Periodic Reporting for period 1 - PERFHeart (Development of three dimensional coronary blood perfusion model in beating heart using advanced computational and experimental techniques.) Reporting period: 2021-02-01 to 2023-01-31 Summary of the context and overall objectives of the project Despite dramatic medical advances over the last few decades, CVD remain a leading cause of death globally and the number one cause of death in the European Union (EU).While present day finite element(FE)models compute stress and strain in the heart muscle,they donot compute the regional blood perfusion and therefore missthe key factor that may lead to cell necrosis and failure of the heart.Coronary vascular disease has been studied for many decades and has been found to be a complexproblem. Despite the tedious and creative work by many expert scientists from many differentperspectives, the disease has only partially been understood. The current state of the art in cardiac FE modelling provides the capability to compute myocardial stresses and strains and has led to successful commercialisation of the code for simulation of the ability of cardiac devices to improve the performance ofthe heart in different pathologies. Despite the importance of coronary vascular perfusion, FEmodelling of cardiac tissue has greatly overlooked "perfusion"as a key component of cardiac health. The objectives of the study is to explore the role ofcoronary perfusion in cardiac health by developing simulation of cardiac cycle using experimental and computational modelling Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far The expertimental study involved creating entire structure of the microvascular geometry with complex coronary circulation as polymer cast from the coronary tree of porcine heart. The computational study used the continuum approach to include microstructure into the finite element model without accounting for each blood vessel separately. SOLID WORKS and MATLAB code to analyse the myocardial blood perfusion in the Left ventricle accounting for a rigid microvasculature. (Sumesh et.al "Failure of Myocardial tissue: Simulation of Blood Perfusion, 14th World Congress in Computational Mechanics (WCCM) 2020). This approach overcomes the disadvantage of using lumped parameter models that do not integrate the actual structure of the microvasculature. Eventually successfully implemented (Sumesh et al, Multiscale Finite element models with Poromechanics for Myocardial Blood Perfusion, 14th InterPore Annual Meeting 2022) the mixed hybrid finite element method (for the numerical treatment of the differential equations ensuring local mass balance) on 2D and 3D porous models for use in coronary perfusion. . The myocardial space was subdivided in a solid volume fraction and a fluid volume fraction. The fluid compartment has been built into finite deformation model of the beating heart using mixed hybrid finite element to implement the multiple fluid compartment model of a non-deforming compliant microvasculature. Both models were tuned separately and integrated to experimental data from the literature. The results of the study has been communicated in international journals and presented in three international conferences. As part of MSCA outreach program, ER engaged with school students and provided networking support at event, Science is Wonderful 2021, by the European Commission. The event attracted over 3000 teachers and 20000 pupils from across Europe. As part of career development plan, ER took lectures and tutorials for undergrad students and guiding projects for master students . The ER also obtained the Certificate in Graduate Diploma in Teaching, Learning and Scholarship (21 credits) from University of Limerick (2022), Ireland. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) The scope of the studyisusage of FEmodelling for autoregulation ofcoronary perfusion which extendsthe applications of FE model to common pathologies such as ischemic heart disease, infarction or reperfusion issues and devicessuch as stents or cardiac assist devices thatimprove coronary blood perfusion. Lumped parameter approaches have been successful in modelling the overall conductance and capacitance of the coronary system. Lumped parameter models, however do not integrate the actual structure of the microvasculature. The continuum approach proposed by supervisor Huyghe's group does include microstructure into the model while abstaining from accounting for each vessel separately.The approach taken here differed in basic tenets from earlier approaches, in that it implemented the FE model that computes the key quantity: regional coronary blood perfusion as a measure of cardiac health.Thus the proposed project will advance the state of the art by opening the gateway to detailed numerical modelling of the full mechanobiology of this vital organ including oxygen delivery, CO2draining, autoregulation, balance between energy expenditure and supply.A well validated model of the myocardial contraction and perfusion of the patient‟s heart,based on hemodynamic data collected by the cardiologist, may improve the quantification of the fractional flow reserve(technique used in coronary catheterization acrossacoronaryarterystenosistodeterminethe likelihood that the stenosisimpedes oxygen delivery to the heart muscle) of the patient and hence the decision of the cardiologist to go forward with stent surgery orconservativetreatment.