Vision for the 12 LABOURS Digital Twin Platform.

Clinical translation of personalised computational physiology workflows and digital twins can revolutionise healthcare by providing a better understanding of an individual's physiological processes and any changes that could lead to serious health consequences. However, the lack of common infrastructure for developing these workflows and digital twins has hampered the realisation of this vision. The Auckland Bioengineering Institute's 12 LABOURS project aims to address these challenges by developing a Digital Twin Platform to enable researchers to develop and personalise computational physiology models to an individual's health data in clinical workflows. This will allow clinical trials to be more efficiently conducted to demonstrate the efficacy of these personalised clinical workflows. We present a demonstration of the platform's capabilities using publicly available data and an existing automated computational physiology workflow developed to assist clinicians with diagnosing and treating breast cancer. We also demonstrate how the platform facilitates the discovery and exploration of data and the presentation of workflow results as part of clinical reports through a web portal. Future developments will involve integrating the platform with health systems and remote-monitoring devices such as wearables and implantables to support home-based healthcare. Integrating outputs from multiple workflows that are applied to the same individual's health data will also enable the generation of their personalised digital twin.Clinical Relevance- The proposed 12 LABOURS Digital Twin Platform will enable researchers to 1) more efficiently conduct clinical trials to assess the efficacy of their computational physiology workflows and support the clinical translation of their research; 2) reuse primary and derived data from these workflows to generate novel workflows; and 3) generate personalised digital twins by integrating the outputs of different computational physiology workflows.

Roadmap for an imaging and modelling paediatric study in rural NZ.

Our study methodology is motivated from three disparate needs: one, imaging studies have existed in silo and study organs but not across organ systems; two, there are gaps in our understanding of paediatric structure and function; three, lack of representative data in New Zealand. Our research aims to address these issues in part, through the combination of magnetic resonance imaging, advanced image processing algorithms and computational modelling. Our study demonstrated the need to take an organ-system approach and scan multiple organs on the same child. We have pilot tested an imaging protocol to be minimally disruptive to the children and demonstrated state-of-the-art image processing and personalized computational models using the imaging data. Our imaging protocol spans brain, lungs, heart, muscle, bones, abdominal and vascular systems. Our initial set of results demonstrated child-specific measurements on one dataset. This work is novel and interesting as we have run multiple computational physiology workflows to generate personalized computational models. Our proposed work is the first step towards achieving the integration of imaging and modelling improving our understanding of the human body in paediatric health and disease.

Four-dimensional flow cardiovascular magnetic resonance in tetralogy of Fallot: a systematic review.

BACKGROUND: Patients with repaired Tetralogy of Fallot (rTOF) often develop cardiovascular dysfunction and require regular imaging to evaluate deterioration and time interventions such as pulmonary valve replacement. Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) enables detailed assessment of flow characteristics in all chambers and great vessels. We performed a systematic review of intra-cardiac 4D flow applications in rTOF patients, to examine clinical utility and highlight optimal methods for evaluating rTOF patients. METHODS: A comprehensive literature search was undertaken in March 2020 on Google Scholar and Scopus. A modified version of the Critical Appraisal Skills Programme (CASP) tool was used to assess and score the applicability of each study. Important clinical outcomes were assessed including similarities and differences. RESULTS: Of the 635 articles identified, 26 studies met eligibility for systematic review. None of these were below 59% applicability on the modified CASP score. Studies could be broadly classified into four groups: (i) pilot studies, (ii) development of new acquisition methods, (iii) validation and (vi) identification of novel flow features. Quantitative comparison with other modalities included 2D phase contrast CMR (13 studies) and echocardiography (4 studies). The 4D flow study applications included stroke volume (18/26;69%), regurgitant fraction (16/26;62%), relative branch pulmonary artery flow(4/26;15%), systolic peak velocity (9/26;35%), systemic/pulmonary total flow ratio (6/26;23%), end diastolic and end systolic volume (5/26;19%), kinetic energy (5/26;19%) and vorticity (2/26;8%). CONCLUSIONS: 4D flow CMR shows potential in rTOF assessment, particularly in retrospective valve tracking for flow evaluation, velocity profiling, intra-cardiac kinetic energy quantification, and vortex visualization. Protocols should be targeted to pathology. Prospective, randomized, multi-centered studies are required to validate these new characteristics and establish their clinical use.

Right Ventricular Flow Vorticity Relationships With Biventricular Shape in Adult Tetralogy of Fallot.

Remodeling in adults with repaired tetralogy of Fallot (rToF) may occur due to chronic pulmonary regurgitation, but may also be related to altered flow patterns, including vortices. We aimed to correlate and quantify relationships between vorticity and ventricular shape derived from atlas-based analysis of biventricular shape. Adult rToF (n = 12) patients underwent 4D flow and cine MRI imaging. Vorticity in the RV was computed after noise reduction using a neural network. A biventricular shape atlas built from 95 rToF patients was used to derive principal component modes, which were associated with vorticity and pulmonary regurgitant volume (PRV) using univariate and multivariate linear regression. Univariate analysis showed that indexed PRV correlated with 3 modes (r = -0.55,-0.50, and 0.6, all p < 0.05) associated with RV dilatation and an increase in basal bulging, apical bulging and tricuspid annulus tilting with more severe regurgitation, as well as a smaller LV and paradoxical movement of the septum. RV outflow and inflow vorticity were also correlated with these modes. However, total vorticity over the whole RV was correlated with two different modes (r = -0.62,-0.69, both p < 0.05). Higher vorticity was associated with both RV and LV shape changes including longer ventricular length, a larger bulge beside the tricuspid valve, and distinct tricuspid tilting. RV flow vorticity was associated with changes in biventricular geometry, distinct from associations with PRV. Flow vorticity may provide additional mechanistic information in rToF remodeling. Both LV and RV shapes are important in rToF RV flow patterns.