Flow Dynamics in Cardiovascular Devices: A Comprehensive Review

This review explores flow dynamics in cardiovascular devices, focusing on fundamental fluid mechanics principles and normal blood flow patterns. It discusses the role of different structures in maintaining flow dynamics and the importance of stents, heart valves, artificial hearts, and ventricular assist devices in cardiovascular interventions. The review emphasizes the need for optimized designs and further research to enhance knowledge of flow dynamics in cardiovascular devices, advancing the field and improving patient care in cardiovascular interventions

Optimization of craniosynostosis surgery: virtual planning, intraoperative 3D photography and surgical navigation

Mención Internacional en el título de doctorCraniosynostosis is a congenital defect defined as the premature fusion of one or more cranial sutures. This fusion leads to growth restriction and deformation of the cranium, caused by compensatory expansion parallel to the fused sutures. Surgical correction is the preferred treatment in most cases to excise the fused sutures and to normalize cranial shape. Although multiple technological advancements have arisen in the surgical management of craniosynostosis, interventional planning and surgical correction are still highly dependent on the subjective assessment and artistic judgment of craniofacial surgeons. Therefore, there is a high variability in individual surgeon performance and, thus, in the surgical outcomes. The main objective of this thesis was to explore different approaches to improve the surgical management of craniosynostosis by reducing subjectivity in all stages of the process, from the preoperative virtual planning phase to the intraoperative performance. First, we developed a novel framework for automatic planning of craniosynostosis surgery that enables: calculating a patient-specific normative reference shape to target, estimating optimal bone fragments for remodeling, and computing the most appropriate configuration of fragments in order to achieve the desired target cranial shape. Our results showed that automatic plans were accurate and achieved adequate overcorrection with respect to normative morphology. Surgeons’ feedback indicated that the integration of this technology could increase the accuracy and reduce the duration of the preoperative planning phase. Second, we validated the use of hand-held 3D photography for intraoperative evaluation of the surgical outcome. The accuracy of this technology for 3D modeling and morphology quantification was evaluated using computed tomography imaging as gold-standard. Our results demonstrated that 3D photography could be used to perform accurate 3D reconstructions of the anatomy during surgical interventions and to measure morphological metrics to provide feedback to the surgical team. This technology presents a valuable alternative to computed tomography imaging and can be easily integrated into the current surgical workflow to assist during the intervention. Also, we developed an intraoperative navigation system to provide real-time guidance during craniosynostosis surgeries. This system, based on optical tracking, enables to record the positions of remodeled bone fragments and compare them with the target virtual surgical plan. Our navigation system is based on patient-specific surgical guides, which fit into the patient’s anatomy, to perform patient-to-image registration. In addition, our workflow does not rely on patient’s head immobilization or invasive attachment of dynamic reference frames. After testing our system in five craniosynostosis surgeries, our results demonstrated a high navigation accuracy and optimal surgical outcomes in all cases. Furthermore, the use of navigation did not substantially increase the operative time. Finally, we investigated the use of augmented reality technology as an alternative to navigation for surgical guidance in craniosynostosis surgery. We developed an augmented reality application to visualize the virtual surgical plan overlaid on the surgical field, indicating the predefined osteotomy locations and target bone fragment positions. Our results demonstrated that augmented reality provides sub-millimetric accuracy when guiding both osteotomy and remodeling phases during open cranial vault remodeling. Surgeons’ feedback indicated that this technology could be integrated into the current surgical workflow for the treatment of craniosynostosis. To conclude, in this thesis we evaluated multiple technological advancements to improve the surgical management of craniosynostosis. The integration of these developments into the surgical workflow of craniosynostosis will positively impact the surgical outcomes, increase the efficiency of surgical interventions, and reduce the variability between surgeons and institutions.Programa de Doctorado en Ciencia y Tecnología Biomédica por la Universidad Carlos III de MadridPresidente: Norberto Antonio Malpica González.- Secretario: María Arrate Muñoz Barrutia.- Vocal: Tamas Ung

A New Paradigm for the Personalized Delivery of Iodinated Contrast Material at Cardiothoracic, Computed Tomography Angiography

