A Multi-scale Learning of Data-driven and Anatomically Constrained Image Registration for Adult and Fetal Echo Images

Temporal echo image registration is a basis for clinical quantifications such as cardiac motion estimation, myocardial strain assessments, and stroke volume quantifications. Deep learning image registration (DLIR) is consistently accurate, requires less computing effort, and has shown encouraging results in earlier applications. However, we propose that a greater focus on the warped moving image's anatomic plausibility and image quality can support robust DLIR performance. Further, past implementations have focused on adult echo, and there is an absence of DLIR implementations for fetal echo. We propose a framework combining three strategies for DLIR for both fetal and adult echo: (1) an anatomic shape-encoded loss to preserve physiological myocardial and left ventricular anatomical topologies in warped images; (2) a data-driven loss that is trained adversarially to preserve good image texture features in warped images; and (3) a multi-scale training scheme of a data-driven and anatomically constrained algorithm to improve accuracy. Our experiments show that the shape-encoded loss and the data-driven adversarial loss are strongly correlated to good anatomical topology and image textures, respectively. They improve different aspects of registration performance in a non-overlapping way, justifying their combination. We show that these strategies can provide excellent registration results in both adult and fetal echo using the publicly available CAMUS adult echo dataset and our private multi-demographic fetal echo dataset, despite fundamental distinctions between adult and fetal echo images. Our approach also outperforms traditional non-DL gold standard registration approaches, including Optical Flow and Elastix. Registration improvements could also be translated to more accurate and precise clinical quantification of cardiac ejection fraction, demonstrating a potential for translation

The fluid shear stress environment of the normal and congenital bicuspid aortic valve and the implications on valve calcification

Calcific aortic valve disease is highly prevalent, especially in the elderly. Currently, the exact mechanism of the calcification process is not completely understood, limiting our ability to prevent or cure the disease. Ex vivo investigations, however, have provided evidence that the aortic valve's biological response is sensitive to mechanical forces, including fluid shear stresses, leading to the hypothesis that adverse fluid shear stress environment play a role in leading to valve calcification. This thesis seeks to investigate this hypothesis. A method for performing experimental measurement of time-varying shear stress on aortic valve leaflets under physiologic flow conditions was first developed, based on the Laser Doppler Velocimetry technique, and was systematically validated. This method was then applied to both the aortic surface and the ventricular surface of a normal tricuspid the aortic valve, and then on a congenital bicuspid aortic valve, using suitable in vitro valve models and an in vitro pulsatile flow loop. It was found that in the tricuspid valve, the peak shear stress on the aortic surface under adult resting condition was approximately 15-19 dyn/cm². Aortic surface shear stresses were elevated during mid- to late-systole, with the development of the sinus vortex, and were low during all other instances. Aortic surface shear stresses were observed to increase with increasing stroke volume and with decreasing heart rate. On the ventricular surface, shear stresses had a systolic peak of approximately 64-71 dyn/cm² under adult resting conditions. During late systole, due to the Womersley effect, shear stresses were observed to reverse in direction to a substantial magnitude for a substantial period of time. Further, it was found that a moderately stenotic bicuspid aortic valve can experience excessive unsteadiness in shear stress experienced by its leaflets, most likely due to the turbulent forward flow resulting from the stenosis, and due to the skewed forward flow. To demonstrate that the measured shear stresses can have an effect on the aortic valve biology, ex vivo experiments were performed in specific to determine the effects of these various shear stress characteristics on the biological response of porcine aortic valve leaflets, using the cone and plate bioreactor. It was found that unsteady shear stress measured in the bicuspid valve resulted in increased calcium accumulation. Further, it was found that low shear stresses and high frequency shear stresses resulted in increased calcium accumulation. Thus, shear stress was found to affect aortic valve pathology, and low and unsteady fluid shear stresses can enhance pathology.PhDCommittee Chair: Yoganathan, Ajit P.; Committee Member: Giddens, Don P.; Committee Member: Gleason, Rudolph L. Jr.; Committee Member: Glezer, Ari; Committee Member: Jo, Hanjoong; Committee Member: Taylor, W. Rober

Supplementary Data used for plots in the publication

Supplementary Data Supporting Publication</p

Fluid mechanics of the left atrial ligation chick embryonic model of hypoplastic left heart syndrome

10.1007/s10237-021-01447-3Biomechanics and Modeling in Mechanobiology2041337-135

Characterizaton of the Vessel Geometry, Flow Mechanics and Wall Shear Stress in the Great Arteries of Wildtype Prenatal Mouse

