Bergamo, Italy
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Morbiducci U.,Polytechnic University of Turin | Gallo D.,Polytechnic University of Turin | Massai D.,Polytechnic University of Turin | Ponzini R.,Interuniversity Consortium | And 4 more authors.
Journal of Biomechanics | Year: 2011

Here we present a study on the impact of assumptions on image-based hemodynamic simulations of healthy carotid bifurcations. In particular, we evaluate to which extent assumptions on blood rheology influence bulk flow features, driven by the fact that few studies have provided adequate insights into the influence of assumptions to confidently model the 4D hemodynamics within the bifurcation. The final goal is to complement, integrate and extend with a quantitative characterization of the bulk flow the description currently adopted to classify altered hemodynamics, which is based on wall shear stress (WSS).Hemodynamic simulations of two image-based carotid bifurcation geometries were carried out assuming a reference Newtonian viscosity, two non-Newtonian rheology models and Newtonian viscosities based on characteristic shear rates. WSS-based and Lagrangian-based metrics for helical flow quantification and for vorticity dynamics quantification were calculated. Our findings suggest that the assumption of Newtonian rheology: (1) could be reasonable for bulk flow metrics (differences from non-Newtonian behavior are lower than 10%); (2) influences at different levels the WSS-based indicators, depending on the bifurcation model, even if in our study it is lower than the major source of uncertainty as recognized by the literature (i.e., uncertainty on geometry reconstruction). © 2011 Elsevier Ltd.

Remuzzi G.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Benigni A.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Finkelstein F.O.,Yale University | Grunfeld J.-P.,Hopital Necker Enfants Malades | And 11 more authors.
The Lancet | Year: 2013

Although in some parts of the world acute and chronic kidney diseases are preventable or treatable disorders, in many other regions these diseases are left without any care. The nephrology community needs to commit itself to reduction of this divide between high-income and low-income regions. Moreover, new and exciting developments in fields such as pharmacology, genetic, or bioengineering, can give a boost, in the next decade, to a new era of diagnosis and treatment of kidney diseases, which should be made available to more patients. © 2013 Elsevier Ltd.

Van Canneyt K.,Ghent University | Swillens A.,Ghent University | Lovstakken L.,Norwegian University of Science and Technology | Antiga L.,Orobix s.r.l | And 2 more authors.
Journal of Vascular Access | Year: 2013

Purpose: Maturation of an arterio-venous fistula (AVF) frequently fails, with low post-operative fistula flow as a prognostic marker for this event. As pulsed wave Doppler (PWD) is commonly used to assess volume flow, we studied the accuracy of this measurement in the setting of a radio-cephalic AVF. Methods: As in-vivo validation of fistula flow measurements is cumbersome, we performed simulations, integrating computational fluid dynamics with an ultrasound (US) simulator. Flow in the arm was calculated, based on a patient-specific model of the arm vasculature pre and post AVF creation. Raw ultrasound signals were subsequently simulated, from which Doppler spectra were calculated in both a proximal and a distal location. Results: The velocity component in the direction of the PWD-US beam (vPWD), in a centered, small, sample volume, can be captured accurately using PWD spectrum mean-tracking (maximum bias [mB] 8.1%). However, when deriving flow rate from these measurements, a high degree of inaccuracy occurs. First, the angle-correction of vPWD towards the velocity along the axis of the vessel is largely influenced by the radial velocity components in the complex flow field (mB=16.3%). Second, the largest error is introduced when transferring the centerline velocity to the cross-sectional mean velocity without any knowledge of the flow profile (mB=97.7%). Conclusions: In the setting of a forearm AVF, flow estimates based on PWD are hampered by the complex flow patterns. Overall, flow estimation based on centerline measurement, analyzed by mean-tracking of the RF-spectral estimates, under the assumption of a parabolic flow profile, appeared to provide the most reasonable values. © 2013 Wichtig Editore.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.2.1-1 | Award Amount: 7.03M | Year: 2013

Traumatic brain injury (TBI) is among the leading causes of death and disability and the main cause of death among the under-45s. Most patients with moderate to severe TBI are admitted to intensive care units (ICUs) The PROSAFE ICU network was recently established in 6 European countries through EU funding (PHEA 2007331), and has continued to collect high-quality data beyond the grant duration. In 2011, 225 ICUs had joined PROSAFE, recruiting a total of 73,163 patients, 2,694 of whom were admitted for TBI. Hence the network can expect to enrol 7-9,000 moderate to severe TBI patients in 4 years. The PROSAFE consortium has already focused attention on TBI and has just started collecting additional information on this condition in order to develop a prognostic model to identify centres of excellence in TBI management Aims of proposal are to consolidate the existing network in order to better describe the epidemiology of moderate-severe TBI in 7 countries (Greece has now joined the consortium); build a prognostic model based on short- and long-term outcome measures; identify most effective clinical interventions for optimally treating TBI patients, and recognize the determinants of optimal vs suboptimal performance All TBI-CDEs endorsed by InTBIR will be collected, along with other items needed to develop a sensible prognostic model, permitting the consortium to join forces with international collaborative initiatives in the field Availing of the coordinating institutes biobank and consolidated expertise in biochemical and genetic biomarkers, the aim is to identify prognostic markers and underlying genetic factors influencing response to treatment and final outcome The PROSAFE consortium is thus in a position to guarantee superior quality data collection in 7 countries and ensure it continues beyond the life of the project. These conditions are essential if the consortium is to contribute to Europe playing a key role in the success of the InTBIR initiative

