Biological effects of high-frequency ultrasound exposure during mouse organogenesis

Brown, Alan; Reid, Angela D; Leamen, Lisa; Cucevic, Viviene; Foster, F. Stuart

doi:10.1016/j.ultrasmedbio.2004.07.020

Cited by 15 publications

(10 citation statements)

References 40 publications

(53 reference statements)

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“…However, anesthetizing pregnant mice poses some concern for the developing fetuses. While isofluorane exposure has been reported to have a deleterious effect on early mouse embryo development [28], recent reports have demonstrated that fetal exposure to isofluorane during ultrasonography on GD 8.5 or GD 10.5 has no significant adverse biological effects [29], which is consistent with the lack of negative effects observed in the current study. Given that the model described herein requires the use of isofluorane during late gestation, perhaps the deleterious effects that isofluorane has on early mouse embryo development were avoided.…”

Section: Resultssupporting

confidence: 90%

In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging

Greene

Dunaway

Bowers

et al. 2011

Reprod Biol Endocrinol

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BackgroundVascular endothelial growth factor receptor-2 (VEGFR2) plays a pivotal role in angiogenesis by eliciting vascular endothelial cell growth when bound to VEGF, a powerful pro-angiogenic ligand. While Vegf and Vegfr2 are expressed throughout gestation, the latter third of gestation in mice is characterized by a marked increase in fetoplacental angiogenesis. Thus, the objective of this study was to determine the feasibility of monitoring fetoplacental Vegfr2 gene activity non-invasively using a Vegfr2-luc reporter transgenic mouse and bioluminescent imaging.MethodsImaging parameters were optimized using two wild-type (WT) females, bearing Vegfr2-luc fetuses. Then, seven WT females, bred to Vegfr2-luc males, were imaged from gestational day (GD) 12 to 18 to determine the usefulness of the Vegfr2-luc mouse as a model for studying fetoplacental Vegfr2 activity during pregnancy. Semi-quantitative RT-PCR of Vegfr2 was also performed on whole fetoplacental units during this time. Additionally, resultant neonates were imaged at postnatal day (PND) 7, 14 and 21 to monitor Vegfr2 activity during post-natal development.ResultsFetoplacental Vegfr2 gene activity was detected as light emissions beginning on GD 12 of gestation and increased throughout the imaging period (P < 0.05), and this paralleled the Vegfr2 mRNA data obtained from RT-PCR analysis. A decline in fetoplacental light emissions was associated with a poor pregnancy outcome in one pregnancy, indicating that this approach has potential use for studies monitoring pregnancy well being. Additionally, neonatal Vegfr2 activity was detected at PND 7, 14 and 21 but declined with time (P < 0.0001).ConclusionsIn utero fetoplacental Vegfr2 gene activity was monitored longitudinally in a quantitative manner using a luciferase reporter gene and bioluminescent imaging during the latter third of gestation. This study demonstrates the feasibility of using the Vegfr2-luc mouse to monitor late gestation fetoplacental angiogenic activity under normal and experimental conditions. Additionally, neonatal Vegfr2 gene activity was monitored for three weeks postpartum, allowing continuous monitoring of Vegfr2 activity during the latter third of gestation and postnatal development within the same animals.

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Section: Resultssupporting

confidence: 90%

In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging

Greene

Dunaway

Bowers

et al. 2011

Reprod Biol Endocrinol

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“…No significant bioeffects on the adult mice were observed but minimal bioeffects on growth and malformations of their offspring were found. 16 It appears that it is prudent to study carefully the bioeffects of acoustic beam at high frequency and high acoustic intensity before it is used for in vivo studies.…”

mentioning

confidence: 99%

A feasibility study of in vivo applications of single beam acoustic tweezers

Liu

Lee

Chen

et al. 2014

Applied Physics Letters

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Tools that are capable of manipulating micro-sized objects have been widely used in such fields as physics, chemistry, biology, and medicine. Several devices, including optical tweezers, atomic force microscope, micro-pipette aspirator, and standing surface wave type acoustic tweezers have been studied to satisfy this need. However, none of them has been demonstrated to be suitable for in vivo and clinical studies. Single beam acoustic tweezers (SBAT) is a technology that uses highly focused acoustic beam to trap particles toward the beam focus. Its feasibility was first theoretically and experimentally demonstrated by Lee and Shung several years ago. Since then, much effort has been devoted to improving this technology. At present, the tool is capable of trapping a microparticle as small as 1 lm, as well as a single red blood cell. Although in comparing to other microparticles manipulating technologies, SBAT has advantages of providing stronger trapping force and deeper penetration depth in tissues, and producing less tissue damage, its potential for in vivo applications has yet been explored. It is worth noting that ultrasound has been used as a diagnostic tool for over 50 years and no known major adverse effects have been observed at the diagnostic energy level. This paper reports the results of an initial attempt to assess the feasibility of single beam acoustic tweezers to trap microparticles in vivo inside of a blood vessel. The acoustic intensity of SBAT under the trapping conditions that were utilized was measured. The mechanical index and thermal index at the focus of acoustic beam were found to be 0.48 and 0.044, respectively, which meet the standard of commercial diagnostic ultrasound system. V C 2014 AIP Publishing LLC.[http://dx.doi.org/10.1063/1.4900716] Similar to physics involved in optical trapping, 1 a steep intensity gradient of the acoustic microbeam coupled with a minimal difference in acoustic impendence between microparticles and the surrounding medium results in a net acoustic radiation force (gradient force) on the particle in moving it towards the beam axis. It was first theoretically and experimentally demonstrated by Lee and Shung. 2 Several in vitro applications of single beam acoustic tweezers (SBAT) have been explored. It has been demonstrated to be capable of manipulating a single cell and estimating the deformability of red blood cells and assaying the invasion potential of breast cancer cells. 3,4 However, its enormous potentials for in vivo applications have not been explored.Obviously, technologies like micro-pipette aspiration and atomic force microscopy, which have very short working distance or requires direct contact with the objects to be controlled, are not suitable for the in vivo study. Technologies for noncontact manipulation of microparticles also are available, i.e., laser beam 1 and electron beam, 5 but they suffer from poor penetration in skin and other human tissues. Additionally, heat generated by the highly focused laser and electron beams may cause tissue dama...

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“…This is further strengthened by observations on postnatal body length changes found in our studies. However, Brown et al (2004) did not find any significant difference in pup weight, body length, or crown-rump length when CD-1 mice were exposed to Doppler ultrasound at a frequency of 40 MHz.…”

Section: Discussionmentioning

confidence: 66%

Gestational stage sensitivity to ultrasound effect on postnatal growth and development of mice

Rao

Ovchinnikov

McRae

2006

Birth Defects Research

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Biological effects of high-frequency ultrasound exposure during mouse organogenesis

Cited by 15 publications

References 40 publications

In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging

In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging

A feasibility study of in vivo applications of single beam acoustic tweezers

Gestational stage sensitivity to ultrasound effect on postnatal growth and development of mice

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