Heart valve tissue engineering (HVTE) stands as a potential intervention that could reduce the prevalence of congenital heart valve disease in juvenile patients. Prior studies in our laboratory have utilized mechanobiological testing to quantify the forces involved in the development of heart valve tissue, utilizing a Flow-Stretch-Flexure (FSF) bioreactor to condition bone marrow stem cells (BMSCs)-derived valve tissue. Simulations have demonstrated that certain sets of flow conditions can introduce specific levels of oscillatory shear stress (OSS)-induced stimuli, augmenting the growth of engineered valves as well as influencing collagen formation, extracellular matrix (ECM) composition and gene expression. The computational findings discussed in this thesis outline the methods in which flow conditions, when physiologically relevant, induce specific oscillatory shear stresses which could not only lead to an optimized valve tissue phenotype (at 0.18≤ OSI≤ 0.23), but could identify native valve tissue remodeling indicative of aortic valve disease.

Οι καρδιαγγειακές παθήσεις αποτελούν την κύρια αιτία θανάτου στις αναπτυγμένες χώρες. Η στένωση σε μία αρτηρία, είτε αυτή προκαλείται από μία πάθηση όπως το ανεύρυσμα, είτε προκαλείται από μία περίδεση, όπως στις περιπτώσεις των συγγενών καρδιοπαθειών, μπορεί να μεταβάλλει σε σημαντικό βαθμό τα χαρακτηριστικά της ροής του αίματος. Η μελέτη της φυσιολογικής παλλόμενης ροής μέσα από στένωση είναι ιδιαίτερα σημαντική για τη διάγνωση και αντιμετώπιση των αγγειακών νόσων. Το ιατρικό πρόβλημα το οποίο εξετάζουμε στην παρούσα εργασία, είναι η στένωση της πνευμονικής αρτηρίας από περίδεση. Η περίδεση γίνεται προφανώς για να μειωθεί η υψηλή αρτηριακή πίεση και τελικά η ροή του αίματος προς τους πνεύμονες. Πρόκειται για μία χειρουργική μέθοδο αντιμετώπισης συγγενών καρδιοπαθειών. Η περίδεση της πνευμονικής αρτηρίας (pulmonary artery banding - PAB) είτε με συμβατικό τρόπο, ή με την πλέον σύγχρονη μέθοδο μέσω της συσκευής FloWatchTM προκαλεί τη στένωσή της. Με τον συμβατικό τρόπο η στένωση μπορεί να θεωρηθεί αξονικά συμμετρική, ωστόσο με τη χρήση του FloWatchTM είναι μη αξονικά συμμετρική. Έχει αποδειχθεί ότι τόσο η αξονικά συμμετρική, όσο και η μη συμμετρική περίδεση δημιουργεί διαφόρου βαθμού ίνωση του τοιχώματος της πνευμονικής αρτηρίας. Η αναδόμηση της πνευμονικής αρτηρίας είναι πολύ ηπιότερη στην περίπτωση της περίδεσης με το FloWatchTM. Η διαφοροποίηση αυτή έγκειται κυρίως στο ότι η συμβατική περίδεση προκαλεί για συγκεκριμένη μείωση της διατομής ισχυρότερη μείωση της περιμέτρου της διατομής από εκείνης της περίδεσης με το FloWatchTM. Στην παρούσα εργασία γίνεται αναφορά και ανάλυση των διαφόρων περιπτώσεων ροής σε στενώσεις αρτηριών, των συγγενών καρδιοπαθειών και των τεχνικών περίδεσης της πνευμονικής αρτηρίας. Επιπρόσθετα, μελετήθηκαν και υπολογίστηκαν η μόνιμη και η παλλόμενη ροή σε αξονικά συμμετρική 25% στένωση προκαλούμενη από συμβατική περίδεση, καθώς και η μόνιμη και παλλόμενη ροή σε μη συμμετρική 25% στένωση της πνευμονικής αρτηρίας όπως προκαλείται από το FloWatchTM, μέσω των πακέτων Fluent και Gambit. Η υπολογιστική μελέτη του πεδίου ροής περιλαμβάνει την κατανομή ταχυτήτων, τον προσδιορισμό των περιοχών ανακυκλοφορίας, την κατανομή των πιέσεων και την σύγκριση των παραπάνω μεγεθών με τα αντίστοιχα αποτελέσματα της βιβλιογραφίας. Τέλος, με βάση τα αποτελέσματα γίνεται η σύγκριση των δύο μελετούμενων μεθόδων περίδεσης. Αριθμητικά ρεαλιστικά δεδομένα ελήφθησαν από την καρδιοχειρουργική κλινική του νοσοκομείου Παίδων «Αγία Σοφία». / Cardiovascular diseases are the leading cause of death in developed countries. A stenosis in an artery , caused either by a disease such as an aneurism or by a banding (such as in congenital diseases) can change the characteristics of the blood flow very seriously. The study of the physiological pulsatile flow through a stenosis is very important for the diagnosis and treatment of the arterial diseases. The medical problem which is examined in this study is pulmonary artery stenosis caused by a banding. The banding takes place to reduce the high arterial pressure and finally the blood flow from the heart to the lungs. It is a surgical method used for treatment of congenital heart diseases. The pulmonary artery banding either with the use of the conventional method or the most modern with the use of the FloWatchTM technology causes stenosis of the artery. With the conventional method, stenosis can be considered axially symmetrical while with the use of FloWatchTM it is asymmetrical. It has been proven that both the axially symmetrical and asymmetrical banding cause fibrosis of the pulmonary artery walls of different degrees. The reconstruction of the pulmonary artery is milder where there is banding with FloWatchTM. This differentiation is based mainly on the fact that the conventional banding causes, for a specific decrease of the cross-section, a decrease in the perimeter of the cross-section higher than that of banding with FloWatchTM. In this assignment there is a report of different cases of flow in arterial stenosis, in congenital heart diseases and pulmonary banding techniques. In addition what was studied and appreciated was the steady and pulsatile flow in axially symmetrical 25% stenosis caused by the conventional banding, as well as the steady and pulsatile flow in asymmetrical 25% stenosis of pulmonary artery caused by FloWatchTM with the use of Fluent and Gambit. The numerical study of flow distribution includes velocity distribution, designation of back flow area, distribution of pressure and comparison of these quantities with the results in bibliography. Finally, based on the results, there is a comparison of the two banding methods under study. The numerical realistic data were received from the cardio-surgical clinic of children’s hospital “Aghia Sophia”.