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.77M | Year: 2013

The REtinal VAscular Modeling, Measurement And Diagnosis (REVAMMAD) project will train a new generation of scientists able to effectively translate the latest vascular modeling theory and computerized image analysis techniques into effective interventions for some of the most important chronic medic conditions afflicting the EU, including hypertension and diabetes. It will particularly ensure that there is rich clinical and industrial involvement to ensure that the training is focused with end-users and exploitation in mind. The vasculature undergoes changes in response to early stages of these diseases, reflecting fundamental physiological processes within the vessels. The retina provides a unique window onto the vasculature, allowing it to be viewed and measurements made in vivo, and advances in imaging technologies make it increasingly possible to measure subtle changes using computer vision algorithms, including through routine medical checks such as eye tests. The field is currently fragmented, with many excellent pockets of collaboration focused on defined specialisms, particularly between clinicians and modelers, or clinicians and measurement specialists, but lacking overall structure. Despite the importance and incidence of the diseases and the evidence for the possibility of better diagnosis through imaging, there has been relatively little translation of theory into clinical practice. Integrative action is required to train researchers who understand the medical, clinical, technological and commercial aspects of the problem domain and to establish common working methodologies and tools across the field. REVAMMAD will train early careers researchers who combine these skills in order to motivate the introduction of high impact interventions in the future.

Kononowicz A.A.,Karolinska Institutet | Kononowicz A.A.,Jagiellonian University | Narracott A.J.,University of Sheffield | Manini S.,Mario Negri Institute for Pharmacological Research | And 5 more authors.
Journal of Medical Internet Research | Year: 2014

Background: Virtual patients are increasingly common tools used in health care education to foster learning of clinical reasoning skills. One potential way to expand their functionality is to augment virtual patients' interactivity by enriching them with computational models of physiological and pathological processes. Objective: The primary goal of this paper was to propose a conceptual framework for the integration of computational models within virtual patients, with particular focus on (1) characteristics to be addressed while preparing the integration, (2) the extent of the integration, (3) strategies to achieve integration, and (4) methods for evaluating the feasibility of integration. An additional goal was to pilot the first investigation of changing framework variables on altering perceptions of integration. Methods: The framework was constructed using an iterative process informed by Soft System Methodology. The Virtual Physiological Human (VPH) initiative has been used as a source of new computational models. The technical challenges associated with development of virtual patients enhanced by computational models are discussed from the perspectives of a number of different stakeholders. Concrete design and evaluation steps are discussed in the context of an exemplar virtual patient employing the results of the VPH ARCH project, as well as improvements for future iterations. Results: The proposed framework consists of four main elements. The first element is a list of feasibility features characterizing the integration process from three perspectives: the computational modelling researcher, the health care educationalist, and the virtual patient system developer. The second element included three integration levels: basic, where a single set of simulation outcomes is generated for specific nodes in the activity graph; intermediate, involving pre-generation of simulation datasets over a range of input parameters; advanced, including dynamic solution of the model. The third element is the description of four integration strategies, and the last element consisted of evaluation profiles specifying the relevant feasibility features and acceptance thresholds for specific purposes. The group of experts who evaluated the virtual patient exemplar found higher integration more interesting, but at the same time they were more concerned with the validity of the result. The observed differences were not statistically significant. Conclusions: This paper outlines a framework for the integration of computational models into virtual patients. The opportunities and challenges of model exploitation are discussed from a number of user perspectives, considering different levels of model integration. The long-term aim for future research is to isolate the most crucial factors in the framework and to determine their influence on the integration outcome.

Caroli A.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Perico N.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Perna A.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | Antiga L.,Irccs Instituto Of Ricerche Farmacologiche Mario Negri | And 19 more authors.
The Lancet | Year: 2013

Summary Background Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no eff ective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the eff ect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder. Methods We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in fi ve hospitals in Italy. Adult (>18 years) patients with estimated glomerular fi ltration rate (GFR) of 40 mL/min per 1·73 m2 or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratifi ed by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modifi ed intention to treat. This study is registered with, NCT00309283. Findings Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased signifi cantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the diff erence was not signifi cant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related. Interpretation These fi ndings provide the background for large randomised controlled trials to test the protective eff ect of somatostatin analogues against renal function loss and progression to end-stage kidney disease. Funding Polycystic Kidney Disease Foundation.

