ABSTRACT
Establishing connections between changes in linear DNA sequences and complex downstream mesoscopic pathology remains a major challenge in biology. Herein, we report a novel, multi-modal and multiscale imaging approach for comprehensive assessment of cardiovascular physiology in Drosophila melanogaster We employed high-speed angiography, optical coherence tomography (OCT) and confocal microscopy to reveal functional and structural abnormalities in the hdp2 mutant, pre-pupal heart tube and aorta relative to controls. hdp2 harbor a mutation in wupA, which encodes an ortholog of human troponin I (TNNI3). TNNI3 variants frequently engender cardiomyopathy. We demonstrate that the hdp2 aortic and cardiac muscle walls are disrupted and that shorter sarcomeres are associated with smaller, stiffer aortas, which consequently result in increased flow and pulse wave velocities. The mutant hearts also displayed diastolic and latent systolic dysfunction. We conclude that hdp2 pre-pupal hearts are exposed to increased afterload due to aortic hypoplasia. This may in turn contribute to diastolic and subtle systolic dysfunction via vascular-heart tube interaction, which describes the effect of the arterial loading system on cardiac function. Ultimately, the cardiovascular pathophysiology caused by a point mutation in a sarcomeric protein demonstrates that complex and dynamic micro- and mesoscopic phenotypes can be mechanistically explained in a gene sequence- and molecular-specific manner.
ABSTRACT
Magnetic resonance electrical impedance tomography (MREIT) is a method for reconstructing a three-dimensional image of the conductivity distribution in a target volume using magnetic resonance (MR). In MREIT, currents are applied to the volume through surface electrodes and their effects on the MR induced magnetic fields are analyzed to produce the conductance image. However, current injection through surface electrodes poses technical problems such as the limitation on the safely applicable currents. In this paper, we present a new method called magnetic resonance driven electrical impedance tomography (MRDEIT), where the magnetic resonance in each voxel is used as the applied magnetic field source, and the resultant electromagnetic field is measured through surface electrodes or radio-frequency (RF) detectors placed near the surface. Because the applied magnetic field is at the RF frequency and eddy currents are the integral components in the method, a vector wave equation for the electric field is used as the basis of the analysis instead of a quasi-static approximation. Using computer simulations, it is shown that complex permittivity images can be reconstructed using MRDEIT, but that improvements in signal detection are necessary for detecting moderate complex permittivity changes.