Nov 28, 2018

Functionalized Anatomical Models for Computational Life Sciences

Esra Neufeld, Bryn Lloyd, Beatrice Schneider, Wolfgang Kainz, and Niels Kuster, Frontiers in Physiology, section Computational Physiology and Medicine, 9:1594, online 16 November 2018; doi: 10.3389/fphys.2018.01594

The advent of detailed computational anatomical models has opened new avenues for computational life sciences (CLS). To date, anatomically representative static models have been used in many applications, but these are insufficient when the anatomically geometric variability is inseparable from physics and physiology due to body dynamics. Obvious examples of such situations include the assessment of thermal hazards in magnetic resonance imaging and planning for radiofrequency and acoustic cancer treatment, where posture and physiology-related changes in shape (e.g., breathing) or tissue behavior (e.g., thermoregulation) affect the impact. The use of advanced functionalized anatomical models can overcome these limitations and dramatically broaden the applicability of CLS in basic research, the development of novel devices and therapies, and the assessment of their safety and efficacy, e.g., via in silico clinical trials. The various forms of functionalization discussed in this paper include shape parametrization (e.g., heartbeat, population variability), physical property distributions (e.g., image-based inhomogeneity, blood flow boundary conditions), physiological dynamics (e.g., tissue and organ behavior), and integration of simulation and measurement data (e.g., exposure conditions, ‘validation evidence’ supporting model tuning and validation). Although functionalization may represent only a small part of the physiology of current models, it already facilitates the next steps towards realism by pushing consolidation and consistency of the anatomy with the various functionalization layers, while highlighting interdependencies, enabling 3rd-party use of validated functionalization layers as established simulation tools, thereby facilitating their application as building blocks in networked or multi-scale computational models. Integration in functionalized anatomical models thus leverages and potentiates the value of sub-models and simulation and measurement data towards ever-increasing simulation realism. In our o2S2PARC platform, we propose to expand the concept of functionalized anatomical models to establish a service for integration and sharing of heterogeneous computational models, ranging from the molecular to the organ level. The objective of the o2S2PARC project – Open Online Simulations for Stimulating Peripheral Activity to Relieve Conditions – is to integrate all models developed within the National Institutes of Health (NIH) SPARC initiative in a unified anatomical and computational environment to facilitate the investigation of the role of the peripheral nervous system in the control of organ physiology. The functionalization concept, as outlined for the o2S2PARC platform, could form the basis for many other CLS application areas.

The scientific and technical impact of the study can be summarized as:

  • Functionalization of computational anatomical models with geometry parameterization, physical and physiological dynamics, and simulated/measured data empowers consideration of the coupled nature of anatomy and physiology for increased model dynamism and realism
  • The development and application of functionalized models dramatically broadens the range of applicability of CLS for in silico treatment optimization and personalization, medical device research and development, as well as for safety and efficacy assessment, towards the goal of replacing clinical human trials with in silico human trials
  • Functionalized anatomical models can serve as critical avenues of integration in collaborative efforts, e.g., via the o2S2PARC platform, with leveraging of individual model components with maintenance of consistency between the underlying anatomical model and the functionalization layers