Piccinelli M.,Emory University | Steinman D.A.,University of Toronto | Hoi Y.,University of Toronto | Tong F.,Emory University | And 3 more authors.
Annals of Biomedical Engineering | Year: 2012

Geometric indices defined on intracranial aneurysms have been widely used in rupture risk assessment and surgical planning. However, most indices employed in clinical settings are currently evaluated based on twodimensional images that inevitably fail to capture the threedimensional nature of complex aneurysmal shapes. In addition, since measurements are performed manually, they can suffer from poor inter and intra operator repeatability. The purpose of the current work is to introduce objective and robust techniques for the 3D characterization of intracranial aneurysms, while preserving a close connection to the way aneurysms are currently characterized in clinical settings. Techniques for automatically identifying the neck plane, key aneurysm dimensions, shape factors, and orientations relative to the parent vessel are demonstrated in a population of 15 sidewall and 15 terminal aneurysms whose surface has been obtained by two trained operators using both level-set segmentation and thresholding, the latter reflecting typical clinical practice. Automatically-identified neck planes are shown to be in concordance with those manually positioned by an expert neurosurgeon, and automatically-derived geometric indices are shown to be largely insensitive to segmentation method or operator. By capturing the 3D nature of aneurysmal sacs and by minimizing observer variability, our approach allows large retrospective and prospective studies on aneurysm geometric risk factors to be performed using routinely acquired clinical images. © 2012 Biomedical Engineering Society.

Schneiders J.J.,University of Amsterdam | Marquering H.A.,University of Amsterdam | Antiga L.,Orobix Srl | Van Den Berg R.,University of Amsterdam | And 2 more authors.
American Journal of Neuroradiology | Year: 2013

BACKGROUND AND PURPOSE: 3DRA is considered the reference standard for the assessment of intracranial aneurysm morphology. However, it has been shown that 3DRA may overestimate neck size compared with 2D DSA. The purpose of this study was to determine the impact of neck size overestimation with 3DRA on intra-aneurysmal hemodynamics. MATERIALS AND METHODS: In a series of 20 patients, 20 intracranial aneurysms were analyzed for aneurysm neck size overestimation with 3DRA compared with 2D DSA. 3DRA-derived vascular models were modified to agree with 2D DSA. Geometric and hemodynamic variables of the original and modified vascular models were compared. RESULTS: In 8 of the 20 evaluated cases, 3DRA-derived aneurysm models showed neck size overestimation compared with 2D DSA images. The average neck diameter reduction after modification was 19%, which was, on average, 0.85mm(±0.32 mm). Modification of the neck resulted in differences in location of inflow jet (2/8), impingement zone (3/8), and low WSS area (4/8). In 1 case, the maximal WSS increased by 98% after modification. The change of impingement zone location resulted in a different classification of the impingement zone region in 2 cases. CONCLUSIONS: Neck size overestimation on 3DRA can have non-negligible consequences for hemodynamic features determined with CFD.

Remuzzi A.,Mario Negri Institute for Pharmacological Research | Remuzzi A.,University of Bergamo | Manini S.,Orobix Srl
Journal of Vascular Access | Year: 2014

Background: The creation and management of an autologous arteriovenous fistula (AVF) as vascular access (VA) for hemodialysis patients is still a critical procedure. The placement of a functional and long-lasting VA derives from adequate planning of the surgical procedure based on physical examination, vascular mapping and selection of the best modality for arteriovenous anastomosis. The risk of AVF non-maturation and early failure is high, even when all precautions are taken to minimize these events. In addition, AVF surgery may develop very high blood flow exposing the patient to the risk of heart failure or hand ischemia. Methods: The choices of the surgeons on the modalities to perform a surgical intervention for AVF should take into consideration several factors including patient clinical condition, arterial and venous vessel sizes and elasticity. However, these evaluations cannot give direct indication on VA outcome in terms of blood flow after AVF maturation. We then took advantage of theoretical models of vascular network hemodynamics and of computational fluid dynamics to develop a numerical tool for the prediction of potential blood flow of a planned VA surgery on the basis of preoperative ultrasound evaluation of arterial and venous sizes and blood flow. Results: Here we present the numerical model, previously developed and tested, and we describe the web-based application that has been developed to help during surgical planning. Conclusions: The use of this tool in the clinical setting should allow to reduce the incidence of AVF non-maturation as well as incidence of VA complications. © 2014 Wichtig Publishing.

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