Quantitative 3D imaging of heart development and malformation

Sigolène Meilhac, PhD, Research Director, Unit of Heart Morphogenesis at the Institut Imagine and Institut Pasteur, Paris

Abstract: From the tubular primordium to the four-chambered organ, the heart undergoes extensive remodeling during in utero development. Genetic engineering and molecular analyses in animal models have provided insight into the gene regulatory networks of heart development. However, untangling the specific contributions of different factors requires more resolutive quantifications of the phenotype. We have developed 3D imaging procedures coupled to quantitative analyses and computer simulations of shape changes to provide novel mechanistic insight into mouse heart development. We have dissected the specific contribution of genetic factors such as Nodal, as well as of mechanical constraints in shaping the heart tube. This is relevant to structural congenital heart defects.

Morphological and Functional Characterization of Human Heart Organoids Using Optical Coherence Tomography

Chao Zhou, PhD, Associate Professor the Department of Biomedical Engineering, Washington University in St. Louis

Abstract: Organoids are self-organizing, organ-like three-dimensional (3D) cell cultures developing organ-specific cell types and functions. Organoids play an increasingly important role as in vitro models for studying organ development, disease mechanisms, and drug discovery. Recently, we developed a custom spectral-domain OCT (SD-OCT) system to study human heart organoids derived from iPSC cells. We demonstrated the capability of OCT to generate high-resolution 3D images in a fast, label-free and non-destructive manner over 30 days. The OCT imaging system and human heart organoid models are presented as novel research platforms to study heart development and disease mechanisms.

Delineating Advanced Brain Imaging Health Related Outcome in Single-Ventricle Heart Disease

Ashok Panigrahy, MD, Professor of Radiology, Bioinformatics, Bio-engineering and Developmental Biology at the University of Pittsburgh Medical Center, and Radiologist in Chief at Children’s Hospital of Pittsburgh of UPMC

Abstract: Our research harnesses the power of neuroimaging biomarkers to improve our understanding of the underpinnings of poor neurodevelopmental outcomes in patients with single ventricle disease across the lifespan. The current presentation will cover three topics with reference to on-going work in progress in the laboratory: (1) preclinical-human translational modeling (in collaboration with Dr. Cecilia Lo) in which we inter-relate high resolution episcopic microscopy of brain structures of murine cardiac single ventricle mutants to that of single ventricle heart disease patients; (2) imaging harmonization (empirical bayes) and data mining of multi-modal imaging (including non-invasive physiological imaging of cerebral blood flow); (3) improving neuroimaging access to both critically ill and diverse/low resource cohorts combing innovations in rapid/low-field MR and EEG neural biomarkers which can be deployed in the field.