In North America more than 40 million doses of iodinated X-Ray contrast medium are delivered to patients undergoing CT imaging every year. This particular pharmaceutical is necessary to enable Computed Tomography of soft tissue, tumors, and vasculature. Very few of the contrast enhanced procedures are performed with the dose of the drug tailored to the individual patient or procedure and nearly every patient receives the same dose of contrast material. This dissertation presents a methodology to allow the routine administration of a personalized dose of contrast material to generate contrast enhancement sufficient for diagnosis during cardiothoracic CT Angiography imaging. Parameter estimation of a patient specific model is performed using Maximum Likelihood Estimation (MLE) with data generated from the scanner during a pre-diagnostic "test" injection of contrast agent. A non-parametric system identification technique, using the truncated Singular Value Decomposition, is also developed for deriving a patient specific prediction of contrast enhancement. The MLE technique produces contrast enhancement predictions with less error than the tSVD method. It is also shown that the MLE method is less sensitive to data length and has greater noise immunity. A novel, patient-specific contrast protocol generation algorithm is also presented. It is based upon a constrained minimization (Sequential Quadratic Programming) that enforces constraints on the input parameters while minimizing the volume of contrast sufficient to achieve a prospectively chosen enhancement target. A physiologically based pharmacokinetic (PBPK) numeric model is developed and used to validate the contrast prediction and protocol generation techniques. Finally, a novel, instrumented, flow phantom is developed and used to validate the identification and protocol generation techniques

4D flow imaging of the thoracic aorta: is there an added clinical value?

Four-dimensional (4D) flow MRI has emerged as a powerful non-invasive technique in cardiovascular imaging, enabling to analyse in vivo complex flow dynamics models by quantifying flow parameters and derived features. Deep knowledge of aortic flow dynamics is fundamental to better understand how abnormal flow patterns may promote or worsen vascular diseases. In the perspective of an increasingly personalized and preventive medicine, growing interest is focused on identifying those quantitative functional features which are early predictive markers of pathological evolution. The thoracic aorta and its spectrum of diseases, as the first area of application and development of 4D flow MRI and supported by an extensive experimental validation, represents the ideal model to introduce this technique into daily clinical practice. The purpose of this review is to describe the impact of 4D flow MRI in the assessment of the thoracic aorta and its most common affecting diseases, providing an overview of the actual clinical applications and describing the potential role of derived advanced hemodynamic measures in tailoring follow-up and treatment

Simulation of Clinical PET Studies for the Assessment of Quantification Methods

On this PhD thesis we developed a methodology for evaluating the robustness of SUV measurements based on MC simulations and the generation of novel databases of simulated studies based on digital anthropomorphic phantoms. This methodology has been applied to different problems related to quantification that were not previously addressed. Two methods for estimating the extravasated dose were proposed andvalidated in different scenarios using MC simulations. We studied the impact of noise and low counting in the accuracy and repeatability of three commonly used SUV metrics (SUVmax, SUVmean and SUV50). The same model was used to study the effect of physiological muscular uptake variations on the quantification of FDG-PET studies. Finally, our MC models were applied to simulate 18F-fluorocholine (FCH) studies. The aim was to study the effect of spill-in counts from neighbouring regions on the quantification of small regions close to high activity extended sources

