An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Safety and efficacy of long-acting somatostatin treatment in autosomal-dominant polycystic kidney disease

BACKGROUND: The fluid filling renal cysts in human polycystic kidneys is secreted chiefly by the tubular epithelium lining the cysts via secondary chloride transport. Inhibiting this process by somatostatin therapy should induce shrinking of renal cysts. METHODS: In this randomized, cross-over, placebo-controlled trial we compared the risk/benefit profile of 6-month treatment with long-acting somatostatin (octreotide-LAR, 40 mg intramuscularly every 28 days) or placebo in autosomal-dominant polycystic kidney disease (ADPKD) patients with mild-to-moderate renal insufficiency and no evidence of other kidney disease. Volumes of kidney structures were evaluated by a two-slice computed tomography (CT) scanner; while glomerular filtration rate (GFR) was estimated by iohexol plasma clearance. RESULTS: One patient on somatostatin and one on placebo were prematurely withdrawn because of nonsymptomatic, reversible colelithiasis and asthenia, respectively. In the remaining 12 patients somatostatin was well tolerated. Kidney volume increased by 71 +/- 107 mL (P < 0.05) on somatostatin and by 162 +/- 114 mL (P < 0.01) on placebo. The percent increase was significantly lower on somatostatin (2.2 +/- 3.7% vs. 5.9 +/- 5.4%) (P < 0.05). Cystic volume tended to increase less on somatostatin than on placebo (3.0 +/- 6.5% vs. 5.6 +/- 5.8%). The "parenchymal" volume nonsignificantly increased by 2.5 +/- 8.4% on placebo and slightly decreased by 4.4 +/- 8.9% on somatostatin. The GFR did not change significantly during both treatment periods. CONCLUSION: In ADPKD patients, 6-month somatostatin therapy is safe and may slow renal volume expansion. This may reflect an inhibited growth in particular of smallest cysts beyond the detection threshold of CT scan evaluation. Whether this effect may prove renoprotective in the long term should be tested in additional trials of longer duration.     

Comparative Finite Element Model Analysis of Ascending Aortic Flow in Bicuspid and Tricuspid Aortic Valve

In bicuspid aortic valve (BAV) disease, the role of genetic and hemodynamic factors influencing ascending aortic pathology is controversial. To test the effect of BAV geometry on ascending aortic flow, a finite element analysis was undertaken. A surface model of aortic root and ascending aorta was obtained from magnetic resonance images of patients with BAV and tricuspid aortic valve using segmentation facilities of the image processing code Vascular Modeling Toolkit (developed at the Mario Negri Institute). Analytical models of bicuspid (antero‐posterior [AP], type 1 and latero‐lateral, type 2 commissures) and tricuspid orifices were mathematically defined and turned into a volumetric mesh of linear tetrahedra for computational fluid dynamics simulations. Numerical simulations were performed with the finite element code LifeV. Flow velocity fields were assessed for four levels: aortic annulus, sinus of Valsalva, sinotubular junction, and ascending aorta. Comparison of finite element analysis of bicuspid and tricuspid aortic valve showed different blood flow velocity pattern. Flow in bicuspid configurations showed asymmetrical distribution of velocity field toward the convexity of mid‐ascending aorta returning symmetrical in distal ascending aorta. On the contrary, tricuspid flow was symmetrical in each aortic segment. Comparing type 1 BAV with type 2 BAV, more pronounced recirculation zones were noticed in the latter. Finally, we found that in both BAV configurations, maximum wall shear stress is highly localized at the convex portion of the mid‐ascending aorta level. Comparison between models showed asymmetrical and higher flow velocity in bicuspid models, in particular in the AP configuration. Asymmetry was more pronounced at the aortic level known to be more exposed to aneurysm formation in bicuspid patients. This supports the hypothesis that hemodynamic factors may contribute to ascending aortic pathology in this subset of patients.     

An Integrated Framework to Quantitatively Link Mouse-Specific Hemodynamics to Aneurysm Formation in Angiotensin II-infused ApoE −/− mice

Locally disturbed flow has been suggested to play a (modulating) role in abdominal aortic aneurysm (AAA) formation, but no longitudinal studies have been performed yet due to (a.o.) a lack of human data prior to AAA formation. In this study we made use of recent advances in small animal imaging technology in order to set up entirely mouse-specific computational fluid dynamics (CFD) simulations of the abdominal aorta in an established ApoE −/− mouse model of AAA formation, combining (i) in vivo contrast-enhanced micro-CT scans (geometrical model) and (ii) in vivo high-frequency ultrasound scans (boundary conditions). Resulting areas of disturbed flow at baseline were compared to areas of AAA at end-stage. Qualitative results showed that AAA dimension is maximal in areas that are situated proximal to those areas that experience most disturbed flow in three out of four S developing an AAA. Although further quantitative analysis did not reveal any obvious relationship between areas that experience most disturbed flow and the end-stage AAA dimensions, we cannot exclude that hemodynamics play a role in the initial phases of AAA formation. Due to its mouse-specific and in vivo nature, the presented methodology can be used in future research to link detailed and animal-specific (baseline) hemodynamics to (end-stage) arterial disease in longitudinal studies in mice.     

Developing Regulatory-compliant Electronic Case Report Forms for Clinical Trials: Experience with The Demand Trial

The use of electronic case report forms (CRF) to gather data in randomized clinical trials has grown to progressively replace paper-based forms. Computerized form designs must ensure the same data quality expected of paper CRF, by following Good Clinical Practice rules. Electronic data capture (EDC) tools must also comply with applicable statutory and regulatory requirements. Here the authors focus on the development of computerized systems for clinical trials implementing FDA and EU recommendations and regulations, and describe a laptop-based electronic CRF used in a randomized, multicenter clinical trial.     

Multi-trajectories automatic planner for StereoElectroEncephaloGraphy (SEEG)

Purpose

StereoElectroEncephaloGraphy (SEEG) is done to identify the epileptogenic zone of the brain using several multi-lead electrodes whose positions in the brain are pre-operatively defined. Intracranial hemorrhages due to disruption of blood vessels can cause major complications of this procedure ( \(<\) 1 %). In order to increase the intervention safety, we developed and tested planning tools to assist neurosurgeons in choosing the best trajectory configuration.

Methods

An automated planning method was developed that maximizes the distance of the electrode from the vessels and avoids the sulci as entry points. The angle of the guiding screws is optimized to reduce positioning error. The planner was quantitatively and qualitatively compared with manually computed trajectories on 26 electrodes planned for three patients undergoing SEEG by four neurosurgeons. Quantitative comparison was performed computing for each trajectory using (a) the Euclidean distance from the closest vessel and (b) the incidence angle.

Results

Quantitative evaluation shows that automatic planned trajectories are safer in terms of distance from the closest vessel with respect to manually planned trajectories. Qualitative evaluation performed by four neurosurgeons showed that the automatically computed trajectories would have been preferred to manually computed ones in 30 % of the cases and were judged good or acceptable in about 86 % of the cases. A significant reduction in time required for planning was observed with the automated system (approximately 1/10).

Conclusion

The automatic SEEG electrode planner satisfied the essential clinical requirements, by providing safe trajectories in an efficient timeframe.