Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide causing in only Europe 3.9 million deaths corresponding the 45% of total deaths. In particular, among CVD, the congenital heart disease (CHD) is one of the most serious heart defect with an incidence of 8 per 1,000 live births. Purpose: In recent years, the role of imaging techniques in the diagnosis and follow-up of these patients has become increasingly important due to their progressive technological advancement. This doctoral thesis shows the results that we achieved in the use of cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) examination in patients with CHD. Section I – Cardiac computed tomography in CHD patients: In this chapter, we propose a study showing the possibility to obtain an impressively low ionizing dose reduction in pediatric CHD patients. Indeed, because the CCT can give valuable anatomic information on CHD in children but implies radiation exposure in subjects who are more radiosensitive than adult patients and that have a longer lifetime to develop stochastic effects from radiation, is very important to perform high-quality but low-dose examinations in this kind of patients. Thus, we evaluated a total of 100 pediatric CCT performed using 80, 100, or 120 kVp, showing that a high-quality pediatric CT can be performed using a 64-slice scanner, with a radiation effective dose close to 2 mSv in about 50% of the cases. Section II – Heart and great vessels CMR evaluation: In this section, are shown four studies focused on the use of CMR as a non-invasive imaging tool for the morpho-functional evaluation of heart and great vessels in patients with CHD. Concerning the study of heart dysfunction we published one paper on patients with non-obstructive hypertrophic cardiomyopathy (HCM) and another one on patients with functional univentricular heart (FUH); while regarding the study of great vessels we focused on the evaluation of the aortic strain and flow measurement in patients with different CVD, including CHD. The 2% HCM patients have a left ventricle wall thickness that reaches 13-15 mm, overlapped with those measured in mild forms of HCM. This overlap makes clinically relevant to differentiate athlete’s heart from mild forms of non-obstructive HCM. Thus, we decide to assess the left ventricle wall thickness and the myocardial metabolism of HCM patients compared to competitive athletes (CAs) using the magnetic resonance spectroscopy (MRS). We demonstrated that at the 1H-MRS there is a significant increase in myocardial lipids in HCM patients compared to competitive athletes, leading to the fact that it may be used as an additional final phase of a CMR protocol including standard morphologic and functional imaging in the differential diagnosis between HCM and athlete’s heart. Starting from the results of an our previous study showing that the inclusion of the hypoplastic chamber during the segmentation of cine images of FC patients may result in a less accurate measurement of the ejection fraction, we decided to validated a blood-threshold (BT) segmentation method for CMR cine images in FUH patients. Thus, we successfully validated in a pool of 44 FUH patients the use of a BT technique for the segmentation of cine images observing that a high intra- and inter-reader reproducibility for the assessment of ventricular stroke volume (SV) and an excellent agreement with aortic flow values used as a benchmark. Arterial stiffness is one of the earliest manifestations of adverse structural and functional changes within the vessel wall. When the aorta is considered, stiffness is a main determinant of age-related systolic and pulse pressure increase, a major predictor of stroke and myocardial infarction, and has been associated with heart failure. Previous authors showed that ascending aortic strain (AAS) measured at CMR is markedly decreased before the fifth decade of life and that can be considered as an early manifestation of vascular aging. Our aim was to evaluate the AAS in 1,027 consecutive patients with different types of CVD who underwent CMR , showing that differences in age, gender, and cardiovascular disease independently affect ascending aorta strain; in particular the lower ascending aorta strain observed in tetralogy of Fallot (ToF) fosters its assessment during follow-up in adulthood. Blood flow measurements are based on the segmentation of a vessel contour that may be performed manually or, more typically, semi-automatically, with the use of computer software likely impacting on measurement reproducibility. Reader experience may play a role as well. Thus, we aimed to estimate the intra- and inter-reader reproducibility of blood flow CMR measurements through the ascending aorta and main pulmonary artery in 50 patients affected with CHD or with aortic and/or pulmonary valve disease; also investigating the impact on reproducibility of the reader’s experience with CMR. Our results showed a good-to-excellent reproducibility for all variables except the backward flow of the ascending aorta, with a limited impact of operator’s training. Section III – To share or not to share our trial data?: In clinical research, spontaneous data sharing is not yet as common as it is in other fields such as genetics, astronomy or physics. However, the concept of data sharing has been suggested for many reasons, including the patient-centred nature of medical research and healthcare and the expectation that knowledge from existing data should be maximized to benefit all stakeholders. Although a transition to data sharing is a process that will take time and planning, those who adopt the principles and practices of open science will likely benefit from it. In addition, the emergence of data sharing as a potential requirement by some agencies and journals warrants attention by the imaging community. Indeed, from July 1st, 2018 the International Committee of Medical Journal Editors (ICMJE) will require a data sharing statement as a condition of consideration for publication of clinical trials. Thus, considering the amount of results that we collected in these three years of my PhD program, we asked ourselves about the potential advantages and disadvantages in sharing our source data with the scientific world. Our conclusions, enclosed in a paper published this year on European Radiology, have been discussed in this section. Conclusions: Both imaging modalities have limitations and advantages. CMR can evaluate heart function and vessel flow but require a long acquisition time and in same patients a long sedation time. CCT has a very high spatial resolution and short acquisition time but implies ionizing radiation exposure. This PhD thesis confirms the crucial role of CMR in functional analysis and the relevant possibilities of x-ray dose reduction in CCT, leading the foundations for future studies on the application of imaging techniques in the diagnosis and prognosis of CVD.

COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING FOR THE STUDY OF CONGENITAL HEART DISEASES / M. Ali' ; co-advisor: F. Secchi ; advisor: F. Sardanelli. - : . DIPARTIMENTO DI SCIENZE BIOMEDICHE PER LA SALUTE, 2019 Jan 16. ((31. ciclo, Anno Accademico 2018. [10.13130/ali-marco_phd2019-01-16].

COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING FOR THE STUDY OF CONGENITAL HEART DISEASES

M. Ali'
2019-01-16

Abstract

Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide causing in only Europe 3.9 million deaths corresponding the 45% of total deaths. In particular, among CVD, the congenital heart disease (CHD) is one of the most serious heart defect with an incidence of 8 per 1,000 live births. Purpose: In recent years, the role of imaging techniques in the diagnosis and follow-up of these patients has become increasingly important due to their progressive technological advancement. This doctoral thesis shows the results that we achieved in the use of cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR) examination in patients with CHD. Section I – Cardiac computed tomography in CHD patients: In this chapter, we propose a study showing the possibility to obtain an impressively low ionizing dose reduction in pediatric CHD patients. Indeed, because the CCT can give valuable anatomic information on CHD in children but implies radiation exposure in subjects who are more radiosensitive than adult patients and that have a longer lifetime to develop stochastic effects from radiation, is very important to perform high-quality but low-dose examinations in this kind of patients. Thus, we evaluated a total of 100 pediatric CCT performed using 80, 100, or 120 kVp, showing that a high-quality pediatric CT can be performed using a 64-slice scanner, with a radiation effective dose close to 2 mSv in about 50% of the cases. Section II – Heart and great vessels CMR evaluation: In this section, are shown four studies focused on the use of CMR as a non-invasive imaging tool for the morpho-functional evaluation of heart and great vessels in patients with CHD. Concerning the study of heart dysfunction we published one paper on patients with non-obstructive hypertrophic cardiomyopathy (HCM) and another one on patients with functional univentricular heart (FUH); while regarding the study of great vessels we focused on the evaluation of the aortic strain and flow measurement in patients with different CVD, including CHD. The 2% HCM patients have a left ventricle wall thickness that reaches 13-15 mm, overlapped with those measured in mild forms of HCM. This overlap makes clinically relevant to differentiate athlete’s heart from mild forms of non-obstructive HCM. Thus, we decide to assess the left ventricle wall thickness and the myocardial metabolism of HCM patients compared to competitive athletes (CAs) using the magnetic resonance spectroscopy (MRS). We demonstrated that at the 1H-MRS there is a significant increase in myocardial lipids in HCM patients compared to competitive athletes, leading to the fact that it may be used as an additional final phase of a CMR protocol including standard morphologic and functional imaging in the differential diagnosis between HCM and athlete’s heart. Starting from the results of an our previous study showing that the inclusion of the hypoplastic chamber during the segmentation of cine images of FC patients may result in a less accurate measurement of the ejection fraction, we decided to validated a blood-threshold (BT) segmentation method for CMR cine images in FUH patients. Thus, we successfully validated in a pool of 44 FUH patients the use of a BT technique for the segmentation of cine images observing that a high intra- and inter-reader reproducibility for the assessment of ventricular stroke volume (SV) and an excellent agreement with aortic flow values used as a benchmark. Arterial stiffness is one of the earliest manifestations of adverse structural and functional