Morphological phenotyping of mouse hearts using optical coherence tomography

Abstract

Transgenic mouse models have been instrumental in the elucidation of the molecular mechanisms behind many genetically based cardiovascular diseases such as Marfan syndrome (MFS). However, the characterization of their cardiac morphology has been hampered by the small size of the mouse heart. In this report, we adapted optical coherence tomography (OCT) for imaging fixed adult mouse hearts, and applied tools from computational anatomy to perform morphometric analyses. The hearts were first optically cleared and imaged from multiple perspectives. The acquired volumes were then corrected for refractive distortions, and registered and stitched together to form a single, high-resolution OCT volume of the whole heart. From this volume, various structures such as the valves and myofibril bundles were visualized. The volumetric nature of our dataset also allowed parameters such as wall thickness, ventricular wall masses, and luminal volumes to be extracted. Finally, we applied the entire acquisition and processing pipeline in a preliminary study comparing the cardiac morphology of wild-type mice and a transgenic mouse model of MFS.

Aortic and Cardiac Structure and Function Using High-Resolution Echocardiography and Optical Coherence Tomography in a Mouse Model of Marfan Syndrome

“…The OCT volumes of the mouse heart were semi-automatically segmented using Amira software. The ventricular tissue and lumen were segmented and then quantified by considering the number of assigned voxels and the size of each voxel [27]. For the ventricular mass, the specific gravity of myocardium was taken to be 1.055 g·cm -3 .…”

Optical Coherence Tomography for Brain Imaging and Developmental Biology

“…tethers connecting the endocardium to the myocardium) [132], as well as assessment of fast dynamics of a beating heart in vivo . Next, we focus our discussion on applications of OCT on heart development in various animal models, including Xenopus [11, 133–135], zebrafish [40, 136], avian [43, 137–144], mouse [44, 145–154]and Drosophila [45, 155–163]. …”

“…Measured chamber volumes and wall thicknesses showed large variations between mutant hearts and normal ones. Quantification of chamber volumes and wall thicknesses can be applied in study of transgenic adult mouse [154]. …”

Rotational imaging optical coherence tomography for full-body mouse embryonic imaging

“…A similar concept has also been applied to mouse embryo cardiac phenotyping. 35 In our current setup, a small tilt is introduced between the glass surface and the beam (to avoid specular reflection from the glass surface) that might lead to imperfect overlapping of the images during the registration process. In the future, antireflection coating on the glass surface could reduce specular reflections and minimize the incidence angle.…”