TY - JOUR
T1 - Longitudinal in Utero Analysis of Engrailed-1 Knockout Mouse Embryonic Phenotypes Using High-Frequency Ultrasound
AU - Aristizábal, Orlando
AU - Qiu, Ziming
AU - Gallego, Estefania
AU - Aristizábal, Matias
AU - Mamou, Jonathan
AU - Wang, Yao
AU - Ketterling, Jeffrey A.
AU - Turnbull, Daniel H.
N1 - Funding Information:
This research was funded by National Institutes of Health Grant R01 EB022950. We thank Dr. Alexandra Joyner (Memorial Sloan Kettering Cancer Center) and Dr. Cynthia Loomis (NYU Grossman School of Medicine) for discussions and advice on the En1-ko embryo phenotypes, and Dr. Alexandra Joyner for providing the En1 +/– mice used for breeding. We also thank Alfred Yu and Billy Yiu (University of Waterloo) for providing the core GPU code used for the real-time beamforming.
Funding Information:
This research was funded by National Institutes of Health Grant R01 EB022950. We thank Dr. Alexandra Joyner (Memorial Sloan Kettering Cancer Center) and Dr. Cynthia Loomis (NYU Grossman School of Medicine) for discussions and advice on the En1-ko embryo phenotypes, and Dr. Alexandra Joyner for providing the En1+/– mice used for breeding. We also thank Alfred Yu and Billy Yiu (University of Waterloo) for providing the core GPU code used for the real-time beamforming. The authors have no conflicts of interest to declare. All data included in this article will be made available upon request.
Publisher Copyright:
© 2022 World Federation for Ultrasound in Medicine & Biology
PY - 2023/1
Y1 - 2023/1
N2 - Large-scale international efforts to generate and analyze loss-of-function mutations in each of the approximately 20,000 protein-encoding gene mutations are ongoing using the “knockout” mouse as a model organism. Because one-third of gene knockouts are expected to result in embryonic lethality, it is important to develop non-invasive in utero imaging methods to detect and monitor mutant phenotypes in mouse embryos. We describe the utility of 3-D high-frequency (40-MHz) ultrasound (HFU) for longitudinal in utero imaging of mouse embryos between embryonic days (E) 11.5 and E14.5, which represent critical stages of brain and organ development. Engrailed-1 knockout (En1-ko) mouse embryos and their normal control littermates were imaged with HFU in 3-D, enabling visualization of morphological phenotypes in the developing brains, limbs and heads of the En1-ko embryos. Recently developed deep learning approaches were used to automatically segment the embryonic brain ventricles and bodies from the 3-D HFU images, allowing quantitative volumetric analyses of the En1-ko brain phenotypes. Taken together, these results show great promise for the application of longitudinal 3-D HFU to analyze knockout mouse embryos in utero.
AB - Large-scale international efforts to generate and analyze loss-of-function mutations in each of the approximately 20,000 protein-encoding gene mutations are ongoing using the “knockout” mouse as a model organism. Because one-third of gene knockouts are expected to result in embryonic lethality, it is important to develop non-invasive in utero imaging methods to detect and monitor mutant phenotypes in mouse embryos. We describe the utility of 3-D high-frequency (40-MHz) ultrasound (HFU) for longitudinal in utero imaging of mouse embryos between embryonic days (E) 11.5 and E14.5, which represent critical stages of brain and organ development. Engrailed-1 knockout (En1-ko) mouse embryos and their normal control littermates were imaged with HFU in 3-D, enabling visualization of morphological phenotypes in the developing brains, limbs and heads of the En1-ko embryos. Recently developed deep learning approaches were used to automatically segment the embryonic brain ventricles and bodies from the 3-D HFU images, allowing quantitative volumetric analyses of the En1-ko brain phenotypes. Taken together, these results show great promise for the application of longitudinal 3-D HFU to analyze knockout mouse embryos in utero.
KW - In utero imaging
KW - Longitudinal 3-D ultrasound
KW - Mouse embryo
KW - Mutant phenotype analysis
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U2 - 10.1016/j.ultrasmedbio.2022.09.008
DO - 10.1016/j.ultrasmedbio.2022.09.008
M3 - Article
C2 - 36283941
AN - SCOPUS:85140747711
VL - 49
SP - 356
EP - 367
JO - Ultrasound in Medicine and Biology
JF - Ultrasound in Medicine and Biology
SN - 0301-5629
IS - 1
ER -