Blood contrast enhancement with a novel, non-gaseous nanoparticle contrast agent.
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Animals↗
Biomedical subjects
John S Allen
Publications and source records attributed to John S Allen.
Dynamics and fragmentation of thick-shelled microbubbles.
Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 microm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 microm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.
Contrast Media↗
The magnitude of radiation force on ultrasound contrast agents.
High-speed photography of insonified bubbles with a time resolution of 10 ns allows observations of translation due to radiation force, in addition to the visualization of radial oscillations. A modified version of the Rayleigh-Plesset equation is used to estimate the radius-time behavior of insonified microbubbles, and the accuracy of this model is verified experimentally. The translation of insonified microbubbles is calculated using a differential equation relating the acceleration of the bubble to the forces due to acoustic radiation and the drag imposed by the fluid. Simulations and experiments indicate that microbubbles translate significant distances with clinically relevant parameters. A 1.5 micron radius contrast agent can translate over 5 microns during a single 20-cycle, 2.25 MHz, 380 kPa acoustic pulse, achieving velocities over 0.5 m/s. Therefore, radiation force should be considered during an ultrasonic examination because of the possibility of influencing the position and flow velocity of the contrast agents with the interrogating acoustic beam.
Contrast Media↗
The aging brain: the cognitive reserve hypothesis and hominid evolution.
Compared to other primates, humans live a long time and have large brains. Recent theories of the evolution of human life history stages (grandmother hypothesis, intergenerational transfer of information) lend credence to the notion that selection for increased life span and menopause has occurred in hominid evolution, despite the reduction in the force of natural selection operating on older, especially post-reproductive, individuals. Theories that posit the importance (in an inclusive fitness sense) of the survival of older individuals require them to maintain a reasonably high level of cognitive function (e.g., memory, communication). Patterns of brain aging and factors associated with healthy brain aging should be relevant to this issue. Recent neuroimaging research suggests that, in healthy aging, human brain volume (gray and white matter) is well-maintained until at least 60 years of age; cognitive function also shows only nonsignificant declines at this age. The maintenance of brain volume and cognitive performance is consistent with the idea of a significant post- or late-reproductive life history stage. A clinical model, "the cognitive reserve hypothesis," proposes that both increased brain volume and enhanced cognitive ability may contribute to healthy brain aging, reducing the likelihood of developing dementia. Selection for increased brain size and increased cognitive ability in hominid evolution may therefore have been important in selection for increased lifespan in the context of intergenerational social support networks.
Aging↗