O1: Virtual populations
The final public version of the virtual population is launched and publicly available as online dashboard (
https://mdmtest.shinyapps.io/INSIST-VP/(si apre in una nuova finestra)) enabling users to visualize and download virtual stroke patient cohorts according to their characteristics of interest (i.e. inclusion and exclusion criteria of a study population). A final statistical model (module III) that relates image outcome to clinical outcome was also developed and the performance of this final model was assessed with internal and external validation. Module III includes two statistical models, which can accurately predict functional outcome at 3 months and NIHSS 24-48 hours after EVT for AIS.
O2: thrombosis & thrombolysis
The goal of WP3 was to develop numerical models for thrombosis and thrombolysis, driven by the objectives of simplicity and computational efficiency, while providing a quantitative description of the phenomena and a predictive approach. We developed a 3D Lattice-Boltzmann solver with hemodynamic capabilities and simplified lysis mechanisms. The main effort during this last period was the validation of the numerical models and their improvements. In terms of thrombolysis, an innovative experiment was developed to study the lysis process in a flow situation which revealed several unknown features that were included in our 3D thrombolysis model. They gave rise to an analytical surrogate model giving the speed of lysis as a function of the biophysical conditions.
O3: thrombectomy
A new constitutive law was developed for non-linear inelastic behaviour of blood clots based on deformation induced bond formation and dissociation of the fibrin network. Lap shear fracture tests and cohesive zone fracture modelling was performed to simulate mixed-mode crack propagation in blood clots. 100 patient-specific vascular models were reconstructed from computer tomography images of stroke patients. For each case in-silico thrombectomy simulations were performed to predict the outcomes of two stent designs (TREVO and EmboTrap). A high success rate was predicted for both devices (over 80%). A combined in silico mechanical thrombectomy (MT) with stent-retriever and aspiration catheters, both balloon guided catheter and double aspiration catheter, is developed and validated with in vitro experiments. Three different MT procedures were performed in the same vessel-like 3D-printed silicone phantom. The 3D phantom was designed in order to replicate the physiological dimension of the cerebral arteries. The model truthfully replicated the experimentally measured modes of thrombus fragmentation during thrombectomy retrieval.
O4: perfusion defects & tissue damage
In WP5, the focus of the final period of the project has been to provide detailed validation of the models of blood flow and perfusion, using both novel animal data and large clinical datasets. This has resulted in the most detailed and highly validated model of its type in the world for the effects of microthrombi on perfusion and tissue viability. In particular, the multi-scale approach has enabled us to link together both newly acquired animal data and clinical data within the same modelling framework.
O5: stroke trial platform & in silico clinical trial
The above work culminates here. We created an INSIST ISCT Computing environment. with a python command line interface, and parallel capabilities to scale up the cohort sizes that can be simulated in the trials. All final delivered versions of the WP2–5 models were integrated and EasyVVUQ has been integrated with the INSIST framework to enable easy implementation of VVUQ methodologies. EasyVVUQ has been integrated with the INSIST framework to enable easy implementation of VVUQ methodologies. A validation study has been performed using the MR CLEAN Trial clinical data but found the trial is currently only credible for use in testing thrombectomy surgical outcome on populations with M1 occlusions. In addition to the validation trial, two exploratory trials were run: comparing thrombus composition and thrombectomy device. Given the results of the validation, these two trials focussed on the outcome of the thrombectomy procedure.
