Hemodynamics in healthy and pathological thoracic aorta: integration of in-vivo data in CFD simulations and in in-vitro experiments

A comparison between the results of the CFD simulations and the in-vitro experiments carried out on a circulatory mock loop is presented. Both approaches integrate in-vivo measurements obtained from a patient-specific clinical data set. Three thoracic-aorta geometries are analyzed: a healthy aorta, an aneurysmatic aorta, and a coarctated aorta. The healthy geometry is obtained from Magnetic Resonance Imaging (MRI) acquisitions, together with the patient-specific flow-rate waveform, whereas the diseased ones are derived from the former geometry by locally morphing the vessel's wall. The open-source code Simvascular is used for simulations. The in-vitro results are measured in a fully controlled and sensorized circulatory mock loop for 3D-printed aortic models. Differently from in-vivo acquisitions, the experimental set-up eliminates some of the uncontrollable uncertainties that characterize MRI data. Indeed, perfect control of the flow rate and full knowledge of the wall model characteristics (rigid walls in the present case) is allowed in experiments and, thus, clear indications can be obtained to validate and improve the accuracy of numerical models. The numerical and experimental results are in good agreements for the three analyzed geometries and the flow-rate conditions. In-vivo data from the healthy case are in a satisfactory agreement with numerical/in-vitro results, and they can be ascribed to possible differences between MRI and numerical/in-vitro set-ups. The velocity fields obtained through CFD are consistent with the echographic results in in-vitro experiments, showing the same flow patterns in healthy and pathological cases

analysis of non animal methods and models for research in cardiovascular disease

Cardiovascular diseases (CVD) are disorders of the heart and blood vessels and represent 31% of all global deaths. In the contest of CVD, the use of animal experiments has been a contentious subject for many years. In recent years, in vitro and in silico models and methods have been proposed according to the 3Rs statement. However, an exhaustive report regarding the state of art in terms of in vitro and in silico experiments has not been reported yet. This work is focused on providing a collection of non-animal models and methods in use for basic and applied CVD research. The standardized descriptions of such studies will ultimately feed into EURL ECVAM database on alternative methods. Two are the research main phases. Firstly, the exclusion/ inclusion criteria and the list of relevant information resources of the research have been defined. The second phase regards the search, selection and detailed description of the literature papers by analysing records on Scopus and Pubmed databases

Fabrication of deformable patient-specific AAA models by material casting techniques

BackgroundAbdominal Aortic Aneurysm (AAA) is a balloon-like dilatation that can be life-threatening if not treated. Fabricating patient-specific AAA models can be beneficial for in-vitro investigations of hemodynamics, as well as for pre-surgical planning and training, testing the effectiveness of different interventions, or developing new surgical procedures. The current direct additive manufacturing techniques cannot simultaneously ensure the flexibility and transparency of models required by some applications. Therefore, casting techniques are presented to overcome these limitations and make the manufactured models suitable for in-vitro hemodynamic investigations, such as particle image velocimetry (PIV) measurements or medical imaging.MethodsTwo complex patient-specific AAA geometries were considered, and the related 3D models were fabricated through material casting. In particular, two casting approaches, i.e. lost molds and lost core casting, were investigated and tested to manufacture the deformable AAA models. The manufactured models were acquired by magnetic resonance, computed tomography (CT), ultrasound imaging, and PIV. In particular, CT scans were segmented to generate a volumetric reconstruction for each manufactured model that was compared to a reference model to assess the accuracy of the manufacturing process.ResultsBoth lost molds and lost core casting techniques were successful in the manufacturing of the models. The lost molds casting allowed a high-level surface finish in the final 3D model. In this first case, the average signed distance between the manufactured model and the reference was (−0.2±0.2) mm. However, this approach was more expensive and time-consuming. On the other hand, the lost core casting was more affordable and allowed the reuse of the external molds to fabricate multiple copies of the same AAA model. In this second case, the average signed distance between the manufactured model and the reference was (0.1±0.6) mm. However, the final model’s surface finish quality was poorer compared to the model obtained by lost molds casting as the sealing of the outer molds was not as firm as the other casting technique.ConclusionsBoth lost molds and lost core casting techniques can be used for manufacturing patient-specific deformable AAA models suitable for hemodynamic investigations, including medical imaging and PIV

Early neurotransmitters changes in prodromal frontotemporal dementia: A GENFI study