changes within the vessel wall. When the aorta is considered, stiffness is a main determinant of age-related systolic and pulse pressure increase, a major predictor of stroke and myocardial infarction, and has been associated with heart failure. Previous authors showed that ascending aortic strain (AAS) measured at CMR is markedly decreased before the fifth decade of life and that can be considered as an early manifestation of vascular aging. Our aim was to evaluate the AAS in 1,027 consecutive patients with different types of CVD who underwent CMR , showing that differences in age, gender, and cardiovascular disease independently affect ascending aorta strain; in particular the lower ascending aorta strain observed in tetralogy of Fallot (ToF) fosters its assessment during follow-up in adulthood. Blood flow measurements are based on the segmentation of a vessel contour that may be performed manually or, more typically, semi-automatically, with the use of computer software likely impacting on measurement reproducibility. Reader experience may play a role as well. Thus, we aimed to estimate the intra- and inter-reader reproducibility of blood flow CMR measurements through the ascending aorta and main pulmonary artery in 50 patients affected with CHD or with aortic and/or pulmonary valve disease; also investigating the impact on reproducibility of the reader’s experience with CMR. Our results showed a good-to-excellent reproducibility for all variables except the backward flow of the ascending aorta, with a limited impact of operator’s training. Section III – To share or not to share our trial data?: In clinical research, spontaneous data sharing is not yet as common as it is in other fields such as genetics, astronomy or physics. However, the concept of data sharing has been suggested for many reasons, including the patient-centred nature of medical research and healthcare and the expectation that knowledge from existing data should be maximized to benefit all stakeholders. Although a transition to data sharing is a process that will take time and planning, those who adopt the principles and practices of open science will likely benefit from it. In addition, the emergence of data sharing as a potential requirement by some agencies and journals warrants attention by the imaging community. Indeed, from July 1st, 2018 the International Committee of Medical Journal Editors (ICMJE) will require a data sharing statement as a condition of consideration for publication of clinical trials. Thus, considering the amount of results that we collected in these three years of my PhD program, we asked ourselves about the potential advantages and disadvantages in sharing our source data with the scientific world. Our conclusions, enclosed in a paper published this year on European Radiology, have been discussed in this section. Conclusions: Both imaging modalities have limitations and advantages. CMR can evaluate heart function and vessel flow but require a long acquisition time and in same patients a long sedation time. CCT has a very high spatial resolution and short acquisition time but implies ionizing radiation exposure. This PhD thesis confirms the crucial role of CMR in functional analysis and the relevant possibilities of x-ray dose reduction in CCT, leading the foundations for future studies on the application of imaging techniques in the diagnosis and prognosis of CVD.
SARDANELLI, FRANCESCO
computed tomography; magnetic resonance imaging; congenital heart disease
Settore MED/36 - Diagnostica per Immagini e Radioterapia
COMPUTED TOMOGRAPHY AND MAGNETIC RESONANCE IMAGING FOR THE STUDY OF CONGENITAL HEART DISEASES / M. Ali' ; co-advisor: F. Secchi ; advisor: F. Sardanelli. - : . DIPARTIMENTO DI SCIENZE BIOMEDICHE PER LA SALUTE, 2019 Jan 16. ((31. ciclo, Anno Accademico 2018. [10.13130/ali-marco_phd2019-01-16].
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/608210
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