Indiana University-Purdue University Indianapolis (IUPUI) / With the recent advancement of computation and imaging technology, Image-based computational fluid dynamics (ICFD) has emerged as a great non-invasive capability to study biomedical flows. These modern technologies increase the potential of computation-aided diagnostics and therapeutics in a patient-specific environment. I studied three components of this image-based computational fluid dynamics process in this work. To ensure accurate medical assessment, realistic computational analysis is needed, for which patient-specific image segmentation of the diseased vessel is of paramount importance. In this work, image segmentation of several human arteries, veins, capillaries, and organs was conducted to use them for further hemodynamic simulations. To accomplish these, several open-source and commercial software packages were implemented. This study incorporates a new computational platform, called InVascular, to quantify the 4D velocity field in image-based pulsatile flows using the Volumetric Lattice Boltzmann Method (VLBM). We also conducted several parametric studies on an idealized case of a 3-D pipe with the dimensions of a human renal artery. We investigated the relationship between stenosis severity and Resistive index (RI). We also explored how pulsatile parameters like heart rate or pulsatile pressure gradient affect RI. As the process of ICFD analysis is based on imaging and other hemodynamic data, it is often time-consuming due to the extensive data processing time. For clinicians to make fast medical decisions regarding their patients, we need rapid and accurate ICFD results. To achieve that, we also developed surrogate models to show the potential of supervised machine learning methods in constructing efficient and precise surrogate models for Hagen-Poiseuille and Womersley flows.

<p>  </p> <p>With the recent advancement of computation and imaging technology, Image-based computational fluid dynamics (ICFD) has emerged as a great non-invasive capability to study biomedical flows. These modern technologies increase the potential of computation-aided diagnostics and therapeutics in a patient-specific environment. I studied three components of this image-based computational fluid dynamics process in this work.</p> <p>To ensure accurate medical assessment, realistic computational analysis is needed, for which patient-specific image segmentation of the diseased vessel is of paramount importance. In this work, image segmentation of several human arteries, veins, capillaries, and organs was conducted to use them for further hemodynamic simulations. To accomplish these, several open-source and commercial software packages were implemented. </p> <p>This study incorporates a new computational platform, called <em>InVascular</em>, to quantify the 4D velocity field in image-based pulsatile flows using the Volumetric Lattice Boltzmann Method (VLBM). We also conducted several parametric studies on an idealized case of a 3-D pipe with the dimensions of a human renal artery. We investigated the relationship between stenosis severity and Resistive index (RI). We also explored how pulsatile parameters like heart rate or pulsatile pressure gradient affect RI.</p> <p>As the process of ICFD analysis is based on imaging and other hemodynamic data, it is often time-consuming due to the extensive data processing time. For clinicians to make fast medical decisions regarding their patients, we need rapid and accurate ICFD results. To achieve that, we also developed surrogate models to show the potential of supervised machine learning methods in constructing efficient and precise surrogate models for Hagen-Poiseuille and Womersley flows.</p>

No / PURPOSE: To investigate cerebrospinal fluid (CSF) dynamics in the aqueduct of Sylvius (AoS) in chronic cerebrospinal venous insufficiency (CCSVI)-positive and -negative healthy individuals using cine phase contrast imaging. MATERIALS AND METHODS: Fifty-one healthy individuals (32 CCSVI-negative and 19 age-matched CCSVI-positive subjects) were examined using Doppler sonography (DS). Diagnosis of CCSVI was established if subjects fulfilled >/=2 venous hemodynamic criteria on DS. CSF flow and velocity measures were quantified using a semiautomated method and compared with clinical and routine 3T MRI outcomes. RESULTS: CCSVI was associated with increased CSF pulsatility in the AoS. Net positive CSF flow was 32% greater in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.008). This was accompanied by a 28% increase in the mean aqueductal characteristic signal (ie, the AoS cross-sectional area over the cardiac cycle) in the CCSVI-positive group compared with the CCSVI-negative group (P = 0.021). CONCLUSION: CSF dynamics are altered in CCSVI-positive healthy individuals, as demonstrated by increased pulsatility. This is accompanied by enlargement of the AoS, suggesting that structural changes may be occurring in the brain parenchyma of CCSVI-positive healthy individuals.