Radiopharmaceutical dosimetry in targeted radionuclide therapy

La médecine nucléaire est une spécialité médicale dont l'une des applications est l'étude de la physiologie des organes et du métabolisme de divers types de tumeurs. Les produits pharmaceutiques liés à un isotope radioactif (médicament radio-pharmaceutique, MRP) sont étudiés en préclinique avant d'être utilisés chez l'homme. Les rongeurs sont généralement utilisés pour étudier la bio-cinétique du traceur dans un groupe d'organes prédéfinis. L'extrapolation des résultats de ces études de l'animal à l'homme permet d'avoir une estimation du comportement des MRP et de l'irradiation délivrée en clinique. Trois nouveaux MRP ont été mis au point, l'un en France (CHU-Hôpital Purpan) et deux en Uruguay (CUDIM). Deux visent à étudier le cerveau et un vise à diagnostiquer le cancer de la prostate. Dans ce travail, l'extrapolation des résultats précliniques est présentée, les doses absorbées et efficaces sont estimées en utilisant les logiciels OLINDA/EXM V1.0, V2.0 et IDAC2.1. Les différences entre les résultats de chaque programme sont discutées. Au niveau clinique, les protocoles dosimétriques incluent la détermination du facteur d'étalonnage, la segmentation, le recalage, l'ajustement des courbes et le calcul de la dose absorbée. Dans ce travail, l'étalonnage développé pour un SPECT/CT est présenté en utilisant différentes sources d'étalonnage et différentes géométries. L'influence de la méthode de reconstruction sur la détermination du facteur d'étalonnage et les courbes du facteur de récupération sont présentées. Par ailleurs, quatre logiciels commerciaux sont comparés sur la base des informations cliniques de deux patients atteints de tumeurs gastro-entéro- pancréatiques d'origine neuroendocrine et traitées au 177Lu-DOTATATE. Deux cycles de traitement pour chaque patient ont été utilisés afin d'estimer les temps de résidence des reins, du foie, de la rate, de la moelle osseuse et du corps entier. Le calcul des doses absorbées a été initialement réalisé à l'aide de OLINDA/EXM V1.0 & V2.0, en ajustant la masse de chaque organe/tissu. Dans le cas de la moelle osseuse, une nouvelle méthodologie est présentée pour estimer la dose absorbée sans qu'il soit nécessaire de procéder à des mesures de corps entier. Il est possible de constater que le recalage des images a un impact sur la détermination de la dose absorbée. Les résultats sont donc calculés en employant d'un outil permettant de recaler indépendamment chaque organe et non pas toute l'image du champ de vue. Différents algorithmes de calcul ont été utilisés pour déterminer la dose absorbée délivrée aux patients, par exemple le modèle de sphère d'OLINDA/EXM V2.0, les méthodes de convolution et le dépôt d'énergie local de PLANET®Onco Dose de Dosisoft. Les résultats trouvés avec les différents outils sont comparés et discutés.Nuclear medicine is a medical specialty in which one of whose applications is the study of the physiology of organs and the metabolism of various types of tumours. Pharmaceuticals labelled with radionuclides (radiopharmaceuticals) are studied at pre-clinical level before being used in humans. Rodents are generally used to study the biokinetics of tracer in a group of predefined organs. The extrapolation of the results of these studies from animals to humans provides an estimate of the behaviour of the radiopharmaceuticals and the irradiation delivered clinically. Three new radiopharmaceuticals were developed, one in France (CHU-Hôpital Purpan) and two in Uruguay (CUDIM). Two aim to study the brain and one aims to diagnose prostate cancer. In this work, extrapolation of pharmacokinetics preclinical results to the human is presented; absorbed and effective doses are estimated using OLINDA/EXM V1.0, V2.0 and IDAC2.1 software. The differences between the results of each program are discussed. At a clinical level, dosimetric protocols include calibration factor determination, segmentation, registration, curve fitting, and calculation of absorbed dose. In this work, the calibration developed for a SPECT/CT is presented using different calibration sources and different geometries. The influence of the reconstruction method in the determination of the calibration factor and the recovery coefficient curves are shown. In addition, four commercial software are compared based-on clinical information of two patients with gastro-entero-pancreatic tumours of neuroendocrine origin treated with 177Lu-DOTATATE. Two cycles of treatment for each patient were used to estimate residence times for the kidneys, liver, spleen, bone marrow and whole body. Calculation of absorbed dose was initially developed using OLINDA/EXM V1.0 & V2.0, adjusting the mass of each organ/tissue. In the case of the bone marrow, a novel methodology is presented to estimate the absorbed dose without the need for whole-body measurements. It can be seen that the registration of the images has an impact on the determination of the absorbed dose. The results are thus calculated by employing a tool allowing to register independently each organ and not all the image of the field of view. Different calculation algorithms were used to determine the absorbed dose delivered to patients, for example the OLINDA/EXM V2.0 sphere model, convolution and local energy deposition methods of PLANET®Onco Dose from Dosisoft. The results found with the different tools are compared and discussed