Rationale: Coronary artery disease (CAD) is the leading cause of death worldwide, but there are currently no methods to stimulate artery growth or regeneration in diseased hearts. Studying how arteries are built during development could illuminate strategies for re-building these vessels during ischemic heart disease. We previously found that Dach1 deletion in mouse embryos resulted in small coronary arteries. However, it was not known whether Dach1 gain-of-function would be sufficient to increase arterial vessels and whether this could benefit injury responses. Objective: We investigated how Dach1 overexpression in endothelial cells affected transcription and artery differentiation, and how it influenced recovery from myocardial infarction (MI). Methods and Results: Dach1 was genetically overexpressed in coronary endothelial cells (ECs) in either developing or adult hearts using ApjCreER. This increased the length and number of arterial end branches expanded arteries during development, in both the heart and retina, by inducing capillary ECs to differentiate and contribute to growing arteries. Single-cell RNA sequencing (scRNAseq) of ECs undergoing Dach1-induced arterial specification indicated that it potentiated normal artery differentiation, rather than functioning as a master regulator of artery cell fate. ScRNAseq also showed that normal arterial differentiation is accompanied by repression of lipid metabolism genes, which were also repressed by Dach1. In adults, Dach1 overexpression did not cause a statistically significant change artery structure prior to injury, but increased the number of perfused arteries in the injury zone post-MI. Conclusions: Our data demonstrate that increasing Dach1 is a novel method for driving artery specification and extending arterial branches, which could be explored as a means of mitigating the effects of CAD.

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Segmentation of the geometric morphology of abdominal aortic aneurysm is important for interventional planning. However, the segmentation of both the lumen and the outer wall of aneurysm in magnetic resonance (MR) image remains challenging. This study proposes a registration based segmentation methodology for efficiently segmenting MR images of abdominal aortic aneurysms. The proposed methodology first registers the contrast enhanced MR angiography (CE-MRA) and black-blood MR images, and then uses the Hough transform and geometric active contours to extract the vessel lumen by delineating the inner vessel wall directly from the CE-MRA. The proposed registration based geometric active contour is applied to black-blood MR images to generate the outer wall contour. The inner and outer vessel wall are then fused presenting the complete vessel lumen and wall segmentation. The results obtained from 19 cases showed that the proposed registration based geometric active contour model was efficient and comparable to manual segmentation and provided a high segmentation accuracy with an average Dice value reaching 89.79%.

We propose a new numerical model to describe thrombus formation in cerebral aneurysms. This model combines CFD simulations with a set of bio-mechanical processes identified as being the most important to describe the phenomena at a large space and time scales. The hypotheses of the model are based on in vitro experiments and clinical observations. We document that we can reproduce very well the shape and volume of patient specific thrombus segmented in giant aneurysms. are co-directors of this work.

Purpose: Segmentation of cardiac medical images, an important step in measuring cardiac function, is usually performed either manually or semi-automatically. Fully automatic segmentation of the left ventricle (LV), the right ventricle (RV) as well as the myocardium of 3D magnetic resonance (MR) images throughout the entire cardiac cycle (4D), remains challenging. This study proposes a deformable-based segmentation methodology for efficiently segmenting 4D (3D+t) cardiac MR images. Methods: The proposed methodology first used the Hough transform and the local Gaussian distribution method (LGD) to segment the LV endocardial contours from cardiac MR images. Following that a novel level set-based shape prior method was applied to generate the LV epicardial contours and the RV boundary. Results: This automatic image segmentation approach has been applied to studies on 17 subjects. The results demonstrated that the proposed method was efficient compared to manual segmentation, achieving a segmentation accuracy with average Dice values of 88.62±5.47%, 87.35±7.26%, and 82.63±6.22% for the LV endocardial, LV epicardial and RV contours, respectively. Conclusions: We have presented a method for accurate LV and RV segmentation. Compared to three existing methods, the proposed method can successfully segment the LV and yields the highest Dice value. This makes it an option for clinical assessment of the volume, size and thickness of the ventricles.

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PurposeMitraClip is the sole percutaneous device approved for functional mitral regurgitation (MR; FMR) but MR recurs in over one third of patients. As device-induced mechanical effects are a potential cause for MR recurrence, we tested the hypothesis that MitraClip increases leaflet stress and procedure-related strain in sub-valvular left ventricular (LV) myocardium in FMR associated with coronary disease (FMR-CAD).MethodsSimulations were performed using finite element models of the LV + mitral valve based on MRI of 5 sheep with FMR-CAD. Models were modified to have a 20% increase in LV volume (↑LV_VOLUME) and MitraClip was simulated with contracting beam elements (virtual sutures) placed between nodes in the center edge of the anterior (AL) and posterior (PL) mitral leaflets. Effects of MitraClip on leaflet stress in the peri-MitraClip region of AL and PL, septo-lateral annular diameter (SLAD), and procedure-related radial strain (Err) in the sub-valvular myocardium were calculated.ResultsMitraClip increased peri-MitraClip leaflet stress at end-diastole (ED) by 22.3±7.1 kPa (p<0.0001) in AL and 14.8±1.2 kPa (p<0.0001) in PL. MitraClip decreased SLAD by 6.1±2.2 mm (p<0.0001) and increased Err in the sub-valvular lateral LV myocardium at ED by 0.09±0.04 (p<0.0001)). Furthermore, MitraClip in ↑LV_VOLUME was associated with persistent effects at ED but also at end-systole where peri-MitraClip leaflet stress was increased in AL by 31.9±14.4 kPa (p = 0.0268) and in PL by 22.5±23.7 kPa (p = 0.0101).ConclusionsMitraClip for FMR-CAD increases mitral leaflet stress and radial strain in LV sub-valvular myocardium. Mechanical effects of MitraClip are augmented by LV enlargement.