Introduction Abnormal fluid mechanical environment in the pre-natal cardiovascular system is hypothesized to play a significant role in causing structural heart malformations. It is thus important to improve our understanding of the prenatal cardiovascular fluid mechanical environment at multiple developmental time-points and vascular morphologies. We present such a study on fetal great arteries on the wildtype mouse from embryonic day 14.5 (E14.5) to near-term (E18.5). Methods Ultrasound bio-microscopy (UBM) was used to measure blood velocity of the great arteries. Subsequently, specimens were cryo-embedded and sectioned using episcopic fluorescent image capture (EFIC) to obtain high-resolution 2D serial image stacks, which were used for 3D reconstructions and quantitative measurement of great artery and aortic arch dimensions. EFIC and UBM data were input into subject-specific computational fluid dynamics (CFD) for modeling hemodynamics. Results In normal mouse fetuses between E14.5–18.5, ultrasound imaging showed gradual but statistically significant increase in blood velocity in the aorta, pulmonary trunk (with the ductus arteriosus), and descending aorta. Measurement by EFIC imaging displayed a similar increase in cross sectional area of these vessels. However, CFD modeling showed great artery average wall shear stress and wall shear rate remain relatively constant with age and with vessel size, indicating that hemodynamic shear had a relative constancy over gestational period considered here. Conclusion Our EFIC-UBM-CFD method allowed reasonably detailed characterization of fetal mouse vascular geometry and fluid mechanics. Our results suggest that a homeostatic mechanism for restoring vascular wall shear magnitudes may exist during normal embryonic development. We speculate that this mechanism regulates the growth of the great vessels.</p

Fluid mechanics parameters of flow in mouse great arteries.

<p>a) Reynolds numbers of flow in specific arteries, averaged along the entire arterial centerline, at different developmental stages. DAo: descending aorta; AAo: ascending aorta and aortic arch; PT: pulmonary trunk including the <i>ductus arteriosus</i>. b) Peak flow streamlines in the great arteries of embryonic mouse at E14.5 (left) and fetal mice at E17.5 (right). c) Normalized helicity iso-surfaces in the flow in great arteries of embryonic and fetal mice of various developmental stages, showing the development of classical Dean flow in the great arteries. There was a general increase helicity over age, and equal intensity in right-handed (red, normalized helicity = 0.2) and left-handed (blue, normalized helicity = −0.2) helical structures.</p

Mouse great arterial wall shear stress variation along the length of the arteries.

<p>These plots show how wall shear parameters change from one cross section to the next, moving along the vascular centerline from the great arterial roots to the distal descending aorta. The vertical axis denotes a wall shear parameter, which is either wall shear stress (a, c) or wall shear rate (b, d); and the horizontal axis denotes the location on the centerline of vessels. Wall shear parameters are averaged over the entire cross section at each vascular centerline location. In plots (a) and (b), the horizontal axis denotes the centerline trajectory from the aortic root boundary to the aortic isthmus to the thoracic descending aorta boundary; while in plots (c) and (d), the horizontal axis denotes the centerline trajectory from the pulmonary root boundary to the ductus arteriosus to the thoracic descending aorta boundary. Centerline distance from the aortic/pulmonary roots were scaled such that the geometric landmarks such as the locations of arterial branches could be plotted at the same location across different ages to allow comparisons of features across different gestation stages.</p

Variation of geometric and mechanics parameters across different vessel sizes.

<p>(a) Wall shear stress, (b) wall shear rate, and (c) centerline velocity averaged for specific vessels, plotted against average cross sectional area of the same vessel. Data for all ages between E14.5 and E18.5 were plotted. Correlation and regression analysis were performed for data for all three vessels cumulatively. AAo: ascending aorta; DAo: descending aorta; PT: pulmonary trunk and the <i>ductus arteriosus</i>.</p

Variation of geometric and mechanics parameters over gestational ages.

<p>(a) Wall shear stress, (b) wall shear rate, (c) centerline velocity, and (d) vessel size averaged within specific arteries and plotted against developmental age. Correlation and regression analysis were performed for data for all three vessels cumulatively. AAo: ascending aorta; DAo: descending aorta; PT: pulmonary trunk and the <i>ductus arteriosus</i>.</p

Human Fetal Hearts with Tetralogy of Fallot has Altered Fluid Mechanical Force Environment from Normal Fetal Hearts

International Fetal Medicine and Surgery Societ