SMARTool: Periodic Technical Report - Part B

The first 18 months of SMARTool Project (42 Months duration) have been dedicated to: o Completing the activities planned to achieve the milestones of the first period for WP6, dissemination-exploitation (MS15) as reported in deliverables D6.1, D6.3 and D6.6, all submitted in due time. Carrying on the planned clinical activity of WP1, as reported in deliverable D1.1, submitted on month 7, which includes the clinical study protocol, ethics application and selection of patients for follow up study under appropriate eligibility and exclusion criteria (clinical and technical) and completing the baseline and follow up CCTA collection and analysis of recalled patients. Results will be reported in deliverables D1.2 and D1.3. o Advancing towards the achievement of three scientific milestones (MS1, MS4 and MS6, month 18), through a devised and well-coordinated execution of Tasks and sub-Tasks of WP1 and WP2 as stated among Consortium partners and clinical Third Parties Hospital Centers in the first Clinical-Technical Meeting (June 2016) and among Consortium partners in the first and second Technical Meetings (Ioannina, November 2016 and Pisa, April 2017). This objective has been reached through an agreement on a unified agenda and workplan of follow up evaluation of selected patients for SMARTool study in all clinical centers o Initialization of the technical implementation regarding the 3D reconstruction using CTCA, plaque growth modeling, FFR calculation based on non-invasive approaches, stent modeling, risk stratification algorithms and the platform integration. o Reaching a definite agreement among all Partners at the first Technical Meeting (November 2016) on the overall ICT platform architecture (the main Project outcome) and completing the activities required to achieve the objectives of WP1 and WP2 to reach MS1 - MS6 (Technical Meeting of Pisa, April 2017), i.e. patient specific imaging (CCTA) and non-imaging (clinical and blood molecular) data collection at two time points (retrospective-baseline and prospective-follow up) in a selected population of 321 subjects. These objectives have been reached through the development and refinement of a unified online data entry gateway (CRFA) to collect all imaging and non-imaging data of the selected population to be recalled into an organized data base for data sharing among Consortium partners, as well as through a secure on cloud storage of collected patient information (baseline and follow up). However, as stated during the first SMARTool Plenary Meeting (June 2017) two milestones (MS1 and MS4) due at M18 and are currently delayed to M24 and M25 following activation of the R1 mitigation plan (see WP1 for details). The specific results of WPs applicable to the reporting period (M1-M18) are summarized below: 1. WP1: Clinical Study protocol and all Ethical Application documents required for approval of follow up study (Task 1.1) have been arranged and Ethical Approval obtained by all clinical partners. After selecting SMARTool patients (N=321) from existing EVINCI clinical/imaging database, all retrospective non-imaging and imaging data have been uploaded on the CRFA. Patient recall has started in FTGM in September 2016, and follow up clinical data of 153 patients have been uploaded (M18) on the CRFA for secure on- cloud- storage (Task 1.3). Baseline and follow up plaque characterization and follow up evaluation of plaque progression by CCTA visual (116 scan pairs) and quantitative analysis (QCTA, 101 scan pairs) have been also accomplished (Task 1.2) and will be reported in deliverable D1.3 (Month 20). 2. WP2: Task 2.1 Baseline retrospective biohumoral data of 219 patients selected for recall have been uploaded on the CRFA and stored plasma samples retrieved for molecular characterization. A SOP for blood sampling at follow up has been created and downloadable from the CRFA. Blood sampling of 153 patients recalled by FTGM, UTU, UZH and Third Parties Warsaw, Barcelona, Viareggio and Naples has been performed according to SOP up to M18. Blood tests by clinical centers and biohumoral analysis by CNR Core Lab have been performed and uploaded on the CRFA. Baseline and follow up biohumoral data collection and preliminary analysis will be reported in D2.1 which will be submitted at Month 19 in a draft version, due to the delay of activities for R1 mitigation plan. Task 2.2 Molecular inflammatory markers (ICAM, VCAM, IL6 and hsCRP) have been tested for a subpopulation of the total enrolled patients (80 cases) Characterization of monocyte subpopulations on fresh blood has been performed in 66 cases (FTGM). Lipid classes to be analysed in baseline and follow up plasma samples have been identified, internal standard tested and the complete list of lipids to be tested in plasma defined. 3. WP3: During M1-M18, work has been focused on establishing and implementing criteria for efficient collection and analysis of samples (Tasks 3.1; 3.1.1, 3.1.2). The first sets of 68 blood samples was analysed using RNASeq and DNASeq. A first version of the project's Case Report Form Application (CFRA) software has been released, as a unified gateway of retrospective and follow up non imaging and imaging data to be uploaded on the on-cloud repository (Task 3.3), which is being used for the collection and storage of all clinical and molecular data Task 3.4 has been started at M12 and application of several statistical methods tested by a binary problem (CAD-no CAD) using available clinical and molecular features in order to select the most appropriate approach for developing the pre-imaging CAD stratification algorithm. 4. WP4: Task 4.1 (Refinement of multiscale and multilevel site specific models for plaque progression), has been carried on during M4-M18 and updates in the 3D reconstruction tool achieved on (i) centerline extraction algorithm, (ii) lumen, plaques and outer wall extraction (iii) extension of the level set method (iv) compensation of blooming effect and (v) coupled level sets for non-intersecting smooth geometries for blood flow simulations. Data Management Plan has been reported in deliverable D 4.1 submitted at Month 18. Task 4.2, Non-invasive FFR computation was refined into a more accurate measure of stenosis and flow, the Virtual Functional Assessment Index (vFAI). Task 4.3 (: Refinement of medical therapy and virtual angioplasty decision support methods) has been dedicated to virtual angioplasty, nonlinear stent modelling with nitinol material with fluid-structure interaction finite element solver PAK and interaction with specific Arbitrary Lagrangian Eulerian (ALE) formulation. 5. WP5: Task 5.1 activity, i.e. User requirements, functional specifications and architecture of the SMARTool platform, has been completed and will be reported in D5.1, submitted on Month 20, including a user requirements questionnaire for potential clinical and technical users. 6. WP6: Initial dissemination activities are reported in deliverable D6.1. In deliverable D6.3, the first scientific dissemination results and dissemination plans of the partners are reported and a first version of the exploitation plan of the platform is described in D6.6, all submitted in due time.