Background: Neurotransmitters deficits in Frontotemporal Dementia (FTD) are still poorly understood. Better knowledge of neurotransmitters impairment, especially in prodromal disease stages, might tailor symptomatic treatment approaches.Methods: In the present study, we applied JuSpace toolbox, which allowed for cross-modal correlation of Mag-netic Resonance Imaging (MRI)-based measures with nuclear imaging derived estimates covering various neurotransmitter systems including dopaminergic, serotonergic, noradrenergic, GABAergic and glutamatergic neurotransmission.We included 392 mutation carriers (157 GRN, 164 C9orf72, 71 MAPT), together with 276 non-carrier cognitively healthy controls (HC). We tested if the spatial patterns of grey matter volume (GMV) alterations in mutation carriers (relative to HC) are correlated with specific neurotransmitter systems in prodromal (CDR (R) plus NACC FTLD = 0.5) and in symptomatic (CDR (R) plus NACC FTLD >= 1) FTD. Results: In prodromal stages of C9orf72 disease, voxel-based brain changes were significantly associated with spatial distribution of dopamine and acetylcholine pathways;in prodromal MAPT disease with dopamine and serotonin pathways, while in prodromal GRN disease no significant findings were reported (p < 0.05, Family Wise Error corrected). In symptomatic FTD, a widespread involvement of dopamine, serotonin, glutamate and acetylcholine pathways across all genetic subtypes was found. Social cognition scores, loss of empathy and poor response to emotional cues were found to correlate with the strength of GMV colocalization of dopamine and serotonin pathways (all p < 0.01).Conclusions: This study, indirectly assessing neurotransmitter deficits in monogenic FTD, provides novel insight into disease mechanisms and might suggest potential therapeutic targets to counteract disease-related symptoms

Altered plasma protein profiles in genetic FTD – a GENFI study

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with genetic frontotemporal dementia. Methods: Blood samples from 693 participants in the GENetic Frontotemporal Dementia Initiative study were analysed using a multiplexed antibody array targeting 158 proteins. Results: We found 13 elevated proteins in symptomatic mutation carriers, when comparing plasma levels from people diagnosed with genetic FTD to healthy non-mutation controls and 10 proteins that were elevated compared to presymptomatic mutation carriers. Conclusion: We identified plasma proteins with altered levels in symptomatic mutation carriers compared to non-carrier controls as well as to presymptomatic mutation carriers. Further investigations are needed to elucidate their potential as fluid biomarkers of the disease process.Open access funding provided by Karolinska Institute. C.G. received funding from EU Joint Programme—Neurodegenerative Disease Research -Prefrontals Vetenskapsrådet Dnr 529–2014-7504, Vetenskapsrådet 2015–02926, Vetenskapsrådet 2018–02754, the Swedish FTD Inititative-Schörling Foundation, Alzheimer Foundation, Brain Foundation, Dementia Foundation and Region Stockholm ALF-project. PN received funding from KTH Center for Applied Precision Medicine (KCAP) funded by the Erling-Persson Family Foundation, the Swedish FTD Inititative-Schörling Foundation and Åhlén foundation. D.G. received support from the EU Joint Programme—Neurodegenerative Disease Research and the Italian Ministry of Health (PreFrontALS) grant 733051042. E.F. has received funding from a Canadian Institute of Health Research grant #327387. F.M. received funding from the Tau Consortium and the Center for Networked Biomedical Research on Neurodegenerative Disease. J.B.R. has received funding from the Welcome Trust (103838) and is supported by the Cambridge University Centre for Frontotemporal Dementia, the Medical Research Council (SUAG/051 G101400) and the National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215–20014). J.C.V.S. was supported by the Dioraphte Foundation grant 09–02-03–00, Association for Frontotemporal Dementias Research Grant 2009, Netherlands Organization for Scientific Research grant HCMI 056–13-018, ZonMw Memorabel (Deltaplan Dementie, project number 733 051 042), Alzheimer Nederland and the Bluefield Project. J.D.R. is supported by the Bluefield Project and the National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and a Miriam Marks Brain Research UK Senior Fellowship. M.M. has received funding from a Canadian Institute of Health Research operating grant and the Weston Brain Institute and Ontario Brain Institute. M.O. has received funding from Germany’s Federal Ministry of Education and Research (BMBF). R.S-V. is supported by Alzheimer’s Research UK Clinical Research Training Fellowship (ARUK-CRF2017B-2) and has received funding from Fundació Marató de TV3, Spain (grant no. 20143810). R.V. has received funding from the Mady Browaeys Fund for Research into Frontotemporal Dementia. This work was also supported by the EU Joint Programme—Neurodegenerative Disease Research GENFI-PROX grant [2019–02248; to J.D.R., M.O., B.B., C.G., J.C.V.S. and M.S.info:eu-repo/semantics/publishedVersio

