Four‐dimensional live imaging of hemodynamics in mammalian embryonic heart with Doppler optical coherence tomography

Garcia

Lopez

et al. 2016

Biomed. Opt. Express

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Abstract:Neural tube closure is a critical feature of central nervous system morphogenesis during embryonic development. Failure of this process leads to neural tube defects, one of the most common forms of human congenital defects. Although molecular and genetic studies in model organisms have provided insights into the genes and proteins that are required for normal neural tube development, complications associated with live imaging of neural tube closure in mammals limit efficient morphological analyses. Here, we report the use of optical coherence tomography (OCT) for dynamic imaging and quantitative assessment of cranial neural tube closure in live mouse embryos in culture. Through time-lapse imaging, we captured two neural tube closure mechanisms in different cranial regions, zipper-like closure of the hindbrain region and button-like closure of the midbrain region. We also used OCT imaging for phenotypic characterization of a neural tube defect in a mouse mutant. These results suggest that the described approach is a useful tool for live dynamic analysis of normal neural tube closure and neural tube defects in the mouse model. 131-137 (1991). 7. G. Morriss-Kay, H. Wood, and W. H. Chen, "Normal neurulation in mammals," Ciba Foundation symposium 181, 51-63 (1994). 8. L. R. Campbell, D. H. Dayton, and G. S. Sohal, "Neural tube defects: A review of human and animal studies on the etiology of neural tube defects," Teratology 34(2), 171-187 (1986). 9. Y. Yamaguchi and M. Miura, "How to form and close the brain: insight into the mechanism of cranial neural tube closure in mammals," Cell. Mol. Life Sci. 70(17), 3171-3186 (2013). 10. D. M. Juriloff and M. J. Harris, "Mouse models for neural tube closure defects," Hum. Mol. Genet. 9(6), 993-1000 (2000).

Section: Introductionmentioning

confidence: 99%

Dynamic imaging and quantitative analysis of cranial neural tube closure in the mouse embryo using optical coherence tomography

Garcia

Lopez

et al. 2016

Biomed. Opt. Express

Self Cite

“…Doppler OCT was conducted based on windowed Kasai autocorrelation function . The details of the Doppler OCT imaging of the cardiac blood flow in the mouse embryo were previously reported in by our group and the same method was applied in this study. Doppler processing was performed from the same dataset where SV‐OCT imaging was obtained.…”

Section: Methodsmentioning

confidence: 89%

Speckle variance optical coherence tomography of blood flow in the beating mouse embryonic heart

Grishina

Journal of Biophotonics

Larina

2017

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Efficient separation of blood and cardiac wall in the beating embryonic heart is essential and critical for experiment-based computational modelling and analysis of early-stage cardiac biomechanics. Although speckle variance optical coherence tomography (SV-OCT) relying on calculation of intensity variance over consecutively acquired frames is a powerful approach for segmentation of fluid flow from static tissue, application of this method in the beating embryonic heart remains challenging because moving structures generate SV signal indistinguishable from the blood. Here, we demonstrate a modified four-dimensional SV-OCT approach that effectively separates the blood flow from the dynamic heart wall in the beating mouse embryonic heart. The method takes advantage of the periodic motion of the cardiac wall and is based on calculation of the SV signal over the frames corresponding to the same phase of the heartbeat cycle. Through comparison with Doppler OCT imaging, we validate this speckle-based approach and show advantages in its insensitiveness to the flow direction and velocity as well as reduced influence from the heart wall movement. This approach has a potential in variety of applications relying on visualization and segmentation of blood flow in periodically moving structures, such as mechanical simulation studies and finite element modelling. Four-dimensional speckle variance OCT imaging shows the blood flow inside the beating heart of an E8.5 mouse embryo.

“…The postprocessing method for a combined 4D structural and Doppler OCT reconstruction of the entire beating embryonic heart was previously established. 20 Briefly, based on the OCT complex signal I ¼ x þ iy, structural images were obtained with the intensity jIj of each pixel in the logarithm scale, and Doppler images were achieved by the windowed Kasai autocorrelation function, 39 where axial flow velocity v a was mapped to each pixel. The calculation for the spatial location (m; n) was via E Q -T A R G E T ; t e m p : i n t r a l i n k -; e 0 0 1 ; 1 1…”

Section: Oct System and 4d Imagingmentioning

confidence: 99%

Live mechanistic assessment of localized cardiac pumping in mammalian tubular embryonic heart

Larina

2020

J. Biomed. Opt.

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Significance: Understanding how the valveless embryonic heart pumps blood is essential to elucidate biomechanical cues regulating cardiogenesis, which is important for the advancement of congenital heart defects research. However, methods capable of embryonic cardiac pumping analysis remain limited, and assessing this highly dynamic process in mammalian embryos is challenging. New approaches are critically needed to address this hurdle. Aim: We report an imaging-based approach for functional assessment of localized pumping dynamics in the early tubular embryonic mouse heart. Approach: Four-dimensional optical coherence tomography was used to obtain structural and Doppler hemodynamic imaging of the beating heart in live mouse embryos at embryonic day 9.25. The pumping assessment was performed based on the volumetric blood flow rate, flow resistance within the heart tube, and pressure gradient induced by heart wall movements. The relation between the blood flow, the pressure gradient, and the resistance to flow were evaluated through temporal analyses and Granger causality test. Results: In the ventricles, our method revealed connections between the temporal profiles of pressure gradient and volumetric blood flow rate. Statistically significant causal relation from the pressure gradient to the blood flow was demonstrated. Our analysis also suggests that cardiac pumping in the early ventricles is a combination of suction and pushing. In contrast, in the outflow tract, where the conduction wave is slower than the blood flow, we did not find significant causal relation from pressure to flow, suggesting that, different from ventricular regions, the local active contraction of the outflow tract is unlikely to drive the flow in that region. Conclusions: We present an imaging-based approach that enables localized assessment of pumping dynamics in the mouse tubular embryonic heart. This method creates a new opportunity for functional analysis of the pumping mechanism underlying the developing mammalian heart at early stages and could be useful for studying biomechanical changes in mutant embryonic hearts that model congenital heart defects.