81) either due to patient motion, artifacts or fast heart rate.
Ten patients (12%) had a pre-CMR diagnosis of suspected abnormal coronary artery origin by echocardiogram (Table 4). From these, 70% (7/10) had a chief complaint of chest pain or syncope. Fifty percent of patients (5/10) had normal coronary arteries on CMR, while 40% (4/10) had an abnormality in their origin or course. Only one patient's right coronary artery was not visualized due to an artifact caused by dental braces.

Discussion
Patients with complex congenital or acquired heart diseases require an in depth assessment of their cardiac anatomy and function through their life, by means of multiple and repetitive imaging studies [1][2][3]. CMR has expanded its role in the diagnosis and management of congenital and acquired heart disease in children and young adults by providing high quality images that not only help to outline complex thoracic vasculature, but also provides highly-detailed cardiac anatomy images, coronary artery course and vessel wall details, cardiac function and perfusion, with the bene t of obviating the risks from invasive catheterization, iodinated contrast agent use and ionizing radiation exposure [8][9][10].
In our study, we found that CMR provided good quality images in up to 90% of all patients with acquired and congenital heart diseases that highly delineated their coronary anatomy.
Nineteen subjects (28%) had delayed myocardial enhancement abnormalities detected by CMR. In one of the subjects who had a history of Duchenne's muscular dystrophy, we found extensive myocardial delayed enhancement involving lateral, anterolateral and inferolateral walls of the left ventricle. We also identi ed a patch of delayed myocardial enhancement involving the interventricular septum but with normal coronary artery study (Figure 1). One patient with aortic stenosis had diffuse circumferential subendocardial delayed myocardial enhancement (Figure 2).
In our study population, 6% of patients (5/81) had history of Kawasaki disease and CMR showed aneurysms involving multiple coronary arteries in four of the ve subjects. One of these patients had a giant aneurysm of the right coronary artery with a partially occlusive thrombus in the aneurysmal right coronary segment. In this patient, there was a rst-pass myocardial perfusion defect both at rest and with adenosine stress consistent with a xed perfusion defect (irreversible ischemic change). This patient also had evidence of delayed myocardial enhancement involving the sub-endocardium which correlates with the area of the rst-pass myocardial perfusion defect. (Figure 3).
Seven patients (8.64%) had anomalous aortic origin of coronary arteries. One of them had anomalous origin of left coronary artery from right coronary sinus with inter-arterial course and underwent unroo ng of the coronary artery. Post repair CMR showed a widely patent unroofed left coronary artery with normal rst pass myocardial perfusion (at rest and with adenosine stress) and no evidence of delayed myocardial enhancement (Figure 4). Another patient had anomalous right coronary artery from the left coronary sinus with inter-arterial course and preoperative CMR demonstrating the anatomy of the anomalous coronary artery. The patient underwent successful unroo ng of the anomalous right coronary artery. There was no evidence of delayed myocardial enhancement in this patient.
There were two patients (2.5%) with Marfan's syndrome who underwent valve sparing aortic root replacement with coronary re-implantation. CMR showed widely patent re-implanted coronary arteries in one patient. In the second patient, the left coronary artery was demonstrated but the right coronary artery was not well visualized due to artifact from a spinal fusion rod. There was no evidence of myocardial scar or brosis in either of these subjects.
There were 22 patients (27%) with a history of right-ventricle to pulmonary artery conduit placement. Coronary artery images by CMR were acquired in all patients, with good diagnostic quality images observed in 91% of them (20/22). Fifty nine percent of patients (13/22) had a history of tetralogy of Fallot. Nine patients (11%) had a history of arterial switch operation for dextro-transposition of great arteries. Their coronary anatomy was well delineated with CMR ( Figure 5). There was no evidence of myocardial scar or brosis on the late Gadolinium enhancement study of these subjects.
CMR was also performed in 12% of all patients (10/81) who had a suspected abnormal coronary artery origin detected by echocardiogram. Normal coronary arteries were observed in 50% of these patients (5/10), while an abnormal origin or course was detected in 40% of them (4/10); two patients had a RCA arising from the left coronary sinus (Figure 6), while one patient had clockwise rotation of the origin of coronary arteries and another patient had fusion of right and left coronary cusps.

Conclusions
Cardiac magnetic resonance imaging is a valuable tool that can reliably evaluate the coronary anatomy, rst pass myocardial perfusion defect and myocardial scar in children and young adults with acquired and congenital heart diseases. Funding: This research received no speci c grant from any funding agency, commercial or non-for-pro t sectors.
Con ict of interest: The authors declare that they have no con ict of interest.
Availability of data or material: Data is available up on request.