Studio di fattibilita di una monoscocca in materiale composito per la torretta di un carro armato

L’elaborato seguente è stato sviluppato all’interno dell’azienda OTO Melara di La Spezia. Lo scopo della tesi è stato quello di valutare la fattibilità per la realizzazione del guscio anteriore della torretta da carro armato HITFACT®2 in materiale composito come possibile alternativa alla soluzione attuale in alluminio. Il guscio in composito è stato studiato in modo da poter presentare vantaggi, rispetto alla soluzione attuale, in termini di peso, resistenza balistica, coibentazione, rigidezza, precisione di tiro, resistenza strutturale e riparabilità. Lo studio si è focalizzato anche sulle tecniche costruttive del manufatto e in tal senso è stata affrontata un’analisi economica

Modelling and numerical simulations of the Cardioband procedure for mitral valve regurgitation repair

The study reported in this dissertation is designed to characterize the Cardioband trascatheter annuloplasty procedure used in the repair of mitral regurgitation. A full in silico approach was considered to develop a simulative workflow to evaluate the outcomes of the Cardioband procedure in reducing mitral regurgitation in patient-specific cases. First, the mechanical behaviour of the Cardioband device was analysed through a physically based schematization of its components. The analytical formulation of this process and its numerical implementation to simulate the entire Cardioband process was achieved. Two simulation methods integrating clinical image processing and the finite element method were presented. The first method, called hybrid, was based on coupling equations modelling the equilibrium of forces and the geometric coherence of the device components with finite element equations relating to the behaviour of the cardiac structures. The latter, called full-fem, was based on the full finite element formulation of both the device and the surrounding structures. The routines were validated by simulating the clinical procedure on five different patient cases and comparing the numerical results with clinical data. Once the in-silico method was validated, the second step concerned the study of the effects of the Cardioband implant morphology on the outcomes of the procedure. Four different configurations were defined based on the implant size and the deployment strategy. The performance of the device customizability were evaluated by presenting the results. In the final step, a computational method based on the finite element approach was presented to investigate the effects of the Cardioband procedure on the dynamics of the regurgitant mitral valve. In particular, two types of simulations were defined, starting from an image-based modelling of the mitral apparatus. The first simulation was designed to reproduce the behaviour of the regurgitant mitral valve before Cardioband activation, while in the second simulation the valve is subjected to device activation and the loads resulting from the subsequent cardiac cycle. The two simulations were compared to evaluate the changes in mitral valve behaviour induced by the procedure

Development and Realization of an Experimental Bench Test for Synchronized Small Angle Light Scattering and Biaxial Traction Analysis of Tissues

Insights into the mechanical and microstructural status of biological soft tissues are fundamental in analyzing diseases. Biaxial traction is the gold standard approach for mechanical characterization. The state of the art methods for microstructural assessment have different advantages and drawbacks. Small angle light scattering (SALS) represents a valuable low energy technique for soft tissue assessment. The objective of the current work was to develop a bench test integrating mechanical and microstructural characterization capabilities for tissue specimens. The setup’s principle is based on the integration of biaxial traction and SALS analysis. A dedicated control application was developed with the objective of managing the test procedure. The different components of the setup are described and discussed, both in terms of hardware and software. The realization of the system and the corresponding performances are then presented

Development and Realization of an Experimental Bench Test for Synchronized Small Angle Light Scattering and Biaxial Traction Analysis of Tissues

Insights into the mechanical and microstructural status of biological soft tissues are fundamental in analyzing diseases. Biaxial traction is the gold standard approach for mechanical characterization. The state of the art methods for microstructural assessment have different advantages and drawbacks. Small angle light scattering (SALS) represents a valuable low energy technique for soft tissue assessment. The objective of the current work was to develop a bench test integrating mechanical and microstructural characterization capabilities for tissue specimens. The setup’s principle is based on the integration of biaxial traction and SALS analysis. A dedicated control application was developed with the objective of managing the test procedure. The different components of the setup are described and discussed, both in terms of hardware and software. The realization of the system and the corresponding performances are then presented