2-D and 3-D high frame-rate Pulse Wave Imaging for the characterization of focal vascular disease

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels

Noninvasive vascular elastography for carotid artery characterization

96 σ.Ο σκοπός της διπλωματικής εργασίας ήταν η ανάπτυξη μεθοδολογίας για την εξαγωγή ελαστογραφημάτων από ακολουθίες εικόνων υπερήχων Β-σάρωσης καθώς και ο έλεγχος και η αξιολόγηση των αποτελεσμάτων της. Η μεθοδολογία αυτή περιλαμβάνει την ανάλυση κίνησης των σημείων μιας επιλεγμένης περιοχής ενδιαφέροντος μεταξύ ζευγών εικόνων υπερήχων, τον υπολογισμό των αντίστοιχων μηχανικών καταπονήσεων και τελικά την απεικόνισή τους με κατάλληλο χρωματισμό του αντίστοιχου σημείου της εικόνας. Η τεχνική που αναπτύχθηκε εφαρμόστηκε σε συνθετικές ακολουθίες εικόνων της καρωτίδας και ελέγχθηκε η επίδραση αυξανόμενων επιπέδων θορύβου στα αποτελέσματά της. Τελικά διαπιστώθηκε ότι, η αύξηση του θορύβου προκαλεί σημαντικές διακυμάνσεις στο χρωματισμό των περιοχών ενδιαφέροντος. Εν συνεχεία, η παραπάνω τεχνική εφαρμόστηκε σε πραγματικές ακολουθίες εικόνων της καρωτίδας από υγιή άτομα. Συγκεκριμένα, υπολογίστηκαν ελαστογραφήματα μεταξύ ζευγών εικόνων σε διάρκεια ενός καρδιακού κύκλου. Η διαδικασία αυτή επαναλήφθηκε για 4 υγιή άτομα και με βάση τα ελαστογραφήματα που εξήχθησαν μελετήθηκε η καταπόνηση του κάτω τοιχώματος της καρωτίδας. Επίσης, ελαστογραφήματα κατασκευάστηκαν και από πραγματικές ακολουθίες εικόνων από δύο ασθενείς με αθηρωμάτωση, εστιάζοντας στην αθηρωματική πλάκα και το περιβάλλον τοίχωμα. Με τη βοήθεια των ελαστογραφημάτων αυτών μελετήθηκε η μηχανική συμπεριφορά των αθηρωματικών πλακών κατά τη διάρκεια του καρδιακού κύκλου. Παράλληλα υπολογίστηκαν οι μέσες καταπονήσεις ανά σημείο της περιοχής ενδιαφέροντος για κάθε εξεταζόμενο κατά τη διάρκεια ενός καρδιακού κύκλου και συγκρίθηκαν τα αποτελέσματα. Η μεθοδολογία ανάπτυξης ελαστογραφημάτων μπορεί να αποτελέσει ένα συμπληρωματικό εργαλείο μελέτης των μηχανικών ιδιοτήτων των τοιχωμάτων της καρωτίδας. Επίσης, μπορεί να συμβάλει στον εντοπισμό και στην εξέταση των ελαστικών ιδιοτήτων και της μηχανικής συμπεριφοράς των αθηρωματικών πλακών καθώς και στην αξιολόγηση του κινδύνου που συνιστούν. Περαιτέρω εφαρμογή της μεθόδου σε υγιείς και ασθενείς εξεταζόμενους αναμένεται να παράσχει περισσότερα στοιχεία σχετικά με τη μηχανική συμπεριφορά των ιστών της καρωτίδας.The purpose of this thesis was the development of a methodology, in order to construct elastograms using B-mode ultrasound images and also to investigate its performance. This methodology consists of the motion analysis of points from a selected region of interest between pairs of ultrasound images, of the calculation of the corresponding mechanical strains and finally of their imaging, via appropriate coloring of the corresponding points of the image. The methodology was applied to synthetic sequences of images of the carotid and the influence of increased levels of image noise was checked. Finally, it was found that increasing noise caused serious fluctuation to the coloring of the regions of interest Then this methodology was applied to real sequences of images of the carotid artery from healthy subjects. Specifically elastograms were computed between pairs of images across a single cardiac cycle. This procedure was repeated for 4 healthy subjects and according to the resulting elastograms the movement of the lower arterial wall of the carotid was studied. Moreover, elastograms were computed using real sequences of images of the carotid artery from patients with atherosclerosis, focusing on the atheromatic plaque and the surrounding arterial wall. With the aid of the resulting elastograms the mechanical properties of the atheromatic plaques were studied during a single cardiac circle. In addition to this, the average strains per point of the region of interest for every subject during a single cardiac circle were computed and subsequently they were compared to each other. This methodology of constructing elastograms can become a useful supplementary tool for the study of the mechanical properties of the carotid artery. In addition to this, it can contribute to locating atheromatic plaques, studying their mechanical properties and also assessing their risk of rupture. Additional application of this method to healthy and pathological subjects can lead to a great deal of information about the mechanical properties of the carotid tissues.Ιάσων-Ζαχαρίας Ν. Αποστολάκη